TW201915004A - Thienopyridine compound, and preparing method, pharmaceutical composition and application thereof for preparing a medicament capable of preventing or treating tumor growth and metastasis - Google Patents

Thienopyridine compound, and preparing method, pharmaceutical composition and application thereof for preparing a medicament capable of preventing or treating tumor growth and metastasis Download PDF

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TW201915004A
TW201915004A TW106136612A TW106136612A TW201915004A TW 201915004 A TW201915004 A TW 201915004A TW 106136612 A TW106136612 A TW 106136612A TW 106136612 A TW106136612 A TW 106136612A TW 201915004 A TW201915004 A TW 201915004A
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piperazinyl
carbonyl
pyridinyl
methyl
sulfonyl
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TWI780077B (en
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鄧賢明
張保錠
劉雙
董超
孫細歡
黃曉星
鄧舟
李雲展
魯嶽
李莉
胡志鈺
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大陸商南京紅云生物科技有限公司
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

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Abstract

The present invention relates to a thienopyridine compound, and a preparing method, a pharmaceutical composition and an application thereof and, more particularly, to a type of compounds having ALK and/or c-Met selectively inhibitory activity, a preparing method thereof, a pharmaceutical composition comprising the same, the use of the compounds in preparation of a medicament for preventing or treating a disease related to a progressive lymphoma kinase in vivo, and the use thereof in the preparation of a medicament for preventing or treating a disease related to angiogenesis or cancer metastasis, particularly in the preparation of a medicament for preventing or treating tumor growth and metastasis.

Description

噻吩並嘧啶類化合物、其製備方法、藥用組合物及其應用Thienopyrimidine compounds, preparation method thereof, medicinal composition and application thereof

本發明涉及藥物化學領域，具體地，涉及一類具有 ALK和/或 c-Met選擇性抑制活性的化合物，其製備方法、包含該化合物的藥物組合物，以及這些化合物在製備用於預防或治療與生物體內漸變性淋巴瘤激酶相關的疾病的藥物中的用途，以及在製備用於預防或治療與血管新生或癌轉移相關的疾病的藥物中的用途，尤其是在製備用於預防或治療腫瘤生長與轉移的藥物中的用途。The present invention relates to the field of medicinal chemistry, in particular, to a class of compounds with ALK and/or c-Met selective inhibitory activity, methods for their preparation, pharmaceutical compositions containing the compounds, and preparation of these compounds for prevention or treatment and Use in a medicament for gradual lymphoma kinase-related diseases in organisms, and in the preparation of a medicament for the prevention or treatment of diseases related to angiogenesis or cancer metastasis, especially in preparation for the prevention or treatment of tumor growth Use with transferred drugs.

漸變性淋巴瘤酶（ALK）是一種受體酪氨酸激酶，隸屬於胰島素受體超家族。蛋白結構從N端到C端依次為胞外受體結構域、跨膜區和胞內酪氨酸激酶結構域。正常的ALK蛋白主要在中樞神經和末梢神經系統中表達，人體中ALK基因的表達水準隨腦部發育程度呈現下降趨勢，尤其在成熟腦組織中的量很少。而在其他系統尤其是造血體統中尚未發現ALK的表達，證明其表達和分佈具有一定的區域性。Progressive lymphoma enzyme (ALK) is a receptor tyrosine kinase that belongs to the insulin receptor superfamily. The protein structure from N-terminal to C-terminal is the extracellular receptor domain, transmembrane domain and intracellular tyrosine kinase domain. Normal ALK protein is mainly expressed in the central nervous system and peripheral nervous system. The expression level of ALK gene in human body shows a downward trend with the degree of brain development, especially in mature brain tissue. However, the expression of ALK has not been found in other systems, especially the hematopoietic system, which proves that its expression and distribution have a certain regionality.

正常情況下，人源的 ALK基因可以編碼 1602個氨基酸、200kDa的 I型穿膜蛋白 ALK，但該基因通常處於休眠狀態。在與其他基因發生融合的情況下，ALK基因可以成為非常強力的致癌基因。目前已經發現的可以與ALK基因發生融合的基因有核磷蛋白基因（NPM，漸變性大細胞淋巴瘤ALCL），棘皮動物微管相關蛋白樣4基因（EML4，非小細胞肺癌NSCLC），原肌球蛋白3基因（TPM3，炎性肌纖維母細胞瘤IMT）等等（Nat. Rev. Cancer, 2008, 8, 11–23.；Nat. Rev. Cancer, 2013, 13, 685-700.；Expert Opin. Ther. Pat., 2014. 24(4): p. 417-42.）。Under normal circumstances, the human ALK gene can encode the 1602 amino acid, 200kDa type I penetrating protein ALK, but the gene is usually dormant. In the case of fusion with other genes, the ALK gene can become a very powerful oncogene. The genes that have been found to be fused with the ALK gene include the nucleophosphoprotein gene (NPM, gradual large cell lymphoma ALCL), the echinoderms microtubule-associated protein-like 4 gene (EML4, non-small cell lung cancer NSCLC), and the original muscle Globulin 3 gene (TPM3, inflammatory myofibroblastoma IMT), etc. (Nat. Rev. Cancer, 2008, 8, 11-23.; Nat. Rev. Cancer, 2013, 13, 685-700.; Expert Opin . Ther. Pat., 2014. 24(4): p. 417-42.).

在非小細胞肺癌中，主要是與 EML4基因發生融合，該融合基因（EML4-ALK）在 NSCLC中的發生率為 4%-7%。隨著對非小細胞肺癌（NSCLC）在分子生物學上的研究不斷深入，基於分子標記物（biomarker）的個性化治療已經從實驗室走向了臨床，並在對晚期非小細胞肺癌患者的治療上取得了較大的臨床進展。這意味著除了對 NSCLC可以進行傳統的病理組織學分類外，還可以根據具體患者的不同分子標記物的不同表達水準進行分子表型分類。NSCLC患者在接受治療前進行相關分子標記物檢測。在臨床上醫生可以根據其腫瘤分子表型特徵進行有針對性的治療，從而提高治療效果。在這樣的背景下，以與腫瘤發生、發展密切相關的驅動基因或其編碼蛋白為靶點研究開發新藥物已經成為抗腫瘤藥物研究的熱點。In non-small cell lung cancer, it is mainly fused with the EML4 gene. The incidence of this fusion gene (EML4-ALK) in NSCLC is 4%-7%. With the continuous in-depth research on molecular biology of non-small cell lung cancer (NSCLC), personalized treatment based on molecular markers (biomarker) has moved from the laboratory to the clinic, and is in the treatment of patients with advanced non-small cell lung cancer Great clinical progress has been made. This means that in addition to traditional histopathological classification of NSCLC, molecular phenotype classification can also be carried out according to the different expression levels of different molecular markers in specific patients. NSCLC patients undergo relevant molecular marker testing before receiving treatment. In clinic, doctors can carry out targeted treatment according to their tumor molecular phenotypic characteristics, thereby improving the treatment effect. In this context, the research and development of new drugs targeting the driver genes or their coded proteins closely related to tumor occurrence and development has become a hot spot in the research of anti-tumor drugs.

目前，美國食品和藥物管理局已經批准輝瑞（Pfizer）公司開發的小分子抑制劑 CrizotInib（J. Thorac. Oncol., 2010. 5(12): p. 2044-6.）、諾華（Novartis）公司開發的 Ceritinib（J. Med. Chem., 2013. 56(14): p. 5675-90.）、 Chugai PharmaceutICal開發的Alectinib（Cancer Lett., 2014. 351(2): p. 215-21.）上市。但是，也有臨床研究表明有部分患者對 Crizotinib已經出現了耐藥性，同時，Crizotinib的生物利用度也有待提高。Ceritinib可以針對部分對 Crizotinib出現耐藥性或不耐受的患者。因此，臨床實踐中非常需要它們的替代化合物已提高藥效和應對耐藥性。 At present, the US Food and Drug Administration has approved the small molecule inhibitor CrizotInib developed by Pfizer (J. Thorac. Oncol., 2010. 5(12): p. 2044-6.) and Novartis Ceritinib (J. Med. Chem., 2013. 56(14): p. 5675-90.), Alectinib (Cancer Lett., 2014. 351(2): p. 215-21.) developed by Chugai PharmaceutICal Listed. However, there are also clinical studies that show that some patients have developed resistance to Crizotinib, and at the same time, the bioavailability of Crizotinib needs to be improved. Ceritinib can target some patients who are resistant or intolerant to Crizotinib. Therefore, there is a great need for their alternative compounds in clinical practice to improve the efficacy and cope with drug resistance.

本發明發明人為了尋找新ALK抑制劑，經過廣泛深入的研究，設計、合成了一系列結構新穎、安全性高、對多種酪氨酸激酶（EGFR、PDGFR、c-Met等），尤其是對ALK具有較高的活性的多取代噻吩並嘧啶(噻吩[3,2-d]嘧啶)衍生物，並且研究了這一類新型衍生物的抗腫瘤活性。 化合物的通式：IIn order to find new ALK inhibitors, the inventors of the present invention, after extensive and in-depth research, designed and synthesized a series of novel structure, high safety, and a variety of tyrosine kinases (EGFR, PDGFR, c-Met, etc.), especially for ALK has a high-activity multi-substituted thienopyrimidine (thiophene [3,2-d] pyrimidine) derivative, and the anti-tumor activity of this new type of derivative has been studied. The general formula of the compound: I

其中取代基和符號的定義下面詳細說明。The definitions of substituents and symbols are explained in detail below.

本發明的一目的是提供一類具有 ALK和/或 c-Met選擇性抑制活性的化合物及其藥學上可接受的鹽或藥學上可接受的溶劑合物； 本發明的另一目的是提供一種上述化合物的製備方法； 本發明的另一目的是提供一種包含上述化合物的藥物組合物； 本發明的另一目的是提供上述化合物在製備用於預防或治療與生物體內漸變性淋巴瘤酶相關的伴隨細胞異常增殖、形態變化以及運動功能亢進等的疾病的藥物中的用途，以及在製備用於預防或治療與血管新生或癌轉移相關的疾病的藥物中的用途，尤其是在製備用於預防或治療腫瘤生長與轉移的藥物中的用途。One object of the present invention is to provide a class of compounds having ALK and/or c-Met selective inhibitory activity and pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof; another object of the present invention is to provide a kind of the above The preparation method of the compound; Another object of the present invention is to provide a pharmaceutical composition containing the above-mentioned compound; Another object of the present invention is to provide the above-mentioned compound in the preparation for the prevention or treatment of the concomitant associated with gradual lymphoma enzyme in vivo Use in drugs for diseases such as abnormal cell proliferation, morphological changes, and hypermotor function, and in the preparation of drugs for the prevention or treatment of diseases related to angiogenesis or cancer metastasis, especially in preparation for prevention or Use in drugs for the treatment of tumor growth and metastasis.

本發明是通過下面技術方案實現的。The present invention is achieved through the following technical solutions.

第一方面，本發明提供了一種下面通式 I表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，I 其中：R’為氫，氯或溴； R1 選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基，N-甲基-4-呱啶基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪-1-基磺醯基，4-乙醯基呱嗪-1-基磺醯基，4-叔丁氧羰基呱嗪-1-基磺醯基，4-(2-羥基乙基)呱嗪-1-基磺醯基，4-(2-氰基乙基)呱嗪-1-基磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基磺醯基，4-(2-N,N-二乙基乙基)呱嗪-1-基磺醯基，4-(3-羥基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基磺醯基，嗎啉-1-基磺醯基，3, 5-二甲基嗎啉-1-基磺醯基，4-(四氫吡咯基)呱啶-1-基磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪-1-基磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，4-(四氫吡咯基)呱啶基--1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基羰基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基羰基，4-(3-羥基丙基)呱嗪-1-基羰基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基羰基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-呱嗪-1-基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪-1-基羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪-1-基甲醯氨基，4-乙基呱嗪-1-基甲醯氨基，4-乙醯基呱嗪-1-基甲醯氨基，4-叔丁氧羰基呱嗪-1-基甲醯氨基，4-(2-羥基乙基)呱嗪-1-基甲醯氨基，4-(2-氰基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基甲醯氨基，4-(3-羥基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基甲醯氨基，嗎啉-1-基甲醯氨基，3, 5-二甲基嗎啉-1-基甲醯氨基，4-(四氫吡咯基)呱啶-1-基甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶-1-基甲醯氨基，4-(4-乙基呱嗪-1-基)呱啶-1-基甲醯氨基，4-(4-乙醯基-呱嗪-1基)呱啶-1-基甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪-1-基甲醯氨基；或 （11）氨基乙醯氨基，2-二甲氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，四氫吡咯基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，3-N, N-二乙基氨基四氫吡咯基乙醯氨基，4-甲基呱嗪基乙醯氨基，4-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-羥基乙基)呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-羥基丙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，嗎啉基乙醯氨基，3, 5-二甲基嗎啉基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-(N-甲基-4-呱啶基)呱嗪基乙醯氨基，4-(四氫吡咯-1-基)呱啶基乙醯氨基；2-甲基氨基乙醯氨基，2-(1-甲基乙基)氨基乙醯氨基；N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； A為直接鍵或亞甲基； X為NH，S或O； R2 選自： 1）C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，二甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 3）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基； 4）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為N，Y3 為C-A13 ，Y4 為N，O或S； Y2 為O或S，Y3 為N-A13 ，Y4 為CH； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基。In the first aspect, the present invention provides a compound represented by the following general formula I, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, I Wherein: R'is hydrogen, chlorine or bromine; R 1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N- Diethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-di Methylaminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine ) Base propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N -Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl 5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4- Pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, N-methyl-4-pyridinyl, (3) N, N- Dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-( 4-methylpiperazinyl) ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropyl Aminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino , N-isopropylpiperidine-4-amino, (4) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N- Diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxypiperazinyl)ethoxy, 2-morpholinylethoxy, 2 -Thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-Diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetyrazinyl)propoxy, 3-morpholinylpropoxy , 3-Thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethyl Oxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-dimethylamino Pyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5-dimethyl Morpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazine Group, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4- acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methylsulfonyl azizinyl, 4- (2-Hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4- (3-N, N-Diethylaminopropyl) pyrazinyl, 2-oxo-piperazin-4-yl, imidazolyl, 4-methylimidazolyl, (6) 4-(4-methyl Piperazine) piperidyl, 4-(4-ethyl piperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4-(4-acetyl piperazine) (Azinyl) piperidinyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidinyl, 4-(4-methanesulfonyl piperazinyl) piperidinyl, 4-(4-(2-hydroxyl) Ethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidine Group, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2-N, N-diethylaminoethyl) piperazine Yl) pyridinyl, 4-(4-(3-N, N-dimethylaminopropyl) pyrazine) pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) Yl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl, 4-(N-methyl 4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethyl Aminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1- Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrole 1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-ylsulfonyl, 4-acetylpiperazine-1-ylsulfonyl , 4-tert-Butoxycarbonylpiperazine-1-ylsulfonyl, 4-(2-hydroxyethyl)piperazine-1-ylsulfonyl, 4-(2-cyanoethyl)piperazine-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl)piperazine-1-ylsulfonyl, 4-(2-N,N-diethylethyl)piperazine- 1-ylsulfonyl, 4-(3-hydroxypropyl)piperazine-1-ylsulfonyl, 4-(3-N, N-dimethylaminopropyl)piperazine-1-ylsulfonyl Group, 4-(3-N, N-diethylaminopropyl) piperazin-1-ylsulfonyl, morpholin-1-ylsulfonyl, 3,5-dimethylmorpholine-1- 4-(tetrahydropyrrolyl)piridin-1-ylsulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4- (4-Ethylpiperazine-1-yl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-( N-Methyl-4-pyridinyl)piperazine-1-ylsulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropyl Aminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1- Carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, 4-(tetra (Pyrrolyl)pyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethyl Aminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2 -N, N-Dimethylaminoethyl) piperazin-1-ylcarbonyl, 4-(2-N, N-diethylaminoethyl) piperazin-1-ylcarbonyl, 4-(3-hydroxyl Propyl) piperazin-1-ylcarbonyl, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylcarbonyl, 4-(3-N, N-diethylaminopropyl ) Piperazine-1-ylcarbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piperidine- 1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetinyl-piperazin-1-yl) piperidyl-1-carbonyl , 4-(N-Methyl-4-pyridinyl) piperazin-1-ylcarbonyl, (9) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxy Carbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropyl Cyclobutylaminomethylamino, cyclobutylaminomethylamino, cyclopentylaminomethylamino, pyridyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N -Dimethylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-Dimethylaminotetrahydropyrrolyl-1-methylamino, 3-N, N-diethylaminotetrahydropyrrolyl-1-methanoamino, 4-methylpiperazine-1-ylmethylamino Amino, 4-ethylpiperazin-1-ylmethylamino, 4-acetazin-1-ylmethylamino, 4-tert-butoxycarbonylpiperazin-1-ylmethylamino, 4-( 2-hydroxyethyl) piperazin-1-ylmethylamino, 4-(2-cyanoethyl) piperazin-1-ylmethylamino, 4-(2-N, N-dimethylaminoethyl Yl)piperazine-1-ylcarboxamido, 4-(2-N, N-diethylaminoethyl)piperazine-1-ylcarboxamido, 4-(3-hydroxypropyl)piperazine- 1-ylmethylamino, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylmethylamino, 4-(3-N, N-diethylaminopropyl) Azin-1-ylcarboxamido, morpholin-1-ylcarboxamido, 3,5-dimethylmorpholin-1-ylcarboxamido, 4-(tetrahydropyrrolyl)piridin-1-yl Carboxamido, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarboxamido, 4-(4-ethyl Piperazine-1-yl) piperidin-1-ylmethylamino, 4-(4-acetin-1-yl) piperidin-1-ylmethylamino, 4-(N-methyl- 4-(pyridinyl) piperazin-1-ylmethylamino; or (11) aminoacetylamino, 2-dimethylaminoacetylamino, N-tert-butoxycarbonylacetylamino, N-acetylamino Acetylamino, acrylamide, cyclopropylamino, chloroacetamino, pyridylacetamino, 4-hydroxypyridylacetamino, 4-N, N-dimethylaminopyridylacetamide Amino, 4-N, N-diethylaminopyridinylacetamino, tetrahydropyrrolylacetamino, 3-N, N-dimethylaminotetrahydropyrrolylacetamino, 3-N, N -Diethylaminotetrahydropyrrolylacetamino, 4-methylpiperazinylacetamino, 4-ethylpiperazinylacetamino, 4-acetazinylacetamino, 4-tert Butoxycarbonyloxazinylacetamido, 4-(2-hydroxyethyl)oxazinylacetamido, 4-(2-cyanoethyl)oxazinylacetamido, 4-(2-N, N-Dimethylaminoethyl) Pirazinyl Acetylamino, 4-(2-N, N-Diethylaminoethyl) Pirazinyl Acetylamino, 4-(3-Hydroxypropyl) Piperazine 4-(3-N, N-Dimethylaminopropyl) Pyrazinyl Acetylamino, 4-(3-N, N-Diethylaminopropyl) Pyrazinyl Acetylamino , Morpholinyl acetamino, 3, 5-dimethylmorpholinyl acetamino, 4-(4-methyl-piperazine-1-yl) pyridinyl acetamino, 4-(4-ethyl Pyridine-1-pyridinyl) pyridinyl acetylamino, 4-(4-acetinyl-1-piperazinyl) pyridyl acetinyl amino, N-(N-methyl-4-pyridinyl )Pazizinylacetamino, 4-(tetrahydropyrrol-1-yl)pyridinylacetamino; 2-methylaminoacetamino, 2-(1-methylethyl)aminoacetamino; N-benzyloxycarbonyl-2methylaminoacetamino; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituent may be selected From the above substituents the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from the same as Z 1 The above-mentioned substituents, 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; A is a direct bond or a methylene group; X is NH, S or O; R 2 is selected from: 1) C1-C6 alkyl , C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, dimethylaminosulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, iso Butoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl , Dimethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl, 3) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl; 4) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl , Cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl; Y 2 , Y 3 , Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is N, Y 3 is CA 13 , Y 4 is N , O or S; Y 2 is O or S, Y 3 is NA 13 , Y 4 is CH; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 5) pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropyl Aminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5-dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydro Pyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetylpiperazine Group, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4 -(3-Hydroxypropyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazin Group, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl.

在一些實施方案中，R’為氫。In some embodiments, R'is hydrogen.

在一些實施方案中，其中，R1 選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-(N-甲基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，硝基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基，N-甲基-4-呱啶基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基， 3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基， 3-N, N-二異丙基氨基丙氧基， 3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，3-N, N-二甲基四氫吡咯-1-基磺醯基，3-N, N-二乙基氨基四氫吡咯-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪-1-基磺醯基，4-乙醯基呱嗪-1-基磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，N-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪-1-基磺醯基，4-(3-羥基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基磺醯基，4-(4-乙醯基呱嗪-1-基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪-1-基磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基羰基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基羰基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基羰基，嗎啉-1-基羰基，3, 5-二甲基嗎啉-1-基羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基羰基，4-(N-甲基-4-呱啶基)呱嗪-1-基羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，4-乙醯基呱嗪-1-基甲醯氨基，4-(2-羥基乙基)呱嗪-1-基甲醯氨基，4-(2-氰基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基甲醯氨基，嗎啉-1-基甲醯氨基，4-(4-乙醯基呱嗪-1-基)呱啶-1-基甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪-1-基甲醯氨基；或 （11）氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，N-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，N-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同。In some embodiments, wherein R 1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylamino Ethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, C3-C6 cycloalkyl, 4-N, N-Dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N-isopropyl- 4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, nitro, (2) C1-C6 alkyl, C1-C6 alkoxy Group, C1-C6 oxygen-containing alkyl group, C1-C6 fluorine-containing alkyl group, C1-C6 fluorine-containing alkoxy group, N-methyl-4-pyridinyl group, (3) N, N-dimethylamino group, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 3-morpholinopropylamino , 3-(4-Methylpiperazine) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, (4) 2-N, N-dimethyl Aminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2 -(4-Acetylazizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-di Isopropylaminopropoxy, 3-(4-acetazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenolinylpropoxy, 3-pyridinylpropoxy Group, pyridin-2-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-di Methylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5 -Dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(3- N, N-Diethylaminopropyl) piperazinyl, 2-oxo- piperazin-4-yl, imidazolyl, 4-methylimidazolyl, (6) 4-(4-methylpiperazinyl) ) Piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4-(4-acetylpiperazinyl) piperidine Group, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methanesulfonyl piperazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazine Yl) pyridinyl, 4-(4-(3-hydroxypropyl) pyrazine) pyridinyl, 4-(4-(2-N, N-dimethylaminoethyl) pyrazine) quat Ridinyl, 4-(4-(2-N, N-diethylaminoethyl)pirazinyl)piridinyl, 4-(4-(3-N, N-dimethylaminopropyl)quat Azinyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, 4-(N-methyl-4-pyridinyl) pyrinyl, 4-( N-Ethyl-4-pyridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylsulfonyl醯基, Cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 3-N , N-Dimethyltetrahydropyrrol-1-ylsulfonyl, 3-N, N-diethylaminotetrahydropyrrol-1-ylsulfonyl, 4-methylpiperazine-1-ylsulfonyl , 4-ethylpiperazine-1-ylsulfonyl, 4-acetylpiperazine-1-ylsulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, N-( 2-hydroxyethyl)piperazine-1-sulfonyl, 4-(2-cyanoethyl)piperazine-1-ylsulfonyl, 4-(3-hydroxypropyl)piperazine-1- Sulfonyl, 4-(3-N, N-dimethylaminopropyl)piperazine-1-ylsulfonyl, 4-(3-N, N-diethylaminopropyl)piperazine- 1-ylsulfonyl, 4-(4-acetoxypiperazine-1-yl)piridin-1-ylsulfonyl, 4-(N-methyl-4-piridinyl)piperazine-1 -Sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, Piperidinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl -1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Azin-1-ylcarbonyl, 4-(2-N, N-diethylaminoethyl) piperazin-1-ylcarbonyl, 4-(3-N, N-diethylaminopropyl) piperazin- 1-ylcarbonyl, morpholin-1-ylcarbonyl, 3,5-dimethylmorpholin-1-ylcarbonyl, 4-(4-methyl-piperazin-1-yl)piridin-1-ylcarbonyl , 4-(4-Acetyl-1-piperinyl)piridin-1-ylcarbonyl, 4-(N-methyl-4-piridinyl)piperazine-1-ylcarbonyl, (9) methyl Oxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethyl Amino, isopropylaminomethylamino, cyclopropylaminomethylamino, pyridyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylamino Piperidinyl-1-methylamino, 4-N, N-diethylaminopyridinyl-1-methylamino, 4-acetylpyrazine-1-ylmethylamino, 4-(2- Hydroxyethyl) piperazin-1-ylcarboxamido, 4-(2-cyanoethyl) piperazin-1-ylcarboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazin-1-ylcarboxamido, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylcarboxamido, 4-(3-N, N-diethylaminopropyl Yl)piperazine-1-ylmethylamino, morpholin-1-ylmethylamino, 4-(4-acetylpiperazine-1-yl)piperidine-1- 4-(N-methyl-4-pyridinyl) piperazin-1-ylmethylamino; or (11) aminoacetamido, N-tert-butoxycarbonylacetamido, N- Acetylaminoacetamino, acrylamide, cyclopropylamino, chloroacetamino, pyridylacetamino, 4-hydroxypyridylacetamino, 4-N, N-dimethylamino Pyridinylacetylamino, 4-N, N-diethylaminopyridylacetylamino, 3-N, N-dimethylaminotetrahydropyrrolylacetylamino, N-ethylpiperazinylacetylamino Amino, 4-acetylazinylacetamino, 4-tert-butoxycarbonylazinylacetamino, 4-(2-cyanoethyl)azinylacetamino, N-(2-N , N-Dimethylaminoethyl) Pirazinyl Acetylamino, 4-(2-N, N-Diethylaminoethyl) Pirazinyl Acetylamino, 4-(3-N, N-Di Methylaminopropyl) piperazinylacetamino, 4-(3-N, N-diethylaminopropyl)piperazinylacetamino, 4-(4-methyl-piperazin-1-yl ) Pyridyl acetylamino, 4-(4-ethyl-1-pyrazine) pyridyl acetylamino, 4-(4-acetyl-1-pyrazine) pyridyl acetylamino , N-benzyloxycarbonyl-2methylaminoacetamido; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents can be It is selected from the above-mentioned substituents the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from Z 1 The same substituents as above, 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above.

在一些實施方案中，R1 選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，硝基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基， 3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基， 3-N, N-二異丙基氨基丙氧基， 3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，，苯基甲氧基，單鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （11）氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，4-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 2），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 3），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同。In some embodiments, R 1 is selected from: 1) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, nitro, (2) C1-C6 alkyl, C1-C6 alkoxy Group, C1-C6 fluorine-containing alkyl group, C1-C6 fluorine-containing alkoxy group, (3) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-Dimethylaminoethylamino, 2-morpholinoethylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methyl Pyperidine-4-amino, N-ethylpiperidine-4-amino, (4) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-Diisopropylaminoethoxy, 2-(4-methyloxizinyl)ethoxy, 2-(4-ethyrazinyl)ethoxy, 2-morpholine Ethoxy group, 2-thiophenolinylethoxy group, 2-pyridinylethoxy group, 3-N, N-diisopropylaminopropoxy group, 3-(4-acetyloxazine group ) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, phenylmethoxy, mono Halogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-di Isopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3,5-dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylamino Tetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetinyl Piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 2-oxo-piperazin-4-yl, imidazole Group, 4-methylimidazolyl, (6) 4-(4-methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropyl) Pirazinyl)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methylsulfonyl) Piperazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4- (4-(2-N, N-Dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidine Group, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl, 4-(N-methyl-4-piridinyl)pirazinyl, 4-(N-ethyl- 4-pyridinyl) azizinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropyl Aminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 3-N, N -Dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)pezinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl)pezinyl -1-sulfonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylamino Carbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N- Dimethylaminopiridinyl-1-carbonyl, 4-N, N-diethylaminopiridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetra Hydropyrrolyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazine Carbonyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1 -Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, (9) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tertiary Butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, piridyl- 1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4-N, N-diethylamino Pyridinyl-1-carboxamido, 4-acetamidoprazinyl-1-carboxamido, 4-(2-hydroxyethyl)prazinyl-1-carboxamido, 4-(2-cyano Ethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(3-N, N-dimethylamino 4-(3-N, N-diethylaminopropyl) piperazinyl-1-methylamino, morpholinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-methylamino, morpholinyl-1-methylamino , 4-(4-acetyl-1-pyridinyl)pyridinyl-1-carboxamido, 4-(N-methyl-4-pyridinyl)piperazinyl-1-carboxinylamino; Or (11) Aminoacetylamino, N-tert-butoxycarbonylacetylamino, N-acetylaminoacetylamino, allylamino, cyclopropylamino, chloroacetylamino, pyridylacetamino, 4-Hydroxypyridinylacetamido, 4-N, N-dimethylaminopyridinylacetamido, 4-N, N-diethylaminopyridinylacetamido, 3-N, N- Dimethylaminotetrahydropyrrolylacetamino, 4-ethylpiperazinylacetamino, 4 -Acetazinylacetamino, 4-tert-butoxycarbonyloxazinylacetamino, 4-(2-cyanoethyl)azinylacetamino, 4-(2-N, N- Dimethylaminoethyl) azizinyl acetamido, 4-(2-N, N-diethylaminoethyl) azizinyl acetamido, 4-(3-N, N-dimethylamino Propyl) piperazinyl acetamino, 4-(3-N, N-diethylaminopropyl) piperazinyl acetamino, 4-(4-methyl-piperazin-1-yl) piperidine 4-(4-ethyl-1-piperazinyl) pyridylacetamino, 4-(4-ethyl-1-piperazinyl)pyridylacetamino, N- Benzyloxycarbonyl-2methylaminoacetamido; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituent may be selected from The above-mentioned substituents that are the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from the same as those of Z 1 Substituents, 2) , Where Z 2 , Z 3 , Z 4 , Z 5 are the same as defined in 2) above; 3) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above.

在一些實施方案中，A為直接鍵。In some embodiments, A is a direct bond.

在一些實施方案中，A為亞甲基。In some embodiments, A is methylene.

在一些實施方案中，R2 選自： 1）C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基， （2）甲硫基，乙硫基，異丙硫基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，環丁基氨基羰基，甲氨基羰基，二甲氨基羰基，異丙氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 3）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環戊基氨基羰基； 4）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丁基氨基羰基，甲基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基。In some embodiments, R 2 is selected from: 1) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, (2) methylthio, ethylthio, iso Propylthio, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropylsulfonyl, tert-butylsulfinyl, dimethylaminosulfinyl, methylsulfonyl Amino, methoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, cyclobutylaminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, dimethylphosphine Diethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl, 3) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopentylaminocarbonyl; 4) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclobutylaminocarbonyl, methylsulfinyl Group, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl; Y 2 , Y 3 , and Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 5) pyridinyl, 4-N, N-dimethyl Aminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5- Dimethylmorpholinyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylquarazinyl, 4-ethylpyrrolyl Azinyl, 4-isopropyl azinyl, 4- acetylazinyl, 4-(2-N, N-diethylaminoethyl) azinyl, 4-(3-N, N- Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl.

在一些實施方案中，R2 選自： 1），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯， （2）甲硫基，乙硫基，異丙硫基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，環丁基氨基羰基，甲氨基羰基，二甲氨基羰基，異丙氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 2）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環戊基氨基羰基； 3）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丁基氨基羰基，甲基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基。In some embodiments, R 2 is selected from: 1) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, (2) methylthio, ethylthio, isopropylthio, ethanesulfinyl Acetyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropylsulfonyl, tert-butylsulfonyl, dimethylaminosulfinyl, methylsulfinylamino, methoxycarbonyl, Isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, cyclobutylaminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, dimethylphosphinyl, diethylamino Phosphonyl, diisopropylphosphinyl, 2) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopentylaminocarbonyl; 3) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclobutylaminocarbonyl, methylsulfinyl Group, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl; Y 2 , Y 3 , and Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl.

在一些實施方案中，所述藥學上可接受的鹽為無機酸鹽或有機酸鹽，其中，該無機酸鹽為鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硝酸鹽、碳酸氫鹽和碳酸鹽、硫酸鹽或磷酸鹽，該有機酸鹽為甲酸鹽、乙酸鹽、丙酸鹽、苯甲酸鹽、馬來酸鹽、富馬酸鹽、琥珀酸鹽、酒石酸鹽、檸檬酸鹽、抗壞血酸鹽、α-酮戊二酸鹽、三氟乙酸鹽、α-甘油磷酸鹽、烷基磺酸鹽或芳基磺酸鹽；較佳地，該烷基磺酸鹽為甲基磺酸鹽或乙基磺酸鹽；該芳基磺酸鹽為苯磺酸鹽或對甲苯磺酸鹽。In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate And carbonate, sulfate or phosphate, the organic acid salt is formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citric acid Salt, ascorbate, α-ketoglutarate, trifluoroacetate, α-glycerol phosphate, alkyl sulfonate or aryl sulfonate; preferably, the alkyl sulfonate is methyl sulfonate Acid salt or ethyl sulfonate; the aryl sulfonate is benzene sulfonate or p-toluene sulfonate.

第二方面，本發明提供了一種具有式V結構化合物、其立體異構體、其前藥、或者其藥學上可接受的鹽或藥學上可接受的溶劑合物：V 其中：W 為氧代，硫代，或氫； n = 0，或1； R3 ，R4 ，R5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基； R6 選自： （1）氫，C1-C6烷基，乙醯基，丙醯基，正丁醯基，異丁醯基， （2）氨基乙醯基，2-N, N-二甲基乙醯基，2-N, N-二乙基乙醯基，2-N, N-二異丙基乙醯基，呱啶基乙醯基，4-羥基呱啶基乙醯基，4-N, N-二甲基氨基呱啶基乙醯基，4-N, N-二乙基氨基呱啶基乙醯基，四氫吡咯基乙醯基，3-N, N-二甲基氨基四氫吡咯基乙醯基，3-N, N-二乙基氨基四氫吡咯基乙醯基，4-甲基呱嗪基乙醯基，4-乙基呱嗪基乙醯基，4-乙醯基呱嗪基乙醯基，4-叔丁氧羰基呱嗪基乙醯基，4-(2-羥基乙基)呱嗪基乙醯基，4-(2-氰基乙基)呱嗪基乙醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯基，4-(3-羥基丙基)呱嗪基乙醯基， 4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯基，嗎啉基乙醯基，3, 5-二甲基嗎啉基乙醯基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯基，4-(4-乙基-1-呱嗪基)呱啶基乙醯基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯基，4-(N-甲基-4-呱啶基)呱嗪基乙醯基； A，X，R2 與上述技術方案中定義相同。In the second aspect, the present invention provides a compound having the structure of formula V, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvate: V Wherein: W is oxo, thio, or hydrogen; n = 0, or 1; R 3 , R 4 , and R 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro , Cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy; R 6 is selected from: (1) Hydrogen, C1-C6 alkyl, acetyl, propyl, n-butyryl, isobutyryl, (2) amino acetyl, 2-N, N-dimethyl acetyl, 2-N, N-diethyl acetyl, 2-N, N-diisopropyl acetyl, pyridyl acetyl, 4-hydroxypyridyl acetyl, 4-N, N-dimethylamino Pyridinylacetyl, 4-N, N-diethylaminopyrrolylacetyl, tetrahydropyrrolylacetyl, 3-N, N-dimethylaminotetrahydropyrrolylacetyl, 3-N, N-Diethylaminotetrahydropyrrolylacetoxy, 4-methylpirazinylacetoxy, 4-ethylpiperazinylacetoxy, 4-acetoxypiperazinylacetoxy Group, 4-tert-butoxycarbonyl piperazinyl acetyl, 4-(2-hydroxyethyl) piperazinyl acetyl, 4-(2-cyanoethyl) piperazinyl acetyl, 4- (2-N, N-Dimethylaminoethyl) Pirazinyl Acetyl, 4-(2-N, N-Diethylaminoethyl) Pirazinyl Acetyl, 4-(3-Hydroxy Propyl) piperazinyl acetyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl acetyl, 4-(3-N, N-diethylaminopropyl) quan Azinyl acetyl, morpholinyl acetyl, 3, 5-dimethylmorpholinyl acetyl, 4-(4-methyl-piperazine-1-yl) pyridyl acetyl, 4 -(4-Ethyl-1-piperazinyl)piridinylacetinyl, 4-(4-acetinyl-1-piperazinyl)piridinylacetinyl, 4-(N-methyl- 4-(pyridinyl) azizinyl acetyl group; A, X, R 2 are the same as defined in the above technical scheme.

在一些實施方案中，W 為氧代。In some embodiments, W is oxo.

在一些實施方案中，n＝1。In some embodiments, n=1.

在一些實施方案中，n＝0。In some embodiments, n=0.

在一些實施方案中，R3 ，R4 ，R5 各自獨立地選自： （1）氫，氟，氯，溴，碘； （2）C1-C6烷基，C1-C6烷氧基。In some embodiments, R 3 , R 4 , and R 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, and iodine; (2) C1-C6 alkyl, C1-C6 alkoxy.

在一些實施方案中，R6 選自： （1）氫，C1-C6烷基，乙醯基，丙醯基， （2）氨基乙醯基，2-N, N-二甲基乙醯基，2-N, N-二乙基乙醯基，2-N, N-二異丙基乙醯基，呱啶基乙醯基，4-羥基呱啶基乙醯基，4-N, N-二甲基氨基呱啶基乙醯基，4-N, N-二乙基氨基呱啶基乙醯基，四氫吡咯基乙醯基，4-乙醯基呱嗪基乙醯基，4-叔丁氧羰基呱嗪基乙醯基，4-(2-羥基乙基)呱嗪基乙醯基，4-(2-氰基乙基)呱嗪基乙醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯基，嗎啉基乙醯基，3, 5-二甲基嗎啉基乙醯基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯基，4-(4-乙基-1-呱嗪基)呱啶基乙醯基。In some embodiments, R 6 is selected from: (1) hydrogen, C1-C6 alkyl, acetyl, propyl, (2) amino acetyl, 2-N, N-dimethyl acetyl , 2-N, N-Diethyl acetyl, 2-N, N-diisopropyl acetyl, pyridyl acetyl, 4-hydroxypyridyl acetyl, 4-N, N -Dimethylaminopyridinylacetinyl, 4-N, N-diethylaminopyridinylacetinyl, tetrahydropyrrolylacetinyl, 4-acetinylpyrinylacetinyl, 4 -Tert-Butoxycarbonyl azizinyl acetyl, 4-(2-hydroxyethyl) azizinyl acetyl, 4-(2-cyanoethyl) azizinyl acetyl, 4-(2- N, N-Dimethylaminoethyl) azizinyl acetyl, 4-(2-N, N-diethylaminoethyl) azizinyl acetyl, morpholinyl acetyl, 3, 5-Dimethylmorpholinylacetinyl, 4-(4-methyl-piperazine-1-yl)piridinylacetinyl, 4-(4-ethyl-1-piperazine)piperidine Base Acetyl.

在一些實施方案中，該藥學上可接受的鹽為無機酸鹽或有機酸鹽，其中，該無機酸鹽為鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硝酸鹽、碳酸氫鹽和碳酸鹽、硫酸鹽或磷酸鹽，該有機酸鹽為甲酸鹽、乙酸鹽、丙酸鹽、苯甲酸鹽、馬來酸鹽、富馬酸鹽、琥珀酸鹽、酒石酸鹽、檸檬酸鹽、抗壞血酸鹽、α-酮戊二酸鹽、三氟乙酸鹽、α-甘油磷酸鹽、烷基磺酸鹽或芳基磺酸鹽；較佳地，該烷基磺酸鹽為甲基磺酸鹽或乙基磺酸鹽；該芳基磺酸鹽為苯磺酸鹽或對甲苯磺酸鹽。In some embodiments, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate, and Carbonate, sulfate or phosphate, the organic acid salt is formate, acetate, propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate , Ascorbate, α-ketoglutarate, trifluoroacetate, α-glycerol phosphate, alkyl sulfonate or aryl sulfonate; preferably, the alkyl sulfonate is methanesulfonic acid Salt or ethyl sulfonate; the aryl sulfonate is benzene sulfonate or p-toluene sulfonate.

第三方面，本發明提供了一種下面通式IA表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In the third aspect, the present invention provides a compound represented by the following general formula IA, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基， （4）N-甲基-4-呱啶基， （5）4-甲基呱嗪基， （6）4-(4-甲基呱嗪基)呱啶基， （7）4-(四氫吡咯-1-基)呱啶基，或 （8）Z2 與 Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, (4) N-methyl-4- Piperidinyl, (5) 4-Methyl piperazinyl, (6) 4-(4-Methyl piperazinyl) piperidyl, (7) 4-(Tetrahydropyrrol-1-yl) piperidyl , Or (8) Z 2 and Z 3 or Z 3 and Z 4 are formed or .

在一些實施方案中，R1選自： 1），其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 或 Z2 與Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from: 1) , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4 -Pyridyl, 4-methyl pyrazine, 4-(4-methyl pyrazine) pyridyl, 4-(tetrahydropyrrol-1-yl) pyridyl, or Z 2 and Z 3 or Z 3 and Z 4 form or .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methanesulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第四方面，本發明提供了一種下面通式IB表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，2-氧代-呱嗪-4-基， （5）嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基， （6）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基， 4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基， 4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （7）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-(2-羥基乙基)呱嗪3-N, N-二乙基氨基四氫吡咯基-1-羰基，基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，3, 5-二甲基嗎啉基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （8）吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，或 （9）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a fourth aspect, the present invention provides a compound represented by the following general formula IB, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 3,5-dimethylmorpholinyl, thiophenolinyl, (6) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methyl Piperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetazine-1-sulfonyl, 4-(2-hydroxyethyl)piperazine 1-sulfonyl, 4-(2-cyanoethyl)gua Azinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) azizinyl-1-sulfonyl, 4-(2-N,N-diethylethyl) Piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)perazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1 -Sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piperidine- 1-ylsulfonyl, 4-(4-ethyl-1-oxizinyl)piridin-1-ylsulfonyl, 4-(N-methyl-4-piridinyl)pirazinyl-1 -Sulfonyl, (7) 4-(4-methyl-piperazin-1-yl)piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl -1-carbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, piperidinyl-1-carbonyl, 4-hydroxypiridinyl-1-carbonyl, 4-N, N-dimethylaminopiridinyl- 1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-Dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-(2-hydroxyethyl)piperazine 3 -N, N-Diethylaminotetrahydropyrrolyl-1-carbonyl, base-1-carbonyl, 4-(3-hydroxypropyl)piperazinyl-1-carbonyl, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, hydroxycarbonyl, Aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, 3,5-dimethylmorpholin-1-carbonyl, methoxycarbonyl, ethoxycarbonyl , Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, (8) pyridin-2-ylmethoxy, pyridin-3-ylmethoxy , Pyridin-4-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, or (9) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or For substituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基) （6）嗎啉基，3, 5-二甲基嗎啉基， （7）4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，羥基磺醯基，氨基磺醯基，甲氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-乙基呱嗪基-1-磺醯基， （8）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基， （9）吡啶-2-基甲氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，或 （10）Z2 與Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 2），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 3），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同。In some embodiments, R1 is selected from: 1) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) N -Methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpyrrolidinyl)pyridinyl, 4-(tetrahydropyrrolyl)pyridinyl, pyridinyl, 4- N, N-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, (5) 4-methylpiperazine Group, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetylpiperazinyl, 4-tert-butoxycarbonylpiperazinyl, 4-methylsulfonylpiperazinyl, 4- (2-Hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4- (3-N, N-Diethylaminopropyl) piperazinyl, 2-oxo- piperazin-4-yl) (6) morpholinyl, 3,5-dimethylmorpholinyl, (7 ) 4-Hydroxypiperidine-1-ylsulfonyl, 4-methylpiperazine-1-ylsulfonyl, hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, propylaminosulfonyl, Isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-Dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N , N-Dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-ethylpiperazinyl-1-sulfonyl Acetyl, (8) 4-(4-methyl-piperazin-1-yl)piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, cyclobutylaminocarbonyl, cyclopentyl Aminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-diethylamino Pyridine-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-carbonyl, 4-(3-hydroxypropyl)pirazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl)pirazinyl-1-carbonyl, 4-(3 -N, N-Diethylaminopropyl) piperazinyl-1-carbonyl, morpholin-1-carbonyl, (9) pyridin-2-ylmethoxy, pyridin-2-ylmethoxy, pyridine -3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, or (10) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, and the substituent may be selected from the same substituents as described above for Z 1; 2) , Where Z 2 , Z 3 , Z 4 , Z 5 are the same as defined in 2) above; 3) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above.

在一些實施方案中，R1選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基、乙氧基、異丙氧基， （4）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-二甲氨基-呱啶基， （5）4-甲基呱嗪基，4-叔丁氧羰基呱嗪基， （6）嗎啉基， （7）4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基， （8）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基， （9）吡啶-2-基甲氧基， （10）2-二甲氨基乙醯氨基，， （11）–F， （12）Z2 與 Z3 或Z3 與Z4 形成或， 2），其中Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自：嗎啉基，4-甲基呱嗪基，4-羥基呱啶基； 3），其中Z1 ，Z3 ，Z4 ，Z5 各自獨立地選自：嗎啉基，4-羥基呱啶基。In some embodiments, R1 is selected from: 1) , Where Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, ethoxy, isopropoxy, ( 4) N-methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-Dimethylamino-piperidinyl, (5) 4-methylpiperazinyl, 4-tert-butoxycarbonyl piperazinyl, (6) morpholinyl, (7) 4-hydroxypiperidin-1-yl Sulfonyl, 4-methylpiperazine-1-ylsulfonyl, (8) 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-methylpiperazine -1-ylcarbonyl, (9)pyridin-2-ylmethoxy, (10)2-dimethylaminoacetamido, , (11)–F, (12) Z 2 and Z 3 or Z 3 and Z 4 are formed or , 2) , Wherein Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: morpholinyl, 4-methylpiperazinyl, 4-hydroxypyridinyl; 3) , Wherein Z 1 , Z 3 , Z 4 , and Z 5 are each independently selected from: morpholinyl, 4-hydroxypyridinyl.

在一些實施方案中，R1選自： 1），其中Z1 和Z5 二者之一為氫，另一選自：甲氧基、乙氧基、異丙氧基； Z2 和Z4 二者之一為氫，另一為甲基，2-二甲氨基乙醯氨基，； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-甲基呱嗪基，4-叔丁氧羰基呱嗪基，嗎啉基，4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，吡啶-2-基甲氧基，4-二甲氨基-呱啶基，-F；或 Z2 與Z3 或Z3 與Z4 形成或， 2），其中Z3 選自：嗎啉基，4-甲基呱嗪基，4-羥基呱啶基；Z1 、Z2 和Z4 都為氫； 3），其中Z3 選自：嗎啉基，4-羥基呱啶基；Z1 、Z2 和Z4 都為氫。In some embodiments, R1 is selected from: 1) , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, and isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl, 2-Dimethylaminoacetamido, ; Z 3 is selected from: N-methyl-4-piridinyl, 4-hydroxypiridinyl, 4-(4-methylpirazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl) Piperidinyl, 4-methylpiperazinyl, 4-tert-butoxycarbonyl piperazinyl, morpholinyl, 4-hydroxypiperidin-1-ylsulfonyl, 4-methylpiperazin-1-ylsulfonyl Amino, 4-(4-methyl-piperazine-1-yl)piperidine-1-ylcarbonyl, 4-methylpiperazine-1-ylcarbonyl, pyridin-2-ylmethoxy, 4-di Methylamino-pyridinyl, -F; or Z 2 and Z 3 or Z 3 and Z 4 are formed or , 2) , Where Z 3 is selected from: morpholinyl, 4-methylpiperazine, 4-hydroxypiperdinyl; Z 1 , Z 2 and Z 4 are all hydrogen; 3) , Where Z 3 is selected from: morpholinyl, 4-hydroxypyridinyl; Z 1 , Z 2 and Z 4 are all hydrogen.

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自：（1）氫，（2）異丙基磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第五方面，本發明提供了一種下面通式IO表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In the fifth aspect, the present invention provides a compound represented by the following general formula IO, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Pirazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piridinyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) azizinyl) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, (4) 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl Group, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N -Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazin Group, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl-4- (Primidyl) azizinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethyl Amino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethyl Aminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine -4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N -Diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-acetylpiperazinyl) ) Ethoxy, 2-? Alkylethoxy, 2-Thiophenanthrylethoxy, 2-Perridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropyl Oxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetazinyl)propoxy, 3 -Morpholinylpropoxy, 3-thiophenanthrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-yl Methoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonyl, aminosulfonyl Group, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetinyl Piperazinyl-1-sulfonyl, 4-tert-butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2- Cyanoethyl) piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-sulfonyl, 4-(2-N,N- Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl )Pepazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1-sulfonyl, morpholin-1-sulfonyl, 3, 5 -Dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl-1-piper) (Azinyl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-(N-methyl-4-piperidine Group) pyrazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, Cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-di Ethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetra Hydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-butoxy Carbonyl piperazinyl-1-carbonyl, 4 -(2-Hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1-carbonyl, 4 -(3-N, N-Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl -1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-(4-ethyl -1-piperinyl)piridinyl-1-carbonyl, 4-(4-acetinyl-1-piperinyl)piridinyl-1-carbonyl, 4-(N-methyl-4-piperidine Yl)pirazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, ( 9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethylamino, cyclopentan Aminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4 -N, N-Diethylaminopyridinyl-1-methylamino, tetrahydropyrrolyl-1-methylamino, 3-N, N-dimethylaminotetrahydropyrrolyl-1-methylamino , 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-Acetyl piperazinyl-1-methanoamino, 4-tert-butoxycarbonyl piperazinyl-1-methanoamino, 4-(2-hydroxyethyl) piperazinyl-1-methanoamino, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carboxamido, 4-(2 -N, N-Diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carboxamido, morpholinyl-1-methyl Amino, 3,5-dimethylmorpholinyl-1-carboxamido, 4-(4-methyl-piperazine-1-yl)piridinyl-1-carboxamido, 4-(4- Ethyl-1-prazinyl) pyridinyl-1-methanylamino, 4-(4-acetinyl-1-methazinyl) pyridinyl-1-methanylamino, 4-(N-methyl (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six Membered ring, the substituent may be selected from the same substituents as described above as Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethyl Phosphinyl, diisopropylphosphinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基 或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , (4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4- Methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethyl Aminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N -Ethyl-4-pyridinyl) piperazinyl or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring, and the substituent may be selected from Z 1 is the same as the above-mentioned substituents.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基 （3）4-(4-甲基呱嗪-1-基)呱啶基，4-甲基呱嗪基，4-二甲氨基-呱啶基， （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy (3) 4-(4-methylpiperazine- 1-yl) pyridinyl, 4-methyl pyrazine, 4-dimethylamino-pyridinyl, (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring .

在一些實施方案中，R1選自：，其中， Z1 為甲氧基，且Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，其餘為氫；或 Z3 與Z4 形成，且Z1 為甲氧基，其餘為氫。In some embodiments, R1 is selected from: , Wherein Z 1 is a methoxy group, and Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, and the rest Is hydrogen; or Z 3 and Z 4 are formed , And Z 1 is a methoxy group, and the rest are hydrogen.

在一些實施方案中，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫；（2）叔丁磺醯基。In some embodiments, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) tert-butylsulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為叔丁磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is tert-butylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第六方面，本發明提供了一種下面通式IC表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基， （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； R2選自：1）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基； 2）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N，或 Y2 為N，Y3 為N-A13 ，Y4 為CH或N； 其中A13 為氫，C1-C6烷基。In the sixth aspect, the present invention provides a compound represented by the following general formula IC, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, or (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N- Dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N -Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethyl (Aminopiperazine) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl)prazinyl-1-methylamino, (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered Ring, the substituent may be selected from the same substituents as described above as Z 1 ; R2 is selected from: 1) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl; 2) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl , Cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl; Y 2 , Y 3 , Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, or Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N ; Wherein A 13 is hydrogen, C1-C6 alkyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）4-羥基呱啶基，呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-hydroxypyridinyl, pyridinyl , N-Methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropyl Amino piperidinyl, (4) 4-methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazin Group, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl Group, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N -Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-Ethyl-4-piperidyl)piperidyl, (5) 4-(4-methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl , 4-(4-isopropylpiperazinyl)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-Methanesulfonylquarazinyl)piridinyl, 4-(4-(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl) (Quazizinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl ) Piperidyl, 4-(4-(2-N, N-diethylaminoethyl) Piperazinyl) Piperidyl, 4-(4-(3-N, N-Dimethylaminopropyl ) Piperazinyl) piperidyl, 4-(4-(3-N, N-diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4- (3-N, N-Dimethylaminotetrahydropyrrolyl) pyridinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring , The substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-羥基呱啶基， （4）4-甲基呱嗪基， （5）4-(4-甲基呱嗪基)呱啶基，或 （6）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, (4) 4-methyl Pyrazinyl, (5) 4-(4-methylprazinyl) pyridinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基，Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與Z3 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, the other is methoxy, Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form .

在一些實施方案中，R2選自：其中A12 選自： （1）氫，甲基，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N，或 Y2 為N，Y3 為N-A13 ，Y4 為CH或N； 其中A13 為氫，C1-C6烷基。In some embodiments, R2 is selected from: Wherein A 12 is selected from: (1) hydrogen, methyl, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxy Carbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropyl Aminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, Isopropylsulfonyl; Y 2 , Y 3 , Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, or Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; wherein A 13 is hydrogen, C1-C6 alkyl.

在一些實施方案中，R2選自：其中A12 選自： （1）氫，甲基， （2）異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N， 其中A13 為氫，C1-C6烷基。In some embodiments, R2 is selected from: Wherein A 12 is selected from: (1) hydrogen, methyl, (2) isopropylsulfonyl; Y 2 , Y 3 , and Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , and Y 4 is N, where A 13 is hydrogen and C1-C6 alkyl.

在一些實施方案中，R2選自：其中A12 選自異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合：Y2 為C，Y3 為N-A13 ，Y4 為N，其中A13 為甲基。In some embodiments, R2 is selected from: Wherein A 12 is selected from isopropylsulfonyl; Y 2 , Y 3 , and Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, and A 13 is methyl.

第七方面，本發明提供了一種下面通式 ID表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In the seventh aspect, the present invention provides a compound represented by the following general formula ID, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基、異丙氧基， （4）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （5）4-甲基呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, isopropoxy, (4) N- Methyl-4-piperidyl, 4-(4-methylpiperazinyl)piperidyl, 4-(tetrahydropyrrol-1-yl)piperidyl, (5) 4-methylpiperazinyl, Or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z2 和Z4 二者之一為氫，另一為甲基， Z1 和Z5 二者之一為氫，另一選自：甲氧基、異丙氧基， Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 2 and Z 4 is hydrogen, the other is methyl, one of Z 1 and Z 5 is hydrogen, the other is selected from: methoxy, isopropoxy, and Z 3 is selected from : N-Methyl-4-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, Or Z 2 and Z 3 or Z 3 and Z 4 .

在一些實施方案中，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫；（2）甲氧基羰基。In some embodiments, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) methoxycarbonyl.

在一些實施方案中，R2選自：，其中A2 和A4 二者之一為氫，另一為甲氧基羰基；A1 ，A3 ，A5 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 2 and A 4 is hydrogen, and the other is methoxycarbonyl; A 1 , A 3 , and A 5 are all hydrogen.

第八方面，本發明提供了一種下面通式 IE表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基。In an eighth aspect, the present invention provides a compound represented by the following general formula IE, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl) piperazinyl-1-methylamino; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基，乙氧基，異丙氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, ethoxy, isopropoxy, (3) N -Methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, (4) 4-Methylpiperazinyl.

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一選自：甲氧基、乙氧基、異丙氧基; Z2 和Z4 二者之一為氫，另一為甲基; Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基、4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4-piperidyl, 4-hydroxypiperidyl, 4-methylpiperazinyl, 4-(4-methylpiperazinyl)piperidyl, 4-(tetra Hydropyrrol-1-yl)pyridinyl.

在一些實施方案中，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲氧基羰基。In some embodiments, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methoxycarbonyl.

在一些實施方案中，R2選自，其中A1 和A5 二者之一為氫，另一為甲氧基羰基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from , Wherein one of A 1 and A 5 is hydrogen, and the other is methoxycarbonyl; A 2 , A 3 , and A 4 are all hydrogen.

第九方面，本發明提供了一種下面通式 IF表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(N-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a ninth aspect, the present invention provides a compound represented by the following general formula IF, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(N-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methylprazinyl, 4-ethylprazinyl, 4-isopropylprazinyl, 4-acetylprazinyl, 4-tert-butoxycarbonylprazinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， 或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-methylpiperazinyl, 4- Ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyl Ethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N , N-Diethylaminopropyl)pirazinyl, 4-(N-methyl-4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (4) Piridinyl, N-methyl-4-piridinyl, 4-N, N-dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-Diisopropylaminopiperdinyl, 4-hydroxypiperdinyl, 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4- (4-isopropylpirazinyl)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-( 4-Methylsulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl ) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidine Group, 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazine Yl) pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, 4- (3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring , The substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-甲基呱嗪基， （4）4-(4-甲基呱嗪基)呱啶基，或 （5）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-methylpiperazine, (4) 4- (4-Methyl azizinyl) pyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-methylpiperazine, 4-(4-methylpiperazine) Pyridinyl, or Z 2 and Z 3 form .

在一些實施方案中，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）氟，（3）甲氨基羰基。In some embodiments, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) fluorine, (3) methylaminocarbonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為選自：氟，甲氨基羰基；且A2 和A4 二者之一為氫，另一為選自：氟，甲氨基羰基；A3 為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is selected from: fluorine, methylaminocarbonyl; and one of A 2 and A 4 is hydrogen, and the other is selected from: fluorine, methylaminocarbonyl ; A 3 is hydrogen.

在一些實施方案中，R2選自：，其中，A1 和A5 二者之一為氫，另一為甲氨基羰基；且A2 和A4 二者之一為氫，另一為氟；A3 為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methylaminocarbonyl; and one of A 2 and A 4 is hydrogen, and the other is fluorine; A 3 is hydrogen.

第十方面，本發明提供了一種下面通式 IG表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基。In a tenth aspect, the present invention provides a compound represented by the following general formula IG, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （8）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylamino Sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl , 4-Hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-yl Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-sulfonyl, 4-methylpiperazin-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-Butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl) piperazinyl-1-sulfonyl, 4-(2-cyanoethyl) piperazinyl-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl Yl)piperazinyl-1-sulfonyl, 4-(2-N,N-diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl- 1-sulfonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazine 1-sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl) Pyridine-1-yl sulfonyl, 4-(4-ethyl-1-pyrazine) pyridine-1-yl sulfonyl, 4-(4-acetinyl-1-pyrazine) quan Pyridin-1-yl sulfonyl, 4-(N-methyl-4-pyridinyl) azizinyl-1-sulfonyl, or (8) Z 2 and Z 3 or Z 3 and Z 4 form a compound containing A nitrogen or oxygen-containing substituted or unsubstituted five-membered ring, and the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）氨基磺醯基， 或 （5）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) N-methyl-4-pyridinyl , 4-Hydroxypyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, (4) aminosulfonyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4 -Pyridinyl, 4-hydroxy pyridinyl, 4-(4-methyl pyrrolidinyl) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, aminosulfonyl, or Z 2 Form with Z 3 or Z 3 and Z 4 .

在一些實施方案中，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲磺醯氨基。In some embodiments, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonylamino.

在一些實施方案中，R2選自：，其中A2 和A4 二者之一為氫，另一為甲磺醯氨基；A1 ，A3 ，A5 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 2 and A 4 is hydrogen, and the other is methanesulfonylamino; A 1 , A 3 , and A 5 are all hydrogen.

第十一方面，本發明提供了一種下面通式 IH表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自： 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基。In an eleventh aspect, the present invention provides a compound represented by the following general formula IH, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinoethyl, 2-(4-4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl , 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4 -Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-iso Oxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2 ) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as Z 1 ; R2 is selected from: 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基 （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （6）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperdinyl (4) 4-(4-methylpiperazine)piridyl, 4-(4-ethylpiperazine)piridinyl, 4-(4-isopropylpiperazine)quat Ridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piperidine Ridinyl, 4-(4-(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-( 3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2-N , N-Diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4- (3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrole (5) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetylpiperazine, 4-tert-butoxycarbonyl Azinyl, 4-methanesulfonyl azizinyl, 4-(2-hydroxyethyl) azizinyl, 4-(2-cyanoethyl) azizinyl, 4-(3-hydroxypropyl) azinyl Azinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl , 4-(N-ethyl-4-piridinyl)pirazinyl, (6) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, Isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridine-1-ylsulfonyl, 4-hydroxypiperidin-1-yl Sulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1 -Sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methyl Pyrazin-1-ylsulfonyl, 4-ethylprazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylprazinyl- 1-sulfonyl, 4-(2-hydroxyethyl)pezinyl-1-sulfonyl, 4-(2-cyanoethyl)pezinyl-1-sulfonyl, 4-(2- N, N-Dimethylaminoethyl) piperazinyl-1-sulfonyl, 4- (2-N,N-Diethylethyl)piazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piazinyl-1-sulfonyl, 4-(3-N, N -Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1- Sulfonyl, 3,5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)peridine-1-ylsulfonyl, 4-(4 -Ethyl-1-piperazinyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N- Methyl-4-pyridinyl) pyrazine-1-sulfonyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or For the six-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基， （5）氨基磺醯基，或 （6）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) N-methyl-4-pyridinyl, 4- Hydroxypiperdinyl, 4-(4-methylpiperazine), 4-(tetrahydropyrrol-1-yl)piperdinyl, (4) 4-methylpiperazine, (5) amino Sulfonyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 Z2 與 Z3 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: N-methyl-4-pyridinyl, 4-hydroxypyridinyl, 4 -Methylpiperazinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, aminosulfonyl, or Z 2 and Z 3 form .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲磺醯氨基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonamide.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯氨基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methanesulfonylamino; A 2 , A 3 , and A 4 are all hydrogen.

第十二方面，本發明提供了一種下面通式 II表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In the twelfth aspect, the present invention provides a compound represented by the following general formula II, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl) piperazinyl-1-methylamino; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基、乙氧基、異丙氧基； （3）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-羥基呱啶基； （4）4-甲基呱嗪基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, ethoxy, and isopropoxy; (3) N -Methyl-4-piperidinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-hydroxypyridinyl; (4) 4-Methylpiperazinyl.

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一選自：甲氧基、乙氧基、異丙氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, and isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4-piperidyl, 4-methylpiperazinyl, 4-hydroxypiperidyl, 4-(4-methylpiperazinyl)piperidyl, 4-(tetrazinyl) Hydropyrrol-1-yl)pyridinyl.

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫；（2）甲氨基羰基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) methylaminocarbonyl.

在一些實施方案中，R2選自，其中A1 和A5 二者之一為氫，另一為甲氨基羰基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from , Wherein one of A 1 and A 5 is hydrogen, and the other is methylaminocarbonyl; A 2 , A 3 , and A 4 are all hydrogen.

第十三方面，本發明提供了一種下面通式IPQ表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a thirteenth aspect, the present invention provides a compound represented by the following general formula IPQ, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Pirazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piridinyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) azizinyl) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, (4) 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl Group, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N -Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazin Group, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl-4- (Primidyl) azizinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethyl Amino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethyl Aminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine -4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N -Diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-acetylpiperazinyl) ) Ethoxy, 2-? Alkylethoxy, 2-Thiophenanthrylethoxy, 2-Perridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropyl Oxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetazinyl)propoxy, 3 -Morpholinylpropoxy, 3-thiophenanthrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-yl Methoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonyl, aminosulfonyl Group, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetinyl Piperazinyl-1-sulfonyl, 4-tert-butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2- Cyanoethyl) piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-sulfonyl, 4-(2-N,N- Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl )Pepazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1-sulfonyl, morpholin-1-sulfonyl, 3, 5 -Dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl-1-piper) (Azinyl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-(N-methyl-4-piperidine Group) pyrazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, Cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-di Ethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetra Hydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-butoxy Carbonyl piperazinyl-1-carbonyl, 4 -(2-Hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1-carbonyl, 4 -(3-N, N-Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl -1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-(4-ethyl -1-piperinyl)piridinyl-1-carbonyl, 4-(4-acetinyl-1-piperinyl)piridinyl-1-carbonyl, 4-(N-methyl-4-piperidine Yl)pirazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, ( 9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethylamino, cyclopentan Aminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4 -N, N-Diethylaminopyridinyl-1-methylamino, tetrahydropyrrolyl-1-methylamino, 3-N, N-dimethylaminotetrahydropyrrolyl-1-methylamino , 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-Acetyl piperazinyl-1-methanoamino, 4-tert-butoxycarbonyl piperazinyl-1-methanoamino, 4-(2-hydroxyethyl) piperazinyl-1-methanoamino, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carboxamido, 4-(2 -N, N-Diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carboxamido, morpholinyl-1-methyl Amino, 3,5-dimethylmorpholinyl-1-carboxamido, 4-(4-methyl-piperazine-1-yl)piridinyl-1-carboxamido, 4-(4- Ethyl-1-prazinyl) pyridinyl-1-methanylamino, 4-(4-acetinyl-1-methazinyl) pyridinyl-1-methanylamino, 4-(N-methyl (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six Membered ring, the substituent may be selected from the same substituents as described above as Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazine group) piperidyl group, 4-(4-tert-butoxycarbonyl piperazinyl group) piperidyl group, 4-(4-methylsulfonyl piperazinyl group) piperidyl group, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , (4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4- Methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethyl Aminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N -Ethyl-4-pyridinyl) azizinyl; or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring, and the substituent may be selected from The above-mentioned substituents are the same as Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基，4-二甲氨基-呱啶基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(4-methylpiperazine) Group) pyridinyl, 4-methylpyrazine, 4-dimethylamino-pyridinyl.

在一些實施方案中，R1選自：，其中， Z1 為甲氧基，且Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，其餘為氫；或 Z3 與Z4 形成，且Z1 為甲氧基，其餘為氫。In some embodiments, R1 is selected from: , Wherein Z 1 is a methoxy group, and Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, and the rest Is hydrogen; or Z 3 and Z 4 are formed , And Z 1 is a methoxy group, and the rest are hydrogen.

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫，（2）異丙氨基羰基，二甲氨基羰基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylaminocarbonyl, dimethylaminocarbonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙氨基羰基或二甲氨基羰基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is isopropylaminocarbonyl or dimethylaminocarbonyl; A 2 , A 3 , and A 4 are all hydrogen.

第十四方面，本發明提供了一種下面通式 IJ表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(N-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a fourteenth aspect, the present invention provides a compound represented by the following general formula IJ, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(N-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methylprazinyl, 4-ethylprazinyl, 4-isopropylprazinyl, 4-acetylprazinyl, 4-tert-butoxycarbonylprazinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基， 或 （5）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) N-methyl-4-pyridinyl , 4-N, N-Dimethylaminopiridinyl, 4-(4-methylpiperazine)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, (4)4- Methyl piperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基，Z2 和Z4 二者之一為氫，另一為甲基， Z3 選自：N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, the other is methoxy, one of Z 2 and Z 4 is hydrogen, the other is methyl, and Z 3 is selected from: N-methyl-4 -Pepridyl, 4-N, N-dimethylaminopyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrole-1 -Radical) pyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）異丙亞磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfinyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙亞磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylsulfinyl; A 2 , A 3 , and A 4 are all hydrogen.

第十五方面，本發明提供了一種下面通式 IK表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a fifteenth aspect, the present invention provides a compound represented by the following general formula IK, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）4-甲基呱嗪基， （4）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 4-N, N-二甲基氨基呱啶基，或 （5）Z2 與 Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) 4-methylpiperazinyl, (4 ) N-Methyl-4-pyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-N, N-dimethyl Aminopyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed or .

在一些實施方案中，R1選自，其中Z2 和Z4 二者之一為氫，另一為甲基，Z1 和Z5 二者之一為氫，另一為甲氧基， Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 4-N, N-二甲基氨基呱啶基，或 Z2 與Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from , Wherein one of Z 2 and Z 4 is hydrogen, the other is methyl, one of Z 1 and Z 5 is hydrogen, the other is methoxy, Z 3 is selected from: N-methyl-4 -Pepridyl, 4-methylpiperazinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-N, N-di Methylaminopyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 form or .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）二甲基次膦醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) dimethylphosphinyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為二甲基次膦醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is dimethylphosphinyl; A 2 , A 3 , and A 4 are all hydrogen.

第十六方面，本發明提供了一種下面通式 IRS表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a sixteenth aspect, the present invention provides a compound represented by the following general formula IRS, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Piperazine) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, 4-(tetrahydro (Pyrrol-1-yl) pyridinyl, (4) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diiso Propylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethyl Aminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methyl Pyperazine group) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazine) Ethoxy, 2-( 4-acetinyl(azizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethyl Aminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3 -(4-Acetylazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy Group, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted benzene Methoxy, (7) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl , Cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylamino Pyridine-1-ylsulfonyl, 4-N, N-diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pezinyl -1-sulfonyl, 4-(2-N,N-diethylethyl)pezinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl , 4-(3-N, N-Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfon Amino group, morpholinyl-1-sulfonyl group, 3,5-dimethylmorpholinyl-1-sulfonyl group, 4-(4-methyl-piperazine-1-yl)piperidine-1- Sulfonyl, 4-(4-ethyl-1-piperazinyl)piridin-1-ylsulfonyl, 4-(4-acetyl-1-piperazinyl)piridin-1-yl Sulfonyl, 4-(N-methyl-4-pyridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso Propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethyl Aminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl -1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazine-1-ylcarbonyl, 4-ethylpiperazine-1-carbonyl, 4- Acetyl piperazinyl-1-carbonyl, 4 -Tert-Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3 -Hydroxypropyl) piperazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylamino Propyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piper Pyridin-1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl)piperidinyl-1-carbonyl, 4-(4-acetinyl-1-piperazinyl)piperidinyl-1- Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl , Isobutoxycarbonyl, tert-butoxycarbonyl, (9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylamino Carboxamide, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, pyridinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N, N-di Methylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N- Dimethylaminotetrahydropyrrolyl-1-carboxamido, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylpiperazinyl-1-carboxamido, 4-tert-butoxycarbonylpiperazinyl-1-carboxamido, 4-(2- Hydroxyethyl) piperazinyl-1-carboxamido, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-methylamino, 4-(3-hydroxypropyl) piperazinyl-1 -Formylamino, 4-(3-N, N-dimethylaminopropyl) azizinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) azizinyl -1-carboxamido, morpholino-1-carboxamido, 3,5-dimethylmorpholino-1-carboxamido, 4-(4-methyl-piperazine-1-yl)quat Pyridinyl-1-methanylamino, 4-(4-ethyl-1-pyrazineyl)pyridinyl-1-methanylamino, 4-(4-acetyl-1-pyrazineyl)piperidine Group-1-carboxamide, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carboxamido; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as Z 1 ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基； （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , 4-(Tetrahydropyrrol-1-yl)piridyl; (4) 4-methylpirazinyl, 4-ethylpirazinyl, 4-isopropylpirazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (5) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(四氫吡咯-1-基)呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-二甲氨基-呱啶基； （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(tetrahydropyrrole-1- Group) pyridinyl, 4-methyl pyrazine, 4-(4-methyl pyrazine) pyridinyl, 4-dimethylamino-pyridinyl; (4) Z 2 and Z 3 can be formed containing Nitrogen substituted or unsubstituted five-membered ring .

在一些實施方案中，R1選自：，其中 Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methyl Pyrazinyl) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫；（2）二異丙基次膦醯基，二乙基次膦醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) diisopropylphosphinyl, diethylphosphinyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為二異丙基次膦醯基或二乙基次膦醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is diisopropylphosphinyl or diethylphosphinyl; A 2 , A 3 , and A 4 are all hydrogen.

第十七方面，本發明提供了一種下面通式 IL表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，A為亞甲基；X為NH； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a seventeenth aspect, the present invention provides a compound represented by the following general formula IL, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, A is methylene; X is NH; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-di Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N- Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl -5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyridinyl Azolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl azizinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethyl Aminotetrahydropyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl )Prazinyl, 4-(N-ethyl-4-pyridinyl)piperazinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted For a five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基， （4）4-甲基呱嗪基，或 （5）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, 4-(4-methyl Pyrazinyl) pyridinyl, (4) 4-methylpiperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methanesulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第十八方面，本發明提供了一種下面通式 IM表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，A為亞甲基；X為NH； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In an eighteenth aspect, the present invention provides a compound represented by the following general formula IM, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, A is methylene; X is NH; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-di Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N- Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl -5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyridinyl Azolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl azizinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethyl Aminotetrahydropyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted For a five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基， （4）4-甲基呱嗪基，或 （5）Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, 4-(4-methyl Pyrazinyl) pyridinyl, (4) 4-methylpiperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）異丙基磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第十九方面，本發明提供了一種下面通式 IT表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，A為亞甲基；X為O； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a nineteenth aspect, the present invention provides a compound represented by the following general formula IT, its stereoisomers, its prodrugs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates, Wherein, A is methylene; X is O; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-di Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N- Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl -5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyridinyl Azolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Piperazine) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, 4-(tetrahydro (Pyrrol-1-yl) pyridinyl, (4) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diiso Propylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethyl Aminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methyl Pyperazine group) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazine) Ethoxy, 2-( 4-acetinyl(azizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethyl Aminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3 -(4-Acetylazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy Group, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted benzene Methoxy, (7) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl , Cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylamino Pyridine-1-ylsulfonyl, 4-N, N-diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pezinyl -1-sulfonyl, 4-(2-N,N-diethylethyl)pezinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl , 4-(3-N, N-Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfon Amino group, morpholinyl-1-sulfonyl group, 3,5-dimethylmorpholinyl-1-sulfonyl group, 4-(4-methyl-piperazine-1-yl)piperidine-1- Sulfonyl, 4-(4-ethyl-1-piperazinyl)piridin-1-ylsulfonyl, 4-(4-acetyl-1-piperazinyl)piridin-1-yl Sulfonyl, 4-(N-methyl-4-pyridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso Propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethyl Aminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl -1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazine-1-ylcarbonyl, 4-ethylpiperazine-1-carbonyl, 4- Acetyl piperazinyl-1-carbonyl, 4 -Tert-Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3 -Hydroxypropyl) piperazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylamino Propyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piper Pyridin-1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl)piperidinyl-1-carbonyl, 4-(4-acetinyl-1-piperazinyl)piperidinyl-1- Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl , Isobutoxycarbonyl, tert-butoxycarbonyl, (9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylamino Carboxamide, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, pyridinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N, N-di Methylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N- Dimethylaminotetrahydropyrrolyl-1-carboxamido, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylpiperazinyl-1-carboxamido, 4-tert-butoxycarbonylpiperazinyl-1-carboxamido, 4-(2- Hydroxyethyl) piperazinyl-1-carboxamido, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-methylamino, 4-(3-hydroxypropyl) piperazinyl-1 -Formylamino, 4-(3-N, N-dimethylaminopropyl) azizinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) azizinyl -1-carboxamido, morpholino-1-carboxamido, 3,5-dimethylmorpholino-1-carboxamido, 4-(4-methyl-piperazine-1-yl)quat Pyridinyl-1-methanylamino, 4-(4-ethyl-1-pyrazineyl)pyridinyl-1-methanylamino, 4-(4-acetyl-1-pyrazineyl)piperidine Group-1-carboxamide, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carboxamido; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as Z 1 ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl.

在一些實施方案中，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基； （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , 4-(Tetrahydropyrrol-1-yl)piridyl; (4) 4-methylpirazinyl, 4-ethylpirazinyl, 4-isopropylpirazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (5) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，嗎啉基，4-二甲氨基-呱啶基， （4）Z2 與Z3 可以形成含氮的取代或未取代的五元環。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-methylpiperazinyl, 4 -(4-Methylpyrazineyl)pyridinyl, morpholinyl, 4-dimethylamino-pyridinyl, (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring .

在一些實施方案中，R1選自：，其中 Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基或嗎啉基，或 Z2 與Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methyl Pyrazinyl) pyridinyl, 4-methylpiperazinyl or morpholinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫， （2）異丙基磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

第二十方面，本發明提供了一種下面通式 IN表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In a twentieth aspect, the present invention provides a compound represented by the following general formula IN, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl)pirazinyl-1-carboxamido, 4-(3-hydroxypropyl)pirazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （8）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylamino Sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl , 4-Hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-yl Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-sulfonyl, 4-methylpiperazin-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-Butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl) piperazinyl-1-sulfonyl, 4-(2-cyanoethyl) piperazinyl-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl Yl)pirazinyl-1-sulfonyl, 4-(2-N,N-diethylethyl)pirazinyl-1-sulfonyl, 4-(3-hydroxypropyl)pirazinyl- 1-sulfonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazine 1-sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl) Pyridine-1-ylsulfonyl, 4-(4-ethyl-1-pyrazineyl)pyridin-1-ylsulfonyl, 4-(4-acetinyl-1-pyrazine)quan Pyridin-1-ylsulfonyl, 4-(N-methyl-4-pyridinyl) pazizinyl-1-sulfonyl, or (8) Z 2 and Z 3 or Z 3 and Z 4 form a compound containing Nitrogen or oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）4-羥基呱啶基，4-甲基呱嗪基，N-甲基-4-呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 （5）Z2 與Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) 4-hydroxypyridinyl, 4-methyl Piperazinyl, N-methyl-4-piperidyl, (4) 4-(4-methylpiperazinyl) piperidyl, 4-(tetrahydropyrrol-1-yl) piperidyl, amino Sulfonyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed or .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基， Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 氨基磺醯基，或 Z2 與 Z3 或Z3 與Z4 形成或。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, the other is methyl, and Z 3 is selected from: 4-hydroxypyridinyl , 4-Methylpiperazinyl, N-methyl-4-piperidinyl, 4-(4-methylpiperazinyl)piperidinyl, 4-(tetrahydropyrrol-1-yl)piperidinyl, Aminosulfonyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed or .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl.

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲氧羰基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methoxycarbonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為甲氧羰基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is methoxycarbonyl; A 2 , A 3 , and A 4 are all hydrogen.

第二十一方面，本發明提供了一種下面通式 IU表示的化合物、其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物，其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基。In the twenty-first aspect, the present invention provides a compound represented by the following general formula IU, its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate, Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-methanylamino, 4-tert-butoxycarbonylpiperazinyl-1-methionylamino, 4-(2-hydroxyethyl)piperazinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; R2 is selected , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, dimethylaminosulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, iso Butoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl , Dimethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基 （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperdinyl (4) 4-(4-methylpiperazinyl)piridinyl, 4-(4-ethylpiperazinyl)piridinyl, 4-(4-isopropylpiperazinyl)piperidyl Ridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piperidine Ridinyl, 4-(4-(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-( 3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2-N , N-Diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4- (3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethylamino Tetrahydropyrrolyl) piperidinyl, (5) 4-methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butyl Oxycarbonylprazinyl, 4-methanesulfonylprazinyl, 4-(2-hydroxyethyl)prazinyl, 4-(2-cyanoethyl)prazinyl, 4-(3-hydroxypropyl) Group) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3 -N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) Piperazinyl, 4-(N-ethyl-4-pyridinyl) piperazinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five The membered ring, the substituent may be selected from the same substituents as described above for Z 1.

在一些實施方案中，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基， （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環。In some embodiments, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(4-methylpiperazine) (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring .

在一些實施方案中，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成。In some embodiments, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-methylpiperazinyl, 4-(4-methylpiperazinyl)piperidyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed .

在一些實施方案中，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫 （2）二甲氨基磺醯基。In some embodiments, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen (2) dimethylaminosulfonyl.

在一些實施方案中，R2選自：，其中A1 和A5 二者之一為氫，另一為二甲氨基磺醯基；A2 ，A3 ，A4 都為氫。In some embodiments, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is dimethylaminosulfonyl; A 2 , A 3 , and A 4 are all hydrogen.

除非特殊說明，上述基團和取代基具有藥物化學領域的普通含義。Unless otherwise specified, the above-mentioned groups and substituents have ordinary meanings in the field of medicinal chemistry.

需要說明的是，C1-C6含氧烷基是指是指C1-C6烷基骨架被一或複數C1-C6烷氧基取代所成的基團，例如，甲氧基乙基，甲氧基乙氧基甲基等。It should be noted that the C1-C6 oxygen-containing alkyl group refers to a group formed by replacing the C1-C6 alkyl skeleton with one or more C1-C6 alkoxy groups, for example, methoxyethyl, methoxy Ethoxymethyl etc.

術語“C1 -C6 烷基”指的是任意的含有1－6個碳原子的直鏈或支鏈基團，例如甲基、乙基、正丙基、異丙基、正丁基、異丁基、叔丁基、仲丁基、正戊基、叔戊基、正己基等。The term "C 1 -C 6 alkyl" refers to any straight or branched chain group containing 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, Isobutyl, tert-butyl, sec-butyl, n-pentyl, tert-pentyl, n-hexyl, etc.

術語“C2 -C6 烯基”指的是任意的含有2－6個碳原子且含有至少一烯基的直鏈或支鏈基團基團，例如乙烯基、烯丙基、1-丙烯基、異丙烯基、1-丁烯基、2-丁烯基、3-丁烯基、2-戊烯基、1-己烯基等。The term "C 2 -C 6 alkenyl" refers to any straight-chain or branched group containing 2-6 carbon atoms and at least one alkenyl group, such as vinyl, allyl, 1-propene Group, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 1-hexenyl, etc.

術語“C2 -C6 炔基”指的是任意的含有2－6個碳原子且含有至少一炔基的直鏈或支鏈基團，例如乙炔基、2-丙炔基、4-戊炔基等。The term "C 2 -C 6 alkynyl" refers to any straight or branched chain group containing 2-6 carbon atoms and containing at least one alkynyl group, such as ethynyl, 2-propynyl, 4-pentyl Alkynyl etc.

根據本發明和除非另有提供，任意上述基團可以任選地在其任意自由位置上被一或複數基團取代，例如被1-6個基團取代，該基團獨立地選自: 鹵素原子、硝基、氧代(=O)、氰基、C1 -C6 烷基、多氟化烷基、多氟化烷氧基、烯基、炔基、羥基烷基、羥基烷基氨基、羥基雜環基、芳基、芳基-烷基、雜芳基、雜芳基-烷基、雜環基、雜環基-烷基、C3 -C7 環烷基、環烷基-烷基、烷基-芳基、烷基-雜芳基、烷基-雜環基、烷基-環烷基、烷基-芳基-烷基、烷基-雜芳基-烷基、烷基-雜環基-烷基、烷基-環烷基-烷基、烷基-雜環基-雜環基、雜環基-雜環基、雜環基-烷基-雜環基、雜環基-烷基氨基、烷基-雜環基-烷基-氨基、羥基、烷氧基、芳氧基、雜環基氧基、烷基-雜環基氧基、亞甲二氧基、烷基羰基氧基、芳基羰基氧基、環烯基氧基、雜環基羰基氧基、亞烷基氨基氧基、羧基、烷氧基羰基、芳氧基羰基、環烷基氧基羰基、雜環基氧基羰基、氨基、脲基、烷基氨基、氨基-烷基氨基、二烷基氨基、二烷基氨基-雜環基、二烷基氨基-烷基氨基、芳基氨基、芳基烷基氨基、二芳基氨基、雜環基氨基、烷基-雜環基氨基、烷基-雜環基羰基、羰基氨基、烷基羰基氨基、芳基羰基氨基、雜環基羰基氨基、烷基-雜環基羰基氨基、氨基羰基、烷基氨基羰基、二烷基氨基羰基、芳基氨基羰基、雜環基氨基羰基、烷氧基羰基氨基、烷氧基羰基氨基-烷基氨基、烷氧基羰基雜環基-烷基氨基、烷氧基-芳基-烷基、羥基氨基-羰基、烷氧基亞氨基、烷基磺醯基氨基、芳基磺醯基氨基、雜環基磺醯基氨基、甲醯基、烷基羰基、芳基羰基、環烷基羰基、雜環基羰基、烷基磺醯基、芳基磺醯基、氨基磺醯基、烷基氨基磺醯基、二烷基氨基磺醯基、芳基氨基磺醯基、雜環基氨基磺醯基、芳硫基、烷硫基、膦酸酯基和烷基膦酸酯基。According to the present invention and unless otherwise provided, any of the aforementioned groups may be optionally substituted at any of its free positions by one or more groups, for example by 1-6 groups, which groups are independently selected from: halogen Atom, nitro, oxo (=O), cyano, C 1 -C 6 alkyl, polyfluorinated alkyl, polyfluorinated alkoxy, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkylamino , Hydroxyheterocyclyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclyl, heterocyclyl-alkyl, C 3 -C 7 cycloalkyl, cycloalkyl- Alkyl, alkyl-aryl, alkyl-heteroaryl, alkyl-heterocyclyl, alkyl-cycloalkyl, alkyl-aryl-alkyl, alkyl-heteroaryl-alkyl, alkane Group-heterocyclyl-alkyl, alkyl-cycloalkyl-alkyl, alkyl-heterocyclyl-heterocyclyl, heterocyclyl-heterocyclyl, heterocyclyl-alkyl-heterocyclyl, hetero Cyclic-alkylamino, alkyl-heterocyclyl-alkyl-amino, hydroxy, alkoxy, aryloxy, heterocyclyloxy, alkyl-heterocyclyloxy, methylenedioxy, Alkylcarbonyloxy, arylcarbonyloxy, cycloalkenyloxy, heterocyclylcarbonyloxy, alkyleneaminooxy, carboxy, alkoxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl , Heterocyclyloxycarbonyl, amino, ureido, alkylamino, amino-alkylamino, dialkylamino, dialkylamino-heterocyclyl, dialkylamino-alkylamino, arylamino, Arylalkylamino, diarylamino, heterocyclylamino, alkyl-heterocyclylamino, alkyl-heterocyclylcarbonyl, carbonylamino, alkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino , Alkyl-heterocyclylcarbonylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, alkoxycarbonylamino, alkoxycarbonylamino-alkylamino , Alkoxycarbonylheterocyclyl-alkylamino, alkoxy-aryl-alkyl, hydroxyamino-carbonyl, alkoxyimino, alkylsulfonylamino, arylsulfonylamino, heterocyclic Sulfonylamino, formyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclic carbonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, alkylaminosulfonyl Group, dialkylaminosulfonyl, arylaminosulfonyl, heterocyclylaminosulfonyl, arylthio, alkylthio, phosphonate and alkylphosphonate.

進而，如果適合，上述取代基各自可以進一步被一或複數上述舉出的基團取代。Furthermore, if appropriate, each of the above-mentioned substituents may be further substituted by one or more of the above-mentioned groups.

在這方面，術語“鹵原子”指的是氟、氯、溴或碘原子。In this regard, the term "halogen atom" refers to a fluorine, chlorine, bromine or iodine atom.

術語“氰基”指的是-CN殘基。The term "cyano" refers to a -CN residue.

術語“硝基”指的是-NO2 基團。The term "nitro" refers to the -NO 2 group.

術語“烷氧基”、“環基氧基”、“芳基氧基”，“雜環基氧基”及其衍生物指的是任意上述C1 -C6 烷基、C3 -C7 環烷基、芳基或雜環基，其通過氧原子(-O-)連接到分子的其餘部分。The terms "alkoxy", "cyclooxy", "aryloxy", "heterocyclyloxy" and their derivatives refer to any of the aforementioned C 1 -C 6 alkyl, C 3 -C 7 Cycloalkyl, aryl, or heterocyclyl, which is connected to the rest of the molecule through an oxygen atom (-O-).

術語"芳基"是指單-、二-或多-碳環烴，其具有任選地進一步通過單鍵彼此稠合或連接的1至2個環系統，其中該碳環中至少一是“芳族的”，其中術語“芳族的”是指完全共軛的π-電子鍵系統。芳基環可以任選地進一步稠合或連接於芳族的和非芳族的碳環和雜環的環。該芳基的非限制性的實例是苯基、α-或β-萘基。The term "aryl" refers to a mono-, di- or poly-carbocyclic hydrocarbon having 1 to 2 ring systems optionally further fused or connected to each other through a single bond, wherein at least one of the carbocyclic rings is " Aromatic", where the term "aromatic" refers to a fully conjugated π-electron bond system. The aryl ring may optionally be further fused or connected to aromatic and non-aromatic carbocyclic and heterocyclic rings. Non-limiting examples of the aryl group are phenyl, α- or β-naphthyl.

術語"雜芳基"是指芳族的雜環，通常為具有1至3個選自N、O或S的雜原子的5-至8-元的雜環；雜芳基環可以任選地進一步稠合或連接於芳族和非芳族的碳環和雜環。該雜芳基的非限制性的實例為例如吡啶基、吡嗪基、嘧啶基、噠嗪基、吲哚基、咪唑基、噻唑基、異噻唑基、噻噁唑基、吡咯基、苯基-吡咯基、呋喃基、苯基-呋喃基、噁唑基、異噁唑基、吡唑基、噻吩基、苯並噻吩基、異二氫吲哚基、苯並咪唑基、吲唑基、喹啉基、異喹啉基、1,2,3-三唑基、1-苯基-1,2,3-三唑基、2,3-二氫吲哚基、2,3-二氫苯並呋喃基、2,3-二氫苯並噻吩基、苯並吡喃基、2,3-二氫苯並噁嗪基、2,3-二氫喹喔啉基等。The term "heteroaryl" refers to an aromatic heterocyclic ring, usually a 5- to 8-membered heterocyclic ring having 1 to 3 heteroatoms selected from N, O or S; the heteroaryl ring may optionally Further fused or connected to aromatic and non-aromatic carbocyclic and heterocyclic rings. Non-limiting examples of the heteroaryl group are, for example, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, thiazolyl, isothiazolyl, thiazolyl, pyrrolyl, phenyl -Pyrrolyl, furyl, phenyl-furyl, oxazolyl, isoxazolyl, pyrazolyl, thienyl, benzothienyl, isoindolinyl, benzimidazolyl, indazolyl, Quinolinyl, isoquinolinyl, 1,2,3-triazolyl, 1-phenyl-1,2,3-triazolyl, 2,3-indoline, 2,3-dihydro Benzofuranyl, 2,3-dihydrobenzothienyl, benzopyranyl, 2,3-dihydrobenzoxazinyl, 2,3-dihydroquinoxalinyl, etc.

術語“雜環基”(也稱作“雜環烷基”)指的是3-、4-、5-、6-和7-元飽和或部分不飽和碳環，其中一或複數碳原子被雜原子例如氮、氧和硫替代。雜環基的非限制性實例是，例如吡喃、吡咯烷、吡咯啉、咪唑啉、咪唑烷、吡唑烷、吡唑啉、噻唑啉、噻唑烷、二氫呋喃、四氫呋喃、1,3-二氧戊環、呱啶、呱嗪、嗎啉、四氫吡咯基、硫嗎啉基等。The term "heterocyclyl" (also known as "heterocycloalkyl") refers to 3-, 4-, 5-, 6-, and 7-membered saturated or partially unsaturated carbocyclic rings in which one or more carbon atoms are Heteroatoms such as nitrogen, oxygen and sulfur are substituted. Non-limiting examples of heterocyclic groups are, for example, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, thiazoline, thiazolidine, dihydrofuran, tetrahydrofuran, 1,3- Dioxolane, piperidine, piperazine, morpholine, tetrahydropyrrolyl, thiomorpholinyl, etc.

術語“含氮或含氧的取代或未取代的五元環或六元環”， 指的是5-或6-元飽和或部分不飽和碳環，其中一或複數碳原子被雜原子例如氮、氧替代。含氮或含氧的取代或未取代的五元環或六元環選自吡咯烷、吡咯啉、吡咯、咪唑啉、咪唑烷、咪唑、吡唑烷、吡唑啉、吡唑、二氫呋喃、四氫呋喃、呋喃、1,3-二氧戊環、噁唑、二氫噁唑；吡啶、吡嗪、嘧啶、噠嗪、吡喃、呱啶、呱嗪、嗎啉等。The term "nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring" refers to a 5- or 6-membered saturated or partially unsaturated carbon ring in which one or more carbon atoms are heteroatoms such as nitrogen , Oxygen substitution. The nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring is selected from pyrrolidine, pyrroline, pyrrole, imidazoline, imidazolidine, imidazole, pyrazolidine, pyrazoline, pyrazole, dihydrofuran , Tetrahydrofuran, furan, 1,3-dioxolane, oxazole, dihydrooxazole; pyridine, pyrazine, pyrimidine, pyridazine, pyran, piperidine, piperazine, morpholine, etc.

從所有上述描述中，對本領域技術人員顯而易見的是，其名稱是複合名稱的任意基團，例如“芳基氨基”，應該指的是常規地從其衍生的部分例如從被芳基取代的氨基來構建，其中芳基如上文所定義。From all the above descriptions, it is obvious to those skilled in the art that any group whose name is a compound name, such as "arylamino", shall refer to the moiety conventionally derived therefrom, such as an amino group substituted with an aryl group. To construct where the aryl group is as defined above.

同樣，任意術語例如烷硫基、烷基氨基、二烷基氨基、烷氧基羰基、烷氧基羰基氨基、雜環基羰基、雜環基羰基氨基、環烷基氧基羰基等包括基團，其中烷基、烷氧基、芳基、C3 -C7 環烷基和雜環基部分如上文所定義。Likewise, any terms such as alkylthio, alkylamino, dialkylamino, alkoxycarbonyl, alkoxycarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, cycloalkyloxycarbonyl, etc. include groups , Wherein the alkyl, alkoxy, aryl, C 3 -C 7 cycloalkyl and heterocyclyl moieties are as defined above.

如本文所使用，除非另外說明，術語“前藥”是指可以在生物學條件（體外或體內）下水解、氧化或進行其他反應以提供本發明的化合物的衍生物。前藥僅在生物學條件下經過該反應成為活性化合物，或者它們在它們不反應的形式中具有活性。通常可以使用公知的方法製備前藥，例如1 Burger's Medicinal Chemistry and Drug Discovery (1995) 172-178, 949-982 (Manfred E. Wolff編，第5版)中描述的那些方法。As used herein, unless otherwise stated, the term "prodrug" refers to a derivative that can be hydrolyzed, oxidized, or otherwise reacted under biological conditions (in vitro or in vivo) to provide a compound of the present invention. Prodrugs only undergo this reaction under biological conditions to become active compounds, or they are active in their unreactive form. The prodrug can generally be prepared using well-known methods, such as those described in 1 Burger's Medicinal Chemistry and Drug Discovery (1995) 172-178, 949-982 (Manfred E. Wolff ed., 5th edition).

藥學上可以接受的鹽可使用本領域熟知的標準程式獲得，例如，通過將足量的鹼性化合物和提供藥學上可以接受的陰離子的合適的酸反應。Pharmaceutically acceptable salts can be obtained using standard procedures well known in the art, for example, by reacting a sufficient amount of a basic compound with a suitable acid that provides a pharmaceutically acceptable anion.

本文使用的術語“治療”一般是指獲得需要的藥理和/或生理效應。該效應根據完全或部分地預防疾病或其症狀，可以是預防性的；和/或根據部分或完全穩定或治癒疾病和/或由於疾病產生的副作用，可以是治療性的。本文使用的“治療”涵蓋了對患者疾病的任何治療，包括：(a)預防易感染疾病或症狀但還沒診斷出患病的患者所發生的疾病或症狀；(b)抑制疾病的症狀，即阻止其發展；或(c)緩解疾病的症狀，即，導致疾病或症狀退化。The term "treatment" as used herein generally refers to obtaining a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of completely or partially preventing the disease or its symptoms; and/or may be therapeutic in terms of partially or completely stabilizing or curing the disease and/or side effects due to the disease. "Treatment" as used herein covers any treatment of a patient's disease, including: (a) preventing diseases or symptoms in patients who are susceptible to diseases or symptoms but have not yet been diagnosed with the disease; (b) suppressing the symptoms of the disease, That is to prevent its development; or (c) alleviate the symptoms of the disease, that is, cause the disease or symptoms to degenerate.

按照本發明的一種具體技術方案，該化合物、其立體異構體、其前藥、 或者其藥學上可接受的鹽或藥學上可接受的溶劑合物，其中該化合物為下面實施例中該化合物之一。According to a specific technical solution of the present invention, the compound, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvate, wherein the compound is the compound in the following examples one.

另一方面，本發明提供了一種藥物組合物，其包含上述任一技術方案所述的化合物、其立體異構體、其前藥、或者其藥學上可接受的鹽或藥學上可接受的溶劑合物，和藥學上可接受的載體、稀釋劑或賦形劑。In another aspect, the present invention provides a pharmaceutical composition comprising the compound described in any of the above technical solutions, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvent Compound, and a pharmaceutically acceptable carrier, diluent or excipient.

製備各種含有一定量的活性成分的藥物組合物的方法是已知的，或根據本發明的揭露內容對於本領域技術人員是顯而易見的。如Remington’s Pharmaceutical Sciences, Martin, E.W., ed., Mack Publishing Company, 19th ed.(1995)所述，製備該藥物組合物的方法包括摻入適當的藥學賦形劑、載體、稀釋劑等。Methods for preparing various pharmaceutical compositions containing a certain amount of active ingredients are known or obvious to those skilled in the art according to the disclosure of the present invention. As described in Remington's Pharmaceutical Sciences, Martin, E.W., ed., Mack Publishing Company, 19th ed. (1995), the method for preparing the pharmaceutical composition includes incorporating appropriate pharmaceutical excipients, carriers, diluents and the like.

以已知的方法製造本發明的藥物製劑，包括常規的混合、溶解或凍幹方法。本發明的化合物可以製成藥物組合物，並向患者以適於選定的施用方式的各種途徑施用，例如，口服或腸胃外（通過靜脈內、肌內、局部或皮下途徑）。The pharmaceutical preparations of the present invention are manufactured by known methods, including conventional mixing, dissolving or freeze-drying methods. The compounds of the present invention can be formulated into pharmaceutical compositions and administered to patients in various routes suitable for the selected mode of administration, for example, oral or parenteral (by intravenous, intramuscular, topical or subcutaneous routes).

因此，本發明的化合物結合藥學上可以接受的載體（如惰性稀釋劑或可同化的可食用的載體）可以全身施用，例如，口服。它們可以封閉在硬或軟殼的明膠膠囊中，可以壓為片劑。對於口服治療施用，活性化合物可以結合一種或多種賦形劑，並以可吞咽的片劑、頰含片劑、含片、膠囊劑、酏劑、懸浮劑、糖漿、圓片等的形式使用。這種組合物和製劑應該包含至少0.1%的活性化合物。這種組合物和製劑的比例當然可以變化，可以占給定的單位劑型重量的大約1%至大約99%。在這種治療有用的組合物中，活性化合物的量使得能夠獲得有效劑量水準。Therefore, the compound of the present invention combined with a pharmaceutically acceptable carrier (such as an inert diluent or an assimilable edible carrier) can be administered systemically, for example, orally. They can be enclosed in hard or soft gelatin capsules and can be compressed into tablets. For oral therapeutic administration, the active compound can be combined with one or more excipients and used in the form of swallowable tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, discs, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The ratio of such compositions to preparations can of course vary, and can comprise from about 1% to about 99% of the weight of a given unit dosage form. In such therapeutically useful compositions, the amount of active compound is such that an effective dosage level can be obtained.

片劑、含片、丸劑、膠囊劑等也可以包含：黏合劑，如黃蓍膠、阿拉伯膠、玉米澱粉或明膠；賦形劑，如磷酸氫二鈣；崩解劑，如玉米澱粉、馬鈴薯澱粉、藻酸等；潤滑劑，如硬脂酸鎂；和甜味劑，如蔗糖、果糖、乳糖或阿斯巴甜；或調味劑，如薄荷、冬青油或櫻桃香味。當單位劑型是膠囊時，除了上面類型的材料，它還可以包含液體載體，如植物油或聚乙二醇。各種其他材料可以存在，作為包衣，或以其他方式改變固體單位劑型的物理形式。例如，片劑、丸劑或膠囊劑可以用明膠、蠟、蟲膠或糖等包衣。糖漿或酏劑可以包含活性化合物，蔗糖或果糖作為甜味劑，對羥苯甲酸甲酯或對羥苯甲酸丙酯作為防腐劑，染料和調味劑（如櫻桃香料或桔子香料）。當然，用於製備任何單位劑型的任何材料應該是藥學上可以接受的且以應用的量基本上無毒。此外，活性化合物可以摻入緩釋製劑和緩釋裝置中。Tablets, lozenges, pills, capsules, etc. may also contain: binders, such as tragacanth, gum arabic, corn starch or gelatin; excipients, such as dicalcium hydrogen phosphate; disintegrating agents, such as corn starch, potato Starch, alginic acid, etc.; lubricants, such as magnesium stearate; and sweeteners, such as sucrose, fructose, lactose, or aspartame; or flavoring agents, such as peppermint, wintergreen oil, or cherry flavor. When the unit dosage form is a capsule, in addition to the above types of materials, it may also contain a liquid carrier such as vegetable oil or polyethylene glycol. Various other materials may be present as coatings or otherwise modify the physical form of the solid unit dosage form. For example, tablets, pills or capsules can be coated with gelatin, wax, shellac or sugar. Syrups or elixirs may contain active compounds, sucrose or fructose as sweeteners, methyl or propyl paraben as preservatives, dyes and flavors (such as cherry flavor or orange flavor). Of course, any material used to prepare any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amount used. In addition, the active compound can be incorporated into sustained-release preparations and sustained-release devices.

活性化合物也可以通過輸注或注射來靜脈內或腹膜內施用。可以製備活性化合物或其鹽的水溶液，任選地混和無毒的表面活性劑。也可以製備在甘油、液體聚乙二醇、甘油三乙酸酯及其混合物以及油中的分散劑。在普通的儲存和使用條件下，這些製劑包含防腐劑以防止微生物生長。The active compound can also be administered intravenously or intraperitoneally by infusion or injection. An aqueous solution of the active compound or its salt can be prepared, optionally mixed with a non-toxic surfactant. Dispersants in glycerin, liquid polyethylene glycol, triacetin and mixtures thereof, and oils can also be prepared. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

適於注射或輸注的藥物劑型可以包括包含適於無菌的可注射或可輸注的溶液或分散劑的即時製劑的活性成分（任選封裝在脂質體中）的無菌水溶液或分散劑或無菌粉末。在所有情況下，最終的劑型在生產和儲存條件下必須是無菌的、液體的和穩定的。液體載體可以是溶劑或液體分散媒介，包括，例如水、乙醇、多元醇（例如，甘油、丙二醇、液體聚乙二醇等）、植物油、無毒的甘油酯及其合適的混合物。可以維持合適的流動性，例如，通過脂質體的形成，通過在分散劑的情況下維持所需的粒子大小，或通過表面活性劑的使用。可以通過各種抗細菌劑和抗真菌劑（如對羥苯甲酸酯、氯丁醇、苯酚、山梨酸、硫柳汞等）產生預防微生物的作用。在許多情況下，較佳包括等滲劑，如糖、緩衝劑或氯化鈉。通過使用延緩吸收劑的組合物（例如，單硬脂酸鋁和明膠）可以產生可注射的組合物的延長吸收。Pharmaceutical dosage forms suitable for injection or infusion may include sterile aqueous solutions or dispersions or sterile powders containing the active ingredients (optionally encapsulated in liposomes) suitable for sterile injectable or infusion solutions or dispersions for immediate preparation. In all cases, the final dosage form must be sterile, liquid and stable under the conditions of manufacture and storage. The liquid carrier can be a solvent or liquid dispersion medium, including, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol, etc.), vegetable oil, non-toxic glyceride, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersants, or by the use of surfactants. Various antibacterial and antifungal agents (such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, etc.) can be used to prevent microorganisms. In many cases, it is preferable to include isotonic agents such as sugars, buffers or sodium chloride. Prolonged absorption of the injectable composition can be produced by using compositions that delay absorption (for example, aluminum monostearate and gelatin).

通過將合適的溶劑中的需要量的活性化合物與需要的上面列舉的各種其他成分結合，然後進行過濾滅菌，製備無菌可注射溶液。在用於製備無菌注射溶液的無菌粉末的情況下，較佳的製備方法是真空乾燥和冷凍乾燥技術，這會產生活性成分加上任何另外需要的以前無菌過濾溶液中存在的成分的粉末。Sterile injectable solutions are prepared by combining the required amount of the active compound in a suitable solvent with the various other ingredients enumerated above as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are vacuum drying and freeze-drying techniques, which will produce a powder of the active ingredient plus any otherwise required ingredients present in the previously sterile filtered solution.

有用的固體載體包括粉碎的固體（如滑石、黏土、微晶纖維素、二氧化矽、氧化鋁等）。有用的液體載體包括水、乙醇或乙二醇或水-乙醇/乙二醇混合物，本發明的化合物可以任選在無毒的表面活性劑的幫助下以有效含量溶解或分散在其中。可以加入佐劑（如香味）和另外的抗微生物劑來優化對於給定用途的性質。Useful solid carriers include crushed solids (such as talc, clay, microcrystalline cellulose, silica, alumina, etc.). Useful liquid carriers include water, ethanol or ethylene glycol or water-ethanol/ethylene glycol mixtures, and the compound of the present invention can be dissolved or dispersed in an effective content optionally with the help of a non-toxic surfactant. Adjuvants (such as flavors) and additional antimicrobial agents can be added to optimize the properties for a given application.

增稠劑（如合成的聚合物、脂肪酸、脂肪酸鹽和酯、脂肪醇、改性纖維素或改性無機材料）也可和液體載體用於形成可塗覆的糊劑、凝膠、軟膏、肥皂等，直接用於使用者的皮膚上。Thickeners (such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified cellulose or modified inorganic materials) can also be used with liquid carriers to form coatable pastes, gels, ointments, Soap, etc., are directly applied to the user's skin.

化合物或其活性鹽或衍生物的治療需要量，不僅取決於選擇的特定的鹽，而且取決於施藥方式、待治療的疾病的本質和患者的年齡和狀態，最終取決於在場醫師或臨床醫生的決定。The therapeutically required amount of the compound or its active salt or derivative depends not only on the specific salt selected, but also on the method of administration, the nature of the disease to be treated, and the age and state of the patient, and ultimately depends on the physician or clinician present The doctor's decision.

上述製劑可以以單位劑型存在，該單位劑型是含有單位劑量的物理分散單元，適於向人體和其它哺乳動物體給藥。單位劑型可以是膠囊或片劑，或是很多膠囊或片劑。根據所涉及的具體治療，活性成分的單位劑量的量可以在大約0.1到大約1000毫克或更多之間進行變化或調整。The above formulations may be presented in a unit dosage form, which is a physically dispersed unit containing a unit dose, suitable for administration to humans and other mammals. The unit dosage form can be a capsule or tablet, or a number of capsules or tablets. Depending on the specific treatment involved, the unit dose of the active ingredient can be varied or adjusted from about 0.1 to about 1000 mg or more.

此外，還包括各種藥物新劑型如乳脂質體、微球和奈米球的應用，如使用微粒分散體系包括聚合物微胞（polymeric micelles）、奈米乳（nanoemulsion）、亞微乳（submicroemuls微囊（microcapsule）、 微球（microsphere）、脂質體（liposomes）和 類脂囊泡（niosomes）（又稱非離子表面活性劑囊泡）等製備的藥劑。In addition, it also includes the application of various new drug formulations such as milk liposomes, microspheres and nanospheres, such as the use of particle dispersion systems including polymeric micelles, nanoemulsion, and submicroemuls. Drugs prepared from microcapsules, microspheres, liposomes and niosomes (also known as non-ionic surfactant vesicles).

另一方面，本發明還提供了一種上述任一技術方案所述化合物的製備方法，包括下面步驟：該反應的起始原料可以市購得到。On the other hand, the present invention also provides a method for preparing the compound according to any of the above technical solutions, which includes the following steps: The starting materials for this reaction are commercially available.

反應條件：（a）鹼性條件（如二異丙基乙基胺，三乙胺，碳酸鉀等）或酸性條件（三氟乙酸，鹽酸等）的取代反應；（b）酸性條件（三氟乙酸，鹽酸等）或鈀催化的胺化反應。 Reaction conditions: (a) Alkaline conditions (such as diisopropylethylamine, triethylamine, potassium carbonate, etc.) or acidic conditions (trifluoroacetic acid, hydrochloric acid, etc.) substitution reaction; (b) Acidic conditions (trifluoro Acetic acid, hydrochloric acid, etc.) or palladium catalyzed amination reaction.

另一方面，本發明還提供了一種上述任一技術方案所述化合物、其立體異構體、其前藥、或者其藥學上可接受的鹽或藥學上可接受的溶劑合物在製備預防和治療腫瘤的藥物中的用途。較佳地，其中該腫瘤為漸變性大細胞淋巴瘤、炎性肌纖維母細胞瘤、非小細胞肺癌、成神經母細胞瘤、小細胞肺癌、肺腺癌、胰腺癌、乳腺癌、前列腺癌、肝癌、皮膚癌、上皮細胞癌、胃腸間質瘤、白血病、組織細胞性淋巴瘤、鼻咽癌中的任意一種；更佳地，其中該腫瘤為漸變性大細胞淋巴瘤、炎性肌纖維母細胞瘤、非小細胞肺癌或成神經母細胞瘤。 具體實施方式On the other hand, the present invention also provides a compound, its stereoisomer, its prodrug, or its pharmaceutically acceptable salt or pharmaceutically acceptable solvate as described in any of the above technical solutions in the preparation, prevention and Use in drugs for the treatment of tumors. Preferably, the tumor is progressive large cell lymphoma, inflammatory myofibroblastoma, non-small cell lung cancer, neuroblastoma, small cell lung cancer, lung adenocarcinoma, pancreatic cancer, breast cancer, prostate cancer, Liver cancer, skin cancer, epithelial cell carcinoma, gastrointestinal stromal tumor, leukemia, histocytic lymphoma, nasopharyngeal carcinoma; more preferably, the tumor is gradual large cell lymphoma, inflammatory myofibroblast Tumor, non-small cell lung cancer or neuroblastoma. Detailed ways

下面通過具體實施例詳細描述本發明的實施方式，但是無論如何它們不能解釋為對本發明的限制。 通用純化和分析方法The embodiments of the present invention are described in detail below through specific examples, but they cannot be construed as limiting the present invention in any case. General Purification and Analysis Methods

在矽膠GF254預塗覆板（青島海洋化工廠）上進行薄層色譜。在中壓下經矽膠（300-400目，煙臺芝黃務矽膠開發試劑廠)進行柱色譜分離或通過使用ISCO Combiflash Rf200快速純化系統用預裝的矽膠筒(ISCO或Welch)進行柱色譜分離。成分通過UV光(ë: 254 nm)和通過碘蒸氣顯影。當必要時，將化合物通過製備型HPLC製備經Waters Symmetry C18 (19 x 50 mm, 5 µm)柱或經Waters X Terra RP 18 (30 x 150 mm, 5 μm)柱純化，使用裝配有996 Waters PDA檢測器的Waters製備型HPLC 600和Micromass mod. ZMD單四級質譜(電噴霧離子化，陽離子模式)。方法1：相A: 0.1% TFA/MeOH 95/5；相B: MeOH/H2 O 95/5。梯度：10至90% B進行8 min，保持90% B 2 min；流速20 mL/min。方法2：相A: 0.05% NH4 OH/MeOH 95/5；相B: MeOH/H2 O 95/5。梯度：10至100% B進行8 min，保持100% B 2 min。流速20 mL/min。Thin-layer chromatography was performed on a pre-coated silicone GF254 plate (Qingdao Ocean Chemical Factory). Column chromatographic separation by silica gel (300-400 mesh, Yantai Zhihuangwu Silicone Development Reagent Factory) under medium pressure or by using ISCO Combiflash Rf200 rapid purification system with pre-installed silica gel cartridges (ISCO or Welch) for column chromatographic separation. The components are developed by UV light (ë: 254 nm) and by iodine vapor. When necessary, the compound is prepared by preparative HPLC and purified by a Waters Symmetry C18 (19 x 50 mm, 5 µm) column or a Waters X Terra RP 18 (30 x 150 mm, 5 µm) column, using a 996 Waters PDA equipped Waters preparative HPLC 600 and Micromass mod. ZMD single four-stage mass spectrometry (electrospray ionization, positive ion mode) of the detector. Method 1: Phase A: 0.1% TFA/MeOH 95/5; Phase B: MeOH/H 2 O 95/5. Gradient: 10 to 90% B for 8 min and 90% B for 2 min; flow rate 20 mL/min. Method 2: Phase A: 0.05% NH 4 OH/MeOH 95/5; Phase B: MeOH/H 2 O 95/5. Gradient: 10 to 100% B for 8 min, and 100% B for 2 min. The flow rate is 20 mL/min.

將1 H-NMR譜在DMSO-d6 或CDCl3 中經在600 MHz操作的Bruker Avance 600譜儀(對於1 H而言)進行記錄。將殘留溶劑訊號用作參比(ä = 2.50或7.27 ppm)。化學位移(ä)以百萬分率(ppm)進行報導且偶合常數(J) 以Hz計。以下縮寫用於峰裂分: s =單；br. s. =寬訊號；d =雙；t =三；m =多重；dd =雙雙。The 1 H-NMR spectrum was recorded in DMSO-d 6 or CDCl 3 on a Bruker Avance 600 spectrometer (for 1 H) operating at 600 MHz. Use the residual solvent signal as a reference (ä = 2.50 or 7.27 ppm). The chemical shift (ä) is reported in parts per million (ppm) and the coupling constant (J) is reported in Hz. The following abbreviations are used for peak splitting: s = single; br. s. = wide signal; d = double; t = triple; m = multiple; dd = double double.

電噴霧(ESI)質譜經Finnigan LCQ離子阱獲得。Electrospray (ESI) mass spectra were obtained by Finnigan LCQ ion trap.

除非另外說明，所有最終化合物均是均質的(純度不低於95%)，如 高效液相層析(HPLC)所確定。用於評價化合物純度的HPLC-UV-MS分析通過組合離子阱MS裝置與HPLC系統SSP4000 (Thermo Separation Products)來進行，該HPLC系統裝配有自動進樣器LC Pal (CTC Analytics)和UV6000LP二極體陣列檢測器(UV檢測215-400 nm)。用Xcalibur 1.2軟體(Finnigan)進行裝置控制、資料獲取和處理。HPLC色譜法在室溫和1 mL/min流速下進行，其使用Waters X Terra RP 18柱(4.6x 50 mm；3.5 μm)。流動相A是乙酸銨5 mM緩衝液(採用乙酸得到pH 5.5):乙腈 90:10，流動相B乙酸銨5 mM緩衝液(採用乙酸得到pH 5.5):乙腈 10:90；梯度為0至100% B進行7分鐘，然後在再平衡前保持100% B達2分鐘。Unless otherwise specified, all final compounds are homogeneous (purity not less than 95%), as determined by high performance liquid chromatography (HPLC). The HPLC-UV-MS analysis used to evaluate the purity of the compound was performed by a combined ion trap MS device and an HPLC system SSP4000 (Thermo Separation Products), which was equipped with an autosampler LC Pal (CTC Analytics) and UV6000LP diode Array detector (UV detection 215-400 nm). Use Xcalibur 1.2 software (Finnigan) for device control, data acquisition and processing. HPLC chromatography was performed at room temperature and a flow rate of 1 mL/min, using a Waters X Terra RP 18 column (4.6 x 50 mm; 3.5 μm). Mobile phase A is ammonium acetate 5 mM buffer (using acetic acid to obtain pH 5.5): acetonitrile 90:10, mobile phase B is ammonium acetate 5 mM buffer (using acetic acid to obtain pH 5.5): acetonitrile 10:90; gradient is 0 to 100 Perform% B for 7 minutes and then maintain 100% B for 2 minutes before rebalancing.

試劑純化參考Purification of Laboratory Chemicals（Perrin, D. D., Armarego, W. L. F. and Perrins Eds, D. R.; Pergamon Press: Oxford, 1980）一書進行。石油醚是60-90 ℃餾分、乙酸乙酯、甲醇、二氯甲烷均為分析純。 Purification of the reagents was carried out with reference to Purification of Laboratory Chemicals (Perrin, DD, Armarego, WLF and Perrins Eds, DR; Pergamon Press: Oxford, 1980). Petroleum ether is a fraction at 60-90 ℃, ethyl acetate, methanol, and dichloromethane are all analytically pure.

上述通式化合物分成幾類合成製備。 化合物 I的通式 實施例1 化合物 IA的合成通式化合物 3的製備 The compounds of the above general formula are divided into several types of synthetic preparations. General formula of compound I Example 1 Synthesis formula of compound IA Preparation of compound 3

將化合物2（200 mg，1.17 mmol）溶於 N,N-二甲基甲醯胺中（4 mL），在冰浴條件下加入氫化鈉（93.6 mg，2.34 mmol）攪拌 5-10 min，然後加入化合物1（240.0 mg，1.17 mmol），在室溫下攪拌1.0 h（TLC跟蹤）後停止反應。向體系中加入冰水淬滅氫化鈉，加入乙酸乙酯並分液，有機相用飽和氯化鈉溶液洗滌兩次，無水硫酸鈉乾燥，濃縮後經矽膠柱層析（石油醚/乙酸乙酯 = 5/1）得化合物3（固體，270.0 mg，產率為 79.5%），直接用於下一步反應。 MS (ESI) m/z: 340 [M+H]+ 化合物IA的製備方法 A：Compound 2 (200 mg, 1.17 mmol) was dissolved in N,N-dimethylformamide (4 mL), sodium hydride (93.6 mg, 2.34 mmol) was added in an ice bath and stirred for 5-10 min, then Compound 1 (240.0 mg, 1.17 mmol) was added, and the reaction was stopped after stirring at room temperature for 1.0 h (TLC tracking). Ice water was added to the system to quench sodium hydride, ethyl acetate was added and the layers were separated. The organic phase was washed twice with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated and subjected to silica gel column chromatography (petroleum ether/ethyl acetate). = 5/1) Compound 3 (solid, 270.0 mg, yield 79.5%) was obtained, which was directly used in the next reaction. MS (ESI) m/z: 340 [M+H] + Preparation of compound IA Method A:

將化合物 3（30.0 mg，0.09 mmol）、芳胺（0.072 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（7.7 mg，0.016 mmol），三(二亞苄基丙酮)二鈀（9.9 mg，0.011 mmol），碳酸鉀（37 mg，0.27 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至芳胺反應完全（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經矽膠柱層析（二氯甲烷/甲醇）得化合物IA。 方法 B：Compound 3 (30.0 mg, 0.09 mmol) and aromatic amine (0.072 mmol) were dissolved in 1 mL of tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl was added to the solution. Benzene (7.7 mg, 0.016 mmol), tris(dibenzylideneacetone) dipalladium (9.9 mg, 0.011 mmol), potassium carbonate (37 mg, 0.27 mmol), under the protection of nitrogen, place the resulting reaction solution Heat and stir in an oil bath heated to 110 ℃ until the aromatic amine reaction is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated and subjected to silica gel column chromatography (dichloromethane/methanol) to obtain compound IA. Method B:

將化合物 3（30.0 mg，0.09 mmol）、芳胺（0.072 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入2-二環己基膦-2,4,6-三異丙基聯苯（7.7 mg，0.016 mmol），三(二亞苄基丙酮)二鈀（9.9 mg，0.011 mmol），碳酸鉀（37 mg，0.27 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至芳胺反應完全（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經反相製備型 HPLC純化（以含 0.35%三氟乙酸的水溶液和甲醇為流動相），經真空濃縮得化合物IA。Compound 3 (30.0 mg, 0.09 mmol) and aromatic amine (0.072 mmol) were dissolved in 1 mL of tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl was added to the solution. Benzene (7.7 mg, 0.016 mmol), tris(dibenzylideneacetone) dipalladium (9.9 mg, 0.011 mmol), potassium carbonate (37 mg, 0.27 mmol), under the protection of nitrogen, place the resulting reaction solution Heat and stir in an oil bath heated to 110 ℃ until the aromatic amine reaction is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated and purified by reverse-phase preparative HPLC (using 0.35% trifluoroacetic acid in aqueous solution and methanol as mobile phases), and concentrated in vacuo to obtain compound IA.

化合物 IB、IC均可使用類似的方法合成。Compounds IB and IC can be synthesized using similar methods.

下表列出了具體化合物及結構鑒定資料。 表1. 化合物 IA—IC結構及表徵 實施例2 化合物ID的合成通式化合物 5的製備 The following table lists specific compounds and structural identification data. Table 1. Compound IA-IC structure and characterization Example 2 Synthetic general formula of compound ID Preparation of compound 5

將化合物 1（205 mg，1.00 mmol）、化合物4（151 mg，1.00 mmol）溶於 5 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（56 mg，0.12 mmol），三(二亞苄基丙酮)二鈀（37 mg，0.04 mmol），碳酸鉀（415 mg，3.00 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至化合物 1反應完全（LC-MS和TLC跟蹤）。向反應液中加甲醇和二氯甲烷，將體系過濾，濾液濃縮後再用二氯甲烷稀釋，飽和氯化鈉溶液洗滌兩次，無水硫酸鈉乾燥，濃縮後經矽膠柱層析（二氯甲烷/氨甲醇 = 10/1）得化合物5（白色固體，293.5 mg，產率為92.0%），直接用於下一步反應。 MS (ESI) m/z: 320 [M+H]+ 化合物 ID的製備方法 A：Dissolve compound 1 (205 mg, 1.00 mmol) and compound 4 (151 mg, 1.00 mmol) in 5 mL tert-butanol, and then add 2-dicyclohexylphosphine-2,4,6-triisopropyl to the solution Propyl biphenyl (56 mg, 0.12 mmol), tris(dibenzylideneacetone) dipalladium (37 mg, 0.04 mmol), potassium carbonate (415 mg, 3.00 mmol), under the protection of nitrogen, the resulting reaction solution Place it in an oil bath preheated to 110 ℃ with heating and stirring until the reaction of compound 1 is complete (LC-MS and TLC tracking). Methanol and dichloromethane were added to the reaction solution, the system was filtered, the filtrate was concentrated and then diluted with dichloromethane, washed twice with saturated sodium chloride solution, dried with anhydrous sodium sulfate, concentrated and subjected to silica gel column chromatography (dichloromethane /Ammonia methanol = 10/1) to obtain compound 5 (white solid, 293.5 mg, yield 92.0%), which was directly used in the next reaction. MS (ESI) m/z: 320 [M+H] + Preparation of compound ID Method A:

將化合物 5（31.8 mg，0.10 mmol）、芳胺（0.09 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（0.018 mmol），三(二亞苄基丙酮)二鈀（0.012 mmol），碳酸鉀（0.30 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至化合物5反應完全後（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經矽膠柱層析（二氯甲烷/甲醇）得化合物ID。 方法 B：Compound 5 (31.8 mg, 0.10 mmol) and aromatic amine (0.09 mmol) were dissolved in 1 mL tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl group was added to the solution. Benzene (0.018 mmol), tris(dibenzylideneacetone)dipalladium (0.012 mmol), potassium carbonate (0.30 mmol), under the protection of nitrogen, heat the resulting reaction solution in an oil bath preheated to 110 ℃ Stir until the reaction of compound 5 is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated and subjected to silica gel column chromatography (dichloromethane/methanol) to obtain compound ID. Method B:

將化合物 5（31.8 mg，0.10 mmol）、芳胺（0.09 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（0.018 mmol），三(二亞苄基丙酮)二鈀（0.012 mmol），碳酸鉀（0.30 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至化合物5反應完全後（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經反相製備型 HPLC純化（以含 0.35%三氟乙酸的水溶液和甲醇為流動相），經真空濃縮得化合物ID。Compound 5 (31.8 mg, 0.10 mmol) and aromatic amine (0.09 mmol) were dissolved in 1 mL tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl group was added to the solution. Benzene (0.018 mmol), tris(dibenzylideneacetone)dipalladium (0.012 mmol), potassium carbonate (0.30 mmol), under the protection of nitrogen, heat the resulting reaction solution in an oil bath preheated to 110 ℃ Stir until the reaction of compound 5 is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated and purified by reverse-phase preparative HPLC (with 0.35% trifluoroacetic acid in water and methanol as mobile phases), and concentrated in vacuo to obtain compound ID.

化合物 IE、IF、IG、IH、II、IJ、IK均可使用類似的方法合成。Compounds IE, IF, IG, IH, II, IJ, IK can be synthesized using similar methods.

下表列出了具體化合物及結構鑒定資料。 表2. 化合物 ID—IK結構及表徵 實施例3 化合物IL的合成通式化合物 7的製備 The following table lists specific compounds and structural identification data. Table 2. Compound ID-IK structure and characterization Example 3 Synthetic general formula of compound IL Preparation of compound 7

將化合物 6（185.2 mg，1.0 mmol）、三乙基胺（0.418 mL，3.0 mmol）溶於 N,N-二甲基甲醯胺中（1.5 mL），室溫攪拌10 min後滴加到化合物 1（205.0 mg，1.0 mmol）的N,N-二甲基甲醯胺（1.5 mL）溶液中，在室溫下攪拌過夜，（TLC跟蹤）停止反應。向體系加入乙酸乙酯、水萃取，有機相由飽和氯化鈉溶液洗滌，無水硫酸鈉乾燥，濃縮後經矽膠柱層析（石油醚/乙酸乙酯 = 2/1）得化合物 7（固體，120.0 mg，產率為 33.9%），直接用於下一步反應。 MS (ESI) m/z: 354 [M+H]+ 化合物 IL的製備方法 A：Compound 6 (185.2 mg, 1.0 mmol) and triethylamine (0.418 mL, 3.0 mmol) were dissolved in N,N-dimethylformamide (1.5 mL), stirred at room temperature for 10 min, and then added dropwise to the compound 1 (205.0 mg, 1.0 mmol) in N,N-dimethylformamide (1.5 mL) solution, stir overnight at room temperature, (TLC tracking) to stop the reaction. Add ethyl acetate and water to the system for extraction, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated and subjected to silica gel column chromatography (petroleum ether/ethyl acetate = 2/1) to obtain compound 7 (solid, 120.0 mg, yield 33.9%), directly used in the next reaction. MS (ESI) m/z: 354 [M+H] + Preparation of compound IL Method A:

將化合物 7（35.3 mg，0.10 mmol）、芳胺（0.09 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（0.018 mmol），三(二亞苄基丙酮)二鈀（0.012 mmol），碳酸鉀（0.30 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至化合物7反應完全後（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經矽膠柱層析（二氯甲烷/甲醇）得化合物IL。 方法 B：Compound 7 (35.3 mg, 0.10 mmol) and aromatic amine (0.09 mmol) were dissolved in 1 mL tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl group was added to the solution. Benzene (0.018 mmol), tris(dibenzylideneacetone)dipalladium (0.012 mmol), potassium carbonate (0.30 mmol), under the protection of nitrogen, heat the resulting reaction solution in an oil bath preheated to 110 ℃ Stir until the reaction of compound 7 is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated and subjected to silica gel column chromatography (dichloromethane/methanol) to obtain compound IL. Method B:

將化合物 7（35.3 mg，0.10 mmol）、芳胺（0.09 mmol）溶於 1 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（0.018 mmol），三(二亞苄基丙酮)二鈀（0.012 mmol），碳酸鉀（0.30 mmol），在氮氣的保護下，將所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至化合物7反應完全後（LC-MS和 TLC跟蹤）停止反應。向反應液中加甲醇和二氯甲烷，將體系過濾，濃縮後經反相製備型 HPLC純化（以含 0.35%三氟乙酸的水溶液和甲醇為流動相），經真空濃縮得化合物IL。Compound 7 (35.3 mg, 0.10 mmol) and aromatic amine (0.09 mmol) were dissolved in 1 mL tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl group was added to the solution. Benzene (0.018 mmol), tris(dibenzylideneacetone)dipalladium (0.012 mmol), potassium carbonate (0.30 mmol), under the protection of nitrogen, heat the resulting reaction solution in an oil bath preheated to 110 ℃ Stir until the reaction of compound 7 is complete (LC-MS and TLC tracking) to stop the reaction. Methanol and dichloromethane were added to the reaction solution, the system was filtered, concentrated, and purified by reverse-phase preparative HPLC (using 0.35% trifluoroacetic acid-containing aqueous solution and methanol as mobile phases), and concentrated in vacuo to obtain compound IL.

化合物IM可使用類似的方法合成。Compound IM can be synthesized using a similar method.

下表列出了具體化合物及結構鑒定資料。 表3. 化合物 IL—IM結構及表徵 實施例4 化合物IN的合成通式化合物 9的製備 The following table lists specific compounds and structural identification data. Table 3. Compound IL-IM structure and characterization Example 4 Synthetic general formula of compound IN Preparation of compound 9

將化合物 1（500 mg，2.44 mmol）、化合物8（0.09 mmol）溶於 20 mL叔丁醇中，再向該溶液中加入 2-二環己基膦-2,4,6-三異丙基聯苯（135 mg，0.17 mmol），三(二亞苄基丙酮)二鈀（90 mg，0.06 mmol），碳酸鉀（1.01 g，3.0 mmol），在氮氣的保護下，將所得反應液置於預熱至 45 ℃的油浴中加熱攪拌，至化合物1反應完全後（LC-MS和 TLC跟蹤）停止反應。將體系過濾並用甲醇洗滌，濾液濃縮後經矽膠柱層析（二氯甲烷/胺甲醇=5/1）得化合物9（黃色固體，540 mg，產率為65.7%），直接用於下一步反應。 MS (ESI) m/z: 337 [M+H]+ 化合物 IN的製備 Compound 1 (500 mg, 2.44 mmol) and compound 8 (0.09 mmol) were dissolved in 20 mL tert-butanol, and then 2-dicyclohexylphosphine-2,4,6-triisopropyl was added to the solution. Benzene (135 mg, 0.17 mmol), tris(dibenzylideneacetone) dipalladium (90 mg, 0.06 mmol), potassium carbonate (1.01 g, 3.0 mmol), under the protection of nitrogen, place the resulting reaction solution Heat and stir in an oil bath heated to 45 ℃, and stop the reaction after the reaction of compound 1 is complete (LC-MS and TLC tracking). The system was filtered and washed with methanol, the filtrate was concentrated and subjected to silica gel column chromatography (dichloromethane/amine methanol=5/1) to obtain compound 9 (yellow solid, 540 mg, yield 65.7%), which was directly used in the next reaction . MS (ESI) m/z: 337 [M+H] + Preparation of compound IN

將化合物 9（50 mg，0.15 mmol）、芳胺（0.13 mmol）溶於1 mL叔丁醇中，再向該溶液中加入三氟乙酸（35 μL，0.45 mmol）。所得反應液置於預熱至 110 ℃的油浴中加熱攪拌，至芳胺反應完全（LC-MS和 TLC跟蹤）。停止反應，濃縮，經反相製備型 HPLC純化（以含 0.35%三氟乙酸的水溶液和甲醇為流動相），經真空濃縮得化合物 IN。Compound 9 (50 mg, 0.15 mmol) and aromatic amine (0.13 mmol) were dissolved in 1 mL of tert-butanol, and then trifluoroacetic acid (35 μL, 0.45 mmol) was added to the solution. The resulting reaction solution was heated and stirred in an oil bath preheated to 110 ℃ until the aromatic amine reaction was complete (LC-MS and TLC tracking). The reaction was stopped, concentrated, and purified by reverse-phase preparative HPLC (using 0.35% trifluoroacetic acid-containing aqueous solution and methanol as mobile phases), and concentrated in vacuo to obtain compound IN.

下表列出了具體化合物及結構鑒定資料。 表4. 化合物 IN結構及表徵 實施例5 化合物IO The following table lists specific compounds and structural identification data. Table 4. Compound IN structure and characterization Example 5 Compound IO

化合物 IO使用IA類似的方法合成。Compound IO was synthesized using a similar method to IA.

下表列出了具體化合物及結構鑒定資料。 表5. 化合物 IO結構及表徵 實施例6 化合物IP、IQ The following table lists specific compounds and structural identification data. Table 5. Compound IO structure and characterization Example 6 Compound IP, IQ

化合物 IP、IQ使用IA類似的方法合成。Compounds IP and IQ were synthesized using a similar method to IA.

下表列出了具體化合物及結構鑒定資料。 表6. 化合物 IP、IQ結構及表徵 實施例7 化合物IR、IS The following table lists specific compounds and structural identification data. Table 6. Compound IP, IQ structure and characterization Example 7 Compound IR, IS

化合物 IR、IS使用IA類似的方法合成。Compounds IR and IS were synthesized using a similar method to IA.

下表列出了具體化合物及結構鑒定資料。 表7. 化合物 IR、IS結構及表徵 實施例8 化合物IT The following table lists specific compounds and structural identification data. Table 7. Compound IR, IS structure and characterization Example 8 Compound IT

化合物 IT使用IA類似的方法合成。Compound IT was synthesized using a similar method to IA.

下表列出了具體化合物及結構鑒定資料。The following table lists specific compounds and structural identification data.

表8. 化合物 IT結構及表徵 實施例9 化合物IU Table 8. Compound IT structure and characterization Example 9 Compound IU

化合物 IU使用IA類似的方法合成。Compound IU was synthesized using a similar method to IA.

下表列出了具體化合物及結構鑒定資料。The following table lists specific compounds and structural identification data.

表9. 化合物 IU結構及表徵 試驗例 生物活性測試： 化合物對激酶穩轉細胞系的生長抑制活性Table 9. Compound IU structure and characterization Test Example Biological Activity Test: The compound's growth inhibitory activity on the kinase stable transgenic cell line

化合物對激酶 ALK的活性通過其抑制激酶穩轉細胞系 EML4-ALK-BaF3，EML4-ALK(L1196M)-BaF3，NPM-ALK-BaF3，和野生型 BaF3的生長進行評價（Proc. Natl. Acad. Sci. U S A., 2006, 103, 3153-8.）。激酶穩轉的細胞系EML4-ALK-BaF3，EML4-ALK(L1196M)-BaF3和NPM-ALK-BaF3的生長依賴其激酶活性，化合物若能抑制激酶 ALK自身活性或 ALK訊號通路的活性就能抑制其穩轉BaF3細胞的生長。而野生型BaF3的細胞生長不依賴 ALK和 ALK訊號通路的活性，測定化合物對野生型BaF3細胞的生長的影響可以評價其廣譜毒性。因此化合物對野生型 BaF3和激酶穩轉的 EML4-ALK-BaF3，EML4-ALK(L1196M)-BaF3，NPM-ALK-BaF3間 IC50 的比值越大表明具有更好的靶向性。The activity of the compound on the kinase ALK was evaluated by its inhibition of the growth of the kinase stable transduction cell lines EML4-ALK-BaF3, EML4-ALK(L1196M)-BaF3, NPM-ALK-BaF3, and wild-type BaF3 (Proc. Natl. Acad. Sci. US A., 2006, 103, 3153-8.). The growth of kinase-stable cell lines EML4-ALK-BaF3, EML4-ALK(L1196M)-BaF3 and NPM-ALK-BaF3 depend on its kinase activity. If the compound can inhibit the activity of the kinase ALK itself or the activity of the ALK signaling pathway, it can be inhibited. It stabilizes the growth of BaF3 cells. The growth of wild-type BaF3 cells does not depend on the activity of the ALK and ALK signaling pathways. The effects of compounds on the growth of wild-type BaF3 cells can be evaluated to evaluate its broad-spectrum toxicity. Therefore, the greater the IC 50 ratio of the compound to wild-type BaF3 and kinase stable EML4-ALK-BaF3, EML4-ALK(L1196M)-BaF3, NPM-ALK-BaF3 indicates better targeting.

具體試驗方法如下： 1）培養基：DMEM (Dulbecco's modified eagle medium) 或 RPMI1640 (含10% 胎牛血清，100 μg/mL氨苄青黴素，100 μg/mL鏈黴素)。 2）試劑：MTS反應液 (含2 mg/mL的MTS [3-(4，5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺苯基)-2H-四唑，內鹽](3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium, inner salt); 100 μg/mL的PES (phenazine methosulfate)）。 3）化合物測試：將激酶穩轉的細胞（EML4-ALK-BaF3，或EML4-ALK(L1196M)-BaF3或NPM-ALK-BaF3）（2×104 個/孔）接入96-孔培養板，細胞液體積為90 μL，然後加入各梯度濃度化合物10 μL（最高濃度為10 μM，依次按1/3逐級稀釋，共設置8個濃度點，體系中含0.1% DMSO（二甲基亞碸））。混勻化合物的細胞板置於細胞培養箱中（37 ℃；5% CO2 ）培養48 h，再加入20 μL的MTS反應液，混勻後置於細胞培養箱中（37 ℃；5% CO2 ）孵育1-4 hr；採用酶標儀（VARIOSKAN FLASH, Thermo）測量490 nm波長下的OD值。每組實驗設置三個平行，以終濃度為0.1% DMSO為陰性對照，以不含細胞及化合物的培養基為空白對照。細胞生長抑制率由如下公式計算： 細胞抑制率%=1-（OD實驗組-OD空白組）/（OD陰性組- OD空白組）*100% 4）IC50 值計算：根據測量的細胞生長抑制率利用GradPad Prism 5軟體計算化合物作用於細胞生長的半抑制濃度。The specific test methods are as follows: 1) Medium: DMEM (Dulbecco's modified eagle medium) or RPMI1640 (containing 10% fetal bovine serum, 100 μg/mL ampicillin, 100 μg/mL streptomycin). 2) Reagent: MTS reaction solution (containing 2 mg/mL MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -Sulfophenyl)-2H-tetrazolium, inner salt](3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium, inner salt); 100 μg/mL PES (phenazine methosulfate)). 3) Compound test: Connect cells with stable kinase (EML4-ALK-BaF3, or EML4-ALK(L1196M)-BaF3 or NPM-ALK-BaF3) (2×10 4 cells/well) into a 96-well culture plate , The cell fluid volume is 90 μL, and then 10 μL of each gradient concentration compound is added (the highest concentration is 10 μM, which is gradually diluted by 1/3 in sequence, a total of 8 concentration points are set, and the system contains 0.1% DMSO (dimethyl methylene chloride).碸)). The cell plate of the mixed compound was placed in a cell incubator (37 ℃; 5% CO 2 ) for 48 h, and then 20 μL of MTS reaction solution was added, mixed and placed in a cell incubator (37 ℃; 5% CO 2) 2 ) Incubate for 1-4 hr; use a microplate reader (VARIOSKAN FLASH, Thermo) to measure the OD value at a wavelength of 490 nm. Three parallels were set up for each experiment, with a final concentration of 0.1% DMSO as a negative control, and a medium without cells and compounds as a blank control. The cell growth inhibition rate is calculated by the following formula: Cell inhibition rate% = 1-(OD experimental group-OD blank group) / (OD negative group-OD blank group) * 100% 4) IC 50 value calculation: according to the measured cell growth Inhibition rate GradPad Prism 5 software was used to calculate the half-inhibitory concentration of the compound on cell growth.

表 10. 化合物 I系列對激酶穩轉細胞系的生長抑制活性 *數值代表在化合物濃度為3.3 µM下對細胞的生長抑制率，Crizotinib（克唑替尼）做為陽性對照，ND指未測定。 表 11. 化合物 IB-1對其它ALK點突變穩轉的BaF3細胞的生長抑制活性（IC50 /nM） 化合物對腫瘤細胞的生長抑制活性Table 10. Growth inhibitory activity of compound I series on kinase stable transgenic cell lines *The value represents the cell growth inhibition rate at a compound concentration of 3.3 µM. Crizotinib is used as a positive control. ND means not determined. Table 11. Growth inhibitory activity of compound IB-1 on BaF3 cells stably transformed with other ALK point mutations (IC 50 /nM) Growth inhibitory activity of the compound on tumor cells

若測試的腫瘤細胞為懸浮細胞，參照上述（1）的方法進行測定。If the tested tumor cells are suspension cells, refer to the method in (1) above for determination.

若測試的腫瘤細胞為貼壁細胞，以1000-10000細胞/孔加入96-孔培養板中，孵育至貼壁後加化合物。其它參照上述（1）的方法進行。If the tested tumor cells are adherent cells, add 1000-10000 cells/well to a 96-well culture plate, incubate until adherence, and add compound. Others refer to the method of (1) above.

化合物 IB-1對激酶 ALK陽性的肺癌細胞株 H3122和 漸變性大細胞淋巴瘤Karpas-299均有很好的抑制活性。由以上活性資料可以看出，對於活性較好的化合物均具有較好的靶向選擇性。 表 12. 化合物 IB-1對腫瘤細胞和BaF3細胞的生長抑制活性 *Crizotinib（克唑替尼）做為陽性對照，ND指未測定。 體內藥效評價 1. 化合物IB-1在EML4-ALK（G1202R）-Ba/F3裸鼠異種移植瘤模型中顯著抑制腫瘤生長（第1圖）Compound IB-1 has good inhibitory activity on the kinase ALK-positive lung cancer cell line H3122 and the progressive large cell lymphoma Karpas-299. It can be seen from the above activity data that the compounds with better activity have better targeting selectivity. Table 12. Growth inhibitory activity of compound IB-1 on tumor cells and BaF3 cells *Crizotinib (crizotinib) is used as a positive control, ND means not determined. In vivo efficacy evaluation 1. Compound IB-1 significantly inhibited tumor growth in the EML4-ALK(G1202R)-Ba/F3 nude mouse xenograft tumor model (Figure 1)

本次試驗動物選用BALB/c(nu/nu)裸鼠，雌雄各半，4-6週齡，體重約18±2g，SPF級環境飼養，嚴格無菌操作。實驗動物提前1週適應實驗環境，自由取食飲水，保持12 h 晝夜節律。The experimental animals used BALB/c(nu/nu) nude mice, male and female, 4-6 weeks old, weighing about 18±2g, raised in an SPF environment, and strictly aseptic. The experimental animals adapt to the experimental environment one week in advance, eat and drink freely, and maintain a 12-hour circadian rhythm.

實驗所用EML4-ALK(G1202R)-Ba/F3細胞選用PRMI-1640培養液加入10%胎牛血清培養，細胞放置於37 ℃，5% CO2 培養箱環境。The EML4-ALK(G1202R)-Ba/F3 cells used in the experiment were cultured with PRMI-1640 medium and 10% fetal bovine serum. The cells were placed in a 37 ℃, 5% CO 2 incubator environment.

細胞接種法建立腫瘤裸鼠皮下移植模型：過濾收集對數生長期細胞，離心後用PBS清洗，用PRMI-1640培養液重懸為單細胞懸液，按每只裸鼠1×106 /200 μL細胞量。用1 mL注射器(4.5號針頭)在裸鼠右前腋附近皮下注射細胞懸液。當荷瘤小鼠腫瘤長到可測量大小時開始每日測量計算瘤體積，在腫瘤體積達到150 mm3 左右時隨機將小鼠進行分組，每組8只，共三組，分組當日開始給藥。給藥組分為IB-1 60 mg/kg（1次/天），40 mg/kg（2次/天，bid），口服給藥，連續給藥10天，陰性對照組給等量溶劑。試驗期間每天測定動物體重和腫瘤大小，每日觀察記錄小鼠狀態，最後一次給藥6 h 後用5%的水合氯醛麻醉處死小鼠，取腫瘤，稱重並拍照記錄。腫瘤體積（Tumor Volume, TV）的計算公式為：TV = 1/2×a×b2 ，其中a,b分別表示腫瘤長徑和短徑。Cell inoculation method to establish tumor subcutaneous transplantation model in nude mice: filter and collect logarithmic growth phase cells, wash with PBS after centrifugation, and resuspend into single cell suspension with PRMI-1640 culture medium at 1×10 6 /200 μL per nude mouse Cell mass. A 1 mL syringe (4.5 gauge needle) was used to subcutaneously inject the cell suspension near the right anterior axilla of nude mice. When the tumor of the tumor-bearing mice grows to a measurable size, start to measure and calculate the tumor volume every day. When the tumor volume reaches about 150 mm 3 , the mice are randomly divided into groups of 8 mice in each group, a total of three groups, and the drug is administered on the day of grouping . The administration components were IB-1 60 mg/kg (1 time/day), 40 mg/kg (2 times/day, bid), orally, for 10 consecutive days, and the negative control group was given the same amount of solvent. During the experiment, the animal body weight and tumor size were measured every day, and the state of the mice was observed and recorded every day. The mice were anesthetized with 5% chloral hydrate 6 hours after the last administration, and the tumors were taken, weighed, and photographed for recording. The calculation formula of Tumor Volume (TV) is: TV = 1/2×a×b 2 , where a and b represent the long diameter and short diameter of the tumor, respectively.

如第1圖所示，化合物IB-1在EML4-ALK（G1202R）-Ba/F3裸鼠異種移植瘤模型中顯著抑制腫瘤生長。A）化合物IB-1分別在60 mg/kg（1次/天）、40 mg/kg（2次/天，bid）劑量，口服給藥，連續給藥10天，腫瘤生長均被顯著抑制；B）在給藥程序中，給藥組小鼠體重均未出現明顯變化，表明對小鼠對藥物有較好的耐受，IB-1無明顯毒副作用。 2. 化合物IB-1在H3122腫瘤細胞裸鼠異種移植瘤模型中顯著抑制腫瘤生長（第2圖）As shown in Figure 1, compound IB-1 significantly inhibited tumor growth in the EML4-ALK(G1202R)-Ba/F3 nude mouse xenograft tumor model. A) Compound IB-1 was administered orally at 60 mg/kg (1 time/day) and 40 mg/kg (2 times/day, bid) for 10 consecutive days, and tumor growth was significantly inhibited; B) In the administration procedure, the body weight of the mice in the administration group did not change significantly, indicating that the mice have a good tolerance to the drug, and IB-1 has no obvious toxic and side effects. 2. Compound IB-1 significantly inhibited tumor growth in a nude mouse xenograft tumor model with H3122 tumor cells (Figure 2)

本次試驗動物選用BALB/c(nu/nu)裸鼠，雌雄各半，4~6週齡，體重約18±2g，SPF級環境飼養，嚴格無菌操作。實驗動物提前1週適應實驗環境，自由取食飲水，保持12 h 晝夜節律。In this experiment, BALB/c(nu/nu) nude mice were selected, male and female, 4-6 weeks old, weighing about 18±2g, raised in an SPF environment and strictly aseptic. The experimental animals adapt to the experimental environment one week in advance, eat and drink freely, and maintain a 12-hour circadian rhythm.

實驗所用NCI-H3122細胞選用PRMI-1640培養液加入10%胎牛血清培養，細胞放置於37 ℃，5% CO2 培養箱環境。The NCI-H3122 cells used in the experiment were cultured with PRMI-1640 medium and 10% fetal bovine serum. The cells were placed in a 37 ℃, 5% CO 2 incubator environment.

細胞接種法建立腫瘤裸鼠皮下移植模型：過濾收集對數生長期細胞，離心後用PBS清洗，用PRMI-1640培養液重懸為單細胞懸液，按每只裸鼠5×106 /200 μL細胞量。用1 mL注射器(4.5號針頭)在裸鼠右前腋附近皮下注射細胞懸液。當荷瘤小鼠腫瘤長到可測量大小時開始每日測量計算瘤體積，在腫瘤體積達到150 mm3 左右時隨機將小鼠進行分組，每組5只，共四組，分組當日開始給藥。給藥組分為IB-1 30 mg/kg（1次/天），50 mg/kg（1次/天），陽性對照組給Crizotinib 50 mg/kg（1次/天），陰性對照組給等量溶劑，連續給藥18天。試驗期間隔天測定動物體重和腫瘤大小，每日觀察記錄小鼠狀態，最後一次給藥6 h 後用5%的水合氯醛麻醉處死小鼠，取腫瘤，稱重並拍照記錄。腫瘤體積（Tumor Volume, TV）的計算公式為：TV = 1/2×a×b2 ，其中a,b分別表示腫瘤長徑和短徑。Cell inoculation method to establish a tumor subcutaneous transplantation model in nude mice: filter and collect logarithmic growth phase cells, wash with PBS after centrifugation, and resuspend into single cell suspension with PRMI-1640 culture medium at 5×10 6 /200 μL per nude mouse Cell mass. A 1 mL syringe (4.5 gauge needle) was used to subcutaneously inject the cell suspension near the right anterior axilla of nude mice. When the tumor of the tumor-bearing mice grows to a measurable size, start to measure and calculate the tumor volume every day. When the tumor volume reaches about 150 mm 3 , the mice are randomly divided into groups of 5 mice in each group, a total of four groups, and the drug is administered on the day of grouping . The administration components are IB-1 30 mg/kg (1 time/day), 50 mg/kg (1 time/day), the positive control group is given Crizotinib 50 mg/kg (1 time/day), the negative control group is given The same amount of solvent was administered continuously for 18 days. The animal weight and tumor size were measured at intervals of the test period. The state of the mice was observed and recorded daily. The mice were anesthetized with 5% chloral hydrate 6 hours after the last administration, and the tumors were taken, weighed, and recorded with pictures. The calculation formula of Tumor Volume (TV) is: TV = 1/2×a×b 2 , where a and b represent the long diameter and short diameter of the tumor, respectively.

如第2圖所示，化合物IB-1在非小細胞肺癌H3122細胞裸鼠異種移植瘤模型中顯著抑制腫瘤生長。A）化合物IB-1分別在30 mg/kg（1次/天）、50 mg/kg（1次/天）劑量，口服給藥，連續給藥18天，腫瘤生長均被顯著抑制；B）在給藥程序中，給藥組小鼠體重均未出現明顯變化，表明對小鼠對藥物有較好的耐受，IB-1無明顯毒副作用。As shown in Figure 2, compound IB-1 significantly inhibited tumor growth in a non-small cell lung cancer H3122 cell nude mouse xenograft tumor model. A) Compound IB-1 was administered orally at doses of 30 mg/kg (1 time/day) and 50 mg/kg (1 time/day) for 18 consecutive days, and tumor growth was significantly inhibited; B) In the administration procedure, the body weight of the mice in the administration group did not change significantly, indicating that the mice had a good tolerance to the drug, and IB-1 had no obvious toxic and side effects.

以上所述的僅是本發明的一些實施方式。對於本領域的普通技術人員來說，在不脫離本發明創造構思的前提下，還可以做出若干變形和改進，這些都屬於本發明的保護範圍。What has been described above are only some embodiments of the present invention. For those of ordinary skill in the art, without departing from the inventive concept of the present invention, several modifications and improvements can be made, and these all fall within the protection scope of the present invention.

Crizotinib‧‧‧克唑替尼Crizotinib‧‧‧crizotinib

第1圖描述化合物IB-1在EML4-ALK（G1202R）-Ba/F3裸鼠異種移植瘤模型中顯著抑制腫瘤生長。A）化合物IB-1分別在60 mg/kg（1次/天）、40 mg/kg（2次/天，bid）劑量，口服給藥，連續給藥10天，腫瘤生長均被顯著抑制；B）在給藥程序中，給藥組小鼠體重均未出現明顯變化，表明對小鼠對藥物有較好的耐受，IB-1無明顯毒副作用。 第2圖描述化合物IB-1在非小細胞肺癌H3122細胞裸鼠異種移植瘤模型中顯著抑制腫瘤生長。A）化合物IB-1分別在30 mg/kg（1次/天）、50 mg/kg（1次/天）劑量，口服給藥，連續給藥18天，腫瘤生長均被顯著抑制；B）在給藥程序中，給藥組小鼠體重均未出現明顯變化，表明對小鼠對藥物有較好的耐受，IB-1無明顯毒副作用。Figure 1 depicts that compound IB-1 significantly inhibited tumor growth in the EML4-ALK(G1202R)-Ba/F3 nude mouse xenograft tumor model. A) Compound IB-1 was administered orally at 60 mg/kg (1 time/day) and 40 mg/kg (2 times/day, bid) for 10 consecutive days, and tumor growth was significantly inhibited; B) In the administration procedure, the body weight of the mice in the administration group did not change significantly, indicating that the mice have a good tolerance to the drug, and IB-1 has no obvious toxic and side effects. Figure 2 depicts that compound IB-1 significantly inhibited tumor growth in a non-small cell lung cancer H3122 cell nude mouse xenograft tumor model. A) Compound IB-1 was administered orally at doses of 30 mg/kg (1 time/day) and 50 mg/kg (1 time/day) for 18 consecutive days, and tumor growth was significantly inhibited; B) In the administration procedure, the body weight of the mice in the administration group did not change significantly, indicating that the mice had a good tolerance to the drug, and IB-1 had no obvious toxic and side effects.

Claims (27)

以下通式I的化合物：式I 其中， R’為氫，氯或溴；較佳R’為氫； R1 選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基，N-甲基-4-呱啶基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪-1-基磺醯基，4-乙醯基呱嗪-1-基磺醯基，4-叔丁氧羰基呱嗪-1-基磺醯基，4-(2-羥基乙基)呱嗪-1-基磺醯基，4-(2-氰基乙基)呱嗪-1-基磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基磺醯基，4-(2-N,N-二乙基乙基)呱嗪-1-基磺醯基，4-(3-羥基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基磺醯基，嗎啉-1-基磺醯基，3, 5-二甲基嗎啉-1-基磺醯基，4-(四氫吡咯基)呱啶-1-基磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪-1-基磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，4-(四氫吡咯基)呱啶基--1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基羰基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基羰基，4-(3-羥基丙基)呱嗪-1-基羰基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基羰基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-呱嗪-1-基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪-1-基羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪-1-基甲醯氨基，4-乙基呱嗪-1-基甲醯氨基，4-乙醯基呱嗪-1-基甲醯氨基，4-叔丁氧羰基呱嗪-1-基甲醯氨基，4-(2-羥基乙基)呱嗪-1-基甲醯氨基，4-(2-氰基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基甲醯氨基，4-(3-羥基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基甲醯氨基，嗎啉-1-基甲醯氨基，3, 5-二甲基嗎啉-1-基甲醯氨基，4-(四氫吡咯基)呱啶-1-基甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶-1-基甲醯氨基，4-(4-乙基呱嗪-1-基)呱啶-1-基甲醯氨基，4-(4-乙醯基-呱嗪-1基)呱啶-1-基甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪-1-基甲醯氨基；或 （11）氨基乙醯氨基，2-二甲氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，四氫吡咯基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，3-N, N-二乙基氨基四氫吡咯基乙醯氨基，4-甲基呱嗪基乙醯氨基，4-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-羥基乙基)呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-羥基丙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，嗎啉基乙醯氨基，3, 5-二甲基嗎啉基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-(N-甲基-4-呱啶基)呱嗪基乙醯氨基，4-(四氫吡咯-1-基)呱啶基乙醯氨基；2-甲基氨基乙醯氨基，2-(1-甲基乙基)氨基乙醯氨基；N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 較佳，R1 選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-(N-甲基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，硝基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基，N-甲基-4-呱啶基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基， 3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基， 3-N, N-二異丙基氨基丙氧基， 3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，3-N, N-二甲基四氫吡咯-1-基磺醯基，3-N, N-二乙基氨基四氫吡咯-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪-1-基磺醯基，4-乙醯基呱嗪-1-基磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，N-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪-1-基磺醯基，4-(3-羥基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基磺醯基，4-(4-乙醯基呱嗪-1-基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪-1-基磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基羰基，4-(2-N, N-二乙基氨基乙基)呱嗪-1-基羰基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基羰基，嗎啉-1-基羰基，3, 5-二甲基嗎啉-1-基羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基羰基，4-(N-甲基-4-呱啶基)呱嗪-1-基羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，4-乙醯基呱嗪-1-基甲醯氨基，4-(2-羥基乙基)呱嗪-1-基甲醯氨基，4-(2-氰基乙基)呱嗪-1-基甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪-1-基甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪-1-基甲醯氨基，嗎啉-1-基甲醯氨基，4-(4-乙醯基呱嗪-1-基)呱啶-1-基甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪-1-基甲醯氨基；或 （11）氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，N-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，N-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 更佳，R1 選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，硝基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基， 3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基， （4）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基， 3-N, N-二異丙基氨基丙氧基， 3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，，苯基甲氧基，單鹵素取代苯基甲氧基， （5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基，咪唑基，4-甲基咪唑基， （6）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基， （9）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，叔丁氧基羰基， （10）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （11）氨基乙醯氨基，N-叔丁氧羰基乙醯氨基，N-乙醯基氨基乙醯氨基，丙烯醯氨基，環丙醯氨基，氯乙醯氨基，呱啶基乙醯氨基，4-羥基呱啶基乙醯氨基，4-N, N-二甲基氨基呱啶基乙醯氨基，4-N, N-二乙基氨基呱啶基乙醯氨基，3-N, N-二甲基氨基四氫吡咯基乙醯氨基，4-乙基呱嗪基乙醯氨基，4-乙醯基呱嗪基乙醯氨基，4-叔丁氧羰基呱嗪基乙醯氨基，4-(2-氰基乙基)呱嗪基乙醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯氨基，4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯氨基，4-(4-乙基-1-呱嗪基)呱啶基乙醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯氨基，N-苄氧基羰基-2甲基氨基乙醯氨基； （12）Z2 與 Z3 或Z3 與Z4 形成含氧的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， （13）Z2 與 Z3 或Z3 與Z4 形成含氮的取代或未取代的五元環或六元環；取代基可以選自與Z1 相同的上述取代基， 2），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 3），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； A為直接鍵或亞甲基； 較佳A為直接鍵；或者， 較佳A為亞甲基； X為NH，S或O； R2 選自： 1）C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，二甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 3）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基； 4）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為N，Y3 為C-A13 ，Y4 為N，O或S； Y2 為O或S，Y3 為N-A13 ，Y4 為CH； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基，四氫吡咯基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基； 較佳，R2 選自： 1）C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基， （2）甲硫基，乙硫基，異丙硫基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，環丁基氨基羰基，甲氨基羰基，二甲氨基羰基，異丙氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 3）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環戊基氨基羰基； 4）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丁基氨基羰基，甲基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 5）呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，嗎啉基，3, 5-二甲基嗎啉基，3-N, N-二甲基氨基四氫吡咯基，3-N, N-二乙基氨基四氫吡咯基，4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基， 4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基； 更佳，R2 選自： 1），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯， （2）甲硫基，乙硫基，異丙硫基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，環丁基氨基羰基，甲氨基羰基，二甲氨基羰基，異丙氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 2）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環戊基氨基羰基； 3）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丁基氨基羰基，甲基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 , Y3 , Y4 選自以下組合： Y2 為N，Y3 為N-A13 ，Y4 為CH或N； Y2 為O或S，Y3 為C-A13 ，Y4 為N；和 Y2 為C，Y3 為N-A13 ，Y4 為O或S； Y2 為C，Y3 為N-A13 ，Y4 為N； 其中A13 為氫，C1-C6烷基，C2-C6烯基，C2-C6炔基，C3-C6環烷基； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物， 其中，該藥學上可接受的鹽為無機酸鹽或有機酸鹽，其中，該無機酸鹽為鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硝酸鹽、碳酸氫鹽和碳酸鹽、硫酸鹽或磷酸鹽，該有機酸鹽為甲酸鹽、乙酸鹽、丙酸鹽、苯甲酸鹽、馬來酸鹽、富馬酸鹽、琥珀酸鹽、酒石酸鹽、檸檬酸鹽、抗壞血酸鹽、α-酮戊二酸鹽、三氟乙酸鹽、α-甘油磷酸鹽、烷基磺酸鹽或芳基磺酸鹽；較佳地，該烷基磺酸鹽為甲基磺酸鹽或乙基磺酸鹽；該芳基磺酸鹽為苯磺酸鹽或對甲苯磺酸鹽。Compounds of the following general formula I: Formula I wherein R'is hydrogen, chlorine or bromine; preferably R'is hydrogen; R 1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl Group, 2-N, N-diethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl , 3-N, N-dimethylaminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3 -(4-Methylpiperazine) propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl -4-pyridinyl, N-ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4 -Pyrazolyl, 3-methyl-5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4 -Pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, N-methyl-4-pyridinyl, (3) N, N- Dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-( 4-methylpiperazinyl) ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropyl Aminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino , N-isopropylpiperidine-4-amino, (4) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N- Diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxypiperazinyl)ethoxy, 2-morpholinylethoxy, 2 -Thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-Diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetyrazinyl)propoxy, 3-morpholinylpropoxy , 3-Thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethyl Oxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-dimethylamino Pyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5-dimethyl Morpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazine Group, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4- acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methylsulfonyl azizinyl, 4- (2-Hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4- (3-N, N-Diethylaminopropyl) pyrazinyl, 2-oxo-piperazin-4-yl, imidazolyl, 4-methylimidazolyl, (6) 4-(4-methyl Piperazine) piperidyl, 4-(4-ethyl piperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4-(4-acetyl piperazine) (Azinyl) piperidinyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidinyl, 4-(4-methanesulfonyl piperazinyl) piperidinyl, 4-(4-(2-hydroxyl) Ethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidine Group, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2-N, N-diethylaminoethyl) piperazine Yl) pyridinyl, 4-(4-(3-N, N-dimethylaminopropyl) pyrazine) pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) Yl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl, 4-(N-methyl 4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethyl Aminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1- Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrole 1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-ylsulfonyl, 4-acetylpiperazine-1-ylsulfonyl , 4-tert-Butoxycarbonylpiperazine-1-ylsulfonyl, 4-(2-hydroxyethyl)piperazine-1-ylsulfonyl, 4-(2-cyanoethyl)piperazine-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl)piperazine-1-ylsulfonyl, 4-(2-N,N-diethylethyl)piperazine- 1-ylsulfonyl, 4-(3-hydroxypropyl)piperazine-1-ylsulfonyl, 4-(3-N, N-dimethylaminopropyl)piperazine-1-ylsulfonyl Group, 4-(3-N, N-diethylaminopropyl) piperazin-1-ylsulfonyl, morpholin-1-ylsulfonyl, 3,5-dimethylmorpholine-1- 4-(tetrahydropyrrolyl)piridin-1-ylsulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4- (4-Ethylpiperazine-1-yl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-( N-Methyl-4-pyridinyl)piperazine-1-ylsulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropyl Aminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1- Carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, 4-(tetra (Pyrrolyl)pyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethyl Aminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2 -N, N-Dimethylaminoethyl) piperazin-1-ylcarbonyl, 4-(2-N, N-diethylaminoethyl) piperazin-1-ylcarbonyl, 4-(3-hydroxyl Propyl) piperazin-1-ylcarbonyl, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylcarbonyl, 4-(3-N, N-diethylaminopropyl ) Piperazine-1-ylcarbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piperidine- 1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetinyl-piperazin-1-yl) piperidyl-1-carbonyl , 4-(N-Methyl-4-pyridinyl) piperazin-1-ylcarbonyl, (9) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxy Carbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropyl Cyclobutylaminomethylamino, cyclobutylaminomethylamino, cyclopentylaminomethylamino, pyridyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N -Dimethylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-Dimethylaminotetrahydropyrrolyl-1-methylamino, 3-N, N-diethylaminotetrahydropyrrolyl-1-methanoamino, 4-methylpiperazine-1-ylmethylamino Amino, 4-ethylpiperazin-1-ylmethylamino, 4-acetazin-1-ylmethylamino, 4-tert-butoxycarbonylpiperazin-1-ylmethylamino, 4-( 2-hydroxyethyl) piperazin-1-ylmethylamino, 4-(2-cyanoethyl) piperazin-1-ylmethylamino, 4-(2-N, N-dimethylaminoethyl Yl)piperazine-1-ylcarboxamido, 4-(2-N, N-diethylaminoethyl)piperazine-1-ylcarboxamido, 4-(3-hydroxypropyl)piperazine- 1-ylmethylamino, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylmethylamino, 4-(3-N, N-diethylaminopropyl) Azin-1-ylcarboxamido, morpholin-1-ylcarboxamido, 3,5-dimethylmorpholin-1-ylcarboxamido, 4-(tetrahydropyrrolyl)piridin-1-yl Carboxamido, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarboxamido, 4-(4-ethyl Piperazine-1-yl) piperidin-1-ylmethylamino, 4-(4-acetin-1-yl) piperidin-1-ylmethylamino, 4-(N-methyl- 4-(pyridinyl) piperazin-1-ylmethylamino; or (11) aminoacetylamino, 2-dimethylaminoacetylamino, N-tert-butoxycarbonylacetylamino, N-acetylamino Acetylamino, acrylamide, cyclopropylamino, chloroacetamino, pyridylacetamino, 4-hydroxypyridylacetamino, 4-N, N-dimethylaminopyridylacetamide Amino, 4-N, N-diethylaminopyridinylacetamino, tetrahydropyrrolylacetamino, 3-N, N-dimethylaminotetrahydropyrrolylacetamino, 3-N, N -Diethylaminotetrahydropyrrolylacetamino, 4-methylpiperazinylacetamino, 4-ethylpiperazinylacetamino, 4-acetazinylacetamino, 4-tert Butoxycarbonyloxazinylacetamido, 4-(2-hydroxyethyl)oxazinylacetamido, 4-(2-cyanoethyl)oxazinylacetamido, 4-(2-N, N-Dimethylaminoethyl) Pirazinyl Acetylamino, 4-(2-N, N-Diethylaminoethyl) Pirazinyl Acetylamino, 4-(3-Hydroxypropyl) Piperazine 4-(3-N, N-Dimethylaminopropyl) Pyrazinyl Acetylamino, 4-(3-N, N-Diethylaminopropyl) Pyrazinyl Acetylamino , Morpholinyl acetamino, 3, 5-dimethylmorpholinyl acetamino, 4-(4-methyl-piperazine-1-yl) pyridinyl acetamino, 4-(4-ethyl Pyridine-1-pyridinyl) pyridinyl acetylamino, 4-(4-acetinyl-1-piperazinyl) pyridyl acetinyl amino, N-(N-methyl-4-pyridinyl )Pazizinylacetamino, 4-(tetrahydropyrrol-1-yl)pyridinylacetamino; 2-methylaminoacetamino, 2-(1-methylethyl)aminoacetamino; N-benzyloxycarbonyl-2methylaminoacetamino; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituent may be selected From the above substituents the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from the same as Z 1 The above-mentioned substituents, 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; preferably, R 1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazine Group) ethyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N -Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-(N-methyl-4-pyridinyl) -4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, nitro, (2) C1-C6 alkyl, C1-C6 alkoxy Group, C1-C6 oxygen-containing alkyl group, C1-C6 fluorine-containing alkyl group, C1-C6 fluorine-containing alkoxy group, N-methyl-4-pyridinyl group, (3) N, N-dimethylamino group, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 3-morpholinopropylamino , 3-(4-Methylpiperazine) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, (4) 2-N, N-dimethyl Aminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2 -(4-Acetylazizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-di Isopropylaminopropoxy, 3-(4-acetazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenolinylpropoxy, 3-pyridinylpropoxy Group, pyridin-2-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-di Methylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5 -Dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(3- N, N-Diethylaminopropyl) piperazinyl, 2-oxo- piperazin-4-yl, imidazolyl, 4-methylimidazolyl, (6) 4-(4-methylpiperazinyl) ) Piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4-(4-acetylpiperazinyl) piperidine Group, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methanesulfonyl piperazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazine Yl) pyridinyl, 4-(4-(3-hydroxypropyl) pyrazine) pyridinyl, 4-(4-(2-N, N-dimethylaminoethyl) pyrazine) quat Ridinyl, 4-(4-(2-N, N-diethylaminoethyl)pirazinyl)piridinyl, 4-(4-(3-N, N-dimethylaminopropyl)quat Azinyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, 4-(N-methyl-4-pyridinyl) pyrinyl, 4-( N-Ethyl-4-pyridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylsulfonyl醯基, Cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 3-N , N-Dimethyltetrahydropyrrol-1-ylsulfonyl, 3-N, N-diethylaminotetrahydropyrrol-1-ylsulfonyl, 4-methylpiperazine-1-ylsulfonyl , 4-ethylpiperazine-1-ylsulfonyl, 4-acetylpiperazine-1-ylsulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, N-( 2-hydroxyethyl)piperazine-1-sulfonyl, 4-(2-cyanoethyl)piperazine-1-ylsulfonyl, 4-(3-hydroxypropyl)piperazine-1- Sulfonyl, 4-(3-N, N-dimethylaminopropyl)piperazine-1-ylsulfonyl, 4-(3-N, N-diethylaminopropyl)piperazine- 1-ylsulfonyl, 4-(4-acetoxypiperazine-1-yl)piridin-1-ylsulfonyl, 4-(N-methyl-4-piridinyl)piperazine-1 -Sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, Piperidinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl -1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Azin-1-ylcarbonyl, 4-(2-N, N-diethylaminoethyl) piperazin-1-ylcarbonyl, 4-(3-N, N-diethylaminopropyl) piperazin- 1-ylcarbonyl, morpholin-1-ylcarbonyl, 3,5-dimethylmorpholin-1-ylcarbonyl, 4-(4-methyl-piperazin-1-yl)piridin-1-ylcarbonyl , 4-(4-Acetyl-1-piperinyl)piridin-1-ylcarbonyl, 4-(N-methyl-4-piridinyl)piperazine-1-ylcarbonyl, (9) methyl Oxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethyl Amino, isopropylaminomethylamino, cyclopropylaminomethylamino, pyridyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylamino Piperidinyl-1-methylamino, 4-N, N-diethylaminopyridinyl-1-methylamino, 4-acetylpyrazine-1-ylmethylamino, 4-(2- Hydroxyethyl) piperazin-1-ylcarboxamido, 4-(2-cyanoethyl) piperazin-1-ylcarboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazin-1-ylcarboxamido, 4-(3-N, N-dimethylaminopropyl) piperazin-1-ylcarboxamido, 4-(3-N, N-diethylaminopropyl Yl)piperazine-1-ylmethylamino, morpholin-1-ylmethylamino, 4-(4-acetylpiperazine-1-yl)piperidine-1- 4-(N-methyl-4-pyridinyl) piperazin-1-ylmethylamino; or (11) aminoacetamido, N-tert-butoxycarbonylacetamido, N- Acetylaminoacetamino, acrylamide, cyclopropylamino, chloroacetamino, pyridylacetamino, 4-hydroxypyridylacetamino, 4-N, N-dimethylamino Pyridinylacetylamino, 4-N, N-diethylaminopyridylacetylamino, 3-N, N-dimethylaminotetrahydropyrrolylacetylamino, N-ethylpiperazinylacetylamino Amino, 4-acetylazinylacetamino, 4-tert-butoxycarbonylazinylacetamino, 4-(2-cyanoethyl)azinylacetamino, N-(2-N , N-Dimethylaminoethyl) Pirazinyl Acetylamino, 4-(2-N, N-Diethylaminoethyl) Pirazinyl Acetylamino, 4-(3-N, N-Di Methylaminopropyl) piperazinylacetamino, 4-(3-N, N-diethylaminopropyl)piperazinylacetamino, 4-(4-methyl-piperazin-1-yl ) Pyridyl acetylamino, 4-(4-ethyl-1-pyrazine) pyridyl acetylamino, 4-(4-acetyl-1-pyrazine) pyridyl acetylamino , N-benzyloxycarbonyl-2methylaminoacetamido; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents can be It is selected from the above-mentioned substituents the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from Z 1 The same substituents as above, 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; more preferably, R 1 is selected from: 1) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, nitro, (2) C1-C6 alkyl, C1-C6 alkoxy Group, C1-C6 fluorine-containing alkyl group, C1-C6 fluorine-containing alkoxy group, (3) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-Dimethylaminoethylamino, 2-morpholinoethylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methyl Pyperidine-4-amino, N-ethylpiperidine-4-amino, (4) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-Diisopropylaminoethoxy, 2-(4-methyloxizinyl)ethoxy, 2-(4-ethyrazinyl)ethoxy, 2-morpholine Ethoxy group, 2-thiophenolinylethoxy group, 2-pyridinylethoxy group, 3-N, N-diisopropylaminopropoxy group, 3-(4-acetyloxazine group ) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, phenylmethoxy, mono Halogen substituted phenylmethoxy, (5) pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-di Isopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3,5-dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylamino Tetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetinyl Piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 2-oxo-piperazin-4-yl, imidazole Group, 4-methylimidazolyl, (6) 4-(4-methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropyl) Pirazinyl)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methylsulfonyl) Piperazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4- (4-(2-N, N-Dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidine Group, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl, 4-(N-methyl-4-piridinyl)pirazinyl, 4-(N-ethyl- 4-pyridinyl) azizinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropyl Aminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 3-N, N -Dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)pezinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl)pezinyl -1-sulfonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylamino Carbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N- Dimethylaminopiridinyl-1-carbonyl, 4-N, N-diethylaminopiridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetra Hydropyrrolyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazine Carbonyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1 -Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, (9) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tertiary Butoxycarbonyl, (10) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, piridyl- 1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4-N, N-diethylamino Pyridinyl-1-carboxamido, 4-acetamidoprazinyl-1-carboxamido, 4-(2-hydroxyethyl)prazinyl-1-carboxamido, 4-(2-cyano Ethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(3-N, N-dimethylamino 4-(3-N, N-diethylaminopropyl) piperazinyl-1-methylamino, morpholinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-methylamino, morpholinyl-1-methylamino , 4-(4-acetyl-1-pyridinyl)pyridinyl-1-carboxamido, 4-(N-methyl-4-pyridinyl)piperazinyl-1-carboxinylamino; Or (11) Aminoacetylamino, N-tert-butoxycarbonylacetylamino, N-acetylaminoacetylamino, allylamino, cyclopropylamino, chloroacetylamino, pyridylacetamino, 4-Hydroxypyridinylacetamido, 4-N, N-dimethylaminopyridinylacetamido, 4-N, N-diethylaminopyridinylacetamido, 3-N, N- Dimethylaminotetrahydropyrrolylacetamino, 4-ethylpiperazinylacetamino, 4 -Acetazinylacetamino, 4-tert-butoxycarbonyloxazinylacetamino, 4-(2-cyanoethyl)azinylacetamino, 4-(2-N, N- Dimethylaminoethyl) azizinyl acetamido, 4-(2-N, N-diethylaminoethyl) azizinyl acetamido, 4-(3-N, N-dimethylamino Propyl) piperazinyl acetamino, 4-(3-N, N-diethylaminopropyl) piperazinyl acetamino, 4-(4-methyl-piperazin-1-yl) piperidine 4-(4-ethyl-1-piperazinyl) pyridylacetamino, 4-(4-ethyl-1-piperazinyl)pyridylacetamino, N- Benzyloxycarbonyl-2methylaminoacetamido; (12) Z 2 and Z 3 or Z 3 and Z 4 form an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituent may be selected from The above-mentioned substituents that are the same as Z 1 , (13) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing substituted or unsubstituted five-membered ring or six-membered ring; the substituents may be selected from the same as those of Z 1 Substituents, 2) , Where Z 2 , Z 3 , Z 4 , Z 5 are the same as defined in 2) above; 3) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; A is a direct bond or a methylene group; preferably A is a direct bond; or, preferably A is a methylene group; X is NH , S or O; R 2 is selected from: 1) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, dimethylaminosulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, iso Butoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl , Dimethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl, 3) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl; 4) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl , Cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl; Y 2 , Y 3 , Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is N, Y 3 is CA 13 , Y 4 is N , O or S; Y 2 is O or S, Y 3 is NA 13 , Y 4 is CH; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 5) pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropyl Aminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5-dimethylmorpholinyl, thiophenrinyl, tetrahydropyrrolyl, 3-N, N-dimethylaminotetrahydro Pyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetylpiperazine Group, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4 -(3-Hydroxypropyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazin Group, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl; preferably, R 2 is selected from: 1) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, (2) methylthio, ethylthio, iso Propylthio, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropylsulfonyl, tert-butylsulfinyl, dimethylaminosulfinyl, methylsulfonyl Amino, methoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, cyclobutylaminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, dimethylphosphine Diethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl, 3) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopentylaminocarbonyl; 4) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclobutylaminocarbonyl, methylsulfinyl Group, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl; Y 2 , Y 3 , Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; 5) pyridinyl, 4-N, N-dimethyl Aminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, morpholinyl, 3, 5- Dimethylmorpholinyl, 3-N, N-dimethylaminotetrahydropyrrolyl, 3-N, N-diethylaminotetrahydropyrrolyl, 4-methylquarazinyl, 4-ethylpyrrolyl Azinyl, 4-isopropyl azizinyl, 4-acetylazinyl, 4-(2-N, N-diethylaminoethyl) azizinyl, 4-(3-N, N- Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl; more preferably, R 2 is selected from: 1) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, (2) methylthio, ethylthio, isopropylthio, ethanesulfinyl Acetyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropylsulfonyl, tert-butylsulfonyl, dimethylaminosulfinyl, methylsulfinylamino, methoxycarbonyl, Isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, cyclobutylaminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, isopropylaminocarbonyl, dimethylphosphinyl, diethylamino Phosphonyl, diisopropylphosphinyl, 2) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopentylaminocarbonyl; 3) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclobutylaminocarbonyl, methylsulfinyl Group, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl; Y 2 , Y 3 , Y 4 are selected from the following combinations: Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; Y 2 is O or S, Y 3 is CA 13 , Y 4 is N; and Y 2 is C, Y 3 is NA 13 , Y 4 is O or S; Y 2 is C, Y 3 is NA 13 , Y 4 is N; wherein A 13 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl; or stereoisomers of the above compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride or hydrobromide , Hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, the organic acid salt is formate, acetate, propionate, benzoate, maleate, fumarate Acid salt, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoroacetate, α-glycerophosphate, alkyl sulfonate or aryl sulfonate; preferably Preferably, the alkyl sulfonate is methane sulfonate or ethyl sulfonate; the aryl sulfonate is benzene sulfonate or p-toluene sulfonate. 如申請專利範圍第1項的化合物，其為以下式V：V 其中， W 為氧代，硫代，或氫； 較佳W 為氧代；n = 0，或1； 較佳n＝1；或者 較佳選n＝0； R3 ，R4 ，R5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基，C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基； 較佳，R3 ，R4 ，R5 各自獨立地選自： （1）氫，氟，氯，溴，碘； （2）C1-C6烷基，C1-C6烷氧基； R6 選自： （1）氫，C1-C6烷基，乙醯基，丙醯基，正丁醯基，異丁醯基， （2）氨基乙醯基，2-N, N-二甲基乙醯基，2-N, N-二乙基乙醯基，2-N, N-二異丙基乙醯基，呱啶基乙醯基，4-羥基呱啶基乙醯基，4-N, N-二甲基氨基呱啶基乙醯基，4-N, N-二乙基氨基呱啶基乙醯基，四氫吡咯基乙醯基，3-N, N-二甲基氨基四氫吡咯基乙醯基，3-N, N-二乙基氨基四氫吡咯基乙醯基，4-甲基呱嗪基乙醯基，4-乙基呱嗪基乙醯基，4-乙醯基呱嗪基乙醯基，4-叔丁氧羰基呱嗪基乙醯基，4-(2-羥基乙基)呱嗪基乙醯基，4-(2-氰基乙基)呱嗪基乙醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯基，4-(3-羥基丙基)呱嗪基乙醯基， 4-(3-N, N-二甲基氨基丙基)呱嗪基乙醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基乙醯基，嗎啉基乙醯基，3, 5-二甲基嗎啉基乙醯基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯基，4-(4-乙基-1-呱嗪基)呱啶基乙醯基，4-(4-乙醯基-1-呱嗪基)呱啶基乙醯基，4-(N-甲基-4-呱啶基)呱嗪基乙醯基； 較佳，R6 選自： （1）氫，C1-C6烷基，乙醯基，丙醯基， （2）氨基乙醯基，2-N, N-二甲基乙醯基，2-N, N-二乙基乙醯基，2-N, N-二異丙基乙醯基，呱啶基乙醯基，4-羥基呱啶基乙醯基，4-N, N-二甲基氨基呱啶基乙醯基，4-N, N-二乙基氨基呱啶基乙醯基，四氫吡咯基乙醯基，4-乙醯基呱嗪基乙醯基，4-叔丁氧羰基呱嗪基乙醯基，4-(2-羥基乙基)呱嗪基乙醯基，4-(2-氰基乙基)呱嗪基乙醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基乙醯基，4-(2-N, N-二乙基氨基乙基)呱嗪基乙醯基，嗎啉基乙醯基，3, 5-二甲基嗎啉基乙醯基，4-(4-甲基-呱嗪-1-基)呱啶基乙醯基，4-(4-乙基-1-呱嗪基)呱啶基乙醯基； A，X，R2 與上述技術方案中定義相同; 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物； 其中，該藥學上可接受的鹽為無機酸鹽或有機酸鹽，其中，該無機酸鹽為鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硝酸鹽、碳酸氫鹽和碳酸鹽、硫酸鹽或磷酸鹽，該有機酸鹽為甲酸鹽、乙酸鹽、丙酸鹽、苯甲酸鹽、馬來酸鹽、富馬酸鹽、琥珀酸鹽、酒石酸鹽、檸檬酸鹽、抗壞血酸鹽、α-酮戊二酸鹽、三氟乙酸鹽、α-甘油磷酸鹽、烷基磺酸鹽或芳基磺酸鹽；較佳地，該烷基磺酸鹽為甲基磺酸鹽或乙基磺酸鹽；該芳基磺酸鹽為苯磺酸鹽或對甲苯磺酸鹽。For example, the compound of item 1 in the scope of patent application, which is the following formula V: V wherein W is oxo, thio, or hydrogen; preferably W is oxo; n=0, or 1; preferably n=1; or preferably n=0; R 3 , R 4 , R 5 Each is independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1 -C6 fluorine-containing alkyl group, C1-C6 fluorine-containing alkoxy group; preferably, R 3 , R 4 , and R 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, and iodine; (2) C1 -C6 alkyl, C1-C6 alkoxy; R 6 is selected from: (1) hydrogen, C1-C6 alkyl, acetyl, propionyl, n-butyryl, isobutyryl, (2) aminoacetyl, 2-N, N-Dimethyl acetyl, 2-N, N-diethyl acetyl, 2-N, N-diisopropyl acetyl, pyridyl acetyl, 4-hydroxy Pyridinylacetinyl, 4-N, N-dimethylaminopyridinylacetinyl, 4-N, N-diethylaminopyridinylacetinyl, tetrahydropyrrolylacetinyl, 3 -N, N-Dimethylaminotetrahydropyrrolylacetinyl, 3-N, N-Diethylaminotetrahydropyrrolylacetinyl, 4-methylpiperazinylacetinyl, 4-ethyl Pirazinylacetinyl, 4-acetinylpyrazineacetinyl, 4-tert-butoxycarbonylperazinylacetinyl, 4-(2-hydroxyethyl)perazinylacetinyl, 4- (2-Cyanoethyl) pyrazinyl acetyl, 4-(2-N, N-dimethylaminoethyl) pyrazinyl acetyl, 4-(2-N, N-diethyl Aminoethyl) piperazinyl acetyl, 4-(3-hydroxypropyl) piperazinyl acetyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl acetyl, 4-(3-N, N-Diethylaminopropyl) Pirazinyl Acetyl, Morpholinyl Acetyl, 3, 5-Dimethylmorpholinyl Acetyl, 4-(4-Methyl Pyridine-1-yl) pyridinyl acetyl, 4-(4-ethyl-1-pyrazine) pyridyl acetyl, 4-(4-acetinyl-1-pyrazine R 6 is selected from: (1) hydrogen, C1-C6 alkyl, ethyl Acetyl, propionyl, (2) amino acetyl, 2-N, N-dimethyl acetyl, 2-N, N-diethyl acetyl, 2-N, N-diisopropyl Pyridine acetyl, 4-hydroxypyridyl acetyl, 4-N, N-dimethylaminopyridyl acetyl, 4-N, N-diethylamino quat Pyridinylacetinyl, tetrahydropyrrolylacetinyl, 4-acetinylacetinylacetinyl, 4-tert-butoxycarbonylperazinylacetinyl, 4-(2-hydroxyethyl)piperazine 4-(2-cyanoethyl) piperazinyl acetyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl acetyl, 4-(2- N, N-Diethylaminoethyl) azizinyl acetyl, morpholinyl acetyl, 3, 5-dimethylmorpholinyl acetyl, 4-(4- Methyl-piperazine-1-yl)piridinylacetinyl, 4-(4-ethyl-1-piperinyl)piridinylacetinyl; A, X, R 2 are as defined in the above technical scheme The same; or the stereoisomer of the above compound, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate; wherein, the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt , Wherein the inorganic acid salt is hydrochloride, hydrobromide, hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, and the organic acid salt is formate, acetate, Propionate, benzoate, maleate, fumarate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoroacetate, α-glycerophosphate Salt, alkyl sulfonate or aryl sulfonate; preferably, the alkyl sulfonate is methane sulfonate or ethyl sulfonate; the aryl sulfonate is benzene sulfonate or p- Tosylate. 如申請專利範圍第1項的化合物，其為以下式IA：其中R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基， （4）N-甲基-4-呱啶基， （5）4-甲基呱嗪基， （6）4-(4-甲基呱嗪基)呱啶基， （7）4-(四氫吡咯-1-基)呱啶基， 或 （8）Z2 與 Z3 或Z3 與Z4 形成或； 最佳，R1選自： 1），其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 或 Z2 與Z3 或Z3 與Z4 形成或； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IA: Wherein R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N -Diisopropylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N- Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N- Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1- (N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, (4) N-methyl-4- Piperidinyl, (5) 4-Methyl piperazinyl, (6) 4-(4-Methyl piperazinyl) piperidyl, (7) 4-(Tetrahydropyrrol-1-yl) piperidyl , Or (8) Z 2 and Z 3 or Z 3 and Z 4 are formed or ; Best, R1 is selected from: 1) , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4 -Pyridyl, 4-methyl pyrazine, 4-(4-methyl pyrazine) pyridyl, 4-(tetrahydropyrrol-1-yl) pyridyl, or Z 2 and Z 3 or Z 3 and Z 4 form or ; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methanesulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IB：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，2-氧代-呱嗪-4-基， （5）嗎啉基，3, 5-二甲基嗎啉基，硫啡啉基， （6）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基， 4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基， 4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （7）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-(2-羥基乙基)呱嗪3-N, N-二乙基氨基四氫吡咯基-1-羰基，基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，3, 5-二甲基嗎啉基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （8）吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，或 （9）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 3），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 4），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 較佳，R1選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，2-氧代-呱嗪-4-基， （6）嗎啉基，3, 5-二甲基嗎啉基， （7）4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，羥基磺醯基，氨基磺醯基，甲氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-乙基呱嗪基-1-磺醯基， （8）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基， （9）吡啶-2-基甲氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 2），其中Z2 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 3），其中Z1 ，Z3 ，Z4 ，Z5 與上述2）中定義相同； 更佳，R1選自： 1），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基、乙氧基、異丙氧基， （4）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-二甲氨基-呱啶基， （5）4-甲基呱嗪基，4-叔丁氧羰基呱嗪基， （6）嗎啉基， （7）4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基， （8）4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基， （9）吡啶-2-基甲氧基， （10）2-二甲氨基乙醯氨基，， （11）–F， （12）Z2 與 Z3 或Z3 與Z4 形成或， 2），其中Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自：嗎啉基，4-甲基呱嗪基， 4-羥基呱啶基； 3），其中Z1 ，Z3 ，Z4 ，Z5 各自獨立地選自：嗎啉基，4-羥基呱啶基； 最佳，R1選自： 1），其中Z1 和Z5 二者之一為氫，另一選自：甲氧基、乙氧基、異丙氧基； Z2 和Z4 二者之一為氫，另一為甲基，2-二甲氨基乙醯氨基，； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-甲基呱嗪基，4-叔丁氧羰基呱嗪基，嗎啉基，4-羥基呱啶-1-基磺醯基，4-甲基呱嗪-1-基磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-甲基呱嗪-1-基羰基，吡啶-2-基甲氧基，4-二甲氨基-呱啶基，-F；或 Z2 與Z3 或Z3 與Z4 形成或， 2），其中Z3 選自：嗎啉基，4-甲基呱嗪基，4-羥基呱啶基；Z1 、Z2 和Z4 都為氫； 3），其中Z3 選自：嗎啉基，4-羥基呱啶基；Z1 、Z2 和Z4 都為氫； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）異丙基磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IB: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, 2-oxo-piperazin-4-yl, (5) morpholinyl, 3,5-dimethylmorpholinyl, thiophenolinyl, (6) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methyl Piperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetazine-1-sulfonyl, 4-(2-hydroxyethyl)piperazine 1-sulfonyl, 4-(2-cyanoethyl)gua Azinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) azizinyl-1-sulfonyl, 4-(2-N,N-diethylethyl) Piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)perazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1 -Sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piperidine- 1-ylsulfonyl, 4-(4-ethyl-1-oxizinyl)piridin-1-ylsulfonyl, 4-(N-methyl-4-piridinyl)pirazinyl-1 -Sulfonyl, (7) 4-(4-methyl-piperazin-1-yl)piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl -1-carbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, piperidinyl-1-carbonyl, 4-hydroxypiridinyl-1-carbonyl, 4-N, N-dimethylaminopiridinyl- 1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-Dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-(2-hydroxyethyl)piperazine 3 -N, N-Diethylaminotetrahydropyrrolyl-1-carbonyl, base-1-carbonyl, 4-(3-hydroxypropyl)piperazinyl-1-carbonyl, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, hydroxycarbonyl, Aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, 3,5-dimethylmorpholin-1-carbonyl, methoxycarbonyl, ethoxycarbonyl , Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, (8) pyridin-2-ylmethoxy, pyridin-3-ylmethoxy , Pyridin-4-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, or (9) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or For substituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; 3) , Where Z 2 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; 4) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; preferably, R1 is selected from: 1) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) N -Methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpyrrolidinyl)pyridinyl, 4-(tetrahydropyrrolyl)pyridinyl, pyridinyl, 4- N, N-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, (5) 4-methylpiperazine Group, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetylpiperazinyl, 4-tert-butoxycarbonylpiperazinyl, 4-methylsulfonylpiperazinyl, 4- (2-Hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4- (3-N, N-Diethylaminopropyl)pirazinyl, 2-oxo-pirazin-4-yl, (6) morpholinyl, 3,5-dimethylmorpholinyl, (7 ) 4-Hydroxypiperidine-1-ylsulfonyl, 4-methylpiperazine-1-ylsulfonyl, hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, propylaminosulfonyl, Isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-Dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N , N-Dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-ethylpiperazinyl-1-sulfonyl Acetyl, (8) 4-(4-methyl-piperazin-1-yl)piperidin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, cyclobutylaminocarbonyl, cyclopentyl Aminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-diethylamino Pyridine-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-carbonyl, 4-(3-hydroxypropyl)pirazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl)pirazinyl-1-carbonyl, 4-(3 -N, N-Diethylaminopropyl) piperazinyl-1-carbonyl, morpholin-1-carbonyl, (9) pyridin-2-ylmethoxy, pyridin-2-ylmethoxy, pyridine -3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, mono-halogen substituted phenylmethoxy, or (10) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, and the substituent may be selected from the same substituents as described above for Z 1; 2) , Where Z 2 , Z 3 , Z 4 , Z 5 are the same as defined in 2) above; 3) , Where Z 1 , Z 3 , Z 4 , and Z 5 are the same as defined in 2) above; more preferably, R1 is selected from: 1) , Where Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, ethoxy, isopropoxy, ( 4) N-methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-Dimethylamino-piperidinyl, (5) 4-methylpiperazinyl, 4-tert-butoxycarbonyl piperazinyl, (6) morpholinyl, (7) 4-hydroxypiperidin-1-yl Sulfonyl, 4-methylpiperazine-1-ylsulfonyl, (8) 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-methylpiperazine -1-ylcarbonyl, (9)pyridin-2-ylmethoxy, (10)2-dimethylaminoacetamido, , (11)–F, (12) Z 2 and Z 3 or Z 3 and Z 4 are formed or , 2) , Wherein Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: morpholinyl, 4-methylpiperazinyl, 4-hydroxypyridinyl; 3) , Wherein Z 1 , Z 3 , Z 4 , and Z 5 are each independently selected from: morpholinyl, 4-hydroxypyridinyl; most preferably, R1 is selected from: 1) , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, and isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl, 2-Dimethylaminoacetamido, ; Z 3 is selected from: N-methyl-4-piridinyl, 4-hydroxypiridinyl, 4-(4-methylpirazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl) Piperidinyl, 4-methylpiperazinyl, 4-tert-butoxycarbonyl piperazinyl, morpholinyl, 4-hydroxypiperidin-1-ylsulfonyl, 4-methylpiperazin-1-ylsulfonyl Amino, 4-(4-methyl-piperazine-1-yl)piperidine-1-ylcarbonyl, 4-methylpiperazine-1-ylcarbonyl, pyridin-2-ylmethoxy, 4-di Methylamino-pyridinyl, -F; or Z 2 and Z 3 or Z 3 and Z 4 are formed or , 2) , Where Z 3 is selected from: morpholinyl, 4-methylpiperazine, 4-hydroxypiperdinyl; Z 1 , Z 2 and Z 4 are all hydrogen; 3) , Where Z 3 is selected from: morpholinyl, 4-hydroxypyridinyl; Z 1 , Z 2 and Z 4 are all hydrogen; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IO：R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基 （3）4-(4-甲基呱嗪-1-基)呱啶基，4-甲基呱嗪基，4-二甲氨基-呱啶基， （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環； 最佳R1選自：，其中 Z1 為甲氧基，且Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，其餘為氫；或 Z3 與Z4 形成，且Z1 為甲氧基，其餘為氫； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫； （2）叔丁磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為叔丁磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IO: R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N- Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N-di Ethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4 -N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N-iso Propyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1-( N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Pirazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piridinyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) azizinyl) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, (4) 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl Group, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N -Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazin Group, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl-4- (Primidyl) azizinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethyl Amino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethyl Aminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine -4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N -Diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-acetylpiperazinyl) ) Ethoxy, 2-? Alkylethoxy, 2-Thiophenanthrylethoxy, 2-Perridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropyl Oxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetazinyl)propoxy, 3 -Morpholinylpropoxy, 3-thiophenanthrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-yl Methoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonyl, aminosulfonyl Group, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetinyl Piperazinyl-1-sulfonyl, 4-tert-butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2- Cyanoethyl) piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-sulfonyl, 4-(2-N,N- Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl )Pepazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1-sulfonyl, morpholin-1-sulfonyl, 3, 5 -Dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl-1-piper) (Azinyl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-(N-methyl-4-piperidine Group) pyrazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, Cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-di Ethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetra Hydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-butoxy Carbonyl piperazinyl-1-carbonyl, 4 -(2-Hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1-carbonyl, 4 -(3-N, N-Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl -1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-(4-ethyl -1-piperinyl)piridinyl-1-carbonyl, 4-(4-acetinyl-1-piperinyl)piridinyl-1-carbonyl, 4-(N-methyl-4-piperidine Yl)pirazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, ( 9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethylamino, cyclopentan Aminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4 -N, N-Diethylaminopyridinyl-1-methylamino, tetrahydropyrrolyl-1-methylamino, 3-N, N-dimethylaminotetrahydropyrrolyl-1-methylamino , 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylazinyl-1-methanoamino, 4-tert-butoxycarbonylazinyl-1-methanoamino, 4-(2-hydroxyethyl)azinyl-1-methanoamino, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carboxamido, 4-(2 -N, N-Diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carboxamido, morpholinyl-1-methyl Amino, 3,5-dimethylmorpholinyl-1-carboxamido, 4-(4-methyl-piperazine-1-yl)piridinyl-1-carboxamido, 4-(4- Ethyl-1-prazinyl) pyridinyl-1-methanylamino, 4-(4-acetinyl-1-methazinyl) pyridinyl-1-methanylamino, 4-(N-methyl (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six The membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , (4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4- Methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethyl Aminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N -Ethyl-4-pyridinyl) piperazinyl; or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring, and the substituent may be selected from The above-mentioned substituents the same as Z 1; more preferably R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy (3) 4-(4-methylpiperazine- 1-yl) pyridinyl, 4-methyl pyrazine, 4-dimethylamino-pyridinyl, (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring ; The best R1 is selected from: , Wherein Z 1 is a methoxy group, and Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, and the rest are Hydrogen; or Z 3 and Z 4 are formed , And Z 1 is a methoxy group, and the rest are hydrogen; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethyl Phosphinyl, diisopropylphosphinyl; preferably, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) tert-butylsulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is tert-butylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, and their pharmaceutics The above acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IC：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基， （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）4-羥基呱啶基，呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-羥基呱啶基， （4）4-甲基呱嗪基， （5）4-(4-甲基呱嗪基)呱啶基，或 （6）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基，Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與Z3 形成； R2選自：1）或， 其中，Y為NH，S或O原子， A6 ，A7 ，A8 ，A9 ，A10 ，A11 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基； 2）其中A12 選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N，或 Y2 為N，Y3 為N-A13 ，Y4 為CH或N； 其中A13 為氫，C1-C6烷基； 較佳，R2選自：其中A12 選自： （1）氫，甲基，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，甲基亞磺醯基，乙基亞磺醯基，異丙基亞磺醯基，甲基磺醯基，乙基磺醯基，異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N，或 Y2 為N，Y3 為N-A13 ，Y4 為CH或N； 其中A13 為氫，C1-C6烷基； 更佳，R2選自：其中A12 選自： （1）氫，甲基， （2）異丙基磺醯基； Y2 ，Y3 ，Y4 為以下組合： Y2 為C，Y3 為N-A13 ，Y4 為N， 其中A13 為氫，C1-C6烷基； 最佳，R2選自：其中A12 選自異丙基磺醯基； Y2 , Y3 , Y4 為以下組合：Y2 為C，Y3 為N-A13 ，Y4 為N，其中A13 為甲基； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IC: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, or (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N- Dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N -Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethyl (Aminopiperazine) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl)prazinyl-1-methylamino, (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered Ring, the substituent may be selected from the same substituents as described above as Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-hydroxypyridinyl, pyridinyl , N-Methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropyl Amino piperidinyl, (4) 4-methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazin Group, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl Group, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N -Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-Ethyl-4-piperidyl)piperidyl, (5) 4-(4-methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl , 4-(4-isopropylpiperazinyl)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-Methanesulfonylquarazinyl)piridinyl, 4-(4-(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl) (Quazizinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl ) Piperidyl, 4-(4-(2-N, N-diethylaminoethyl) Piperazinyl) Piperidyl, 4-(4-(3-N, N-Dimethylaminopropyl ) Piperazinyl) piperidyl, 4-(4-(3-N, N-diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4- (3-N, N-Dimethylaminotetrahydropyrrolyl) pyridinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring , The substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, (4) 4-methyl Pyrazinyl, (5) 4-(4-methylprazinyl) pyridinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, the other is methoxy, Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form ; R2 is selected from: 1) or , Where Y is an NH, S or O atom, A 6 , A 7 , A 8 , A 9 , A 10 , and A 11 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano , Trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl , Tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl; 2) Wherein A 12 is selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxycarbonyl, propyl Oxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl , Cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl; Y 2 , Y 3 , Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, or Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N ; Wherein A 13 is hydrogen, C1-C6 alkyl; preferably, R2 is selected from: Wherein A 12 is selected from: (1) hydrogen, methyl, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro, (2) methoxycarbonyl, ethoxy Carbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropyl Aminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, Isopropylsulfonyl; Y 2 , Y 3 , Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, or Y 2 is N, Y 3 is NA 13 , Y 4 is CH or N; wherein A 13 is hydrogen, C1-C6 alkyl; more preferably, R2 is selected from: Wherein A 12 is selected from: (1) hydrogen, methyl, (2) isopropylsulfonyl; Y 2 , Y 3 , and Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , and Y 4 is N, where A 13 is hydrogen, C1-C6 alkyl; most preferably, R2 is selected from: Wherein A 12 is selected from isopropylsulfonyl; Y 2 , Y 3 , Y 4 are the following combinations: Y 2 is C, Y 3 is NA 13 , Y 4 is N, wherein A 13 is methyl; or the above compound The stereoisomers, prodrugs, pharmaceutically acceptable salts thereof, or pharmaceutically acceptable solvates thereof. 如申請專利範圍第1項的化合物，其為以下式ID：其中， R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基， （3）甲氧基、異丙氧基， （4）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （5）4-甲基呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z2 和Z4 二者之一為氫，另一為甲基， Z1 和Z5 二者之一為氫，另一選自：甲氧基、異丙氧基， Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫； （2）甲氧基羰基； 更佳，R2選自：，其中A2 和A4 二者之一為氫，另一為甲氧基羰基；A1 ，A3 ，A5 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application, which is the following formula ID: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituents can be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, (3) methoxy, isopropoxy, (4) N- Methyl-4-piperidyl, 4-(4-methylpiperazinyl)piperidyl, 4-(tetrahydropyrrol-1-yl)piperidyl, (5) 4-methylpiperazinyl, Or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 2 and Z 4 is hydrogen, the other is methyl, one of Z 1 and Z 5 is hydrogen, the other is selected from: methoxy, isopropoxy, and Z 3 is selected from : N-Methyl-4-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, Or Z 2 and Z 3 or Z 3 and Z 4 ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl; preferably, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) methoxycarbonyl; more preferably, R2 is selected from: , Wherein one of A 2 and A 4 is hydrogen, and the other is methoxycarbonyl; A 1 , A 3 , and A 5 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IE：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基； 更佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基，乙氧基，異丙氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一選自：甲氧基、乙氧基、異丙氧基; Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基、4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基； 較佳，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲氧基羰基； 更佳，R2選自，其中A1 和A5 二者之一為氫，另一為甲氧基羰基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IE: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl)pirazinyl-1-methylamino; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; more preferably, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, ethoxy, isopropoxy, (3) N -Methyl-4-pyridinyl, 4-hydroxypyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, (4) 4-methylpiperazinyl; most preferably, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, and isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4-piperidinyl, 4-hydroxypiperidinyl, 4-methylpiperazinyl, 4-(4-methylpiperazinyl)piperidinyl, 4-(tetra Hydropyrrol-1-yl)pyridinyl; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl; preferably, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methoxycarbonyl; more preferably, R2 is selected from , Wherein one of A 1 and A 5 is hydrogen, and the other is methoxycarbonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IF：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(N-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-甲基呱嗪基， （4）4-(4-甲基呱嗪基)呱啶基，或 （5）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）氟，（3）甲氨基羰基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為選自：氟，甲氨基羰基；且A2 和A4 二者之一為氫，另一為選自：氟，甲氨基羰基；A3 為氫； 最佳R2選自：，其中，A1 和A5 二者之一為氫，另一為甲氨基羰基；且A2 和A4 二者之一為氫，另一為氟；A3 為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IF: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(N-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methylprazinyl, 4-ethylprazinyl, 4-isopropylprazinyl, 4-acetylprazinyl, 4-tert-butoxycarbonylprazinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-methylpiperazinyl, 4- Ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyl Ethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N , N-Diethylaminopropyl)pirazinyl, 4-(N-methyl-4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (4) Piridinyl, N-methyl-4-piridinyl, 4-N, N-dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-Diisopropylaminopiperdinyl, 4-hydroxypiperdinyl, 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4- (4-isopropylpirazinyl)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-( 4-Methylsulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl ) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidine Group, 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazine Yl) pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, 4- (3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring , The substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-methylpiperazine, (4) 4- (4-Methyl azizinyl) pyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-methylpiperazine, 4-(4-methylpiperazine) Pyridinyl, or Z 2 and Z 3 form ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) fluorine, (3) methylaminocarbonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is selected from: fluorine, methylaminocarbonyl; and one of A 2 and A 4 is hydrogen, and the other is selected from: fluorine, methylaminocarbonyl ; A 3 is hydrogen; the best R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methylaminocarbonyl; and one of A 2 and A 4 is hydrogen, and the other is fluorine; A 3 is hydrogen; or the stereo of the above compound Isomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate. 如申請專利範圍第1項的化合物IG，其為以下式IG：其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （8）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）氨基磺醯基， 或 （5）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基； 較佳，R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲磺醯氨基； 更佳，R2選自：，其中A2 和A4 二者之一為氫，另一為甲磺醯氨基；A1 ，A3 ，A5 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound IG of item 1 in the scope of patent application is the following formula IG: Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylamino Sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl , 4-Hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-yl Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-sulfonyl, 4-methylpiperazin-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-Butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl) piperazinyl-1-sulfonyl, 4-(2-cyanoethyl) piperazinyl-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl Yl)pirazinyl-1-sulfonyl, 4-(2-N,N-diethylethyl)pirazinyl-1-sulfonyl, 4-(3-hydroxypropyl)pirazinyl- 1-sulfonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazine 1-sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl) Pyridine-1-ylsulfonyl, 4-(4-ethyl-1-pyrazineyl)pyridin-1-ylsulfonyl, 4-(4-acetinyl-1-pyrazine)quan Pyridin-1-ylsulfonyl, 4-(N-methyl-4-pyridinyl) pazizinyl-1-sulfonyl, or (8) Z 2 and Z 3 or Z 3 and Z 4 form a compound containing Nitrogen or oxygen-containing substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) N-methyl-4-pyridinyl , 4-Hydroxypyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, (4) aminosulfonyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4 -Pyridinyl, 4-hydroxy pyridinyl, 4-(4-methyl pyrrolidinyl) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, aminosulfonyl, or Z 2 Form with Z 3 or Z 3 and Z 4 ; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl; preferably, R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonylamino; more preferably, R2 is selected from: , Wherein one of A 2 and A 4 is hydrogen, and the other is methanesulfonylamino; A 1 , A 3 , and A 5 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IH：其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （6）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）N-甲基-4-呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基， （5）氨基磺醯基，或 （6）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：N-甲基-4-呱啶基，4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 Z2 與 Z3 形成； R2選自： 2），其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲磺醯氨基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯氨基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IH: Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinoethyl, 2-(4-4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl , 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4 -Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-iso Oxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2 ) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl piperazinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydro (Pyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetinyl azizinyl, 4-tert-butoxycarbonyl Piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) Piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N , N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazin Group, 4-(N-ethyl-4-piridinyl)pirazinyl, (6) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl , Isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylsulfonyl, pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1- Sulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl- 1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4- Methylpiperazin-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetylpiperazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl -1-sulfonyl, 4-(2-hydroxyethyl)pirazinyl-1-sulfonyl, 4-(2-cyanoethyl)pirazinyl-1-sulfonyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl-1-sulfonyl, 4-(2-N,N-Diethylethyl)piazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piazinyl-1-sulfonyl, 4-(3-N , N-Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl- 1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)peridine-1-ylsulfonyl, 4- (4-Ethyl-1-oxizinyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-( N-methyl-4-pyridinyl) pyrazine-1-sulfonyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered Ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) N-methyl-4-pyridinyl, 4- Hydroxypiperdinyl, 4-(4-methylpiperazine), 4-(tetrahydropyrrol-1-yl)piperdinyl, (4) 4-methylpiperazine, (5) amino Sulfonyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: N-methyl-4-pyridinyl, 4-hydroxypyridinyl, 4 -Methylpiperazinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, aminosulfonyl, or Z 2 and Z 3 form ; R2 is selected from: 2) , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl The phosphinyl group, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonylamino; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is mesylamino; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式II：其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基、乙氧基、異丙氧基； （3）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-羥基呱啶基； （4）4-甲基呱嗪基； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一選自: 甲氧基、乙氧基、異丙氧基； Z2 和Z4 二者之一為氫，另一為甲基； Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫； （2）甲氨基羰基； 更佳，R2選自，其中A1 和A5 二者之一為氫，另一為甲氨基羰基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula II: Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-Methyl-4-pyridinyl)pirazinyl-1-methylamino; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, ethoxy, and isopropoxy; (3) N -Methyl-4-piperidinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-hydroxypyridinyl; (4) 4-methylpiperazinyl; most preferably, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is selected from: methoxy, ethoxy, and isopropoxy; one of Z 2 and Z 4 is hydrogen, and the other is methyl; Z 3 is selected from: N-methyl-4-piperidyl, 4-methylpiperazinyl, 4-hydroxypiperidyl, 4-(4-methylpiperazinyl)piperidyl, 4-(tetrazinyl) Hydropyrrol-1-yl)pyridinyl; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen; (2) methylaminocarbonyl; more preferably, R2 is selected from , Wherein one of A 1 and A 5 is hydrogen, and the other is methylaminocarbonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically acceptable Accepted salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IPQ：R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基 或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基，4-二甲氨基-呱啶基； 最佳R1選自：，其中 Z1 為甲氧基，且Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，其餘為氫；或 Z3 與Z4 形成，且Z1 為甲氧基，其餘為氫； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫， （2）異丙氨基羰基，二甲氨基羰基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙氨基羰基或二甲氨基羰基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IPQ: R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N- Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N-di Ethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4 -N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N-iso Propyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1-( N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Pirazinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4-methanesulfonylpirazinyl)piridinyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) azizinyl) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) pyridinyl, (4) 4- Methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl, 4-tert-butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl Group, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4-(2-N, N -Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl) piperazin Group, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl-4- (Primidyl) azizinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-dimethylaminoethyl Amino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N-diethyl Aminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidine -4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N -Diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-acetylpiperazinyl) ) Ethoxy, 2-? Alkylethoxy, 2-Thiophenanthrylethoxy, 2-Perridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N-diethylaminopropyl Oxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylprazinyl)propoxy, 3-(4-acetazinyl)propoxy, 3 -Morpholinylpropoxy, 3-thiophenanthrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-yl Methoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonyl, aminosulfonyl Group, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl , Pyridine-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N- Diethylaminopiperidine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetinyl Piperazinyl-1-sulfonyl, 4-tert-butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2- Cyanoethyl) piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-sulfonyl, 4-(2-N,N- Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-dimethylaminopropyl )Pepazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl)piperazinyl-1-sulfonyl, morpholin-1-sulfonyl, 3, 5 -Dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl-1-piper) (Azinyl)piperidine-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidine-1-ylsulfonyl, 4-(N-methyl-4-piperidine Group) pyrazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, Cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4-N, N-di Ethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N-diethylaminotetra Hydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-butoxy Carbonyl piperazinyl-1-carbonyl, 4 -(2-Hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1-carbonyl, 4 -(3-N, N-Dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl, morpholinyl -1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylcarbonyl, 4-(4-ethyl -1-piperinyl)piridinyl-1-carbonyl, 4-(4-acetinyl-1-piperinyl)piridinyl-1-carbonyl, 4-(N-methyl-4-piperidine Yl)pirazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, ( 9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethylamino, cyclopentan Aminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methylamino, 4 -N, N-Diethylaminopyridinyl-1-methylamino, tetrahydropyrrolyl-1-methylamino, 3-N, N-dimethylaminotetrahydropyrrolyl-1-methylamino , 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylazinyl-1-methanoamino, 4-tert-butoxycarbonylazinyl-1-methanoamino, 4-(2-hydroxyethyl)azinyl-1-methanoamino, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-carboxamido, 4-(2 -N, N-Diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3-N, N- Dimethylaminopropyl) piperazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carboxamido, morpholinyl-1-methyl Amino, 3,5-dimethylmorpholinyl-1-carboxamido, 4-(4-methyl-piperazine-1-yl)piridinyl-1-carboxamido, 4-(4- Ethyl-1-prazinyl) pyridinyl-1-methanylamino, 4-(4-acetinyl-1-methazinyl) pyridinyl-1-methanylamino, 4-(N-methyl (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six The membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , (4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4- Methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxypropyl) piperazinyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethyl Aminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N -Ethyl-4-pyridinyl) piperazinyl or (5) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring, and the substituent may be selected from Z 1 is the same as the above-mentioned substituents; more preferably R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(4-methylpiperazine) Group) pyridinyl, 4-methylpyrazine, 4-dimethylamino-pyridinyl; the best R1 is selected from , Wherein Z 1 is a methoxy group, and Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, and the rest are Hydrogen; or Z 3 and Z 4 are formed , And Z 1 is a methoxy group, and the rest are hydrogen; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylaminocarbonyl, dimethylaminocarbonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylaminocarbonyl or dimethylaminocarbonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, and their predecessors Medicine, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate. 如申請專利範圍第1項的化合物，其為以下式IJ：其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(N-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基，或 （5）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基，Z2 和Z4 二者之一為氫，另一為甲基， Z3 選自：N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）異丙亞磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙亞磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IJ: Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(N-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azinyl) piperidyl, 4-(4-tert-butoxycarbonyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methylprazinyl, 4-ethylprazinyl, 4-isopropylprazinyl, 4-acetylprazinyl, 4-tert-butoxycarbonylprazinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpirazinyl)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (7) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) N-methyl-4-pyridinyl , 4-N, N-Dimethylaminopiridinyl, 4-(4-methylpiperazine)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, (4)4- Methyl piperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, the other is methoxy, one of Z 2 and Z 4 is hydrogen, the other is methyl, and Z 3 is selected from: N-methyl-4 -Pepridyl, 4-N, N-dimethylaminopyridinyl, 4-methylpyrazine, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrole-1 -Radical) pyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed ; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfinyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylsulfinyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IK：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基 （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基 （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （7）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）4-甲基呱嗪基， （4）N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 4-N, N-二甲基氨基呱啶基，或 （5）Z2 與 Z3 或Z3 與Z4 形成或； 最佳，R1選自，其中Z2 和Z4 二者之一為氫，另一為甲基，Z1 和Z5 二者之一為氫，另一為甲氧基， Z3 選自：N-甲基-4-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 4-N, N-二甲基氨基呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成或； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）二甲基次膦醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為二甲基次膦醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IK: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy (4) piperidine Group, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropyl Aminopyridinyl, 4-hydroxypyridinyl (5) 4-(4-methylpiperazinyl)pyridinyl, 4-(4-ethylpiperazinyl)pyridinyl, 4-(4- Isopropylpiperazine)piridinyl, 4-(4-acetazizinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4-methyl Sulfoprazinyl)piridinyl, 4-(4-(2-hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piperidine Group, 4-(4-(3-hydroxypropyl)pirazinyl)piridinyl, 4-(4-(2-N, N-dimethylaminoethyl)pirazinyl)piridinyl, 4 -(4-(2-N, N-Diethylaminoethyl)pirazinyl)piridinyl, 4-(4-(3-N, N-dimethylaminopropyl)pirazinyl)quat Ridinyl, 4-(4-(3-N, N-diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N -Dimethylaminotetrahydropyrrolyl) piperidinyl, (6) 4-methyl piperazinyl, 4-ethyl piperazinyl, 4-isopropyl piperazinyl, 4-acetyl piperazinyl , 4-tert-Butoxycarbonyl piperazinyl, 4-methylsulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4- (3-Hydroxypropyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl , 4-(3-N, N-Dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4 -Pyridinyl) pyrazine, 4-(N-ethyl-4-pyridinyl) pyrazine, or (7) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substitution Or an unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) 4-methylpiperazinyl, (4 ) N-Methyl-4-pyridinyl, 4-(4-methylpyrazine)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-N, N-dimethyl Aminopyridinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed or ; Best, R1 is selected from , Wherein one of Z 2 and Z 4 is hydrogen, the other is methyl, one of Z 1 and Z 5 is hydrogen, the other is methoxy, Z 3 is selected from: N-methyl-4 -Pepridyl, 4-methylpiperazinyl, 4-(4-methylpiperazinyl)pyridinyl, 4-(tetrahydropyrrol-1-yl)pyridinyl, 4-N, N-di Methylaminopyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 form or ; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) dimethylphosphinyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is dimethylphosphinyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, Its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate. 如申請專利範圍第1項的化合物，其為以下式IRS：R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基； （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基 或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(四氫吡咯-1-基)呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-二甲氨基-呱啶基； （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環； 最佳R1選自：，其中 Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫 （2）二異丙基次膦醯基，二乙基次膦醯基， 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為二異丙基次膦醯基或二乙基次膦醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the first compound in the scope of patent application is the following formula IRS: R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N- Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N-di Ethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl, 4 -N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N-iso Propyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1-( N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Piperazine) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, 4-(tetrahydro (Pyrrol-1-yl) pyridinyl, (4) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diiso Propylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethyl Aminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methyl Pyperazine group) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazine) Ethoxy, 2-( 4-acetinyl(azizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethyl Aminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3 -(4-Acetylazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy Group, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted benzene Methoxy, (7) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl , Cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylamino Pyridine-1-ylsulfonyl, 4-N, N-diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pezinyl -1-sulfonyl, 4-(2-N,N-diethylethyl)pezinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl , 4-(3-N, N-Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfon Amino group, morpholinyl-1-sulfonyl group, 3,5-dimethylmorpholinyl-1-sulfonyl group, 4-(4-methyl-piperazine-1-yl)piperidine-1- Sulfonyl, 4-(4-ethyl-1-piperazinyl)piridin-1-ylsulfonyl, 4-(4-acetyl-1-piperazinyl)piridin-1-yl Sulfonyl, 4-(N-methyl-4-pyridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso Propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethyl Aminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl -1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazine-1-ylcarbonyl, 4-ethylpiperazine-1-carbonyl, 4- Acetyl piperazinyl-1-carbonyl, 4 -Tert-Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3 -Hydroxypropyl) piperazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylamino Propyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piper Pyridin-1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl)piperidinyl-1-carbonyl, 4-(4-acetinyl-1-piperazinyl)piperidinyl-1- Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl , Isobutoxycarbonyl, tert-butoxycarbonyl, (9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylamino Carboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, pyridinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N, N-di Methylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N- Dimethylaminotetrahydropyrrolyl-1-carboxamido, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylpiperazinyl-1-carboxamido, 4-tert-butoxycarbonylpiperazinyl-1-carboxamido, 4-(2- Hydroxyethyl) piperazinyl-1-carboxamido, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-methylamino, 4-(3-hydroxypropyl) piperazinyl-1 -Formylamino, 4-(3-N, N-dimethylaminopropyl) azizinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) azizinyl -1-carboxamido, morpholino-1-carboxamido, 3,5-dimethylmorpholino-1-carboxamido, 4-(4-methyl-piperazine-1-yl)quat Pyridinyl-1-methanylamino, 4-(4-ethyl-1-pyrazineyl)pyridinyl-1-methanylamino, 4-(4-acetyl-1-pyrazineyl)piperidine Group-1-carboxamide, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carboxamido; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; preferably, R1 Selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridinyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , 4-(Tetrahydropyrrol-1-yl)piridinyl; (4) 4-methylpiperazine, 4-ethylpiperazine, 4-isopropylpiperazine, 4-acetinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-pyridinyl) piperazinyl, 4-(N-ethyl-4-piperidyl) piperazinyl or (5) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing A substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(tetrahydropyrrole-1- Group) pyridinyl, 4-methyl pyrazine, 4-(4-methyl pyrazine) pyridinyl, 4-dimethylamino-pyridinyl; (4) Z 2 and Z 3 can be formed containing Nitrogen substituted or unsubstituted five-membered ring ; The best R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methyl Pyrazinyl) pyridinyl, 4-(tetrahydropyrrol-1-yl) pyridinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen (2) diisopropylphosphinyl, diethylphosphinyl, more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, the other is diisopropylphosphinyl or diethylphosphinyl; A 2 , A 3 , and A 4 are all hydrogen; or Stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate. 如申請專利範圍第1項的化合物，其為以下式IL：其中，A為亞甲基；X為NH； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基， （3）4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基， （4）4-甲基呱嗪基，或 （5）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）甲磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為甲磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application, which is the following formula IL: Wherein, A is methylene; X is NH; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-di Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N- Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl -5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyridinyl Azolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl azizinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethyl Aminotetrahydropyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted For a five-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, 4-(4-methyl Pyrazinyl) pyridinyl, (4) 4-methylpiperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methanesulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methanesulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically An acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IM：其中，A為亞甲基；X為NH； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲氧基, （3）4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基， （4）4-甲基呱嗪基，或 （5）Z2 與 Z3 或Z3 與Z4 形成； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基；Z4 為氫； Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 形成； R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫， （2）異丙基磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IM: Wherein, A is methylene; X is NH; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-di Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N- Ethyl-4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl -5-isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyridinyl Azolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl piperazinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethyl Aminotetrahydropyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted For a five-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methoxy, (3) 4-hydroxypyridinyl, 4-(4-methyl Pyrazinyl) Pyridinyl, (4) 4-Methylpiperazinyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 4 is hydrogen; Z 3 is selected from: 4-hydroxypyridinyl, 4-methylpyrazine, 4-(4 -Methyl azizinyl) pyridinyl, or Z 2 and Z 3 form ; R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IT：其中A為亞甲基；X為O； R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4--二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基，4-(四氫吡咯-1-基)呱啶基； （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基；或 （5）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，嗎啉基，4-二甲氨基-呱啶基， （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環； 最佳，R1選自：，其中 Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-二甲氨基-呱啶基，4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基或嗎啉基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫， （2）異丙基磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為異丙基磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IT: Wherein A is methylene; X is O; R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethyl Ethylaminoethyl, 2-N, N-diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethyl Aminopropyl, 3-N, N-diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) Propyl, C3-C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl 4-pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl- 5-Isoxazolinyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazole Base; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-Dimethylaminopiridinyl, 4-N, N-diethylaminopiridinyl, 4-N, N-diisopropylaminopiridinyl, 4-hydroxypiridinyl, 4-(4 -Methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetinyl) Piperazine) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4-(2- Hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl Ridinyl, 4-(4-(2-N, N-Dimethylaminoethyl)pirazinyl)piridinyl, 4-(4-(2-N, N-diethylaminoethyl)quat Azinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-diethylamino Propyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, 4-(tetrahydro (Pyrrol-1-yl) pyridinyl, (4) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diiso Propylamino, 2-N, N-dimethylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethyl Aminopropylamino, 3-N, N-diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinopropylamino, 3-(4-methyl Pyperazine group) propylamino, N-methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2-N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazine) Ethoxy, 2-( 4-acetinyl(azizinyl)ethoxy, 2-morpholinylethoxy, 2-thiophenolinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethyl Aminopropoxy, 3-N, N-diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3 -(4-Acetylazizinyl)propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy Group, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted benzene Methoxy, (7) Hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl , Cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylamino Pyridine-1-ylsulfonyl, 4-N, N-diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethyl Aminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethyl Pyrazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-butoxycarbonylpiperazinyl-1-sulfonyl, 4-(2-hydroxyethyl )Pepazinyl-1-sulfonyl, 4-(2-cyanoethyl)piperazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pezinyl -1-sulfonyl, 4-(2-N,N-diethylethyl)pezinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl , 4-(3-N, N-Dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfon Amino group, morpholinyl-1-sulfonyl group, 3,5-dimethylmorpholinyl-1-sulfonyl group, 4-(4-methyl-piperazine-1-yl)piperidine-1- Sulfonyl, 4-(4-ethyl-1-piperazinyl)piridin-1-ylsulfonyl, 4-(4-acetyl-1-piperazinyl)piridin-1-yl Sulfonyl, 4-(N-methyl-4-pyridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso Propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethyl Aminopyridinyl-1-carbonyl, 4-N, N-diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl -1-carbonyl, 3-N, N-diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazine-1-ylcarbonyl, 4-ethylpiperazine-1-carbonyl, 4- Acetyl piperazinyl-1-carbonyl, 4 -Tert-Butoxycarbonyl piperazinyl-1-carbonyl, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4- (2-N, N-Dimethylaminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3 -Hydroxypropyl) piperazinyl-1-carbonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylamino Propyl) piperazinyl-1-carbonyl, morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-piperazin-1-yl)piper Pyridin-1-ylcarbonyl, 4-(4-ethyl-1-piperazinyl)piperidinyl-1-carbonyl, 4-(4-acetinyl-1-piperazinyl)piperidinyl-1- Carbonyl, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl , Isobutoxycarbonyl, tert-butoxycarbonyl, (9) Aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylamino Carboxamido, cyclobutylaminocarboxamido, cyclopentylaminocarboxamido, pyridinyl-1-carboxamido, 4-hydroxypiperidinyl-1-carboxamido, 4-N, N-di Methylaminopyridinyl-1-carboxamido, 4-N, N-diethylaminopiridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N- Dimethylaminotetrahydropyrrolyl-1-carboxamido, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1-carboxamido, 4-acetylpiperazinyl-1-carboxamido, 4-tert-butoxycarbonylpiperazinyl-1-carboxamido, 4-(2- Hydroxyethyl) piperazinyl-1-carboxamido, 4-(2-cyanoethyl) piperazinyl-1-carboxamido, 4-(2-N, N-dimethylaminoethyl) Piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-methylamino, 4-(3-hydroxypropyl) piperazinyl-1 -Formylamino, 4-(3-N, N-dimethylaminopropyl) azizinyl-1-methylamino, 4-(3-N, N-diethylaminopropyl) azizinyl -1-carboxamido, morpholino-1-carboxamido, 3,5-dimethylmorpholino-1-carboxamido, 4-(4-methyl-piperazine-1-yl)quat Pyridinyl-1-methanylamino, 4-(4-ethyl-1-pyrazineyl)pyridinyl-1-methanylamino, 4-(4-acetyl-1-pyrazineyl)piperidine Group-1-carboxamide, 4-(N-methyl-4-pyridinyl) piperazinyl-1-carboxamido; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing Or an oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1; preferably, R1 Selected from , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pepridyl, 4-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypiperidine Group, 4-(4-methylpiperazinyl) piperidyl, 4-(4-ethylpiperazinyl) piperidyl, 4-(4-isopropyl piperazinyl) piperidyl, 4- (4-Acetylazine group) piperidyl group, 4-(4-tert-butoxycarbonyl piperazinyl group) piperidyl group, 4-(4-methylsulfonyl piperazinyl group) piperidyl group, 4- (4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4-(3-hydroxypropyl) ) Piperidyl) Piperidyl, 4-(4-(2-N, N-Dimethylaminoethyl) Piperidyl) Piperidyl, 4-(4-(2-N, N-Diethyl Aminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrolyl)piridinyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl)piridinyl , 4-(Tetrahydropyrrol-1-yl)piridyl; (4) 4-methylpirazinyl, 4-ethylpirazinyl, 4-isopropylpirazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl; or (5) Z 2 and Z 3 or Z 3 and Z 4 form nitrogen-containing or oxygen-containing The substituted or unsubstituted five-membered ring, the substituent may be selected from the same substituents as described above as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-methylpiperazinyl, 4 -(4-Methylpyrazineyl)pyridinyl, morpholinyl, 4-dimethylamino-pyridinyl, (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-dimethylamino-pyridinyl, 4-methylpyrazine, 4-(4-methyl Pyrazinyl) pyridinyl, 4-methylpiperazinyl or morpholinyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butyl Oxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinate Group, diethylphosphinyl, diisopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) isopropylsulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is isopropylsulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IN：其中，R1選自： 1）丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷基， （3）C1-C6烷氧基， （4）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （5）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （6）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基，或 （8）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）甲基，甲氧基， （3）4-羥基呱啶基，4-甲基呱嗪基，N-甲基-4-呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，氨基磺醯基，或 （5）Z2 與 Z3 或Z3 與Z4 形成或； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z2 和Z4 二者之一為氫，另一為甲基， Z3 選自：4-羥基呱啶基，4-甲基呱嗪基，N-甲基-4-呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基， 氨基磺醯基，或 Z2 與 Z3 或Z3 與Z4 形成或； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基， 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，甲亞磺醯基，乙亞磺醯基，甲磺醯基，乙磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基； 更佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，（2）甲氧羰基； 最佳，R2選自：，其中A1 和A5 二者之一為氫，另一為甲氧羰基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application, which has the following formula IN: Wherein, R1 is selected from: 1) propylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3 -N, N-Diethylaminopropyl, 3-N, N-Diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3- C6 cycloalkyl, 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-呱Pyridinyl, N-isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazole Linyl, 1-(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkyl, (3) C1-C6 alkoxy, (4) quaker Ridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diiso Propylaminopiperdinyl, 4-hydroxypiperdinyl, (5) 4-(4-methylpiperazine)piridinyl, 4-(4-ethylpiperazine)piridinyl, 4-( 4-isopropylpiperazine)piridinyl, 4-(4-acetazinyl)piridinyl, 4-(4-tert-butoxycarbonylpiperazine)piridinyl, 4-(4 -Methanesulfonyl (quazinyl) piperidyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) Piperidinyl, 4-(4-(3-hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl , 4-(4-(2-N, N-diethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl ) Pyridinyl, 4-(4-(3-N, N-diethylaminopropyl) pyrazine) pyridinyl, 4-(tetrahydropyrrolyl) pyridinyl, 4-(3-N , N-Dimethylaminotetrahydropyrrolyl)piridinyl, (6) 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetazinyl Azinyl, 4-tert-butoxycarbonyloxazinyl, 4-methanesulfonyloxazinyl, 4-(2-hydroxyethyl)oxazinyl, 4-(2-cyanoethyl)oxazinyl, 4-(3-hydroxypropyl)prazinyl, 4-(2-N, N-dimethylaminoethyl)prazinyl, 4-(2-N, N-diethylaminoethyl)quat Azinyl, 4-(3-N, N-dimethylaminopropyl) azizinyl, 4-(3-N, N-diethylaminopropyl) azizinyl, 4-(N-methyl -4-piridinyl)pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylamino Sulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, pyridin-1-ylsulfonyl , 4-Hydroxypiperidine-1-ylsulfonyl, 4-N, N-dimethylaminopiperidine-1-ylsulfonyl, 4-N, N-diethylaminopiperidine-1-yl Sulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N, N-diethylaminotetrahydropyrrolyl -1-sulfonyl, 4-methylpiperazin-1-ylsulfonyl, 4-ethylpiperazinyl-1-sulfonyl, 4-acetazinyl-1-sulfonyl, 4-tert-Butoxycarbonyl piperazinyl-1-sulfonyl, 4-(2-hydroxyethyl) piperazinyl-1-sulfonyl, 4-(2-cyanoethyl) piperazinyl-1 -Sulfonyl, 4-(2-N, N-dimethylaminoethyl Yl)piperazinyl-1-sulfonyl, 4-(2-N,N-diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl- 1-sulfonyl, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazine 1-sulfonyl, morpholin-1-sulfonyl, 3,5-dimethylmorpholin-1-sulfonyl, 4-(4-methyl-piperazine-1-yl) Pyridine-1-yl sulfonyl, 4-(4-ethyl-1-pyrazine) pyridine-1-yl sulfonyl, 4-(4-acetinyl-1-pyrazine) quan Pyridin-1-yl sulfonyl, 4-(N-methyl-4-pyridinyl) azizinyl-1-sulfonyl, or (8) Z 2 and Z 3 or Z 3 and Z 4 form a compound containing Nitrogen or oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring, the substituent may be selected from the same substituents as Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) methyl, methoxy, (3) 4-hydroxypyridinyl, 4-methyl Piperazinyl, N-methyl-4-piperidyl, (4) 4-(4-methylpiperazinyl) piperidyl, 4-(tetrahydropyrrol-1-yl) piperidyl, amino Sulfonyl, or (5) Z 2 and Z 3 or Z 3 and Z 4 are formed or ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; one of Z 2 and Z 4 is hydrogen, the other is methyl, and Z 3 is selected from: 4-hydroxypyridinyl , 4-Methylpiperazinyl, N-methyl-4-piperidinyl, 4-(4-methylpiperazinyl)piperidinyl, 4-(tetrahydropyrrol-1-yl)piperidinyl, Aminosulfonyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed or ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, methylamino Carbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethylphosphinyl, diethylphosphinyl, two Isopropylphosphinyl, preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfinyl, ethylsulfinyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, Propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, dimethyl Phosphinyl; more preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, (2) methoxycarbonyl; most preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is methoxycarbonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above-mentioned compounds, their prodrugs, and their pharmaceutically acceptable Accepted salt or a pharmaceutically acceptable solvate thereof. 如申請專利範圍第1項的化合物，其為以下式IU：其中，R1選自： 1）C1-C6烷基，2-N, N-二甲基氨基乙基，2-羥基乙基，2-N, N-二乙基氨基乙基，2-N, N-二異丙基氨基乙基，2-嗎啉基乙基，2-(4-甲基呱嗪基)乙基，3-N, N-二甲基氨基丙基，3-N, N-二乙基氨基丙基，3-N, N-二異丙基氨基丙基，3-嗎啉基丙基，3-(4-甲基呱嗪)基丙基，C3-C6環烷基，4-N, N-二甲基氨基環己基，4-N, N-二乙基氨基環己基，N-甲基-4-呱啶基，N-乙基-4-呱啶基，N-異丙基-4-呱啶基，1, 3-二甲基-5-吡唑基，1-甲基-4-吡唑基，3-甲基-5-異噁唑啉基，1-(N-甲基-4-呱啶基)-4-吡唑基，1-(N-叔丁氧羰基-4-呱啶基)-4-吡唑基； 2），其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫，氟，氯，溴，碘，硝基，氰基， （2）C1-C6烷基，C1-C6烷氧基， C1-C6含氧烷基，C1-C6含氟烷基，C1-C6含氟烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基，4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （4）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基， （5）N, N-二甲基氨基，N, N-二乙基氨基，N, N-二異丙基氨基，2-N, N-二甲基氨基乙基氨基，2-嗎啉基乙基氨基，2-(4-甲基呱嗪基)乙基氨基，3-N, N-二甲基氨基丙基氨基，3-N, N-二乙基氨基丙基氨基，3-N, N-二異丙基氨基丙基氨基，3-嗎啉基丙基氨基，3-(4-甲基呱嗪基)丙基氨基，N-甲基呱啶-4-氨基，N-乙基呱啶-4-氨基，N-異丙基呱啶-4-氨基， （6）2-N, N-二甲基氨基乙氧基，2-N, N-二乙基氨基乙氧基，2-N, N-二異丙基氨基乙氧基，2-(4-甲基呱嗪基)乙氧基，2-(4-乙醯基呱嗪基)乙氧基，2-嗎啉基乙氧基，2-硫啡啉基乙氧基，2-呱啶基乙氧基，3-N, N-二甲基氨基丙氧基，3-N, N-二乙基氨基丙氧基，3-N, N-二異丙基氨基丙氧基，3-(4-甲基呱嗪基)丙氧基，3-(4-乙醯基呱嗪基)丙氧基，3-嗎啉基丙氧基，3-硫啡啉基丙氧基，3-呱啶基丙氧基，吡啶-2-基甲氧基，吡啶-3-基甲氧基，吡啶-4-基甲氧基，苯基甲氧基，單鹵素取代苯基甲氧基，偕二鹵素取代苯基甲氧基，雜二鹵素取代苯基甲氧基， （7）羥基磺醯基，氨基磺醯基，甲氨基磺醯基，乙氨基磺醯基，丙氨基磺醯基，異丙氨基磺醯基，環丙基氨基磺醯基，環丁基氨基磺醯基，環戊基氨基磺醯基，呱啶-1-基磺醯基，4-羥基呱啶-1-基磺醯基，4-N, N-二甲基氨基呱啶-1-基磺醯基，4-N, N-二乙基氨基呱啶-1-基磺醯基，四氫吡咯基-1-磺醯基，3-N, N-二甲基氨基四氫吡咯基-1-磺醯基，3-N, N-二乙基氨基四氫吡咯基-1-磺醯基，4-甲基呱嗪-1-基磺醯基，4-乙基呱嗪基-1-磺醯基，4-乙醯基呱嗪基-1-磺醯基，4-叔丁氧羰基呱嗪基-1-磺醯基，4-(2-羥基乙基)呱嗪基-1-磺醯基，4-(2-氰基乙基)呱嗪基-1-磺醯基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-磺醯基，4-(2-N,N-二乙基乙基)呱嗪基-1-磺醯基，4-(3-羥基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-磺醯基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-磺醯基，嗎啉基-1-磺醯基，3, 5-二甲基嗎啉基-1-磺醯基，4-(4-甲基-呱嗪-1-基)呱啶-1-基磺醯基，4-(4-乙基-1-呱嗪基)呱啶-1-基磺醯基，4-(4-乙醯基-1-呱嗪基)呱啶-1-基磺醯基，4-(N-甲基-4-呱啶基)呱嗪基-1-磺醯基， （8）羥基羰基，氨基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，呱啶基-1-羰基，4-羥基呱啶基-1-羰基，4-N, N-二甲基氨基呱啶基-1-羰基，4-N, N-二乙基氨基呱啶基-1-羰基，四氫吡咯基-1-羰基，3-N, N-二甲基氨基四氫吡咯基-1-羰基，3-N, N-二乙基氨基四氫吡咯基-1-羰基，4-甲基呱嗪-1-基羰基，4-乙基呱嗪基-1-羰基，4-乙醯基呱嗪基-1-羰基，4-叔丁氧羰基呱嗪基-1-羰基，4-(2-羥基乙基)呱嗪基-1-羰基，4-(2-氰基乙基)呱嗪基-1-羰基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-羰基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-羰基，4-(3-羥基丙基)呱嗪基-1-羰基，4-(3-N, N-二甲基氨基丙基)呱嗪基-1-羰基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-羰基，嗎啉基-1-羰基，3, 5-二甲基嗎啉基-1-羰基，4-(4-甲基-呱嗪-1-基)呱啶-1-基羰基，4-(4-乙基-1-呱嗪基)呱啶基-1-羰基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-羰基，4-(N-甲基-4-呱啶基)呱嗪基-1-羰基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基， （9）氨基甲醯氨基，甲氨基甲醯氨基，乙氨基甲醯氨基，丙氨基甲醯氨基，異丙氨基甲醯氨基，環丙基氨基甲醯氨基，環丁基氨基甲醯氨基，環戊基氨基甲醯氨基，呱啶基-1-甲醯氨基，4-羥基呱啶基-1-甲醯氨基，4-N, N-二甲基氨基呱啶基-1-甲醯氨基，4-N, N-二乙基氨基呱啶基-1-甲醯氨基，四氫吡咯基-1-甲醯氨基，3-N, N-二甲基氨基四氫吡咯基-1-甲醯氨基，3-N, N-二乙基氨基四氫吡咯基-1-甲醯氨基，4-甲基呱嗪基-1-甲醯氨基，4-乙基呱嗪基-1-甲醯氨基，4-乙醯基呱嗪基-1-甲醯氨基，4-叔丁氧羰基呱嗪基-1-甲醯氨基，4-(2-羥基乙基)呱嗪基-1-甲醯氨基，4-(2-氰基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二甲基氨基乙基)呱嗪基-1-甲醯氨基，4-(2-N, N-二乙基氨基乙基)呱嗪基-1-甲醯氨基，4-(3-羥基丙基)呱嗪基-1-甲醯氨基， 4-(3-N, N-二甲基氨基丙基)呱嗪基-1-甲醯氨基，4-(3-N, N-二乙基氨基丙基)呱嗪基-1-甲醯氨基，嗎啉基-1-甲醯氨基，3, 5-二甲基嗎啉基-1-甲醯氨基，4-(4-甲基-呱嗪-1-基)呱啶基-1-甲醯氨基，4-(4-乙基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(4-乙醯基-1-呱嗪基)呱啶基-1-甲醯氨基，4-(N-甲基-4-呱啶基)呱嗪基-1-甲醯氨基；或 （10）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環或六元環，取代基可以選自與Z1 相同的上述取代基； 較佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地選自： （1）氫， （2）C1-C6烷氧基， （3）呱啶基，N-甲基-4-呱啶基，4-N, N-二甲基氨基呱啶基，4-N, N-二乙基氨基呱啶基，4-N, N-二異丙基氨基呱啶基，4-羥基呱啶基， （4）4-(4-甲基呱嗪基)呱啶基，4-(4-乙基呱嗪基)呱啶基，4-(4-異丙基呱嗪基)呱啶基，4-(4-乙醯基呱嗪基)呱啶基，4-(4-叔丁氧羰基呱嗪基)呱啶基，4-(4-甲磺醯基呱嗪基)呱啶基，4-(4-(2-羥基乙基)呱嗪基)呱啶基，4-(4-(2-氰基乙基)呱嗪基)呱啶基，4-(4-(3-羥基丙基)呱嗪基)呱啶基，4-(4-(2-N, N-二甲基氨基乙基)呱嗪基)呱啶基，4-(4-(2-N, N-二乙基氨基乙基)呱嗪基)呱啶基，4-(4-(3-N, N-二甲基氨基丙基)呱嗪基)呱啶基，4-(4-(3-N, N-二乙基氨基丙基)呱嗪基)呱啶基，4-(四氫吡咯-1-基)呱啶基，4-(3-N, N-二甲基氨基四氫吡咯基)呱啶基， （5）4-甲基呱嗪基，4-乙基呱嗪基，4-異丙基呱嗪基，4-乙醯基呱嗪基，4-叔丁氧羰基呱嗪基，4-甲磺醯基呱嗪基，4-(2-羥基乙基)呱嗪基，4-(2-氰基乙基)呱嗪基，4-(3-羥基丙基)呱嗪基，4-(2-N, N-二甲基氨基乙基)呱嗪基，4-(2-N, N-二乙基氨基乙基)呱嗪基，4-(3-N, N-二甲基氨基丙基)呱嗪基，4-(3-N, N-二乙基氨基丙基)呱嗪基，4-(N-甲基-4-呱啶基)呱嗪基，4-(N-乙基-4-呱啶基)呱嗪基，或 （6）Z2 與 Z3 或Z3 與Z4 形成含氮或含氧的取代或未取代的五元環，取代基可以選自與Z1 相同的上述取代基； 更佳，R1選自：，其中Z1 ，Z2 ，Z3 ，Z4 ，Z5 各自獨立地任選自： （1）氫， （2）C1-C6烷氧基， （3）4-(4-甲基呱嗪基)呱啶基，4-甲基呱嗪基， （4）Z2 與 Z3 可以形成含氮的取代或未取代的五元環； 最佳，R1選自：，其中Z1 和Z5 二者之一為氫，另一為甲氧基； Z3 選自：4-甲基呱嗪基，4-(4-甲基呱嗪基)呱啶基，或 Z2 與 Z3 或Z3 與Z4 形成； R2選自，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地選自： （1）氫，氟，氯，溴，碘，氰基，三氟甲基，三氟甲氧基，硝基， （2）甲硫基，乙硫基，異丙硫基，甲亞磺醯基，乙亞磺醯基，異丙亞磺醯基，甲磺醯基，乙磺醯基，異丙基磺醯基，叔丁磺醯基，二甲氨基磺醯基，甲磺醯氨基，甲氧基羰基，乙氧基羰基，丙氧基羰基，異丙氧基羰基，正丁氧基羰基，異丁氧基羰基，叔丁氧基羰基，甲氨基羰基，乙氨基羰基，丙氨基羰基，異丙氨基羰基，二甲氨基羰基，環丙基氨基羰基，環丁基氨基羰基，環戊基氨基羰基，二甲基次膦醯基，二乙基次膦醯基，二異丙基次膦醯基； 較佳，R2選自：，其中A1 ，A2 ，A3 ，A4 ，A5 各自獨立地任選自： （1）氫 （2）二甲氨基磺醯基； 更佳，R2選自：，其中A1 和A5 二者之一為氫，另一為二甲氨基磺醯基；A2 ，A3 ，A4 都為氫； 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。For example, the compound of item 1 in the scope of patent application is the following formula IU: Wherein, R1 is selected from: 1) C1-C6 alkyl, 2-N, N-dimethylaminoethyl, 2-hydroxyethyl, 2-N, N-diethylaminoethyl, 2-N, N-Diisopropylaminoethyl, 2-morpholinoethyl, 2-(4-methylpiperazinyl)ethyl, 3-N, N-dimethylaminopropyl, 3-N, N -Diethylaminopropyl, 3-N, N-diisopropylaminopropyl, 3-morpholinopropyl, 3-(4-methylpiperazine) propyl, C3-C6 cycloalkyl , 4-N, N-dimethylaminocyclohexyl, 4-N, N-diethylaminocyclohexyl, N-methyl-4-pyridinyl, N-ethyl-4-pyridinyl, N -Isopropyl-4-pyridinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1 -(N-methyl-4-pyridinyl)-4-pyrazolyl, 1-(N-tert-butoxycarbonyl-4-pyridinyl)-4-pyrazolyl; 2) , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, (3) pyridinyl, N-methyl-4-pyridinyl, 4-N, N-dimethylaminopyridinyl, 4-N, N-diethylaminopyridinyl, 4-N, N-diisopropylaminopyridinyl, 4-hydroxypyridinyl, 4-(4-Methylpiperazinyl)piperidyl, 4-(4-ethylpiperazinyl)piperidyl, 4-(4-isopropylpiperazinyl)piperidyl, 4-(4 -Acetyl (azizinyl) piperidyl, 4-(4-tert-butoxycarbonyl piperazinyl) piperidyl, 4-(4-methylsulfonyl piperazinyl) piperidyl, 4-(4 -(2-Hydroxyethyl)pirazinyl)piridinyl, 4-(4-(2-cyanoethyl)pirazinyl)piridinyl, 4-(4-(3-hydroxypropyl)piridyl Azinyl) piperidinyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidinyl, 4-(4-(2-N, N-diethylamino Ethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4-(3-N, N- Diethylaminopropyl) piperazinyl) piperidyl, 4-(tetrahydropyrrolyl) piperidyl, 4-(3-N, N-dimethylaminotetrahydropyrrolyl) piperidyl, ( 4) 4-Methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert-butoxycarbonyl azizinyl, 4-methanesulfonyl Aminoxazinyl, 4-(2-hydroxyethyl)xazinyl, 4-(2-cyanoethyl)xazinyl, 4-(3-hydroxypropyl)xazinyl, 4-(2 -N, N-Dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-(3-N, N-dimethylaminopropyl Group) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl) piperazinyl, 4-(N-ethyl 4-pyridinyl) piperazinyl, (5) N, N-dimethylamino, N, N-diethylamino, N, N-diisopropylamino, 2-N, N-di Methylaminoethylamino, 2-morpholinoethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N, N-dimethylaminopropylamino, 3-N, N -Diethylaminopropylamino, 3-N, N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N- Methylpiperidine-4-amino, N-ethylpiperidine-4-amino, N-isopropylpiperidine-4-amino, (6) 2-N, N-dimethylaminoethoxy, 2 -N, N-diethylaminoethoxy, 2-N, N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-ethoxy) Pyrazinyl) ethoxy Ethoxy, 2-morpholinylethoxy, 2-thiophenrinylethoxy, 2-pyridinylethoxy, 3-N, N-dimethylaminopropoxy, 3-N, N- Diethylaminopropoxy, 3-N, N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl) Propoxy, 3-morpholinylpropoxy, 3-thiophenrinylpropoxy, 3-pyridinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, Pyridin-4-ylmethoxy, phenylmethoxy, monohalogen substituted phenylmethoxy, geminal dihalogen substituted phenylmethoxy, heterodihalogen substituted phenylmethoxy, (7) hydroxysulfonate Group, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentyl Aminosulfonyl, pyridin-1-ylsulfonyl, 4-hydroxypyridin-1-ylsulfonyl, 4-N, N-dimethylaminopyridin-1-ylsulfonyl, 4 -N, N-Diethylaminopyridine-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-sulfonyl , 3-N, N-Diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazine-1-ylsulfonyl, 4-ethylpiperazine-1-sulfonyl, 4-acetylazinyl-1-sulfonyl, 4-tert-butoxycarbonylazinyl-1-sulfonyl, 4-(2-hydroxyethyl)piperazinyl-1-sulfonyl, 4-(2-Cyanoethyl)pirazinyl-1-sulfonyl, 4-(2-N, N-dimethylaminoethyl)pirazinyl-1-sulfonyl, 4-(2 -N,N-Diethylethyl)piperazinyl-1-sulfonyl, 4-(3-hydroxypropyl)piperazinyl-1-sulfonyl, 4-(3-N, N-di Methylaminopropyl) piperazinyl-1-sulfonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-sulfonyl, morpholinyl-1-sulfonyl Group, 3, 5-dimethylmorpholinyl-1-sulfonyl, 4-(4-methyl-piperazine-1-yl)piridin-1-ylsulfonyl, 4-(4-ethyl Pyridine-1-ylsulfonyl) piperidin-1-ylsulfonyl, 4-(4-acetin-1-ylsulfonyl)piperidin-1-ylsulfonyl, 4-(N-methyl -4-piridinyl)pirazinyl-1-sulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, ring Butylaminocarbonyl, cyclopentylaminocarbonyl, pyridinyl-1-carbonyl, 4-hydroxypyridinyl-1-carbonyl, 4-N, N-dimethylaminopyridinyl-1-carbonyl, 4- N, N-Diethylaminopyridinyl-1-carbonyl, tetrahydropyrrolyl-1-carbonyl, 3-N, N-dimethylaminotetrahydropyrrolyl-1-carbonyl, 3-N, N- Diethylaminotetrahydropyrrolyl-1-carbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-ethylpiperazinyl-1-carbonyl, 4-acetylpiperazinyl-1-carbonyl, 4-tert-Butoxycarbonyl piperazinyl-1 -Carbonyl group, 4-(2-hydroxyethyl) piperazinyl-1-carbonyl, 4-(2-cyanoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-dimethyl Aminoethyl) piperazinyl-1-carbonyl, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carbonyl, 4-(3-hydroxypropyl) piperazinyl-1 -Carbonyl group, 4-(3-N, N-dimethylaminopropyl) piperazinyl-1-carbonyl, 4-(3-N, N-diethylaminopropyl) piperazinyl-1-carbonyl , Morpholinyl-1-carbonyl, 3,5-dimethylmorpholinyl-1-carbonyl, 4-(4-methyl-pazine-1-yl)peridine-1-ylcarbonyl, 4-( 4-Ethyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(4-acetyl-1-piperazinyl) piperidyl-1-carbonyl, 4-(N-methyl- 4-(pyridinyl) piperazinyl-1-carbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxy Carbonyl group, (9) aminomethylamino, methylaminomethylamino, ethylaminomethylamino, propylaminomethylamino, isopropylaminomethylamino, cyclopropylaminomethylamino, cyclobutylaminomethyl Amino, cyclopentylaminomethylamino, pyridinyl-1-methylamino, 4-hydroxypyridinyl-1-methylamino, 4-N, N-dimethylaminopyridinyl-1-methyl Amino, 4-N, N-diethylaminopyridinyl-1-carboxamido, tetrahydropyrrolyl-1-carboxamido, 3-N, N-dimethylaminotetrahydropyrrolyl-1 -Carboxamide, 3-N, N-diethylaminotetrahydropyrrolyl-1-carboxamido, 4-methylpiperazinyl-1-carboxamido, 4-ethylpiperazinyl-1- Formylamino, 4-acetazinyl-1-formazinyl, 4-tert-butoxycarbonylazinyl-1-formazinyl, 4-(2-hydroxyethyl)azinyl-1- Formylamino, 4-(2-cyanoethyl) piperazinyl-1-methylamino, 4-(2-N, N-dimethylaminoethyl) piperazinyl-1-methylamino, 4-(2-N, N-diethylaminoethyl) piperazinyl-1-carboxamido, 4-(3-hydroxypropyl) piperazinyl-1-carboxamido, 4-(3- N, N-Dimethylaminopropyl)pirazinyl-1-carboxamido, 4-(3-N, N-diethylaminopropyl)pirazinyl-1-carboxamido, morpholinyl -1-methylamino, 3,5-dimethylmorpholinyl-1-methylamino, 4-(4-methyl-piperazin-1-yl)piridinyl-1-methylamino, 4 -(4-Ethyl-1-pirazinyl)piridinyl-1-carboxamido, 4-(4-acetinyl-1-pirazinyl)piridinyl-1-carboxamido, 4- (N-methyl-4-pyridinyl) piperazinyl-1-methylamino; or (10) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted five -Membered ring or six-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) pyridinyl, N-methyl-4 -Pyridinyl, 4-N, N-dimethylamino pyridinyl, 4-N, N-diethylamino pyridinyl, 4-N, N-diisopropylamino pyridinyl, 4- Hydroxypiperidine, (4) 4-(4-methylpiperazine), 4-(4-ethylpiperazine), 4-(4-isopropylpiperazine) Peridinyl, 4-(4-acetylazizinyl) pyridinyl, 4-(4-tert-butoxycarbonyloxazinyl) pyridinyl, 4-(4-methylsulfonyl azizinyl) Piperidinyl, 4-(4-(2-hydroxyethyl) piperazinyl) piperidyl, 4-(4-(2-cyanoethyl) piperazinyl) piperidyl, 4-(4- (3-Hydroxypropyl) piperazinyl) piperidyl, 4-(4-(2-N, N-dimethylaminoethyl) piperazinyl) piperidyl, 4-(4-(2- N, N-Diethylaminoethyl) piperazinyl) piperidyl, 4-(4-(3-N, N-dimethylaminopropyl) piperazinyl) piperidyl, 4-(4 -(3-N, N-Diethylaminopropyl)pirazinyl)piridinyl, 4-(tetrahydropyrrol-1-yl)piridinyl, 4-(3-N, N-dimethyl Aminotetrahydropyrrolyl) pyridinyl, (5) 4-methyl azizinyl, 4-ethyl azizinyl, 4-isopropyl azizinyl, 4-acetyl azizinyl, 4-tert Butoxycarbonyl piperazinyl, 4-methanesulfonyl piperazinyl, 4-(2-hydroxyethyl) piperazinyl, 4-(2-cyanoethyl) piperazinyl, 4-(3-hydroxyl Propyl) piperazinyl, 4-(2-N, N-dimethylaminoethyl) piperazinyl, 4-(2-N, N-diethylaminoethyl) piperazinyl, 4-( 3-N, N-dimethylaminopropyl) piperazinyl, 4-(3-N, N-diethylaminopropyl) piperazinyl, 4-(N-methyl-4-piperidyl ) Pirazinyl, 4-(N-ethyl-4-piridinyl)pirazinyl, or (6) Z 2 and Z 3 or Z 3 and Z 4 form a nitrogen-containing or oxygen-containing substituted or unsubstituted For a five-membered ring, the substituent may be selected from the same substituents as described above for Z 1 ; more preferably, R1 is selected from: , Wherein Z 1 , Z 2 , Z 3 , Z 4 , and Z 5 are each independently selected from: (1) hydrogen, (2) C1-C6 alkoxy, (3) 4-(4-methylpiperazine) (4) Z 2 and Z 3 can form a nitrogen-containing substituted or unsubstituted five-membered ring ; Best, R1 is selected from: , Wherein one of Z 1 and Z 5 is hydrogen, and the other is methoxy; Z 3 is selected from: 4-methylpiperazinyl, 4-(4-methylpiperazinyl)piperidyl, or Z 2 and Z 3 or Z 3 and Z 4 are formed ; R2 is selected from , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, trifluoromethoxy, nitro (2) Methylthio, ethylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl, methylsulfinyl, ethylsulfinyl, isopropyl Sulfonyl, tert-butylsulfonyl, dimethylaminosulfonyl, methylsulfonylamino, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, iso Butoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl , Dimethylphosphinyl, diethylphosphinyl, diisopropylphosphinyl; preferably, R2 is selected from: , Wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected from: (1) hydrogen (2) dimethylaminosulfonyl; more preferably, R2 is selected from: , Wherein one of A 1 and A 5 is hydrogen, and the other is dimethylaminosulfonyl; A 2 , A 3 , and A 4 are all hydrogen; or the stereoisomers of the above compounds, their prodrugs, and their A pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof. 前述申請專利範圍中的任一項所述的化合物，其中，含氮或含氧的取代或未取代的五元環或六元環指的是5-或6-元飽和或部分不飽和碳環，其中一或複數碳原子被雜原子氮、氧替代；較佳含氮或含氧的取代或未取代的五元環或六元環選自吡咯烷、吡咯啉、吡咯、咪唑啉、咪唑烷、咪唑、吡唑烷、吡唑啉、吡唑、二氫呋喃、四氫呋喃、呋喃、1,3-二氧戊環、噁唑、二氫噁唑；吡啶、吡嗪、嘧啶、噠嗪、吡喃、呱啶、呱嗪、嗎啉。The compound according to any one of the aforementioned patent applications, wherein the nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered ring or six-membered ring refers to a 5- or 6-membered saturated or partially unsaturated carbocyclic ring , Wherein one or more carbon atoms are replaced by heteroatoms nitrogen and oxygen; preferably nitrogen-containing or oxygen-containing substituted or unsubstituted five-membered or six-membered rings are selected from pyrrolidine, pyrroline, pyrrole, imidazoline, imidazolidine , Imidazole, pyrazolidine, pyrazoline, pyrazole, dihydrofuran, tetrahydrofuran, furan, 1,3-dioxolane, oxazole, dihydrooxazole; pyridine, pyrazine, pyrimidine, pyridazine, pyridine Pyridine, pyridine, pyrazine, morpholine. 如申請專利範圍第3項至第22項中任一項的化合物，其中，該藥學上可接受的鹽為無機酸鹽或有機酸鹽，其中，該無機酸鹽為鹽酸鹽、氫溴酸鹽、氫碘酸鹽、硝酸鹽、碳酸氫鹽和碳酸鹽、硫酸鹽或磷酸鹽，該有機酸鹽為甲酸鹽、乙酸鹽、丙酸鹽、苯甲酸鹽、馬來酸鹽、富馬酸鹽、琥珀酸鹽、酒石酸鹽、檸檬酸鹽、抗壞血酸鹽、α-酮戊二酸鹽、三氟乙酸鹽、α-甘油磷酸鹽、烷基磺酸鹽或芳基磺酸鹽；較佳地，該烷基磺酸鹽為甲基磺酸鹽或乙基磺酸鹽；該芳基磺酸鹽為苯磺酸鹽或對甲苯磺酸鹽。For example, the compound of any one of items 3 to 22 in the scope of the patent application, wherein the pharmaceutically acceptable salt is an inorganic acid salt or an organic acid salt, wherein the inorganic acid salt is hydrochloride, hydrobromic acid Salt, hydroiodide, nitrate, bicarbonate and carbonate, sulfate or phosphate, the organic acid salt is formate, acetate, propionate, benzoate, maleate, rich Maleate, succinate, tartrate, citrate, ascorbate, α-ketoglutarate, trifluoroacetate, α-glycerophosphate, alkyl sulfonate or aryl sulfonate; more Preferably, the alkyl sulfonate is methane sulfonate or ethyl sulfonate; the aryl sulfonate is benzene sulfonate or p-toluene sulfonate. 如申請專利範圍第1項至第23項任一項所述的化合物，選自以下： 或上述化合物的立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物。The compound described in any one of items 1 to 23 in the scope of the patent application is selected from the following: Or the stereoisomers of the above-mentioned compounds, their prodrugs, their pharmaceutically acceptable salts or their pharmaceutically acceptable solvates. 製備申請專利範圍第1項至第24項任一項所述的化合物的方法，包括下面步驟： 1）該反應的起始原料可以市購得到； 2）反應條件：（a）鹼性條件（如二異丙基乙基胺，三乙胺，碳酸鉀等）或酸性條件（三氟乙酸，鹽酸等）的取代反應；（b）酸性條件（三氟乙酸，鹽酸等）或鈀催化的胺化反應。The method for preparing the compound described in any one of items 1 to 24 of the scope of patent application includes the following steps: 1) The starting materials for this reaction are commercially available; 2) Reaction conditions: (a) Alkaline conditions (such as diisopropylethylamine, triethylamine, potassium carbonate, etc.) or acidic conditions (trifluoroacetic acid, hydrochloric acid, etc.) substitution reaction; (b) Acidic conditions (trifluoro Acetic acid, hydrochloric acid, etc.) or palladium catalyzed amination reaction. 藥物組合物，其包含申請專利範圍第1項至第24項中任一項的化合物或其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物以及任選的藥學上可以接受的賦形劑。A pharmaceutical composition comprising the compound or its stereoisomer, its prodrug, its pharmaceutically acceptable salt, or its pharmaceutically acceptable solvate according to any one of items 1 to 24 of the scope of patent application And optional pharmaceutically acceptable excipients. 如申請專利範圍第1項至第24項中任一項的化合物或其立體異構體、其前藥、其藥學上可接受的鹽或其藥學上可接受的溶劑合物或者申請專利範圍第21項所述的藥物組合物在製備用於以下的藥物中的用途：預防或治療與生物體內漸變性淋巴瘤酶相關的伴隨細胞異常增殖、形態變化以及運動功能亢進等的疾病，預防或治療與血管新生或癌轉移相關的疾病，尤其是用於預防或治療腫瘤生長與轉移；較佳該腫瘤為漸變性大細胞淋巴瘤、炎性肌纖維母細胞瘤、非小細胞肺癌、成神經母細胞瘤、小細胞肺癌、肺腺癌、胰腺癌、乳腺癌、前列腺癌、肝癌、皮膚癌、上皮細胞癌、胃腸間質瘤、白血病、組織細胞性淋巴瘤、鼻咽癌中的任意一種；更佳地，其中該腫瘤為漸變性大細胞淋巴瘤、炎性肌纖維母細胞瘤、非小細胞肺癌或成神經母細胞瘤。For example, the compound or its stereoisomer, its prodrug, its pharmaceutically acceptable salt or its pharmaceutically acceptable solvate or the compound or its stereoisomers, or its pharmaceutically acceptable solvate in any one of the scope of patent application or the scope of patent application The use of the pharmaceutical composition described in item 21 in the preparation of the following medicines: prevention or treatment of diseases associated with gradual lymphoma enzymes in organisms accompanied by abnormal cell proliferation, morphological changes, and hyperkinesia, prevention or treatment Diseases related to angiogenesis or cancer metastasis, especially for the prevention or treatment of tumor growth and metastasis; preferably, the tumor is gradual large cell lymphoma, inflammatory myofibroblastoma, non-small cell lung cancer, neuroblastoma Any of tumor, small cell lung cancer, lung adenocarcinoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, skin cancer, epithelial cell carcinoma, gastrointestinal stromal tumor, leukemia, histiocytic lymphoma, nasopharyngeal carcinoma; more Preferably, the tumor is gradual large cell lymphoma, inflammatory myofibroblastoma, non-small cell lung cancer or neuroblastoma.
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