CN102333568A - 药物化合物 - Google Patents
药物化合物 Download PDFInfo
- Publication number
- CN102333568A CN102333568A CN2009801574496A CN200980157449A CN102333568A CN 102333568 A CN102333568 A CN 102333568A CN 2009801574496 A CN2009801574496 A CN 2009801574496A CN 200980157449 A CN200980157449 A CN 200980157449A CN 102333568 A CN102333568 A CN 102333568A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- heterocyclic radical
- aryl
- heteroaryl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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Abstract
本发明涉及用于抑制脂肪酸酰胺水解酶(FAAH)的化合物和组合物,所述化合物在治疗中,特别是用于治疗或预防其发生或症状与FAAH酶底物有关的病症中的用途,以及使用所述化合物和组合物的治疗或预防方法。
Description
本发明涉及化合物及其用途,具体而言涉及化合物及其在治疗或预防与底物有关的病症中的治疗用途,所述底物例如神经递质花生四烯酸乙醇胺,其被脂肪酸酰胺水解酶(FAAH)分解。
FAAH酶可分解脂肪酸酰胺例如花生四烯酸乙醇胺(N-花生四烯酰乙醇胺)、N-油酰乙醇胺、N-棕榈酰乙醇胺和油酸酰胺。花生四烯酸乙醇胺——也称作N-花生四烯酰乙醇胺或AEA——是一种存在于动物和人器官中(尤其是脑中)的内源性大麻素神经递质。还发现花生四烯酸乙醇胺可结合辣椒素受体。花生四烯酸乙醇胺可通过脂肪酸酰胺水解酶(FAAH)降解为乙醇胺和花生四烯酸。因此,FAAH抑制剂可导致花生四烯酸乙醇胺水平升高。
花生四烯酸乙醇胺是内源性大麻素系统中的神经递质,并且可刺激大麻素受体。大麻素受体——例如CB1和CB2——是G蛋白偶联受体。CB1主要存在于中枢神经系统中,而CB2主要存在于周围组织中。内源性大麻素系统已参与越来越多的生理功能,既在中枢和外周神经系统也在外周器官中。已表明内源性大麻素系统的活性调节对大范围的不同疾病和病理症状具有潜在的治疗作用。因此,内源性大麻素系统,特别是FAAH酶,已成为用于对许多疾病开发潜在治疗的治疗靶标。内源性大麻素系统已经参与食欲调节、肥胖症、代谢紊乱、恶病质、厌食症、疼痛、炎症、神经毒性、神经外伤、中风、多发性硬化症、脊髓损伤、帕金森氏病(Parkinson’sdisease)、左旋多巴诱导的运动障碍、亨丁顿疾病(Huntington’s disease)、Gilles de la Tourette’s综合征、迟发性运动障碍、张力障碍、肌萎缩性侧索硬化症、阿尔茨海默病(Alzheimer’s disease)、癫痫症、精神分裂症、焦虑症、抑郁症、失眠症、恶心、呕吐、酗酒恶习、药物成瘾(例如阿片、烟碱、可卡因、酒精和精神兴奋剂)、高血压、循环休克、心肌再灌性损伤、动脉粥样硬化、哮喘、青光眼、视网膜病、癌症、炎性肠病、急性和慢性肝病例如肝炎和肝硬化、关节炎和骨质疏松症。内源性大麻素系统和其相关病症的详述见Pacher et al.(2006)Pharmacol.Rev.58:389-462。
为了调节内源性FAAH底物例如花生四烯酸乙醇胺的水平——其又调节内源性大麻素系统,已开发出FAAH酶的抑制剂。这使得与内源性大麻素系统有关的病症和疾病至少部分地被治疗或预防。
因为FAAH的底物可结合于其他受体(例如辣椒素受体),并且/或者参与其他信号传递通路,FAAH的抑制剂还使得与其他通路或系统(例如辣椒素系统)有关的病症或疾病至少部分地被治疗或预防。
FR 2915198和FR 2915199公开了可为FAAH抑制剂的化合物。
US 7,208,504和FR 2915197也公开了与FR 2915198和FR 2915199中公开的那些化合物无异的一系列化合物。这些化合物被公开为分别适合用于抑制激素敏感性脂肪酶(HSL)和单酰基甘油脂肪酶(MAGL)。然而,这些化合物未被公开为适合用于抑制FAAH。
WO 2009/117444公开了可为FAAH和MAGL二者的抑制剂的化合物。
根据本发明的第一方面,提供一种式I或式II的化合物:
其中:
R1和R2可各自独立地选自H、C1-20烷基、C1-6烷氧基、芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、R1a、卤素、OH、OR1a、OCOR1a、SH、SR1a、SCOR1a、NH2、NHR1a、NHSO2NH2、NHSO2R1a、NR1aCOR1b、NHCOR1a、NR1aR1b、COR1a、CSR1a、CN、COOH、COOR1a、CONH2、CONHOH、CONHR1a、CONHOR1a、SO2R1a、SO3H、SO2NH2、CONR1aR1b、SO2NR1aR1b,其中R1a和R1b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1a和R1b可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2为C1-20烷基、烷氧基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、C1-6烷基、C3-8环烷基或者为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1c、卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-10烷基、OH、OR1c、OCOR1c、SH、SR1c、SCOR1c、NH2、NO2、NHR1c、NHSO2NH2、NHSO2R1c、NR1cCOR1d、NHC(NH)NH2、NHCOR1c、NR1cR1d、COR1c、CSR1c、CN、COOH、COOR1c、CONH2、CONHOH、CONHR1c、CONHOR1c、C(NOH)NH2、CONR1cR1d、SO2R1c、SO3H、SO2NH2、SO2NR1cR1d,其中R1c和R1d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1c和R1d可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-6烷基、C3-8环烷基或者为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1e、卤素、C1-10烷基、OH、OR1e、OCOR1e、SH、SR1e、SCOR1e、NH2、NO2、NHR1e、NHSO2NH2、NHSO2R1e、NR1eCOR1f、NHC(NH)NH2、NHCOR1e、NR1eR1f、COR1e、CSR1e、CN、COOH、COOR1e、CONH2、CONHOH、CONHR1e、CONHOR1e、C(NOH)NH2、CONR1eR1f、SO2R1e、SO3H、SO2NH2、SO2NR1eR1f,其中R1e和R1f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1e和R1f可与其所连接的杂原子一起形成杂环基,
不包括R1和R2均为H或均为未取代的甲基,
或者
R1和R2可与其所连接的N一起形成杂芳基或杂环基基团,所述基团中每一个可任选被一个或多个氧原子或一个或多个选自以下的基团取代:芳基、杂芳基、部分或完全饱和的杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R2a、卤素、OH、OR2a、OCOR2a、SH、SR2a、SCOR2a、NH2、NO2、NHR2a、NHSO2NH2、NHSO2R2a、NR2aCOR2b、NHC(NH)NH2、NHCOR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、CONHOH、CONHR2a、CONHOR2a、C(NOH)NH2、CONR2aR2b、SO2R2a、SO3H、SO2NH2、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2a和R2b可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基为芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基,或者为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、羟基、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-6烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基、R2c、OR2c、OCOR2c、SH、SR2c、SCOR2c、NH2、NO2、NHR2c、NHSO2NH2、NHSO2R2c、NR2cCOR2d、NHC(NH)NH2、NHCOR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、CONHOH、CONHR2c、CONHOR2c、C(NOH)NH2、CONR2cR2d、SO2R2c、SO3H、SO2NH2、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基为C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基,或者为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:C1-4烷氧基、R2e、卤素、OH、OR2e、OCOR2e、SH、SR2e、SCOR2e、NH2、NO2、NHR2e、NHSO2NH2、NHSO2R2e、NR2eCOR2f、NHC(NH)NH2、NR2eR2f、NHCOR2e、COR2e、CSR2e、CN、COOH、COOR2e、CONH2、CONHOH、CONHR2e、CONHOR2e、C(NOH)NH2、CONR2eR2f、SO2R2e、SO3H、SO2NH2、SO2NR2eR2f,其中R2e和R2f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2e和R2f可与其所连接的杂原子一起形成杂环基;
环A选自芳基、杂芳基和杂环基部分,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、Ra、C1-10烷基、OH、ORa、OCORa、SH、SRa、SCORa、NH2、NO2、NHRa、NHSO2NH2、NHSO2Ra、NRaCORb、NHCORa、NHC(NH)NH2、NRaRb、CORa、CSRa、CN、COOH、COORa、CONH2、CONHRa、CONHOH、CONHORa、C(NOH)NH2、CONRaRb、SO2Ra、SO3H、SO2NH2、SO2NRaRb,其中Ra和Rb独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Ra和Rb可与其所连接的杂原子一起形成杂环基,
其中,当环A被C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-10烷基、C3-8环烷基取代或被含一个或多个所述部分的基团取代时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、Rc、C1-10烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、OH、ORc、OCORc、SH、SRc、SCORc、NH2、NO2、NHRc、NHSO2NH2、NHSO2Rc、NRcCORd、NHCORc、NHC(NH)NH2、NRcRd、CORc、CSRc、CN、COOH、COORc、CONH2、CONHOH、CONHRc、CONHORc、C(NOH)NH2、CONRcRd、SO2Rc、SO3H、SO2NH2、SO2NRcRd,其中Rc和Rd独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Rc和Rd可与其所连接的杂原子一起形成杂环基;
V可为N、CH或C-R3,其中R3为卤素、C1-10烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3a、OH、OR3a、SH、SR3a、OCOR3a、SCOR3a、NH2、NO2、NHR3a、NHSO2NH2、NHSO2R3a、NR3aCOR3b、NHCOR3a、NHC(NH)NH2、NR3aR3b、COR3a、CSR3a、CN、COOH、COOR3a、CONH2、CONHOH、CONHR3a、CONHOR3a、C(NOH)NH2、CONR3aR3b、SO2R3a、SO3H、SO2NH2、SO2NR3aR3b,其中R3a和R3b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3a和R3b可与其所连接的杂原子一起形成杂环基,
其中,当R3为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选地由选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3c、C1-10烷基、OH、OR3c、OCOR3c、SH、SR3c、SCOR3c、NH2、NO2、NHR3c、NHSO2NH2、NHSO2R3c、NR3cCOR3d、NHCOR3c、NHC(NH)NH2、NR3cR3d、COR3c、CSR3c、CN、COOH、COOR3c、CONH2、CONHOH、CONHR3c、CONHOR3c、C(NOH)NH2、CONR3cR3d、SO2R3c、SO3H、SO2NH2、SO2NR3cR3d,其中R3c和R3d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3c和R3d可与其所连接的杂原子一起形成杂环基,
其中,当R3的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R3e、C1-10烷基、OH、OR3e、OCOR3e、SH、SR3e、SCOR3e、NH2、NO2、NHR3e、NHSO2NH2、NHSO2R3e、NR3eCOR3f、NHCOR3e、NHC(NH)NH2、NR3eR3f、COR3e、CSR3e、CN、COOH、COOR3e、CONH2、CONHOH、CONHR3e、CONHOR3e、C(NOH)NH2、CONR3eR3f、SO2R3e、SO3H、SO2NH2、SO2NR3eR3f,其中R3e和R3f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3e和R3f可与其所连接的杂原子一起形成杂环基;
W可为N、CH或C-R4,其中R4为卤素、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基、R4a、OH、OR4a、SH、SR4a、OCOR4a、SCOR4a、NH2、NO2、NHR4a、NHSO2NH2、NHSO2R4a、NR4aCOR4b、NHCOR4a、NHC(NH)NH2、NR4aR4b、COR4a、CSR4a、CN、COOH、COOR4a、CONH2、CONHOH、CONHR4a、CONHOR4a、C(NOH)NH2、CONR4aR4b、SO2R4a、SO3H、SO2NH2、SO2NR4aR4b,其中R4a和R4b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4a和R4b可与其所连接的杂原子一起形成杂环基,
其中,当R4为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R4c、C1-10烷基、OH、OR4c、OCOR4c、SH、SR4c、SCOR4c、NH2、NO2、NHR4c、NHSO2NH2、NHSO2R4c、NR4cCOR4d、NHCOR4c、NHC(NH)NH2、NR4cR4d、COR4c、CSR4c、CN、COOH、COOR4c、CONH2、CONHOH、CONHR4c、CONHOR4c、C(NOH)NH2、CONR4cR4d、SO2R4c、SO3H、SO2NH2、SO2NR4cR4d,其中R4c和R4d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4c和R4d可与其所连接的杂原子一起形成杂环基,
其中,当R4的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R4e、C1-10烷基、OH、OR4e、OCOR4e、SH、SR4e、SCOR4e、NH2、NO2、NHR4e、NHSO2NH2、NHSO2R4e、NR4eCOR4f、NHCOR4e、NHC(NH)NH2、NR4eR4f、COR4e、CSR4e、CN、COOH、COOR4e、CONH2、CONHOH、CONHR4e、CONHOR4e、C(NOH)NH2、CONR4eR4f、SO2R4e、SO3H、SO2NH2、SO2NR4eR4f,其中R4e和R4f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或R4e和R4f可与其所连接的杂原子一起形成杂环基;
R5可与其所连接的环碳原子一起形成羰基基团,其所连接的式II的环中的双键相应地重排和/或饱和,或者R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHCOR5a、NHC(NH)NH2、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、CONR5aR5b、SO2R5a、SO3H、SO2NH2、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基,
其中,当R5为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5c、C1-6烷基、OH、OR5c、OCOR5c、SH、SR5c、SCOR5c、NH2、NO2、NHR5c、NHSO2NH2、NHSO2R5c、NR5cCOR5d、NHCOR5c、NHC(NH)NH2、NR5cR5d、COR5c、CSR5c、CN、COOH、COOR5c、CONH2、CONHOH、CONHR5c、CONHOR5c、C(NOH)NH2、CONR5cR5d、SO2R5c、SO3H、SO2NH2、SO2NR5cR5d,其中R5c和R5d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或R5c和R5d可与其所连接的杂原子一起形成杂环基,
其中,当R5的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R5e、C1-6烷基、OH、OR5e、OCOR5e、SH、SR5e、SCOR5e、NH2、NO2、NHR5e、NHSO2NH2、NHSO2R5e、NR5eCOR5f、NHCOR5e、NHC(NH)NH2、NR5eR5f、COR5e、CSR5e、CN、COOH、COOR5e、CONH2、CONHOH、CONHR5e、CONHOR5e、C(NOH)NH2、CONR5eR5f、SO2R5e、SO3H、SO2NH2、SO2NR5eR5f,其中R5e和R5f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5e和R5f可与其所连接的杂原子一起形成杂环基;
X可为O(式II中与X连接的环双键相应地用单键替代)、N、CH或C-R6,其中R6选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R6a、卤素、OH、OR6a、SH、SR6a、OCOR6a、SCOR6a、NH2、NO2、NHR6a、NHSO2NH2、NHSO2R6a、NR6aCOR6b、NHCOR6a、NHC(NH)NH2、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、CONHOH、CONHR6a、CONHOR6a、C(NOH)NH2、CONR6aR6b、SO2R6a、SO3H、SO2NH2、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6a和R6b可与其所连接的杂原子一起形成杂环基,
其中,当R6为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R6为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NO2、NHR6c、NHC(NH)NH2、NHSO2NH2、NHSO2R6c、NR6cCOR6d、NHCOR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、CONHR6c、CONHOR6c、CONHOH、C(NOH)NH2、CONR6cR6d、SO2R6c、SO3H、SO2NH2、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6c和R6d可与其所连接的杂原子一起形成杂环基,
其中,当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R6的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6e、C1-6烷基、C1-4烷氧基、OH、OR6e、OCOR6e、SH、SR6e、SCOR6e、NH2、NO2、NHR6e、NHC(NH)NH2、NHSO2NH2、NHSO2R6e、NR6eCOR6f、NHCOR6e、NR6eR6f、COR6e、CSR6e、CN、COOH、COOR6e、CONH2、CONHOH、CONHR6e、CONHOR6e、C(NOH)NH2、CONR6eR6f、SO2R6e、SO3H、SO2NH2、SO2NR6eR6f,其中R6e和R6f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6e和R6f可与其所连接的杂原子一起形成杂环基;
Y可为N、CH或C-R7,其中R7选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R7a、卤素、OH、OR7a、SH、SR7a、OCOR7a、SCOR7a、NH2、NO2、NHR7a、NHSO2NH2、NHSO2R7a、NR7aCOR7b、NHCOR7a、NHC(NH)NH2、NR7aR7b、COR7a、CSR7a、CN、COOH、COOR7a、CONH2、CONHOH、CONHR7a、CONHOR7a、C(NOH)NH2、CONR7aR7b、SO2R7a、SO3H、SO2NH2、SO2NR7aR7b,其中R7a和R7b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7a和R7b可与其所连接的杂原子一起形成杂环基,
其中,当R7为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R7为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R7c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、O7c、OCOR7c、SH、SR7c、SCOR7c、NH2、NO2、NHR7c、NHC(NH)NH2、NHSO2NH2、NHSO2R7c、NR7cCOR7d、NHCOR7c、NR7cR7d、COR7c、CSR7c、CN、COOH、COOR7c、CONH2、CONHR7c、CONHOR7c、CONHOH、C(NOH)NH2、CONR7cR7d、SO2R7c、SO3H、SO2NH2、SO2NR7cR7d,其中R7c和R7d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7c和R7d可与其所连接的杂原子一起形成杂环基,
其中,当R7的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R7的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C1-4烷氧基、R7e、C1-6烷基、OH、OR7e、OCOR7e、SH、SR7e、SCOR7e、NH2、NO2、NHR7e、NHSO2NH2、NHSO2R7e、NHC(NH)NH2、NR7eCOR7f、NHCOR7e、NR7eR7f、COR7e、CSR7e、CN、COOH、COOR7e、CONH2、CONHOH、CONHR7e、CONHOR7e、C(NOH)NH2、CONR7eR7f、SO2R7e、SO3H、SO2NH2、SO2NR7eR7f,其中R7e和R7f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7e和R7f可与其所连接的杂原子一起形成杂环基;
Z可为N、CH或C-R8,其中R8选自C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R8a、卤素、OH、OR8a、SH、SR8a、OCOR8a、SCOR8a、NH2、NO2、NHR8a、NHSO2NH2、NHSO2R8a、NR8aCOR8b、NHCOR8a、NHC(NH)NH2、NR8aR8b、COR8a、CSR8a、CN、COOH、COOR8a、CONH2、CONHOH、CONHR8a、CONHOR8a、C(NOH)NH2、CONR8aR8b、SO2R8a、SO3H、SO2NH2、SO2NR8aR8b,其中R8a和R8b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8a和R8b可与其所连接的杂原子一起形成杂环基,
其中,当R8为C1-6烷基、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR8c、OCOR8c、SH、SR8c、SCOR8c、NH2、NO2、NHR8c、NHSO2NH2、NHSO2R8c、NR8cCOR8d、NHCOR8c、NHC(NH)NH2、NR8cR8d、COR8c、CSR8c、CN、COOH、COOR8c、CONH2、CONHOH、CONHR8c、CONHOR8c、C(NOH)NH2、CONR8cR8d、SO2R8c、SO3H、SO2NH2、SO2NR8cR8d,其中R8c和R8d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8c和R8d可与其所连接的杂原子一起形成杂环基,
其中,当R8的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8e、C1-6烷基、OH、OR8e、OCOR8e、SH、SR8e、SCOR8e、NH2、NO2、NHR8e、NHSO2NH2、NHSO2R8e、NR8eCOR8f、NHCOR8e、NHC(NH)NH2、NR8eR8f、COR8e、CSR8e、CN、COOH、COOR8e、CONH2、CONHOH、CONHR8e、CONHOR8e、C(NOH)NH2、CONR8eR8f、SO2R8e、SO3H、SO2NH2、SO2NR8eR8f,其中R8e和R8f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8e和R8f可与其所连接的杂原子一起形成杂环基;
其中,X、Y和Z表示的原子或基团中至多两个可为N;
其中,当W为N时,CONR1R2基团可连至W,式I中的双键相应地重排;
或者其可药用的盐或酯;
条件是当R1和R2一起形成式I的化合物中的哌啶基时,所述哌啶基不被以下基团取代:甲基、二甲基、乙基、异丙基、叔丁基、甲氧基羰基、三氟甲基、氯、溴或苄基,
条件是R1和R2一起在式I的化合物中不形成6,7-二甲氧基-3,4-二氢-1H-异喹啉-2-基、6-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-氨基-3,4-二氢-1H-异喹啉-2-基、7-硝基-3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-1-基、3,4-二氢-2H-喹啉-1-基、吡咯烷-1-基、3,6-二氢-2H-吡啶-1-基、8-氮杂-螺[4.5]癸-8-基、1,3-二氢异氮茚-2-基、八氢异氮茚-2-基、1,2,6-三氮杂-螺[2.5]辛-1-烯-6-基或氮杂环庚烷-1-基,
条件是当R1或R2为未取代的甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,
条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、哌嗪基、取代的哌啶基或取代的哌嗪基时,在式I化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,和
条件是所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
已发现,本发明的化合物可调节脂肪酸酰胺水解酶(FAAH)的活性。特别是,所述化合物具有对该酶的抑制性质并且在10μM或更低的浓度下显示出体外抑制FAAH。此外,所述化合物许多在100nM或更低的浓度显示出体外强抑制FAAH并且还显示出在中枢神经系统组织和外周组织中体内抑制。还发现本发明的化合物对FAAH相对特异,以至于其显示出对其他丝氨酸水解酶(例如单酰甘油水解酶)的抑制相对较低。所述化合物还代谢相对稳定并且显示出对FAAH的较高亲和性。这意味着预计所述化合物可提供相对较长的FAAH作用抑制。
此外,已发现本发明的一些化合物是选择性的,使得与在外周组织中相比,它们在中枢神经系统组织中会抑制FAAH至更大程度。已发现其他化合物是选择性的,使得与在中枢神经系统组织中相比,它们在外周组织中会抑制FAAH至更大程度。
已发现本发明的某些化合物特别适合给药至受试者的肺。已发现所述化合物可有效地抑制肺中的FAAH,而不进入受试者血流。以此方式,所述化合物具有局部的FAAH抑制效应,而非全身效应。
本文所使用的术语“Cx-y烷基”是指含x至y个碳原子的直链饱和烃基团或支链饱和烃基团。例如,C1-6烷基指含1至6个碳原子的直链饱和烃基团或支链饱和烃基团。C1-6烷基基团的实例包括甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基和己基。优选地,所述烃基团为直链的。基团C1-10烷基优选为C1-6烷基。术语“Cx-y烷基”也用于意指含x至y个碳原子并且其中末端甲基基团进一步被取代(即以便成为Cx-y亚烷基基团)的直链饱和烃基团或支链饱和烃基团。
本文所使用的术语“Cx-y炔基”指含x至y碳原子和至少一个碳碳三键的直链烃基团或支链烃基团。例如,C1-6炔基指含1至6个碳原子的直链烃基团或支链烃基团。C1-6炔基的实例包括乙炔基、甲基丁炔基(即3-甲基-1-丁炔基)、1,3-丁二炔基和1,3,5-己三炔基。
本文所使用的术语“芳基”指其中至少一个环为芳香族的C6-12单环烃环或双环烃环。所述基团的实例包括苯基、萘基和四氢萘基。
本文所使用的术语“杂芳基”是指5-6元芳香单环或稠合的8-10元芳香双环,所述单环或双环包含选自氧、氮和硫的1至4个杂原子。这类芳香单环的实例包括噻吩基、呋喃基、呋吖基(furazanyl)、吡咯基、三唑基、四唑基、咪唑基、噁唑基、噻唑基、噁二唑基、异噻唑基、异噁唑基、噻二唑基、吡喃基、吡唑基、嘧啶基、哒嗪基、吡嗪基、吡啶基、三嗪基、四嗪基等。这类芳香双环的实例包括喹啉基、异喹啉基、喹唑啉基、喹喔啉基、蝶啶基、噌啉基、酞嗪基(phthalazinyl)、萘啶基(naphthyridinyl)、吲哚基、异氮茚基、氮杂吲哚基(azaindolyl)、吲嗪基(indolizinyl)、吲唑基、嘌呤基、吡咯并吡啶基、呋喃并吡啶基、苯并呋喃基、异苯并呋喃基、苯并噻吩基、苯并咪唑基、苯并噁唑基、苯并异噁唑基、苯并噻唑基、苯并异噻唑基、苯并噁二唑基、苯并噻二唑基和咪唑并吡啶基。
术语“被一个或多个氧原子取代的杂芳基”是指具有一个或多个键合于环上的氧原子的杂芳环。这并不意味着所述杂芳环包含一个或多个氧原子作为环原子,尽管在一些实施方案中,所述杂芳环包含一个或多个氧原子作为环原子。优选地,所述一个或多个氧原子键合于所述杂芳环中的氮杂原子。被氧原子取代的杂芳基可包含N-氧化物。被一个或多个氧原子取代的杂芳基的一个实例是吡啶基氮被氧化的1-氧化吡啶基。
术语“杂环基”指可为饱和的或部分不饱和的3-8(优选4-8并且,更优选4-7)元单环或稠合的8-12元双环,所述单环或双环包含选自氧、氮、硅或硫的1至4个杂原子。所述单环的实例包括氧吖丙啶基(oxaziridinyl)、环氧乙烷基(oxiranyl)、二氧乙烷基(dioxiranyl)、吖丙啶基(aziridinyl)、吡咯烷基、氮杂环丁烷基、吡唑烷基、噁唑烷基、哌啶基、哌嗪基、吗啉基、硫代吗啉基、噻唑烷基、乙内酰脲基(hydantoinyl)、戊内酰胺基(valerolactamyl)、环氧乙烷基、氧杂环丁基(oxetanyl)、二氧戊烷基、二氧杂环己烷基、氧硫杂环戊基(oxathiolanyl)、氧硫杂环己基(oxathianyl)、二噻烷基、二氢呋喃基、四氢呋喃基、二氢吡喃基、四氢吡喃基、四氢吡啶基、四氢嘧啶基、四氢苯硫基、四氢噻喃基、二氮杂环庚烷基(diazepanyl)和氮杂环庚烷基(azepanyl)。所述双环的实例包括二氢吲哚基、异二氢吲哚基、苯并吡喃基、奎宁环基、2,3,4,5-四氢-1H-3-苯并氮杂卓、4-(苯并[d][1,3]间二氧杂环戊烯-5-基甲基)哌嗪-1-基和四氢异喹啉基。
术语“被一个或多个氧原子取代的杂环基”指具有一个或多个键合于环上的氧原子的杂环。这不意味着所述杂环包含一个或多个氧原子作为环原子,尽管在一些实施方案中,所述杂环可包含一个或多个氧原子作为环原子。优选地,所述一个或多个氧原子键合于杂环的杂原子例如氮或硫上。由一个或多个氧原子取代的杂环基的一个实例是1,1-二氧-1,3-噻唑烷基。
在双环含义中,术语“双环的”和“稠合的”指经两个原子之间的键连接在一起的两个环(例如萘)、经一系列原子以形成桥连接在一起的两个环(例如奎宁环)或在单个原子上连接在一起以形成螺环化合物的两个环(例如1,4-二氧杂-8-氮杂-螺[4.5]癸烷和N,3,3-二甲基-1,5-二氧杂螺[5.5]十一烷-9-基)连接在一起的两个环。
本文所使用的术语“Cx-y环烷基”指x至y个碳原子的饱和烃环,其可为单环、双环或三环。例如,C3-10环烷基指3至10个碳原子的饱和单环、双环或三环的烃环。C3-10环烷基的实例包括环丙基、环丁基、环戊基、环己基、环庚基、环辛基和金刚烷基。
本文所使用的术语“芳基Cx-y烷基”指连接于如上所定义的Cx-y烷基的如上所定义的芳基。例如,芳基C1-6烷基指连接于含1至6个碳原子的直链或支链饱和烃基团的芳基。芳基C1-6烷基的实例包括苄基、苯乙基、苯丙基、苯丁基、苯戊基和苯己基。
本文所使用的术语“杂芳基Cx-y烷基”、“杂环基Cx-y烷基”和“Cx-y环烷基Cx-y烷基”指连接于如上所定义的Cx-y烷基的如上所定义的杂芳基、杂环基或Cx-y环烷基。
本文所使用的术语“Cx-y烷氧基”指-O-Cx-y烷基,其中Cx-y烷基如上所定义。所述基团的实例包括甲氧基、乙氧基、丙氧基、丁氧基、戊氧基和己氧基。
本文所使用的术语“芳氧基”指-O-芳基。所述基团的实例包括苯氧基。本文所使用的术语“杂芳氧基”和“杂环氧基”分别指-O-杂芳基和-O-杂环基。
除非另外具体指出,本文所使用的术语“卤素”指氟原子、氯原子、溴原子或碘原子。
本文所使用的术语“Cx-y烷氨基”指仲胺基团(-NH(R)),其中R基团选自含x至y个碳原子的直链或支链的饱和烃基团。Cx-y烷氨基的实例包括甲氨基、乙氨基和丙氨基。
本文所使用的术语“Cx-y二烷氨基”指叔胺基团(-NR(R*)),其中R和R*基团各自独立地选自含x至y个碳原子的直链或支链的饱和烃基团。Cx-y二烷氨基的实例包括二甲氨基、甲乙氨基和二乙氨基。
本文在提到各R基团的特性时所使用的术语“取代的C1-6烷基”(例如,在表述“其中R8e和R8f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基”中)意指该特定R基团(例如,R1a、R2c、R4d、R5e等)可被选自以下的一个或多个基团取代:R′、卤素、OH、OR′、SH、SR′、OCOR′、SCOR′、NH2、NO2、NHR′、NHSO2NH2、NHSO2R′、NR′COR″、NHC(NH)NH2、NHCOR′、NR′R″、COR′、CSR′、CN、COOH、COOR′、CONH2、CONHOH、CONHR′、CONR′R″、CONHOR′、C(NOH)NH2、SO2R′、SO3H、SO2NH2、SO2NR′R″,其中R′和R″独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R′和R″可与其所连接的杂原子一起形成杂环基。
本发明的化合物的“可药用的盐”包括与无机碱的盐、与有机碱的盐、与无机酸的盐、与有机酸的盐和与碱性或酸性氨基酸的盐。特别是在某型情形下可使用与酸的盐。示例性盐包括盐酸盐、乙酸盐、三氟乙酸盐、甲磺酸盐、2-羟基丙烷-1,2,3-三羧酸盐、(2R,3R)-2,3-二羟基琥珀酸盐、磷酸盐和草酸盐。本发明的化合物可以溶剂化物(例如水合物)或非溶剂化物(例如非水合物)形式存在。当以溶剂化物形式存在时,另外的溶剂可为醇,例如丙-2醇。
本发明的化合物的“可药用的酯”是指其中所述化合物的一个或多个羧基(即-C(O)OH)基团通过与醇部分U-OH反应而形成-C(O)OU基团的衍生物,其中U可为C1-18烷基(例如C1-6烷基)、芳基、杂芳基、C3-8环烷基或其结合物。
制备盐和酯的一般方法是本领域技术人员所熟知的。盐和酯的可药用性将取决于多种因素,包括制剂加工特性和体内行为,本领域技术人员将能够容易地评价关于本公开内容的这类因素。
当本发明化合物是以不同的对映异构体和/或非对映异构体形式存在时(包括双键的几何异构),所述化合物可制备为同分异构混合物或外消旋化合物,但本发明涉及所有这类对映异构体或同分异构体,不论是以光学纯形式或作为与其他同分异构体的混合物存在。独立的对映异构体或同分异构体可通过本领域已知的方法获得,例如产物或中间体的光学分辨(例如手性色谱分离(例如,手性HPLC)),或对映异构体合成方法。类似地,当本发明化合物可作为替代的互变异构体形式存在(例如,酮/烯醇、酰胺/亚氨酸)时,本发明涉及分离的独立互变异构体,并且涉及所有比例的互变异构体混合物。
在式II的化合物中,X、Y和Z表示的原子或基团中零个、一个或两个可为N。
在一个具体的实施方案中,本发明的化合物具有选自式I或式II的结构式:
其中:
R1和R2可各自独立地选自H、C1-20烷基、烷氧基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,除了H以外所述基团中的每一个可任选被选自以下的一个或多个基团取代:卤素、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、氨基、C1-6烷基氨基和C1-6二烷基氨基,R1和R2均为H除外,或
R1和R2可与其所连接的N一起形成杂芳基或杂环基基团,所述基团中的每一个可任选被选自以下的一个或多个基团取代:羟基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基和杂环氧基,所述基团中的每一个可任选被选自以下的基团取代:卤素、羟基、C1-4烷基、芳基、杂芳基、C1-4烷氧基、芳氧基、杂芳氧基、芳基C1-4烷氧基和杂芳基C1-4烷氧基,除了卤素和羟基以外所述基团中的每一个可任选被C1-4烷氧基取代;
环A选自芳基、杂芳基和杂环基部分,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、羟基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基和杂环氧基,除了卤素和羟基以外所述基团中的每一个可任选被卤素、氰基、酰胺和羧酸取代;
V可为N、CH或C-R3,其中R3为卤素、芳基、杂芳基、杂环基或C3-8环烷基,除了卤素以外所述基团中的每一个可任选被卤素取代;
W可为N、CH或C-R4,其中R4为C1-10烷基、芳基、杂芳基、杂环基或C3-8环烷基,所述基团中的每一个可任选被卤素取代;
R5选自H、C1-6烷基、芳基、杂芳基、杂环基和C3-8环烷基,除了H以外所述基团中的每一个可任选被卤素取代;
X可为N、CH或C-R6,其中R6选自C1-6烷基、芳基、杂芳基和杂环基,除了H以外所述基团中的每一个可任选被选自以下的一个或多个基团取代:卤素、羟基、胺、酰胺、氰基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基和杂环基C1-6烷氧基;
Y可为N、CH或C-R7,其中R7选自C1-6烷基、芳基、杂芳基和杂环基,除了H以外所述基团中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基和杂环基C1-6烷氧基,所述基团中的每一个可任选被以下的基团取代:C1-4烷基、氰基、胺、酰胺、卤素、芳基、杂芳基、杂环基、芳基C1-6烷基、杂芳基C1-6烷基和杂环基C1-6烷基;
Z可为N、CH或C-R8,其中R8选自C1-10烷基、芳基、杂芳基、杂环基或C3-8环烷基,所述基团中的每一个可任选被卤素取代;
或其可药用的盐或酯;
条件是当R1和R2在式I的化合物中一起形成哌啶基时,所述哌啶基不被以下基团取代:甲基、二甲基、乙基、异丙基、叔丁基、三氟甲基、氯、溴或苄基。
根据本发明另一个实施方案,提供一种具有式I或式II的化合物:
其中:
R1和R2可各自独立地选自H、C1-20烷基、烷氧基、芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、R1a、卤素、OH、OR1a、SH、SR1a、OCOR1a、SCOR1a、NH2、NHR1a、NR1aR1b、COR1a、CSR1a、CN、COOH、COOR1a、CONH2、SO2R1a、SO3H、SO2NH2、CONR1aR1b、SO2NR1aR1b,其中R1a和R1b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R1a和R1b可与相邻的杂原子一起形成杂环基,
其中,当R1或R2为C1-20烷基、烷氧基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下的基团取代:R1c、卤素、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-10烷基、OH、OR1c、OCOR1c、SH、SR1c、SCOR1c、NH2、NHR1c、NR1cR1d、COR1c、CSR1c、CN、COOH、COOR1c、CONH2、SO2R1c、SO3H、SO2NH2、CONR1cR1d、SO2NR1cR1d,其中R1c和R1d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R1c和R1d可与相邻的杂原子一起形成杂环基,
其中,当R1或R2的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下的基团取代:R1e、C1-10烷基、OH、OR1e、OCOR1e、SH、SR1e、SCOR1e、NH2、NHR1e、NR1eR1f、COR1e、CSR1e、CN、COOH、COOR1e、CONH2、SO2R1e、SO3H、SO2NH2、CONR1eR1f、SO2NR1eR1f,其中R1e和R1f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R1e和R1f可与相邻杂原子一起形成杂环基,R1和R2均为H除外,或
R1和R2可与其所连接的N一起形成杂芳基或杂环基基团,所述基团中的每一个可任选被选自以下的一个或多个基团取代:羟基、芳基、杂芳基、部分或完全饱和的杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R2a、卤素、OH、OR2a、SH、SR2a、OCOR2a、SCOR2a、NH2、NHR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、SO2R2a、SO3H、SO2NH2、CONR2aR2b、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R2a和R2b可与相邻的杂原子一起形成杂环基,
其中,当由R1和R2一起所形成的杂芳基或杂环基的取代基为芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基,或含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的基团取代:卤素、羟基、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基、R2c、OR2c、SH、SR2c、OCOR2c、SCOR2c、NH2、NHR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、SO2R2c、SO3H、SO2NH2、CONR2cR2d、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R2c和R2d可与相邻的杂原子一起形成杂环基,
其中,当R1和R2一起构成的杂芳基或杂环基的取代基为C1-4烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:C1-4烷氧基、R2e、卤素、OH、OR2e、SH、SR2e、OCOR2e、SCOR2e、NH2、NHR2e、NR2eR2f、COR2e、CSR2e、CN、COOH、COOR2e、CONH2、SO2R2e、SO3H、SO2NH2、CONR2eR2f、SO2NR2eR2f,其中R2e和R2f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R2e和R2f可与相邻的杂原子一起形成杂环基;
环A选自芳基、杂芳基和杂环基部分,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、C1-6烷基、羟基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、Ra、C1-10烷基、OH、ORa、OCORa、SH、SRa、SCORa、NH2、NHRa、NRaRb、CORa、CSRa、CN、COOH、COORa、CONH2、SO2Ra、SO3H、SO2NH2、CONRaRb、SO2NRaRb,其中Ra和Rb独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且Ra和Rb可与相邻的杂原子形成杂环基,
其中,当环A被C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-10烷基、C3-8环烷基取代或被含一个或多个所述部分的基团取代时,所述部分中的每一个可任选被以下基团取代:Rc、C1-10烷基、OH、ORc、OCORc、SH、SRc、SCORc、NH2、NHRc、NRcRd、CORc、CSRc、CN、COOH、COORc、CONH2、SO2Rc、SO3H、SO2NH2、CONRcRd、SO2NRcRd,其中Rc和Rd独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且Rc和Rd可与相邻的杂原子一起形成杂环基;
V可为N、CH或C-R3,其中R3为卤素、C1-10烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3a、OH、OR3a、SH、SR3a、OCOR3a、SCOR3a、NH2、NHR3a、NR3aR3b、COR3a、CSR3a、CN、COOH、COOR3a、CONH2、SO2R3a、SO3H、SO2NH2、CONR3aR3b、SO2NR3aR3b,其中R3a和R3b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R3a和R3b可与相邻的杂原子一起形成杂环基,
其中,当R3为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3c、C1-10烷基、OH、OR3c、OCOR3c、SH、SR3c、SCOR3c、NH2、NHR3c、NR3cR3d、COR3c、CSR3c、CN、COOH、COOR3c、CONH2、SO2R3c、SO3H、SO2NH2、CONR3cR3d、SO2NR3cR3d,其中R3c和R3d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R3c和R3d可与相邻的杂原子一起形成杂环基,
其中,当R3的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R3e、C1-10烷基、OH、OR3e、OCOR3e、SH、SR3e、SCOR3e、NH2、NHR3e、NR3eR3f、COR3e、CSR3e、CN、COOH、COOR3e、CONH2、SO2R3e、SO3H、SO2NH2、CONR3eR3f、SO2NR3eR3f,其中R3e和R3f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R3e和R3f可与相邻的杂原子一起形成杂环基;
W可为N、CH或C-R4,其中R4为卤素、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基、R4a、OH、OR4a、SH、SR4a、OCOR4a、SCOR4a、NH2、NHR4a、NR4aR4b、COR4a、CSR4a、CN、COOH、COOR4a、CONH2、SO2R4a、SO3H、SO2NH2、CONR4aR4b、SO2NR4aR4b,其中R4a和R4b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R4a和R4b可与相邻的杂原子一起形成杂环基,
其中,当R4为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R4c、C1-10烷基、OH、OR4c、OCOR4c、SH、SR4c、SCOR4c、NH2、NHR4c、NR4cR4d、COR4c、CSR4c、CN、COOH、COOR4c、CONH2、SO2R4c、SO3H、SO2NH2、CONR4cR4d、SO2NR4cR4d,其中R4c和R4d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R4c和R4d可与相邻的杂原子一起形成杂环基,
其中,当R4的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R4e、C1-10烷基、OH、OR4e、OCOR4e、SH、SR4e、SCOR4e、NH2、NHR4e、NR4eR4f、COR4e、CSR4e、CN、COOH、COOR4e、CONH2、SO2R4e、SO3H、SO2NH2、CONR4eR4f、SO2NR4eR4f,其中R4e和R4f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R4e和R4f可与相邻的杂原子一起形成杂环基;
R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R5a和R5b可与相邻的杂原子形成杂环基,
其中,当R5为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5c、C1-6烷基、OH、OR5c、OCOR5c、SH、SR5c、SCOR5c、NH2、NHR5c、NR5cR5d、COR5c、CSR5c、CN、COOH、COOR5c、CONH2、SO2R5c、SO3H、SO2NH2、CONR5cR5d、SO2NR5cR5d,其中R5c和R5d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R5c和R5d可与相邻的杂原子形成杂环基,
其中,当R5的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R5e、C1-6烷基、OH、OR5e、OCOR5e、SH、SR5e、SCOR5e、NH2、NHR5e、NR5eR5f、COR5e、CSR5e、CN、COOH、COOR5e、CONH2、SO2R5e、SO3H、SO2NH2、CONR5eR5f、SO2NR5eR5f,其中R5e和R5f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R5e和R5f可与相邻的杂原子形成杂环基;
X可为N、CH或C-R6,其中R6选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R6a、卤素、OH、OR6a、SH、SR6a、OCOR6a、SCOR6a、NH2、NHR6a、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、SO2R6a、SO3H、SO2NH2、CONR6aR6b、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R6a和R6b可与相邻的杂原子形成杂环基,
其中,当R6为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R6c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NHR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、SO2R6c、SO3H、SO2NH2、CONR6cR6d、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R6c和R6d可与相邻的杂原子形成杂环基,
其中,当R6的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R6e、C1-6烷基、OH、OR6e、OCOR6e、SH、SR6e、SCOR6e、NH2、NHR6e、NR6eR6f、COR6e、CSR6e、CN、COOH、COOR6e、CONH2、SO2R6e、SO3H、SO2NH2、CONR6eR6f、SO2NR6eR6f,其中R6e和R6f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R6e和R6f可与相邻的杂原子形成杂环基;
Y可为N、CH或C-R7,其中R7选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R7a、卤素、OH、OR7a、SH、SR7a、OCOR7a、SCOR7a、NH2、NHR7a、NR7aR7b、COR7a、CSR7a、CN、COOH、COOR7a、CONH2、SO2R7a、SO3H、SO2NH2、CONR7aR7b、SO2NR7aR7b,其中R7a和R7b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R7a和R7b可与相邻的杂原子形成杂环基,
其中,当R7为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R7c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、O7c、OCOR7c、SH、SR7c、SCOR7c、NH2、NHR7c、NR7cR7d、COR7c、CSR7c、CN、COOH、COOR7c、CONH2、SO2R7c、SO3H、SO2NH2、CONR7cR7d、SO2NR7cR7d,其中R7c和R7d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R7c和R7d可与相邻的杂原子形成杂环基,
其中,当R7的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R7e、C1-6烷基、OH、OR7e、OCOR7e、SH、SR7e、SCOR7e、NH2、NHR7e、NR7eR7f、COR7e、CSR7e、CN、COOH、COOR7e、CONH2、SO2R7e、SO3H、SO2NH2、CONR7eR7f、SO2NR7eR7f,其中R7e和R7f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R7e和R7f可与相邻的杂原子形成杂环基;
Z可为N、CH或C-R8,其中R8选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R8a、卤素、OH、OR8a、SH、SR8a、OCOR8a、SCOR8a、NH2、NHR8a、NR8aR8b、COR8a、CSR8a、CN、COOH、COOR8a、CONH2、SO2R8a、SO3H、SO2NH2、CONR8aR8b、SO2NR8aR8b,其中R8a和R8b独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R8a和R8b可与相邻的杂原子形成杂环基,
其中,当R8为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R8c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR8c、OCOR8c、SH、SR8c、SCOR8c、NH2、NHR8c、NR8cR8d、COR8c、CSR8c、CN、COOH、COOR8c、CONH2、SO2R8c、SO3H、SO2NH2、CONR8cR8d、SO2NR8cR8d,其中R8c和R8d独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R8c和R8d可与相邻的杂原子形成杂环基,
其中,当R8的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被以下基团取代:R8e、C1-6烷基、OH、OR8e、OCOR8e、SH、SR8e、SCOR8e、NH2、NHR8e、NR8eR8f、COR8e、CSR8e、CN、COOH、COOR8e、CONH2、SO2R8e、SO3H、SO2NH2、CONR8eR8f、SO2NR8eR8f,其中R8e和R8f独立地选自C1-6烷基、取代的C1-6烷基、C3-8环烷基和杂环基,并且R8e和R8f可与相邻的杂原子形成杂环基;
或者其可药用的盐或酯;
条件是当R1和R2在式I的化合物中一起形成哌啶基时,所述哌啶基不被以下基团取代:甲基、二甲基、乙基、异丙基、叔丁基、三氟甲基、氯、溴或苄基,
条件是R1和R2一起在式I的化合物中不形成6,7-二甲氧基-3,4-二氢-1H-异喹啉-2-基、6-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-氨基-3,4-二氢-1H-异喹啉-2-基、7-硝基-3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-1-基、3,4-二氢-2H-喹啉-1-基、吡咯烷-1-基、3,6-二氢-2H-吡啶-1-基、8-氮杂-螺[4.5]癸-8-基、1,3-二氢异氮茚-2-基、八氢异氮茚-2-基、1,2,6-三氮杂-螺[2.5]辛-1-烯-6-基或氮杂环庚烷-1-基,并且
条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I化合物中的环A不形成吡啶、吡嗪、取代的吡啶或取代的吡嗪。
根据本发明的另一个实施方案,提供了一种具有式I或式II的化合物:
其中:
R1和R2可各自独立地选自H、C1-20烷基、C1-6烷氧基、芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、R1a、卤素、OH、OR1a、SH、SR1a、OCOR1a、SCOR1a、NH2、NHR1a、NR1aR1b、COR1a、CSR1a、CN、COOH、COOR1a、CONH2、SO2R1a、SO3H、SO2NH2、CONR1aR1b、SO2NR1aR1b,其中R1a和R1b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1a和R1b可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2为C1-20烷基、烷氧基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1c、卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-10烷基、OH、OR1c、OCOR1c、SH、SR1c、SCOR1c、NH2、NO2、NHR1c、NR1cR1d、COR1c、CSR1c、CN、COOH、COOR1c、CONH2、SO2R1c、SO3H、SO2NH2、CONR1cR1d、SO2NR1cR1d,其中R1c和R1d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1c和R1d可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1e、卤素、C1-10烷基、OH、OR1e、OCOR1e、SH、SR1e、SCOR1e、NH2、NO2、NHR1e、NR1eR1f、COR1e、CSR1e、CN、COOH、COOR1e、CONH2、SO2R1e、SO3H、SO2NH2、CONR1eR1f、SO2NR1eR1f,其中R1e和R1f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1e和R1f可与其所连接的杂原子一起形成杂环基,
R1和R2均为H除外,
或者
R1和R2可与其所连接的N一起形成杂芳基或杂环基基团,所述基团中的每一个可任选被一个或多个氧原子或一个或多个选自以下的基团取代:羟基、芳基、杂芳基、部分或完全饱和的杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R2a、卤素、OH、OR2a、SH、SR2a、OCOR2a、SCOR2a、NH2、NO2、NHR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、SO2R2a、SO3H、SO2NH2、CONR2aR2b、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2a和R2b可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基为芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、羟基、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-6烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基、R2c、OR2c、SH、SR2c、OCOR2c、SCOR2c、NH2、NO2、NHR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、SO2R2c、SO3H、SO2NH2、CONR2cR2d、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基为C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:C1-4烷氧基、R2e、卤素、OH、OR2e、SH、SR2e、OCOR2e、SCOR2e、NH2、NO2、NHR2e、NR2eR2f、NHCOR2e、COR2e、CSR2e、CN、COOH、COOR2e、CONH2、SO2R2e、SO3H、SO2NH2、CONR2eR2f、SO2NR2eR2f,其中R2e和R2f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2e和R2f可与其所连接的杂原子一起形成杂环基;
环A选自芳基、杂芳基和杂环基部分,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、C1-6烷基、羟基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、Ra、C1-10烷基、OH、ORa、OCORa、SH、SRa、SCORa、NH2、NO2、NHRa、NRaRb、CORa、CSRa、CN、COOH、COORa、CONH2、CONHOH、CONHORa、SO2Ra、SO3H、SO2NH2、CONRaRb、SO2NRaRb,其中Ra和Rb独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Ra和Rb可与其所连接的杂原子一起形成杂环基,
其中,当环A被C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-10烷基、C3-8环烷基取代或被含一个或多个所述部分的基团取代时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、Rc、C1-10烷基、芳基C1-6烷基、OH、ORc、OCORc、SH、SRc、SCORc、NH2、NO2、NHRc、NRcRd、CORc、CSRc、CN、COOH、COORc、CONH2、SO2Rc、SO3H、SO2NH2、CONRcRd、SO2NRcRd,其中Rc和Rd独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Rc和Rd可与其所连接的杂原子一起形成杂环基;
V可为N、CH或C-R3,其中R3为卤素、C1-10烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3a、OH、OR3a、SH、SR3a、OCOR3a、SCOR3a、NH2、NO2、NHR3a、NR3aR3b、COR3a、CSR3a、CN、COOH、COOR3a、CONH2、SO2R3a、SO3H、SO2NH2、CONR3aR3b、SO2NR3aR3b,其中R3a和R3b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3a和R3b可与其所连接的杂原子一起形成杂环基,
其中,当R3为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3c、C1-10烷基、OH、OR3c、OCOR3c、SH、SR3c、SCOR3c、NH2、NO2、NHR3c、NR3cR3d、COR3c、CSR3c、CN、COOH、COOR3c、CONH2、SO2R3c、SO3H、SO2NH2、CONR3cR3d、SO2NR3cR3d,其中R3c和R3d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3c和R3d可与其所连接的杂原子一起形成杂环基,
其中,当R3的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R3e、C1-10烷基、OH、OR3e、OCOR3e、SH、SR3e、SCOR3e、NH2、NO2、NHR3e、NR3eR3f、COR3e、CSR3e、CN、COOH、COOR3e、CONH2、SO2R3e、SO3H、SO2NH2、CONR3eR3f、SO2NR3eR3f,其中R3e和R3f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3e和R3f可与其所连接的杂原子一起形成杂环基;
W可为N、CH或C-R4,其中R4为卤素、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基、R4a、OH、OR4a、SH、SR4a、OCOR4a、SCOR4a、NH2、NO2、NHR4a、NR4aR4b、COR4a、CSR4a、CN、COOH、COOR4a、CONH2、SO2R4a、SO3H、SO2NH2、CONR4aR4b、SO2NR4aR4b,其中R4a和R4b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4a和R4b可与其所连接的杂原子一起形成杂环基,
其中,当R4为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R4c、C1-10烷基、OH、OR4c、OCOR4c、SH、SR4c、SCOR4c、NH2、NO2、NHR4c、NR4cR4d、COR4c、CSR4c、CN、COOH、COOR4c、CONH2、SO2R4c、SO3H、SO2NH2、CONR4cR4d、SO2NR4cR4d,其中R4c和R4d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4c和R4d可与其所连接的杂原子一起形成杂环基,
其中,当R4的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R4e、C1-10烷基、OH、OR4e、OCOR4e、SH、SR4e、SCOR4e、NH2、NO2、NHR4e、NR4eR4f、COR4e、CSR4e、CN、COOH、COOR4e、CONH2、SO2R4e、SO3H、SO2NH2、CONR4eR4f、SO2NR4eR4f,其中R4e和R4f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4e和R4f可与其所连接的杂原子一起形成杂环基;
R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基,
其中,当R5为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5c、C1-6烷基、OH、OR5c、OCOR5c、SH、SR5c、SCOR5c、NH2、NO2、NHR5c、NR5cR5d、COR5c、CSR5c、CN、COOH、COOR5c、CONH2、SO2R5c、SO3H、SO2NH2、CONR5cR5d、SO2NR5cR5d,其中R5c和R5d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5c和R5d可与其所连接的杂原子一起形成杂环基,
其中,当R5的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R5e、C1-6烷基、OH、OR5e、OCOR5e、SH、SR5e、SCOR5e、NH2、NO2、NHR5e、NR5eR5f、COR5e、CSR5e、CN、COOH、COOR5e、CONH2、SO2R5e、SO3H、SO2NH2、CONR5eR5f、SO2NR5eR5f,其中R5e和R5f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5e和R5f可与其所连接的杂原子一起形成杂环基;
X可为N、CH或C-R6,其中R6选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R6a、卤素、OH、OR6a、SH、SR6a、OCOR6a、SCOR6a、NH2、NO2、NHR6a、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、SO2R6a、SO3H、SO2NH2、CONR6aR6b、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6a和R6b可与其所连接的杂原子一起形成杂环基,
其中,当R6为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R6为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NO2、NHR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、CONHOH、C(NOH)NH2、SO2R6c、SO3H、SO2NH2、CONR6cR6d、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6c和R6d可与其所连接的杂原子一起形成杂环基,
其中,当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R6的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6e、C1-6烷基、C1-4烷氧基、OH、OR6e、OCOR6e、SH、SR6e、SCOR6e、NH2、NO2、NHR6e、NR6eR6f、COR6e、CSR6e、CN、COOH、COOR6e、CONH2、C(NOH)NH2、SO2R6e、SO3H、SO2NH2、CONR6eR6f、SO2NR6eR6f,其中R6e和R6f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6e和R6f可与其所连接的杂原子一起形成杂环基;
Y可为N、CH或C-R7,其中R7选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R7a、卤素、OH、OR7a、SH、SR7a、OCOR7a、SCOR7a、NH2、NO2、NHR7a、NR7aR7b、COR7a、CSR7a、CN、COOH、COOR7a、CONH2、SO2R7a、SO3H、SO2NH2、CONR7aR7b、SO2NR7aR7b,其中R7a和R7b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7a和R7b可与其所连接的杂原子一起形成杂环基,
其中,当R7为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R7为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R7c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、O7c、OCOR7c、SH、SR7c、SCOR7c、NH2、NO2、NHR7c、NR7cR7d、COR7c、CSR7c、CN、COOH、COOR7c、CONH2、CONHOH、C(NOH)NH2、SO2R7c、SO3H、SO2NH2、CONR7cR7d、SO2NR7cR7d,其中R7c和R7d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7c和R7d可与其所连接的杂原子一起形成杂环基,
其中,当R7的取代基为杂芳基或杂环基,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R7的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C1-4烷氧基、R7e、C1-6烷基、OH、OR7e、OCOR7e、SH、SR7e、SCOR7e、NH2、NO2、NHR7e、NR7eR7f、COR7e、CSR7e、CN、COOH、COOR7e、CONH2、C(NOH)NH2、SO2R7e、SO3H、SO2NH2、CONR7eR7f、SO2NR7eR7f,其中R7e和R7f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7e和R7f可与其所连接的杂原子一起形成杂环基;
Z可为N、CH或C-R8,其中R8选自C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R8a、卤素、OH、OR8a、SH、SR8a、OCOR8a、SCOR8a、NH2、NO2、NHR8a、NR8aR8b、COR8a、CSR8a、CN、COOH、COOR8a、CONH2、SO2R8a、SO3H、SO2NH2、CONR8aR8b、SO2NR8aR8b,其中R8a和R8b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8a和R8b可与其所连接的杂原子一起形成杂环基,
其中,当R8为C1-6烷基、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR8c、OCOR8c、SH、SR8c、SCOR8c、NH2、NO2、NHR8c、NR8cR8d、COR8c、CSR8c、CN、COOH、COOR8c、CONH2、SO2R8c、SO3H、SO2NH2、CONR8cR8d、SO2NR8cR8d,其中R8c和R8d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8c和R8d可与其所连接的杂原子一起形成杂环基,
其中,当R8的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8e、C1-6烷基、OH、OR8e、OCOR8e、SH、SR8e、SCOR8e、NH2、NO2、NHR8e、NR8eR8f、COR8e、CSR8e、CN、COOH、COOR8e、CONH2、SO2R8e、SO3H、SO2NH2、CONR8eR8f、SO2NR8eR8f,其中R8e和R8f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8e和R8f可与其所连接的杂原子一起形成杂环基;
其中,X、Y和Z表示的原子或基团中至多两个可为N;
其中,当W为N时,CONR1R2基团可连至W,式I中的双键相应地重排;
或者其可药用的盐或酯;
条件是当R1和R2在式I的化合物中一起形成哌啶基时,所述哌啶基不被以下基团取代:甲基、二甲基、乙基、异丙基、叔丁基、甲氧基羰基、三氟甲基、氯、溴或苄基,
条件是R1和R2在式I的化合物中一起不形成6,7-二甲氧基-3,4-二氢-1H-异喹啉-2-基、6-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-氨基-3,4-二氢-1H-异喹啉-2-基、7-硝基-3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-1-基、3,4-二氢-2H-喹啉-1-基、吡咯烷-1-基、3,6-二氢-2H-吡啶-1-基、8-氮杂-螺[4.5]癸-8-基、1,3-二氢异氮茚-2-基、八氢异氮茚-2-基、1,2,6-三氮杂-螺[2.5]辛-1-烯-6-基或氮杂环庚烷-1-基,并且
条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶。
优选地,本发明的化合物具有选自以下的结构式:式I、式IIa、式IIb、式IIc和式IId。
更优选地,化合物具有选自以下的结构式:式Ia、式IIa、式IIb和式IId。
在本发明的一个实施方案中,R1优选选自H和C1-4烷基。更优选地,R1选自H和C1-3烷基,甚至更优选地,R1选自H、甲基和乙基,最优选地,R1选自H和甲基。
R2优选选自C1-4烷基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。优选地,所述芳基、杂芳基、杂环基和C3-10环烷基(包括芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基)具有6元单环结构。更优选地,所述芳基、杂芳基、杂环基和C3-10环烷基(包括芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基)选自苯基、环己基、苯基C1-6烷基和环己基C1-6烷基,所述基团中的每一个可为取代的或未取代的。优选地,芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基中的每一个的C1-6烷基为直链烷基。
或者,R2可选自芳基、杂芳基、杂环基、芳基C1-6烷基、杂芳基C1-6烷基和杂环基C1-6烷基,所述基团中的每一个可为取代的或未取代的,并且其中所述芳基、杂芳基和杂环基(包括在芳基C1-6烷基、杂芳基C1-6烷基和杂环基C1-6烷基中)具有双环结构,优选10元双环结构。更优选地,R2选自萘基和萘基C1-6烷基。
R2的芳基、杂芳基、杂环基和C3-10环烷基中(包括在芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基中)的每一个可被一个或多个卤素取代。
或者,所述芳基、杂芳基、杂环基和C3-10环烷基中(包括在芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基中)的每一个可被C1-4烷氧基或芳氧基取代。优选地,所述C1-4烷氧基为甲氧基或乙氧基。优选地,所述芳氧基为单环芳氧基,更优选为苯氧基。
在一个优选实施方案中,R1选自H和C1-4烷基,并且R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1选自H、甲基和乙基,并且R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环的并且可为取代的或未取代的。还更优选地,R2选自饱和的杂环基和C5-8环烷基,所述基团中的每一个为单环的并且可为取代的或未取代的。当R2为单环的C5-8环烷基时,其优选为未取代的。优选地,R2为环己基,例如未取代的环己基。当R2为单环的饱和杂环基时,杂环优选包含单个杂原子。优选地,所述杂原子为氮或氧原子。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。如果所述杂原子为氧原子,则所述杂环基优选为未取代的。如果所述杂原子为氮原子,则所述氮杂原子可为取代的或未取代的。如果氮杂原子为取代的,则其优选被选自以下的基团取代:C1-6烷基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,所述氮杂原子被选自以下的基团取代:C1-4烷基、芳基C1-4烷基、杂芳基C1-4烷基、杂环基C1-4烷基和C5-8环烷基C1-4烷基。更优选地,所述氮杂原子被选自以下的基团取代:芳基C1-4烷基和杂芳基C1-4烷基,其中所述芳基和杂芳基为单环,并且优选为六元。优选地,所述氮杂原子被选自以下的基团取代:苯基C1-2烷基和吡啶基C1-2烷基。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮的位置的4位。当R1和R2如本段中所定义时,所述化合物优选具有式IIa。优选地,当R1和R2如本段中所定义时,R6为取代的或未取代的芳基或杂芳基,并且优选为取代的或未取代的单环的芳基或杂芳基。所述单环的芳基或杂芳基优选为六元。在一个实施方案中,R6为取代的或未取代的芳基(例如苯基),并且优选为未取代的。在另一个实施方案中,R6为取代的或未取代的杂芳基,并且优选为取代的或未取代的吡啶基。在一个实施方案中,所述杂芳基被氧原子取代。例如,吡啶基的氮杂原子可被氧原子取代,从而其被氧化,即形成N-氧化物。
已发现,R1和R2如前段中进行选择的化合物显示出对FAAH的相对高特异性。此外,已发现其中R2为杂环基(例如哌啶基或四氢吡喃基)的化合物是相对代谢稳定的。
在一个替代实施方案中,R2优选为C2-20烷基。更优选地,R2为C3-16烷基,还更优选地,R2为C4-12烷基。优选地,所述烷基为直链烷基。
在一个优选实施方案中,R1选自H和C1-4烷基,并且R2为C2-20烷基。
在多个实施方案中,当R1为:H或C1-4烷基;H或C1-3烷基;H、甲基或乙基;H或甲基;或者甲基时,R2可选自C1-6烷氧基、芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、卤素、OH、OR1a、OCOR1a、SH、SR1a、SCOR1a、NH2、NHR1a、NHSO2NH2、NHSO2R1a、NR1aCOR1b、NHCOR1a、NR1aR1b、COR1a、CSR1a、CN、COOH、COOR1a、CONH2、CONHOH、CONHR1a、CONHOR1a、SO2R1a、SO3H、SO2NH2、CONR1aR1b、SO2NR1aR1b,其中R1a和R1b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1a和R1b可与其所连接的杂原子一起形成杂环基,其中R2可为取代的或未取代的。
或者,在其他实施方案中,当R1为:H和C1-4烷基;H和C1-3烷基;H、甲基和乙基;H和甲基;或者甲基时,R2可选自芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基,其中R2可为取代的或未取代的。
在一个优选实施方案中,R1和R2与其所连接的N一起形成可为取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,并且更优选为5元单环。在某些实施方案中,所述杂环基包含一个或两个,优选1个,另外的杂原子(即除N以外)。所述另外的杂原子可为例如N、O和/或S。优选地,所述杂环基为噁唑烷基。优选地,所述噁唑烷基中的氧原子位于相对于脲氮的3位上。优选地,所述噁唑烷基被一个、两个或三个甲基或乙基基团取代。更优选地,所述噁唑烷基被两个甲基或乙基基团取代。还更优选地,所述噁唑烷基在相同的氮原子上被两个甲基基团取代。更优选地,所述噁唑烷基是4,4-二甲基噁唑烷-3-基。当R1和R2如本段中所定义时,所述化合物优选具有式Ia或IIa。优选地,当R1和R2如本段中所定义并且所述化合物具有式IIa时,R6是取代的或未取代的芳基,并且更优选为苯基。当R1和R2如本段中所定义并且所述化合物具有式Ia时,环A优选为未取代的或取代的苯并部分。
已发现,具有如上段所定义的R1和R2的化合物为相对强的FAAH抑制剂。还发现,所述化合物对FAAH具有相对高的特异性。
在一个替代的实施方案中,R1和R2与其所连接的N一起形成可为取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,并且更优选为6元单环。优选地,R1和R2一起形成吗啉基、哌嗪基、噁唑烷基、吡咯烷基或哌啶基。更优选地,R1和R2一起形成吗啉基或哌嗪基。
优选地,R1和R2一起形成的杂环基被以下基团取代:C1-4烷基、芳基、杂芳基、C3-8环烷基、芳基C1-6烷基、杂芳基C1-6烷基、芳氧基、杂芳氧基、芳基C1-6烷氧基和杂芳基C1-6烷氧基,所述基团中的每一个可被一个或多个卤素或C1-4烷基取代。优选地,所述取代基芳基、杂芳基或C3-8环烷基为5或6元单环。更优选地,R1和R2一起形成的杂环基被芳基、芳基C1-6烷基和芳氧基取代,所述取代基中的每一个可任选被一个或多个卤素取代。还更优选地,R1和R2一起形成的杂环基被苯基、苯基C1-6烷基或苯氧基取代,所述取代基中的每一个可被一个或多个卤素取代。
或者,R1和R2一起形成的杂环基可被杂芳基或杂芳基C1-6烷基取代。在一个实施方案中,所述杂芳基具有双环结构,例如苯并间二氧杂环戊烯基甲基(benzodioxolylmethyl)。或者,所述杂芳基可为单环,例如吡啶基。
在另一个替代实施方案中,R1和R2一起形成的杂环基可被C3-8环烷基取代。优选地,所述C3-8环烷基为单环的环烷基,例如环己基。
在一个实施方案中,R1和R2一起形成的杂环基可为1,4-二氧杂-8-氮杂螺[4.5]癸-8-基、二甲基噁唑烷基、甲基哌嗪基、苄氧基苯基哌嗪基、甲苯氧基哌啶基、吡咯烷基C1-4烷基哌啶基、吡啶基哌啶基、吡啶基氧杂二唑-5-基哌啶基或苄氧基哌啶基。
在一个实施方案中,R1和R2一起形成的杂环基被苯氧基或苯基C1-4烷氧基取代的哌啶基,并且其中所述苯基可被卤素取代。
在本发明的一个实施方案中,当V为C-R3时,R3为H或卤素。
在本发明的另一个实施方案中,当W为C-R4时,R4选自H和芳基。优选地,R4选自H和苯基。更优选地,R4为H。
在本发明的化合物中,环A优选为取代的或未取代的单环芳基或杂芳基部分,并且更优选为单环芳基部分。优选地,环A为取代的或未取代的苯并部分。当环A的单环芳基是取代的时,所述取代基是一个或多个下列基团:卤素、可任选被一个或多个卤素、氰基、羧酸或酰胺取代C1-6烷基或芳基。优选地,所述取代基芳基是单环芳基,并且更优选为苯基。在一个优选实施方案中,具有如本段中所定义的环A的化合物具有式Ia。
在一个实施方案中,环A被选自以下的基团取代:C1-6烷氧基、C1-6烷氧基C1-6烷基和C0-6烷基-CO-C0-6烷基,其中所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的部分取代,其中所述部分中的每一个可被以下基团取代:芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基。优选地,环A被C0-6烷基-CO-C0-6烷基取代,其中所述C0-6烷基-CO-C0-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的部分取代,其中所述部分中的每一个可任选被以下基团取代:芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基。优选地,环A被羰基部分(即C0烷基-CO-C0烷基)取代。优选地,所述C0-6烷基-CO-C0-6烷基被杂环基取代,更优选被单环杂环基取代,还更优选被含一个或多个氮杂原子的杂环基取代,甚至更优选被六元杂环基取代,最优选被哌嗪取代。优选地,所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基是直链。优选地,本段中所述的化合物具有式Ia。
在另一个实施方案中,环A被选自以下的一个或多个基团取代:卤素、C1-6烷基、C1-6烷氧基、OH、ORa、OCORa、SH、SRa、SCORa、NH2、NO2、NHRa、NHSO2NH2、NHSO2Ra、NRaCORb、NHCORa、NHC(NH)NH2、NRaRb、CORa、CSRa、CN、COOH、COORa、CONH2、CONHRa、CONHOH、CONHORa、C(NOH)NH2、CONRaRb、SO2Ra、SO3H、SO2NH2、SO2NRaRb,其中Ra和Rb为C1-6烷基。优选地,环A被选自以下的一个或多个基团取代:卤素、OH、SH、NH2、NO2、NHC(NH)NH2、CN、COOH、CONH2、CONHOH、C(NOH)NH2、SO3H和SO2NH2。更优选地,环A被选自以下的一个或多个基团取代:卤素、OH、NH2、NO2、NHC(NH)NH2、CN、COOH、CONH2、CONHOH、C(NOH)NH2、SO3H和SO2NH2。优选地,如本段中所描述的化合物具有式Ia。
优选地,在本发明化合物中,R5为H或卤素,更优选R5为H。
在一个实施方案中,R5与其所连接的环碳一起不形成羰基基团。所述化合物具有如上所示的式II。
在另一个实施方案中,X不为O。所述化合物具有如上所示的式II。
在式II的化合物中,当X为C-R6时,R6优选为取代的或未取代的芳基。优选地,所述芳基R6为苯基或萘基。更优选地,所述芳基R6为苯基。优选地,所述芳基R6被选自以下的一个或多个基团取代:卤素、C1-4烷氧基、羟基、酰胺、芳基、杂环基、杂芳基、杂环基、芳氧基,所述基团中的每一个可为取代的或未取代的。优选地,R6的芳基取代基可为取代的或未取代的苯基。当R6如本段中所定义时,式II的化合物优选为咪唑(即,X为CH或C-R6,Y为N,Z为CH或C-R8)或为1,2,3-三唑(即,X为CH或C-R6,Y为N,Z为N)。更优选地,所述化合物具有式IIa。
或者,R6优选为H、卤素或芳基,并且更优选为H。当R6如本段中所定义时,式II的化合物优选为吡唑(即,X为CH或C-R6,Y为CH或C-R7,Z为N)。
在本发明的一个实施方案中,当Y为C-R7时,R7选自芳基或杂芳基,所述基团中的每一个可为取代的或未取代的。优选地,所述芳基和杂芳基是单环。优选地,所述芳基或杂芳基被一个或多个卤素取代。在本发明的一个优选实施方案中,R7为取代的或未取代的芳基。当R7如本段中所定义时,式II的化合物优选为吡唑(即,X为CH或C-R6,Y为CH或C-R7,Z为N)或为1,2,4-三唑(即,X为N,Y为CH或C-R7,Z为N)。
在一个实施方案中,当Y为C-R7时,R7为H。
在本发明的另一个实施方案中,当Z为C-R8时,R8选自H和芳基。优选地,R8选自H和苯基。更优选地,R8为H。
在本发明的一个实施方案中,R6为选自芳基、杂芳基、杂环基、C3-10环烷基的基团,其中所述R6基团被选自C1-6烷氧基、C1-6烷氧基C1-6烷基和C0-6烷基-CO-C0-6烷基的基团取代,其中所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的基团取代。优选地,R6为选自芳基、杂芳基、杂环基、C3-10环烷基的基团,其中所述R6基团被选自C1-6烷氧基和C1-6烷氧基C1-6烷基的基团取代,其中所述C1-6烷氧基或C1-6烷氧基C1-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的基团取代。优选地,R6为选自芳基、杂芳基、杂环基、C3-10环烷基的基团,其中所述R6基团被选自C1-6烷氧基和C1-6烷氧基C1-6烷基的基团取代,其中所述C1-6烷氧基或C1-6烷氧基C1-6烷基被杂环基取代。更优选地,R6是被选自C1-6烷氧基和C1-6烷氧基C1-6烷基的基团取代的芳基,其中所述C1-6烷氧基或C1-6烷氧基C1-6烷基被杂环基取代。还更优选地,R6是被C1-6烷氧基取代的芳基,其中所述C1-6烷氧基被杂环基取代。
优选地,R6为芳基。优选地,R6具有单环结构,例如单环的芳基。在一个实施方案中,R6具有六元环结构,例如苯基。
优选地,所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基是直链。
优选地,所述C1-6烷氧基或C1-6烷氧基C1-6烷基的取代基是单环。优选地,所述C1-6烷氧基或C1-6烷氧基C1-6烷基的取代基是六元的。优选地,所述C1-6烷氧基或C1-6烷氧基C1-6烷基的取代基是杂环基。优选地,所述杂环基是完全饱和的。优选地,所述杂环基包含一个或两个杂原子,例如氮或氧。优选地,所述杂环基包含至少一个氮杂原子。在一个实施方案中,所述杂环基是哌啶基、哌嗪基或四氢吡喃基。在该实施方案中,所述化合物优选具有式IIa。
在一个实施方案中,当W为N时,所述CONR1R2基团不连至W。在该实施方案中,所述化合物具有如上所示的式I。
式I和Ia
在式I的化合物中,特别是在式Ia的化合物中,环A优选为取代的或未取代的芳基或杂芳基部分。更优选地,环A为取代的或未取代的单环的芳基或杂芳基部分。还更优选地,环A是取代的或未取代的六元芳基或杂芳基部分。最优选地,环A为取代的或未取代的单环芳基,例如苯并部分。
当环A为取代的时,取代基可为选自以下的一个或多个基团:卤素、OH、C1-4烷基、C1-4烷氧基、SH、NH2、NO2、CN、COOH、CONH2、CONHOH、苯甲酰氧基氨基羰基、SO3H、SO2NH2、芳基、杂芳基、杂环基和C3-8环烷基。当取代基为C1-4烷基、芳基、杂芳基、杂环基或C3-8环烷基时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2、C1-3烷基、C1-3烷氧基和苄基。
优选地,环A的取代基为选自以下的一个或多个基团:卤素、OH、C1-3烷基、C1-3烷氧基、NH2、NO2、CN、COOH、CONH2、单环芳基、单环杂芳基、单环杂环基和C5-8环烷基。当取代基为C1-3烷基、单环芳基、单环杂芳基、单环杂环基或C5-8环烷基时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、CN、COOH、CONH2和C1-3烷氧基。
更优选地,环A的取代基为选自以下的一个或多个基团:卤素、OH、C1-2烷基、C1-2烷氧基和苯基。当取代基为C1-2烷基或苯基时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、CN、COOH、CONH2和C1-3烷氧基。
在式I的化合物、特别是式Ia的化合物的一个优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选为6元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。在一个实施方案中,所述杂环基为吗啉基。在一个替代的实施方案中,所述杂环基为哌嗪基。在其他实施方案中,所述杂环基不包含另外的杂原子(即,其包含单个N原子)。在一个实施方案中,所述杂环基为哌啶基。当所述杂环基为取代的时,其优选被芳基或芳基C1-4烷基取代,其中芳基优选为单环,更优选为苯基。所述烷基优选为直链的。更优选地,所述杂环基被芳基或芳基C1-2烷基取代,其中所述芳基优选为单环,更优选为苯基。
在式I的化合物、特别是式Ia的化合物的一个优选实施方案中,R1选自H和C1-4烷基,R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述取代基中的每一个可为取代的或未取代的。在一个实施方案中,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述取代基中的每一个为单环,并且可为取代的或未取代的。更优选地,R1选自H和甲基。在一个实施方案中,R1为甲基。在一个替代的实施方案中,R1为H。更优选地,R2选自饱和的杂环基和C5-8环烷基,所述取代基中的每一个为单环,并且可为取代的或未取代的。当R2为单环C5-8环烷基时,其优选为未取代的。优选地,R2为环戊基或环己基。更优选地,R2为环己基,例如未取代的环己基。当R2为单环的饱和杂环基时,所述杂环优选包含单个杂原子。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。所述氮杂原子可为取代的或未取代的。
在一个替代的实施方案中,R1选自H、甲基和乙基,R2选自芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C5-8环烷基C1-6烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。更优选地,R2为芳基C1-6烷基,其中所述芳基为单环,并且可为取代的或未取代的。还更优选地,R2为芳基C1-6烷基,其中所述芳基为单环,并且可为取代的或未取代的,并且所述C1-6烷基是直链的。甚至更优选地,R2为苯基C1-6烷基,其可为取代的或未取代的,并且所述C1-6烷基是直链的。在一个实施方案中,所述苯基为未取代的。
在一个替代的实施方案中,R1选自H、甲基和乙基,R2是被选自以下的基团取代的C1-4烷基:芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基和C5-8环烷基C1-4烷氧基,所述基团中的每一个为单环,并且可为取代的或未取代的。优选地,R2为取代的C1-3烷基。在一个实施方案中,R2为取代的C1-2烷基。优选地,R2的取代基为芳基C1-4烷氧基,其中所述芳基为单环,并且可为取代的或未取代的。还更优选地,R2的取代基为芳基C1-4烷氧基,其中所述芳基为单环,并且可为取代的或未取代的,并且所述C1-4烷氧基是直链的。甚至更优选地,R2的取代基为苯基C1-4烷氧基,其可为取代的或未取代的,并且所述C1-4烷氧基是直链的。在一个实施方案中,R2的取代基为芳基C1-3烷氧基,其中所述芳基为单环(例如苯基),并且可为取代的或未取代的,并且所述C1-3烷氧基是直链的。在一些实施方案中,所述苯基为未取代的。
在式I的化合物、特别是式Ia的化合物的又一个实施方案中,R1选自H和C1-4烷基,R2选自取代的或未取代的杂环基。优选地,R1为H、甲基或乙基,R2为取代的或未取代的双环杂环基。更优选地,R1为H或甲基,R2为取代的或未取代的双环杂环基,其中所述杂环基的一个环包含两个氧原子。在一个实施方案中,R2为3,3-二甲基-1,5-二氧杂螺[5.5]十一烷-9-基。
在式I的化合物、特别是式Ia的化合物的一个替代的优选实施方案中,R1选自H和C1-4烷基,R2为C2-20烷基。更优选地,R1为H、甲基或乙基,并且还更优选地,R1为H或甲基。优选地,R2为C3-16烷基,其中所述烷基为直链烷基。更优选地,R2为C4-14烷基,其中所述烷基为直链烷基。
式IIa
在式IIa的化合物的一个优选实施方案中,R1选自H和C1-4烷基,R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。还更优选地,R2选自芳基(例如苯基)、饱和杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。当R2为单环的C5-8环烷基(即,环戊基、环己基、环庚基或环辛基)或芳基时,其优选为未取代的。优选地,R2为环己基,例如未取代的环己基。当R2为单环的饱和杂环基时,所述杂环优选包含单个杂原子,例如氮或氧。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。在一个实施方案中,所述杂原子为取代的或未取代的氮杂原子。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮的位置的4位。在一个实施方案中,所述氮原子被单环芳基(优选苯基)C1-3烷基取代;优选地,所述氮原子被苄基或苯乙基取代;并且,更优选所述氮原子被苄基取代。
在式IIa的化合物的替代优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选5元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。优选地,所述杂环基为噁唑烷基。优选地,所述噁唑烷基中的氧原子位于相对于脲氮的3位。优选地,所述噁唑烷基被一个、两个或三个甲基或乙基取代。更优选地,所述噁唑烷基被两个甲基或乙基取代。还更优选地,所述噁唑烷基在同一碳原子上被两个甲基取代。更优选地,所述噁唑烷基是4,4-二甲基噁唑烷-3-基。
在式IIa的化合物的又一个优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选6元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除了N以外)。所述另外的杂原子可为例如N、O和/或S。在一个实施方案中,所述杂环基为吗啉基。在一个替代的实施方案中,所述杂环基为哌嗪基。在其他实施方案中,所述杂环基不包含另外的杂原子(即,其包含单个N原子)。在一个实施方案中,所述杂环基是哌啶基。当所述杂环基为取代的时,其优选被芳基、芳基C1-4烷基、C5-6环烷基或C5-6环烷基C1-4烷基取代,其中芳基优选为单环,并且更优选为苯基,所述环烷基优选为环己基。所述烷基优选为直链的。在一个实施方案中,所述杂环基被芳基或芳基C1-4烷基(优选C1-2烷基)取代,其中所述芳基优选为单环,并且更优选为苯基。所述芳基可任选被一个或多个卤素原子取代。
在式IIa的化合物中,R5优选选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R5a和R5b可与其所连接的杂原子一起形成杂环基。更优选地,R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R5选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。甚至更优选地,R5选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。还更优选地,R5选自H、C1-2烷基和卤素。甚至更优选地,R5选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R5为H。
在式IIa的化合物中,R6优选选自芳基、杂芳基、杂环基和C3-8环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R6选自芳基和杂芳基,所述基团中的每一个可为取代的或未取代的。在一个实施方案中,所述杂芳基包含一个杂原子,例如氧原子或氮原子。优选地,所述芳基或杂芳基是单环。更优选地,所述芳基或杂芳基是六元单环,例如苯基或吡啶基。在一个实施方案中,所述杂芳基包含被氧原子取代的氮原子,例如氧化吡啶基。在另一个实施方案中,R6为未取代的单环芳基(例如苯基)或被选自以下的一个或多个基团取代的单环芳基(例如苯基):卤素、C1-2烷氧基(任选被一个或多个卤素原子取代)或OH。
在一个实施方案中,R6为未取代的或取代的2-氧-2,3-二氢-1H-苯并[d]咪唑基。
当R6为取代的时,取代基优选为选自以下的一个或多个基团:卤素、C1-4烷氧基、芳基、杂芳基、杂环基、OH、CN、CONH2、NH2、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、NO2、SO2NH2、SO3、C(NOH)NH2、CONHOH、2H-四唑-5-基、二甲基氨基、苄基氨基、甲基磺酰基、吗啉基磺酰基和哌啶基磺酰基。哌啶基磺酰基可任选被芳基甲氧基(优选苄氧基)或OH取代。优选地,所述芳基、杂芳基和杂环基是单环。在一个实施方案中,所述芳基、杂芳基和杂环基是六元单环。在其中R6为单环芳基的具体实施方案中,其可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基(优选C1-2烷氧基)、芳基(例如单环芳基,如苯基)、杂芳基(例如,含一个或两个氮原子或含一个氧原子的单环杂芳基)、杂环基(例如哌嗪基、哌啶基或吗啉基)C1-3烷氧基(优选C1-2烷氧基)、芳基(例如单环芳基,如苯基)C1-3烷氧基(优选C1-2烷氧基)、CONH2、NH2、NO2、OCHF2、SO2NH2、吗啉基磺酰基和C(NOH)NH2。
在其中R6为单环芳基的另一个实施方案中,其任选被选自以下的一个或多个基团取代:卤素、OH、甲氧基、苯基、吡啶基、吡嗪基、吡喃基、哌嗪基甲氧基、哌啶基甲氧基、吗啉基甲氧基、苄氧基、CONH2、NH2、NO2、OCHF2、SO2NH2、吗啉基磺酰基和C(NOH)NH2。
在一个实施方案中,当R6为单环芳基(例如苯基)时,R6的取代基为芳基,优选为单环芳基(例如苯基),其可为取代的或未取代的。当其为取代的时,优选其被CONH2取代。
当R6的取代基为C1-4烷氧基、芳基、杂芳基、杂环基、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基或SO3时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基(其可被一个或多个卤素取代)、CONH2、CN、NCH3CH3、NHCOCH3、甲基羟基丁基和甲基羟基丁炔基。
在式IIa的化合物中,R8优选选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R8a、卤素、OH、OR8a、SH、SR8a、OCOR8a、SCOR8a、NH2、NO2、NHR8a、NR8aR8b、COR8a、CSR8a、CN、COOH、COOR8a、CONH2、SO2R8a、SO3H、SO2NH2、CONR8aR8b、SO2NR8aR8b,其中R8a和R8b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R8a和R8b可与其所连接的杂原子一起形成杂环基。更优选地,R8选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R8选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。甚至更优选地,R8选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。还更优选地,R8选自H、C1-2烷基、卤素和单环芳基(例如苯基)。甚至更优选地,R8选自H、C1-2烷基和卤素(例如F、Cl和Br)。还更优选地,R8选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R8为H。
在式IIa的化合物的一个实施方案中,R1选自H和C1-4烷基,
R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可任选被选自以下的一个或多个基团取代:R2a、卤素、OH、OR2a、OCOR2a、SH、SR2a、SCOR2a、NH2、NHR2a、NHSO2NH2、NHSO2R2a、NR2aCOR2b、NHC(NH)NH2、NHCOR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、CONHOH、CONHR2a、CONHOR2a、C(NOH)NH2、SO2R2a、SO3H、SO2NH2、CONR2aR2b、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或R2a和R2b可与其所连接的杂原子一起形成杂环基,
其中,当R2的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基、杂环基或含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R2c、卤素、OH、OR2c、OCOR2c、SH、SR2c、SCOR2c、NH2、NHR2c、NHSO2NH2、NHSO2R2c、NR2cCOR2d、NHC(NH)NH2、NHCOR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、CONHOH、CONHR2c、CONHOR2c、C(NOH)NH2、SO2R2c、SO3H、SO2NH2、CONR2cR2d、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,
R5选自H、R5a、卤素、OH、OR5a、OCOR5a、SH、SR5a、SCOR5a、NH2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHC(NH)NH2、NHCOR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基,
R6选自芳基、杂芳基、杂环基、C3-10环烷基,所述基团中的每一个可任选被选自以下的一个或多个基团取代:R6a、卤素、OH、OR6a、OCOR6a、SH、SR6a、SCOR6a、NH2、NHR6a、NHSO2NH2、NHSO2R6a、NR6aCOR6b、NHC(NH)NH2、NHCOR6a、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、CONHOH、CONHR6a、CONHOR6a、C(NOH)NH2、SO2R6a、SO3H、SO2NH2、CONR6aR6b、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6a和R6b可与其所连接的杂原子一起形成杂环基,并且其中,当R6为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,
其中,当R6的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基、杂环基或含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R6c、卤素、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NHR6c、NHSO2NH2、NHSO2R6c、NR6cCOR6d、NHC(NH)NH2、NHCOR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、CONHOH、CONHR6c、CONHOR6c、C(NOH)NH2、SO2R6c、SO3H、SO2NH2、CONR6cR6d、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或R2c和R2d与其所连接的杂原子一起形成杂环基,并且其中,当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且
R8选自H、R5a、卤素、OH、OR5a、OCOR5a、SH、SR5a、SCOR5a、NH2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHC(NH)NH2、NHCOR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基。
在以上实施方案中,优选地,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。还更优选地,R2选自杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。优选地,杂环基是完全饱和的。当R2为单环的C5-8环烷基(即,环戊基、环己基、环庚基或环辛基)时,其优选为未取代的。在一个实施方案中,R2为环戊基或环己基,例如未取代的环戊基或未取代的环己基。当R2为单环的饱和杂环基时,所述杂环优选包含单个杂原子,例如氮或氧。优选地,杂环基是六元的,例如哌啶基或四氢吡喃基。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮的位置的4位。在一个实施方案中,杂原子为取代的或未取代的氮杂原子。
在一个具体实施方案中,所述氮原子被选自以下的基团取代:CN、CONH2、C(NOH)NH2、SO2-C1-4烷基、SO2-芳基(任选被C1-4烷基或C1-4卤代烷基例如三氟甲基取代)、CO-杂芳基(任选被杂芳基或卤素取代)、CO-C1-4烷基、COO-C1-4烷基、C1-4烷基(任选被OH、CN、COOH取代)、芳基C1-3烷基、杂芳基C1-3烷基(例如哌啶基C1-3烷基)(任选被COO-C1-3烷基取代)、杂环基C1-3烷基、芳基、杂芳基(任选被一个或多个卤素例如氯取代)和杂环基。优选地,所述氮原子被选自以下的基团取代:CN、CONH2、C(NOH)NH2、SO2-C1-4烷基、SO2-单环芳基(任选被C1-4卤代烷基例如三氟甲基取代)、CO-单环杂芳基(任选被单环杂芳基或卤素取代)、CO-C1-4烷基、COO-C1-4烷基、C1-4烷基(任选被OH、CN、COOH取代)、单环芳基C1-3烷基、单环杂芳基C1-3烷基(例如哌啶基C1-3烷基)(任选被COO-C1-3烷基取代)、单环杂环基C1-3烷基、单环芳基、单环杂芳基(任选被一个或多个卤素例如氯取代)和单环杂环基。更优选地,所述氮原子被选自以下的基团取代:CN、C1-4烷基(任选被OH、CN、COOH取代)、单环芳基C1-3烷基和单环杂芳基C1-3烷基(优选哌啶基C1-3烷基)。还更优选地,所述氮原子被选自以下的基团取代:C1-4烷基(任选被OH、CN、COOH取代)、单环芳基C1-3烷基和单环杂芳基C1-3烷基(优选哌啶基C1-3烷基)。
在一个实施方案中,所述氮原子被单环芳基(优选苯基)C1-3烷基取代;优选地,所述氮原子被苄基或苯乙基取代;更优选地,所述氮原子被苄基取代。
在一个实施方案中,R5为H、卤素、OH或C1-4烷基。优选地,R5为H。
在另一个实施方案中,R6选自芳基、杂芳基和杂环基,所述基团中的每一个可为取代的或未取代的。优选地,R6选自单环芳基(例如苯基)、单环杂芳基(例如吡啶基)和杂环基,所述基团中的每一个可为取代的或未取代的。在一个实施方案中,R6为未取代的芳基。当R6为取代的芳基时,其优选被选自以下的一个或多个基团取代:卤素、R6a、OH、OR6a、NH2、NO2、NHC(NH)NH2、NHR6a、NR6aR6b、C(NOH)NH2、COR6a、COOH、COOR6a、CONH2、CONHOH、SO2R6a、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,
其中,当R6的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基、杂环基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:OR6c、OH和CONH2,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且其中当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代。
优选地,当R6为取代的芳基时,其被选自以下的一个或多个基团取代:卤素、OH、C1-4烷氧基、CONH2、C(NOH)NH2、CONHOH、SO2-C1-4烷基、杂环基(任选被氧原子取代)和芳基(任选被CONH2取代)。在一个实施方案中,R6可被选自以下的一个或多个基团取代:5-氧-4,5-二氢-1,2,4-噁二唑-3-基、3-氨基甲酰基苯基、2H-四唑-5-基、C1-4烷氧基、卤素、OH、CONHOH。
当R6为杂环基时,其优选被氧原子取代。R6的取代基可为2-氧-2,3-二氢-1H-苯并[d]咪唑-5-基或2-氧-2,3-二氢苯并[d]噁唑-5-基。
当R6为杂芳基时,其优选为未取代的或被氧原子取代。例如,所述杂环基可包含N-氧化物。在一个实施方案中,R6为吡啶基或氧化吡啶基。
在另一个实施方案中,R8为H、卤素、OH或C1-4烷基。优选地,R8为H。
式IIb
在式IIb的化合物的一个优选实施方案中,R1选自H和C1-4烷基,R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。还更优选地,R2为单环芳基(例如苯基)并且可为取代的或未取代的。当R2为取代的时,取代基可为芳基、C1-4烷氧基、芳基C1-4烷氧基或芳氧基。优选地,R2的取代基为芳基、C1-3烷氧基、芳基C1-3烷氧基或芳氧基,其中所述芳基为单环,并且更优选为苯基。
当R2为单环C5-8环烷基或芳基时,其优选为未取代的。优选地,R2为环己基,例如未取代的环己基。当R2为单环饱和杂环基时,所述杂环基的环优选包含单个杂原子,例如氮或氧。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。在一个实施方案中,所述杂原子为取代的或未取代的氮杂原子。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮位置的4位。在一个实施方案中,所述氮原子被单环芳基(优选苯基)C1-3烷基取代。
在式IIb的化合物的替代优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,并且更优选为5元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。优选地,所述杂环基为噁唑烷基。优选地,所述噁唑烷基中的氧原子位于相对于脲氮的3位。优选地,所述噁唑烷基被一个、两个或三个甲基或乙基取代。更优选地,所述噁唑烷基被两个甲基或乙基取代。还更优选地,所述噁唑烷基在同一碳原子上被两个甲基取代。更优选地,所述噁唑烷基是4,4-二甲基噁唑烷-3-基。
在式IIb的化合物的又一个优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选为6元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。在一个实施方案中,所述杂环基为吗啉基。在一个替代的实施方案中,所述杂环基为哌嗪基。在其他实施方案中,所述杂环基不包含另外的杂原子(即,其包含单个N原子)。在一个实施方案中,所述杂环基是哌啶基。当所述杂环基为取代的时,其优选被芳基、芳基C1-4烷基、C5-6环烷基或C5-6环烷基C1-4烷基取代,其中所述芳基优选为单环,并且更优选为苯基,并且所述环烷基优选为环己基。烷基优选为直链的。在一个实施方案中,所述杂环基被芳基或芳基C1-4烷基(优选C1-2烷基)取代,其中所述芳基优选为单环,并且更优选地为苯基。所述芳基可任选被一个或多个卤素原子取代。
在式IIb的化合物中,R5优选地选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R5a和R5b可与其所连接的杂原子一起形成杂环基。更优选地,R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R5选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中芳基、杂芳基、杂环基和C5-8环烷基是单环的。甚至更优选地,R5选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中芳基、杂芳基、杂环基和C5-8环烷基是单环。还更优选地,R5选自H、C1-2烷基和卤素。甚至更优选地,R5选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R5为H。
在式IIb的化合物中,R6优选地选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R6a、卤素、OH、OR6a、SH、SR6a、OCOR6a、SCOR6a、NH2、NO2、NHR6a、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、SO2R6a、SO3H、SO2NH2、CONR6aR6b、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R6a和R6b可与其所连接的杂原子一起形成杂环基。更优选地,R6选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R6选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中芳基、杂芳基、杂环基和C5-8环烷基是单环。甚至更优选地,R6选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中芳基、杂芳基、杂环基和C5-8环烷基是单环的。还更优选地,R6选自H、C1-2烷基和卤素。甚至更优选地,R6选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R6为H。
在式IIb的化合物中,R7优选选自芳基、杂芳基、杂环基和C3-8环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R7选自芳基和杂芳基,所述基团中的每一个可为取代的或未取代的。在一个实施方案中,所述杂芳基包含一个杂原子,例如氧原子或氮原子。优选地,所述芳基或杂芳基是单环的。更优选地,所述芳基或杂芳基是六元单环。在一个实施方案中,所述杂芳基包含被氧原子取代的氮原子,例如氧化吡啶基。在另一个实施方案中,R7为未取代的单环芳基(例如苯基)或被选自以下的一个或多个基团取代的单环芳基(例如苯基):卤素、C1-2烷氧基(任选被一个或多个卤素取代)或OH。在一个具体实施方案中,R7为未取代的单环芳基(例如苯基)。
当R7为取代的时,取代基优选为选自以下的一个或多个基团:卤素、C1-4烷氧基、芳基、杂芳基、杂环基、OH、CONH2、NH2、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、NO2、SO2NH2、SO3、C(NOH)NH2和吗啉基磺酰基。优选地,所述芳基、杂芳基和杂环基是单环。在一个实施方案中,芳所述基、杂芳基和杂环基是六元单环。在一个R7为单环芳基的具体实施方案中,其可任选被芳基或杂芳基取代,所述取代基中的每一个是单环。
式IIc
在式IIc的化合物的一个优选实施方案中,R1选自H和C1-4烷基,R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环的并且可为取代的或未取代的。还更优选地,R2选自芳基(例如苯基)、饱和的杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。当R2为单环C5-8环烷基或芳基时,其优选为未取代的。优选地,R2为环己基,例如未取代的环己基。当R2为单环饱和杂环基时,所述杂环基的环优选包含单个杂原子,例如氮或氧。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。在一个实施方案中,所述杂原子是取代的或未取代的氮杂原子。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮位置的4位。在一个实施方案中,所述氮原子被单环芳基(优选苯基)C1-3烷基取代。
在式IIc的化合物的替代优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,并且更优选为5元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。优选地,所述杂环基为噁唑烷基。优选地,所述噁唑烷基中的氧原子位于相对于脲氮的3位。优选地,所述噁唑烷基被一个、两个或三个甲基或乙基取代。更优选地,所述噁唑烷基被两个甲基或乙基取代。还更优选地,所述噁唑烷基在同一碳原子上被两个甲基取代。更优选地,所述噁唑烷基是4,4-二甲基噁唑烷-3-基。
在式IIc的化合物的又一个优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选为6元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。在一个实施方案中,所述杂环基为吗啉基。在一个替代的实施方案中,所述杂环基为哌嗪基。在其他实施方案中,所述杂环基不包含另外的杂原子(即,其包含单个N原子)。在一个实施方案中,所述杂环基是哌啶基。当所述杂环基为取代的时,其优选被芳基、芳基C1-4烷基、C5-6环烷基或C5-6环烷基C1-4烷基取代,其中所述芳基优选为单环,并且更优选为苯基,并且所述环烷基优选为环己基。所述烷基优选为直链的。在一个实施方案中,所述杂环基被芳基或芳基C1-4烷基(优选C1-2烷基)取代,其中所述芳基优选为单环,并且更优选为苯基。所述芳基可任选被一个或多个卤素原子取代。
在式IIc的化合物中,R5优选选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R5a和R5b可与其所连接的杂原子一起形成杂环基。更优选地,R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R5选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。甚至更优选地,R5选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。还更优选地,R5选自H、C1-2烷基和卤素。甚至更优选地,R5选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R5为H。
在式IIc的化合物中,R6优选选自芳基、杂芳基、杂环基和C3-8环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R6选自芳基和杂芳基,所述基团中的每一个可为取代的或未取代的。在一个实施方案中,所述杂芳基包含一个杂原子,例如氧原子或氮原子。优选地,所述芳基或杂芳基是单环。更优选地,所述芳基或杂芳基是六元单环。在一个实施方案中,所述杂芳基包含被氧原子取代的氮原子,例如氧化吡啶基。在另一个实施方案中,R6为未取代的单环芳基(例如苯基)或被选自以下的一个或多个基团取代的单环芳基(例如苯基):卤素、C1-2烷氧基(任选被一个或多个卤素取代)或OH。在一个优选实施方案中,R6为未取代的芳基,并且优选为单环芳基(例如苯基)。
当R6为取代的时,所述取代基优选为选自以下的一个或多个基团:卤素、C1-4烷氧基、芳基、杂芳基、杂环基、OH、CONH2、NH2、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、NO2、SO2NH2、SO3、C(NOH)NH2和吗啉基磺酰基。优选地,所述芳基、杂芳基和杂环基是单环。在一个实施方案中,所述芳基、杂芳基和杂环基是六元单环。在一个R6为单环芳基的具体实施方案中,其可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基、芳基(例如单环芳基,如苯基)、杂芳基(例如,含一个或两个氮原子或含一个氧原子的单环杂芳基)、杂环基(例如,哌嗪基、哌啶基或吗啉基)C1-3烷氧基、芳基(例如单环芳基,如苯基)C1-3烷氧基、CONH2、NH2、NO2、OCHF2、SO2NH2、吗啉基磺酰基和C(NOH)NH2。
在一个实施方案中,当R6为单环芳基(例如苯基)时,R6的取代基为芳基,优选为单环芳基(例如苯基),其可为取代的或未取代的。当其为取代的时,优选其被CONH2取代。
当R6的取代基为C1-4烷氧基、芳基、杂芳基、杂环基、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基或SO3时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基(其可被一个或多个卤素取代)、CONH2、CN、NCH3CH3、NHCOCH3、甲基羟基丁基和甲基羟基丁炔基。
式IId
在式IId的化合物的一个优选实施方案中,R1选自H和C1-4烷基,R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R1为甲基。更优选地,R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。还更优选地,R2选自芳基(例如苯基)、饱和杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。甚至更优选地,R2为芳基,例如苯基,其为单环,并且可为取代的或未取代的。当R2为取代的时,所述取代基优选为一个或多个卤素。
在一个实施方案中,R2为环己基,例如未取代的环己基。当R2为单环饱和杂环基时,所述杂环优选包含单个杂原子,例如氮或氧。更优选地,所述杂环基是六元的,例如哌啶基或四氢吡喃基。在一个实施方案中,所述杂原子是取代的或未取代的氮杂原子。优选地,所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮位置的4位。在一个实施方案中,氮原子被单环芳基(优选苯基)C1-3烷基取代。
在式IId的化合物的一个替代优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,并且更优选为5元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。优选地,所述杂环基为噁唑烷基。优选地,所述噁唑烷基中的氧原子位于相对于脲氮的3位。优选地,所述噁唑烷基被一个、两个或三个甲基或乙基取代。更优选地,所述噁唑烷基被两个甲基或乙基取代。还更优选地,所述噁唑烷基在同一碳原子上被两个甲基取代。更优选地,所述噁唑烷基是4,4-二甲基噁唑烷-3-基。
在式IId的化合物的又一个优选实施方案中,R1和R2与其所连接的N一起形成取代的或未取代的杂环基。优选地,所述杂环基为5或6元单环,更优选为6元单环。在某些实施方案中,所述杂环基包含一个或两个、优选1个另外的杂原子(即,除N以外)。所述另外的杂原子可为例如N、O和/或S。在一个实施方案中,所述杂环基为吗啉基。在一个替代的实施方案中,所述杂环基为哌嗪基。在其他实施方案中,所述杂环基不包含另外的杂原子(即,其包含单个N原子)。在一个实施方案中,所述杂环基是哌啶基。当所述杂环基为取代的时,其优选被芳基、芳基C1-4烷基、C5-6环烷基或C5-6环烷基C1-4烷基取代,其中所述芳基优选为单环,并且更优选为苯基,并且所述环烷基优选为环己基。烷基优选为直链的。在一个实施方案中,所述杂环基被芳基或芳基C1-4烷基(优选C1-2烷基)取代,其中所述芳基优选为单环,并且更优选为苯基。所述芳基可任选被一个或多个卤素原子取代。
在式IId的化合物中,R5优选选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且R5a和R5b可与其所连接的杂原子一起形成杂环基。更优选地,R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2。还更优选地,R5选自H、C1-4烷基、芳基、杂芳基、杂环基、C5-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、卤素、OH、SH、NH2、NO2、CN、COOH、CONH2、SO3H、SO2NH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。甚至更优选地,R5选自H、C1-3烷基、芳基、杂芳基、杂环基、C5-8环烷基、卤素、OH、NH2、COOH和CONH2,其中所述芳基、杂芳基、杂环基和C5-8环烷基是单环。还更优选地,R5选自H、C1-2烷基和卤素。甚至更优选地,R5选自H和卤素(例如F、Cl和Br)。在一个实施方案中,R5为H。
在式IId的化合物中,R7优选选自芳基、杂芳基、杂环基和C3-8环烷基,所述基团中的每一个可为取代的或未取代的。更优选地,R7选自芳基和杂芳基,所述基团中的每一个可为取代的或未取代的。在一个实施方案中,所述杂芳基包含一个杂原子,例如氧原子或氮原子。优选地,所述芳基或杂芳基是单环。更优选地,所述芳基或杂芳基是六元单环。在一个实施方案中,所述杂芳基包含被氧原子取代的氮原子,例如氧化吡啶基。在另一个实施方案中,R7为未取代的单环芳基(例如苯基)或被选自以下的一个或多个基团取代的单环芳基(例如苯基):卤素、C1-2烷氧基(任选被一个或多个卤素取代)或OH。
当R7为取代的时,取代基优选为选自以下的一个或多个基团:卤素、C1-4烷氧基、芳基、杂芳基、杂环基、OH、CONH2、NH2、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、NO2、SO2NH2、SO3、C(NOH)NH2和吗啉基磺酰基。优选地,所述芳基、杂芳基和杂环基是单环。在一个实施方案中,所述芳基、杂芳基和杂环基是六元单环。在一个其中R7为单环芳基的具体实施方案中,其可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基、芳基(例如单环芳基,如苯基)、杂芳基(例如,含一个或两个氮原子或含一个氧原子的单环杂芳基)、杂环基(例如,哌嗪基、哌啶基或吗啉基)C1-3烷氧基、芳基(例如单环芳基,如苯基)C1-3烷氧基、CONH2、NH2、NO2、OCHF2、SO2NH2、吗啉基磺酰基和C(NOH)NH2。在一个实施方案中,当R7为单环芳基(例如苯基)时,R7的取代基为芳基(例如单环芳基,如苯基)C1-3烷氧基。
当R7的取代基为C1-4烷氧基、芳基、杂芳基、杂环基、杂环基C1-4烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基或SO3时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、OH、C1-3烷氧基(其可被一个或多个卤素取代)、CONH2、CN、NCH3CH3、NHCOCH3、甲基羟基丁基和甲基羟基丁炔基。
在本发明的一个替代实施方案中,提供一种具有式I或式II的化合物或其可药用盐或酯:
其中R1、R2、R5、环A、V、W、X、Y和Z如上所定义;
条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,
条件是环A不是未取代的苯并、羟基苯并、苯氧基苯并、氟氯苯并、氯苯并、溴苯并、硝基苯并、氨基苯并、氰基苯并、甲基苯并、三氟甲基苯并、三氟甲基氯苯并、苯基酮苯并、苯基羟基甲基苯并、环己基硫代苯并、甲氧基羰基苯并或甲氧基苯并,
条件是当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且
条件是所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
根据本发明的第二方面,提供了一种包含本发明第一方面的化合物和一种或多种可药用赋形剂的药物组合物。
本发明的药物组合物包含本发明的第一方面的任何化合物和任何可药用载体、助剂或介质。可用于本发明的药用组合物中的可药用载体、助剂和介质是在药用制剂领域中常规使用的那些,包括但不限于,糖、糖醇、淀粉、离子交换剂、氧化铝、硬脂酸铝、卵磷脂、血清蛋白(例如人血清白蛋白)、缓冲物质(例如磷酸盐)、甘油、山梨酸、山梨酸钾、饱和植物脂肪酸的部分甘油酯混合物、水、盐或电解质(例如硫酸鱼精蛋白)、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、胶态氧化硅、三硅酸镁、聚乙烯比咯烷酮、基于纤维素的物质、聚乙二醇、羧甲基纤维素钠、聚丙烯酸酯、蜡、聚乙烯-聚环氧丙烷-嵌段聚合物、聚乙二醇和羊毛脂。
本发明的药物组合物可口服给药、肠胃外给药、通过吸入喷雾给药、直肠给药、鼻内给药、颊内给药、阴道给药或经植入型药盒给药。优选口服给药。本发明的药物组合物可包含任何常规的无毒可药用载体、助剂或介质。本文所使用的术语肠胃外包括皮下、皮内、静脉内、肌肉、关节内、滑膜内、胸骨内、鞘内、病灶内和颅内注射或滴注技术。
所述药物组合物可以是无菌注射剂的形式,例如作为无菌水性或油脂性悬浮液。该悬浮液可根据本领域已知的技术使用合适的分散剂或润湿剂(例如Tween 80)和悬浮剂配制。无菌注射剂也可为在可用于肠胃外给药的无毒稀释剂或溶剂中的无菌注射溶液或悬浮液,例如作为1,3-丁二醇中的溶液。可使用的可用介质和溶剂为甘露醇、水、Ringer′s溶液和等渗氯化钠溶液。此外,无菌的不挥发油常规可用作溶剂或悬浮介质。为此目的,可使用任何温和的不挥发油,包括合成的甘油单酯或甘油二酯。脂肪酸,例如油酸及其甘油酯衍生物可用于可注射制剂中,天然可药用的油也可用于其中,例如橄榄油或蓖麻油,尤其是其聚氧乙烯化形式。所述油溶液或悬浮液还可包含长链醇稀释剂或分散剂(例如描述于Ph.Helv中的那些)或类似的醇。
本发明的药物组合物可以任何可口服的剂型口服给药,所述剂型包括但不限于,胶囊剂、片剂、粉剂、颗粒剂和水性悬浮剂和溶液剂。所述剂型是根据药物制剂领域中所熟知的技术而制得。对于口服使用的片剂,通常使用的载体包括乳糖和玉米淀粉。也通常添加润滑剂(例如硬脂酸镁)。对胶囊形式的口服给药,可用的稀释剂包括乳糖和干燥的玉米淀粉。当水性悬浮剂被口服给药时,活性组分可与乳化剂和悬浮剂结合。如果需要,可添加某些甜味剂和/或调味剂和/或着色剂。
本发明的药物组合物还可以用于直肠给药的栓剂形式给药。所述组合物可通过将本发明化合物与合适的无刺激的赋形剂混合制得,所述赋形剂在室温下为固体但在直肠温度下为液体,因此在直肠中将溶化以释放活性组分。这类物质包括但不限于,可可脂、蜂蜡和聚乙二醇。
本发明的药物组合物可通过鼻用气溶剂或吸入给药。这类组合物可根据药物制剂领域中所熟知的技术制备,并且可使用苯甲醇或其他合适的防腐剂、提高生物利用度的吸收促进剂、碳氟化合物和/或本领域已知的其他增溶剂或分散剂,制备为盐水中的溶液。
本发明的化合物可以每剂约1至约20,000μg/kg的剂量给予,这取决于待治疗或预防的病症以及给予所述化合物的受试者的特性。在许多实例中,所述剂量可为每剂约1至约1500μg/kg。对于所给化合物的剂量方案可由本领域技术人员利用本公开内容容易地确定。
在一个具体实施方案中,本发明的药物组合物还包含一种或多种另外的活性药物组分。本发明的化合物可与一种或多种另外的活性药物组分一块给药。该组合物可以是含本发明化合物和一种或多种另外的活性药物组分的单组合物的形式。或者,该组合物可为两种或多种单独的组合物的形式,其中本发明的化合物包含在一种组合物中,一种或多种另外的活性药物组分包含在一种或多种单独的组合物中。
在第三方面中,本发明提供了本发明第一方面的化合物或第二方面的组合物用于治疗的用途。
在第四方面中,本发明提供了本发明第一方面的化合物或第二方面的组合物用于治疗治疗或预防其发生或症状与FAAH酶的底物有关的病症,其中第一方面仅有的适用条件是i)当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,ii)当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且iii)所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
本发明还提供本发明第一方面的化合物或第二方面的组合物在制备用于治疗或预防其发生或症状与FAAH酶的底物有关的病症的药物中的用途,其中第一方面仅有的适用条件是i)当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,ii)当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且iii)所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
其发生或症状与FAAH酶的底物有关的许多病症是本领域技术人员已知的。它们中的一些在上文中有讨论。
在第五方面中,本发明还提供了一种治疗或预防其发生或症状与FAAH酶的底物有关病症的方法,所述方法包括对需要所述治疗或预防的受试者给予治疗有效量的本发明第一方面的化合物或第二方面的组合物,其中第一方面仅有的适用条件是i)当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,ii)当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且iii)所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
第四方面的化合物或第五方面的方法,其中所述病症是与内源性大麻素系统有关的紊乱。
在某些实施方案中,所述待治疗的病症可选自:
(i)疼痛,特别是急性或慢性神经痛,例如偏头痛和神经性疼痛(例如糖尿病性神经性疼痛、疱疹后神经痛、三叉神经痛);与炎性疾病有关急性或慢性疼痛,所述炎性疾病例如关节炎、类风湿性关节炎、骨关节炎、脊椎炎、痛风、血管炎、克罗恩病(Chrohn’s disease)和应激性肠综合征或慢性外周疼痛;
(ii)头晕、呕吐和恶心,特别是由化疗引起;
(iii)进食障碍,特别是不同性质的厌食症和恶病质;
(iv)神经和精神病状,例如震颤、运动障碍、张力障碍、痉挛状态、强迫症、图雷特综合征(Tourette’s syndrome)、任何性质和来源的所有形式的抑郁和焦虑、心境障碍和精神病;
(v)急性和慢性神经变性疾病,例如帕金森氏病(Parkinson’sdisease)、阿尔茨海默病(Alzheimer’s disease)、老年痴呆、亨丁顿舞蹈症(Huntington’s chorea)、与大脑缺血有关的损伤以及与颅内和骨髓创伤有关的损伤;
(vi)癫痫症;
(vii)睡眠障碍,包括睡眠呼吸暂停;
(viii)心血管疾病,例如心力衰竭、高血压、心律失常、动脉硬化、心脏病发作、心肌缺血和肾脏缺血;
(ix)癌症,例如良性皮肤瘤、脑肿瘤和乳头状瘤、前列腺肿瘤和大脑肿瘤(恶性胶质瘤、髓上皮瘤、髓母细胞瘤、神经母细胞瘤、胚胎来源的肿瘤、星形细胞瘤、星形母细胞瘤、室管膜瘤、少突神经胶质瘤、网状组织肿瘤(plexus tumour)、神经上皮瘤、骨骺肿瘤、室管膜母细胞瘤、恶性脑膜瘤、肉瘤病、恶性黑色素瘤和神经鞘瘤);
(x)免疫系统紊乱,特别是自身免疫性疾病,例如牛皮癣、红斑狼疮、结缔组织疾病或胶原疾病、斯耶格伦综合征(syndrome)、强直性脊柱炎、未分化型脊柱炎、贝切特病(Behcet’s disease)、自身免疫溶血性贫血、多发性硬化、肌萎缩性侧索硬化症、淀粉样变性、移植物排斥、影响浆细胞系的疾病、变应性疾病;速发型或迟发型超敏反应、变应性鼻炎或结膜炎、接触性皮炎;
(xi)寄生物的、病毒的或细菌的感染性疾病,例如AIDS和脑膜炎;
(xii)炎性疾病,特别是关节疾病,例如关节炎、类风湿性关节炎、骨关节炎、脊椎炎、痛风、血管炎、克罗恩病(Chrohn’s disease)和应激性肠综合征;
(xiii)骨质疏松症;
(xiv)眼部病症,例如眼内高压和青光眼;
(xv)肺部病症,包括呼吸道疾病、支气管痉挛、咳嗽、哮喘、慢性支气管炎、呼吸道慢性梗阻和肺气肿;
(xvi)胃肠疾病,例如应激性肠综合征、炎性肠紊乱、溃疡、腹泻、尿失禁和膀胱炎症。
在第六方面中,本发明提供了本发明第一方面的化合物在制备用于治疗或预防其发生或症状与FAAH酶的底物有关的病症的药物中的用途,其中第一方面仅有的适用条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶。
第六方面有关的示例性病症在以上有提及。
在第四、第五或第六方面的某些实施方案中,针对第一方面的其他条件中的一个或两个也适用。
下面将通过仅为示例的方式更加详细地描述本发明:
1.合成方法
用于合成本发明化合物的方法通过下文的一般性路线和随后的制备实施例进行举例说明。所以化合物和中间体通过核磁共振(NMR)表征。在制备所述化合物中使用的起始物质和试剂可从供应商处购得或者可通过本领域技术人员已知的方法制备。所述一般性路线仅仅举例说明了通过其可合成本发明化合物的方法,并且对于已经参考本公开内容的本领域技术人员,所述路线的多种修改是可以做出的并且是得到启示的。
在以下路线中的室温是指20℃至25℃的温度。
苯并三唑
5-溴-1H-苯并[d][1,2,3]三唑(1H-苯并[d][1,2,3]三唑衍生物的形成)
向0-5℃的4-溴苯-1,2-二胺(10g,53.5mmol)于乙酸(20ml,349mmol)和水(100ml)的混合物中的溶液中逐滴加入亚硝酸钠(4.06g,58.8mmol)的水(10ml)溶液。在冰浴中搅拌1h,加入更多乙酸(20ml,349mmol),搅拌下加热至80-85℃持续1h,将溶液热过滤以除去不溶解的黑色物质,冷却至0-5℃,老化30min,收集沉淀,用水洗涤,在45℃下真空干燥。收率9.48g(90%)。
N-环己基-N-甲基-1H-苯并[d][1,2,3]三唑-1-甲酰胺(二取代的三唑-1-甲
酰胺的形成)
将1H-苯并[d][1,2,3]三唑(0.5g,4.20mmol)的四氢呋喃(25ml)溶液逐滴加入0-5℃处于搅拌的20%的光气(5.30ml,10.1mmol)的甲苯溶液中。在20-25℃下,将所述反应混合物搅拌2h(通过TLC检测反应完全)。将氩气鼓泡通过所述溶液15min。然后在真空下蒸发溶剂,得到1H-苯并[d][1,2,3]三唑-1-碳酰氯(0.763g,4.20mmol)清油。产物不经进一步纯化而使用。将吡啶(0.357ml,4.41mmol)逐滴加入0-5℃处于搅拌的所述油的四氢呋喃(25ml)溶液中。接着在0-5℃下逐滴加入N-甲基环己胺(0.499g,4.41mmol)。在20-25℃下,将所述反应混合物搅拌过夜。加入水和EtOAc,将有机层分离,用1M HCl、水和盐水洗涤。将有机层干燥(MgSO4)并在真空下蒸发,得到清油。将所述油自2-丙醇/DCM中重结晶,收集固体物,将其在40-45℃下真空干燥。收率230mg(21%)。
(R)-N-(奎宁环-3-基)-1H-苯并[d][1,2,3]三唑-1-甲酰胺盐酸盐(单取代的
三唑-1-甲酰胺的形成)
在0-5℃下,向1H-苯并[d][1,2,3]三唑(0.238g,2mmol)的干燥DCM(5ml)溶液中加入20%的光气(1.052ml,2.000mmol)的甲苯溶液。在20-25℃下,将所述混合物搅拌30min,冷却至0-5℃,在搅拌下加入三乙胺(0.279ml,2.000mmol)。将所述悬浮物用干燥的DCM(5ml)稀释,在0-5℃下,加入固体(R)-奎宁环-3-胺二盐酸盐(0.398g,2.000mmol)和三乙胺(0.836ml,6.00mmol)。使所述混合物经30min升温至20-25℃,并用2-丙醇稀释,蒸干。将残余物分布在水(15ml)和DCM(15ml)之间,将有机相干燥(MgSO4)、浓缩、柱分离(DCM-MeOH 9∶1)、收集馏分,得到油。将所述油溶于含最少量DCM的醚中,将溶液用2M HCl的乙醚溶液酸化至pH 1-2,收集沉淀,将其用醚洗涤,在45℃下真空干燥。收率0.12g(19.5%)。
N-(4-苯基丁基)-1H-苯并[d][1,2,3]三唑-1-甲酰胺(单取代的三唑-1-甲酰
胺的形成)
将(4-异氰酸根合丁基)苯(463mg,2.64mmol)逐滴加入0-5℃处于搅拌的1H-苯并[d][1,2,3]三唑(300mg,2.52mmol)的DCM(18ml)溶液。在20-25℃下,将澄清的反应混合物搅拌过夜。在真空下除去溶剂,得到清油。将所述油静置固化为无色固体。将产物自2-丙醇中重结晶,收集固体物,在45℃下真空干燥。收率477mg(64%)。
咪唑类:
4-(4-氟苯基)-1H-咪唑(咪唑的合成)
在50ml梨形烧瓶中加入2-溴-1-(4-氟苯基)乙酮(5.93g,27.31mmol)、甲酰胺(13.45ml,339mmol)和水(1ml)。将反应物在140℃加热4小时。然后,将其冷却至室温并倾入150ml水中。将沉淀物过滤出,用水洗涤。将滤液的pH通过加入10%NaOH溶液设定至12。将生成的沉淀物过滤,用水洗涤并在真空下干燥。(收率:2.02g,45%)。
(4-苯基-1H-咪唑-1-基)(4-苯基哌嗪-1-基)甲酮(酰化)
向搅拌的4-苯基-1H-咪唑(577mg,4mmol)的四氢呋喃(20ml)溶液中加入吡啶(0.489ml,6.00mmol)和DMAP(48.9mg,0.400mmol)。将淡黄色溶液用4-苯基哌嗪-1-碳酰氯(944mg,4.20mmol)处理并加热至90℃持续20小时。在这以后,真空除去THF,使残余物在DCM∶IPA(70∶30)混合物和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物自热的IPA中重结晶、过滤并真空干燥。(收率:777mg,58%)。
N-(4-氟苯基)-4-(4-羟基苯基)-N-甲基-1H-咪唑-1-甲酰胺(脱保护)
向甲醇-干冰冷却的N-(4-氟苯基)-4-(4-甲氧基苯基)-N-甲基-1H-咪唑-1-甲酰胺(0.283g,0.870mmol)的二氯甲烷(8ml)溶液中加入三溴化硼(0.164ml,1.740mmol)。将黑色的反应混合物升温至室温并搅拌2小时。TLC显示出反应完全,随后将其倾入冰水混合物中并搅拌30min。无沉淀物。将混合物用DCM∶IPA(70∶30)萃取,并将有机相经MgSO4干燥并过滤。通过真空除去DCM,并将产物从IPA沉淀、过滤并真空干燥。(收率:210mg,78%)。
1,2,4-三唑类:
3-(4-氯苯基)-1H-1,2,4-三唑(环的合成)
将4-氯苯甲酰胺(7.371g,47.4mmol)悬浮于1,1-二甲氧基-N,N-二甲基甲胺(15.73ml,118mmol)中。将所述反应混合物在80℃下加热1小时。然后将其冷却至室温并通过真空除去过量的1,1-二甲氧基-N,N-二甲基甲胺。将生成的固体物与石油醚一起研磨、过滤并真空干燥。(收率:9.44g,95%)。
向搅拌的(E)-4-氯-N-((二甲基氨基)亚甲基)苯甲酰胺(9.4g,44.6mmol)的乙酸(13.5ml)溶液中加入水合肼(1.524ml,49.1mmol)。将所述反应混合物迅速固化并加热至120℃持续2小时。在这以后将其冷却至室温并与甲苯共沸。将结晶残余物用水搅拌片刻。将沉淀物过滤出、用水洗涤并真空干燥。(收率:7.27g,91%)。
(3-(4-甲氧基苯基)-1H-1,2,4-三唑-1-基)(吗啉基)甲酮(酰化)
向搅拌的3-(4-甲氧基苯基)-1H-1,2,4-三唑(701mg,4mmol)的四氢呋喃(20ml)溶液中加入吡啶(0.489ml,6.00mmol)、DMAP(48.9mg,0.400mmol)。将溶液用吗啉-4-碳酰氯(0.490ml,4.20mmol)处理并加热至90℃持续20小时。TLC显示出反应几乎完全。通过真空除去THF,使残余物在DCM和水之间进行分配。将有机相经MgSO4干燥、过滤并蒸发。自热的IPA中重结晶,得到749mg白色晶体(收率:65%)。
1,2,3-三唑类:
4-苯基-1H-1,2,3-三唑(环的合成)
向搅拌的苯基乙炔(1.098ml,10mmol)的无水甲苯(10ml)溶液中一次性加入叠氮基三甲基硅烷(2.65ml,20.00mmol)。将反应物在100℃下加热3天,在这以后,将其冷却至室温并通过真空除去甲苯。使残余物在DCM和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物在石油醚∶EtOAc=2∶1中柱层析。(收率:355mg,24%)。
吗啉基(4-苯基-1H-1,2,3-三唑-1-基)甲酮(酰化)
向搅拌的4-苯基-1H-1,2,3-三唑(0.340g,2.342mmol)的四氢呋喃(12ml)溶液中加入吡啶(0.286ml,3.51mmol)、DMAP(0.029g,0.234mmol)。将所述溶液用吗啉-4-碳酰氯(0.287ml,2.459mmol)处理。将所述反应物加热至90℃持续20小时。然后,通过真空除去THF,使残余物在DCM和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物自IPA中重结晶、过滤并真空干燥。(收率:193mg,29%)。
吡唑类:
3-苯基-1H-吡唑(环的合成)
将苯乙酮(5.89ml,50mmol)溶于1,l-二甲氧基-N,N-二甲基甲胺(13.39ml,100mmol)中。将所述反应混合物在120℃加热24小时。将深红色的溶液冷却至室温并通过真空除去过量的1,1-二甲氧基-N,N-二甲基甲胺。将生成的固体与石油醚一起研磨、过滤并真空干燥。(收率:6.78g,77%)。
向搅拌的(E)-3-(二甲基氨基)-1-苯基丙-2-烯-1-酮(2.63g,15mmol)的乙醇(40ml)溶液中加入水合肼(1.459ml,30.0mmol)。将所述反应物加热至100℃持续2小时。在这以后,将其冷却至室温并通过真空除去乙醇。使所述残余物在DCM和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物通过与石油醚和乙酸乙酯的混合物一起研磨进行纯化。(收率:1.59g,73%)。
吗啉基(3-(吡啶-3-基)-1H-吡唑-1-基)甲酮(酰化)
向搅拌的3-(1H-吡唑-3-基)吡啶(0.435g,3mmol)的四氢呋喃(15ml)溶液中加入吡啶(0.367ml,4.50mmol)、DMAP(18.33mg,0.150mmol)。将所述溶液用4-吗啉碳酰氯(0.368ml,3.15mmol)处理。将所述反应物加热至80℃持续20小时。通过真空除去THF,使残余物在DCM和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物在石油醚∶EtOAc=2∶l中柱层析。(收率:174mg,21%)。
苯并咪唑类:
N-甲基-N-苯基-1H-苯并[d]咪唑-1-甲酰胺(酰化)
向搅拌的1H-苯并[d]咪唑(354mg,3mmol)的四氢呋喃(15ml)溶液中加入吡啶(0.367ml,4.50mmol),接着加入甲基(苯基)氨基甲酰氯(534mg,3.15mmol)。将所述反应物加热至80℃持续20小时。通过真空除去THF,使残余物在DCM和水之间进行分配。将有机相经MgSO4干燥并过滤。在蒸发后,将粗产物在石油醚∶EtOAc=2∶1中柱层析。
(收率:365mg,46%)。
在如下部分中,提供了用于具体化合物的另外的合成实施例。
化合物362的制备
a)N-环己基-N-甲基-4-(吡啶-3-基)-1H-咪唑-1-甲酰胺
向搅拌的3-(1H-咪唑-4-基)吡啶二盐酸盐(1.745g,8mmol)于四氢呋喃(29mL)和DMF(2.90mL)的混合物中的悬浮液中加入2-甲基丙-2醇钾(1.795g,16.0mmol),并将所述混合物回流30分钟。将生成的棕色悬浮物冷却至室温并用吡啶(0.979mL,12mmol)和N,N-二甲基吡啶-4-胺(0.098g,0.8mmol)处理,接着加入环己基(甲基)氨基甲酰氯(1.476g,8.4mmol)。将所述反应物加热至90℃过夜,在这以后将所述混合物用水稀释并用乙酸乙酯萃取。将有机相干燥(MgSO4)并过滤。在蒸发后,将粗产物使用二氯甲烷/甲醇(9∶1)混合物在硅胶上进行层析。将同质馏分合并并蒸发,留下白色粉末,(160mg,7%)。
b)3-(1-(环己基(甲基)氨基甲酰基)-1H-咪唑-4-基)吡啶1-氧化物
向搅拌的N-环己基-N-甲基-4-(吡啶-3-基)-1H-咪唑-1-甲酰胺(90mg,0.317mmol)的氯仿(5mL)溶液中一次性加入3-氯苯并过氧酸(149mg,0.475mmol)。使所述反应物在室温下搅拌20h。TLC显示出反应完全并将所述混合物蒸干。将残余物与乙醚一起研磨并将生成的白色晶体过滤出,并在空气中干燥。自热的异丙醇中重结晶,得到白色粉末(46mg,46%)。
化合物408的制备
N-环己基-N-甲基-4-(3-(2-吗啉基乙氧基)苯基)-1H-咪唑-1-甲酰胺盐酸盐
在氮气气氛下,将N-环己基-4-(3-羟基苯基)-N-甲基-1H-咪唑-1-甲酰胺(170mg,0.568mmol)溶解于无水四氢呋喃(10mL)中,得到无色溶液。加入N-β-羟基乙基吗啉(0.068mL,0.568mmol)并将溶液冷却至0℃。加入三苯基膦(179mg,0.681mmol),然后滴加DEAD(0.108mL,0.68mmol),使加入每一滴后形成的黄色消失后再加入下一滴。使所生成的浅黄色溶液升温至室温并搅拌18h。然后,将所述反应混合物冷却至0℃并加入另一份三苯基膦(179mg,0.681mmol)和DEAD(0.108mL,0.68mmol)。将所述溶液再搅拌6h。将溶剂蒸发并将黄色油通过色谱(硅胶H;9/1、8/2、6/4、5/5、4/6甲苯/丙酮)纯化。将含纯产物的馏分蒸发并将浅黄色油溶解于乙酸乙酯,其随后产生沉淀物。将悬浮物加热以溶解固体,然后将所述溶液冷却至0℃。逐滴加入过量2N HCl的乙醚溶液。在0℃下,将所生成的混合物搅拌10分钟,然后升温至室温并再搅拌15分钟。将所述沉淀物过滤、用乙醚洗涤并干燥。自乙酸乙酯中重结晶,得到乳白色固体物,(39mg,14%)。
化合物397的制备
a)4-(2-(4-(1-(环己基(甲基)氨基甲酰基)-1H-咪唑-4-基)苯氧基)乙基)哌嗪-1-甲酸叔丁基酯
将N-环己基-4-(4-羟基苯基)-N-甲基-1H-咪唑-1-甲酰胺(200mg,0.668mmol)加入50mL梨形烧瓶内处于氮气气氛下的四氢呋喃(10mL)中,得到浅粉色溶液。加入4-(2-羟基乙基)哌嗪-1-羧酸叔丁基酯(184mg,0.8mmol)并将所述溶液冷却至0℃。加入三苯基膦(210mg,0.801mmol),然后滴加DEAD(0.127mL,0.8mmol),使加入每一滴后形成的黄色消失后再加入下一滴。使所生成的浅黄色溶液升温至室温并搅拌24h。将所述溶剂蒸发并将浅黄色油通过色谱(硅胶H;10%、20%、30%、40%、50%、60%丙酮/甲苯)纯化。将含纯产物的馏分蒸发,浅褐色固体(167mg)不经进一步纯化用于下一步骤。
b)N-环己基-N-甲基-4-(4-(2-(哌嗪-1-基)乙氧基)苯基)-1H-咪唑-1-甲酰胺二盐酸盐
在25mL梨形烧瓶中加入4-(2-(4-(1-(环己基(甲基)氨基甲酰基)-1H-咪唑-4-基)苯氧基)乙基)哌嗪-1-羧酸叔丁基酯(167mg,0.326mmol)。加入三氟乙酸(3mL,38.9mmol),得到浅黄色溶液,将所述溶液在室温下搅拌1h。将所述溶剂蒸发,将残余黄色油溶于乙酸乙酯中并冷却至0℃。在这之后,加入过量2N HCl的乙醚溶液。在0℃下,将所述混合物搅拌10分钟,随后升温至室温并搅拌15分钟。将所述混合物蒸发,将残余物自异丙醇中重结晶。将所述晶体过滤,用异丙醇洗涤并干燥,得到白色固体产物(115mg,69%)。
化合物389的制备
a)1-(4,4-二甲基噁唑烷-3-羰基)-1H-苯并[d][1,2,3]三唑-5-羧酸
将1H-苯并[d][1,2,3]三唑-5-羧酸(3g,18.39mmol)于四氢呋喃(90mL)和二甲基甲酰胺(50mL)的混合物中的溶液逐滴加入到0℃处于搅拌的氢化钠(1.839g,46mmol)的四氢呋喃(30mL)悬浮物中。将所述悬浮物在室温下搅拌30分钟,然后在0℃下逐滴加入4,4-二甲基噁唑烷-3-碳酰氯(3.16g,19.31mmol)的四氢呋喃(10mL)溶液。将所述反应混合物在室温下搅拌4h。在0℃下加入水并将所述溶剂蒸发。加入二氯甲烷/异丙醇(7∶3)的混合物,将有机层分离。将水层用二氯甲烷再萃取并将合并的有机层干燥(MgSO4)、过滤并蒸发。将橙色残余物自异丙醇中重结晶,得到浅褐色固体物(840mg),其不经进一步纯化用于下一步骤。
b)1-(4,4-二甲基噁唑烷-3-羰基)-1H-苯并[d][1,2,3]三唑-5-甲酰胺
将亚硫酰氯(0.633mL,8.67mmol)在室温下逐滴加入到搅拌的1-(4,4-二甲基噁唑烷-3-羰基)-1H-苯并[d][1,2,3]三唑-6-羧酸(0.763g,2.63mmol)和吡啶(0.702mL,8.67mmol)的二氯甲烷(17mL)溶液中。在室温下,将黄色溶液搅拌15分钟。然后,将该溶液逐滴加入到0℃的1.75N的氨(15.02mL,26.3mmol)的乙醇溶液中,在这之后形成白色悬浮物。在室温下,将所述反应混合物再搅拌30分钟。加入水并将乙醇蒸发。然后,将残余物用二氯甲烷稀释,将有机层分离并用1N HCl溶液洗涤。将有机层干燥(MgSO4)、过滤并蒸发,得到黄色固体物。将所述固体物自二氯甲烷/乙醇混合物中重结晶,得到浅褐色固体产物(151mg,20%)。
化合物438的制备
N-环己基-4-(4-甲氧基-3-(2H-四唑-5-基)苯基)-N-甲基-1H-咪唑-1-甲酰胺
将4-(3-氰基-4-甲氧基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(305mg,0.901mmol)、二丁基锡烷酮(28.0mg,0.113mmol)和叠氮基三甲基硅烷(0.239ml,1.803mmol)的混合物在甲苯(8mL)中加热至115℃维持20h。然后,将所述混合物冷却至室温并蒸干。将粗产物使用二氯甲烷/甲醇(95∶5)混合物在二氧化硅上进行层析。将同质馏分蒸发后,将剩余产物与乙醚一起研磨、过滤并干燥,得到灰白色晶体产物(196mg,54%)。
化合物576的制备
4-(3-(2H-四唑-5-基)苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺
将搅拌的4-(3-(2-苄基-2H-四唑-5-基)苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(256mg,0.58mmol)、10%钯碳(30.9mg,0.029mmol)和环己烯(1.175ml,11.6mmol)的混合物在封闭管中加热至80℃。然后,将所述反应物冷却至室温,过滤通过硅藻土盘并蒸干。将剩余的油使用二氯甲烷/甲醇(90∶10)的混合物在二氧化硅上进行层析。将同质馏分合并并蒸发,将残余油自乙醚结晶,得到灰白色粉末产物(45mg,21%)。
化合物423的制备
N-(1-苄基哌啶-4-基)-4-(3-(羟基氨基甲酰基)苯基)-N-甲基-1H-咪唑-1-甲酰胺
向-78℃处于搅拌的4-(3-(苄氧基氨基甲酰基)苯基)-N-(1-苄基哌啶-4-基)-N-甲基-1H-咪唑-1-甲酰胺(120mg,0.229mmol)的二氯甲烷(5mL)悬浮物中加入三溴化硼(0.022mL,0.229mmol)。在冷却下,将所述反应物搅拌5分钟,随后经1h升温至室温。将所述混合物冷却至-20℃并用甲醇小心淬灭。在这之后,将所述溶剂蒸掉,将残余物溶于二氯甲烷/异丙醇(7∶3)的混合物中,用饱和NaHCO3溶液洗涤,然后干燥(MgSO4)。在过滤后,将二氯甲烷蒸发至小体积,并将所生成的沉淀物过滤出,用异丙醇洗涤并干燥,得到灰白色粉末产物(58mg,55%)。
化合物551的制备
a)(Z)-N-环己基-4-(4-(N′-羟基甲脒基)苯基)-N-甲基-1H-咪唑-1-甲酰胺
在室温下,将4-(4-氰基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(600mg,1.946mmol)加入25mL圆底烧瓶中的乙醇(9mL)中,得到白色悬浮物。逐滴加入50%的羟胺水溶液(0.298mL,4.86mmol)并将所生成的混合物加热至90℃维持90分钟。然后,将所述混合物冷却至室温,形成一些沉淀物,将所述沉淀物过滤并用乙醇洗涤。将该固体物自热的乙酸乙酯(约70mL)和石油醚(约150mL)的混合物中重结晶。将晶体过滤,用石油醚洗涤并干燥,得到白色固体物(230mg,29%)。
b)(Z)-N-环己基-4-(4-(N′-(甲氧基羰氧基)甲脒基)苯基)-N-甲基-1H-咪唑-1-甲酰胺
在氮气气氛下,将(Z)-N-环己基-4-(4-(N′-羟基甲脒基)苯基)-N-甲基-1H-咪唑-1-甲酰胺(228mg,0.668mmol)加入25mL梨形烧瓶中的无水二氯甲烷(3mL)中,得到白色悬浮物。加入三乙胺(0.102mL,0.735mmol),将所述悬浮物冷却至0℃并搅拌30分钟。在这之后,逐滴加入氯甲酸甲酯(0.065mL,0.835mmol)并在0℃下将混合物搅拌30分钟,然后升温至室温,再搅拌30分钟。将沉淀物过滤出,并溶解于异丙醇和二氯甲烷的混合物(3∶7)中。将该溶液与获自以上的滤液合并,用1N HCl、水和盐水洗涤,然后干燥(MgSO4)、过滤并蒸发,得到白色固体物(228mg,82%)。
c)N-环己基-N-甲基-4-(4-(5-氧-4,5-二氢-1,2,4-噁二唑-3-基)苯基)-1H-咪唑-1-甲酰胺
在氮气气氛下,将(Z)-N-环己基-4-(4-(N′-(甲氧基羰氧基)甲脒基)苯基)-N-甲基-1H-咪唑-1-甲酰胺(200mg,0.501mmol)加入50mL梨形烧瓶中的二甲苯(10mL)中,得到白色悬浮物。将所述混合物加热至140℃维持4h,然后冷却至室温。将所形成的沉淀物过滤出并将滤饼用二甲苯洗涤。在干燥后,将该固体溶于二氯甲烷和异丙醇的混合物中。在蒸发成小体积后,将所述溶液冷却至室温,将所形成的沉淀物滤出并干燥,得到浅粉色固体产物(134mg,69%)。
化合物553的制备
a)4-(3-氨基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺
在室温和氩气气氛下,将10%钯碳(0.122g,0.115mmol)加入搅拌的N-环己基-N-甲基-4-(3-硝基苯基)-1H-咪唑-1-甲酰胺(0.755g,2.299mmol)于乙酸乙酯(46mL)和甲醇(46mL)的混合物中的溶液中。然后,在氢气气氛和室温下,将所述混合物搅拌50分钟。将所述混合物过滤通过硅藻土,并用甲醇洗涤板状物。将合并的滤液蒸发,得到清油/泡沫(691mg,100%),其不经进一步纯化用于下一步骤。
b)N-环己基-4-(3-胍基苯基)-N-甲基-1H-咪唑-1-甲酰胺盐酸盐
在室温下,将气态无水氯化氢(0.096mL,1.156mmol)加入搅拌的4-(3-氨基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(0.345g,1.156mmol)和氨基氰(0.135mL,1.734mmol)的乙醇(1.2mL)悬浮物中。将澄清溶液搅拌回流1h,形成无色固体物。将所述反应混合物继续搅拌回流7h,在这之后使所述混合物冷却。将固体物通过过滤分离并用乙醇洗涤,得到无色固体产物(298mg,68%)。
BIA化合物533的制备
a)N-甲基-N-(哌啶-4-基)-4-(吡啶-3-基)-1H-咪唑-1-甲酰胺二(2,2,2-三氟乙酸酯)
向4-(N-甲基-4-(吡啶-3-基)-1H-咪唑-1-甲酰氨基)哌啶-1-羧酸叔丁基酯(500mg,1.297mmol)中加入三氟乙酸(4mL,51.9mmol),得到浑浊液。在室温下,将所述混合物搅拌1h,在这之后通过蒸发除去溶剂。将油状残余物与乙醚一起研磨,并且将所生成的白色固体物过滤出,得到白色固体(653.2mg,88%收率)。
b)N-甲基-N-(1-(甲基磺酰基)哌啶-4-基)-4-(吡啶-3-基)-1H-咪唑-1-甲酰胺
向冰水冷却的N-甲基-N-(哌啶-4-基)-4-(吡啶-3-基)-1H-咪唑-1-甲酰胺二(2,2,2-三氟乙酸酯)(300mg,0.584mmol)的二氯甲烷(10mL)悬浮液中加入DMAP(35.7mg,0.292mmol),接着滴加三乙胺(0.326mL,2.337mmol),接着依次加入甲磺酰氯(0.072mL,0.934mmol)。在室温下,将所述溶液搅拌过夜,在这之后通过加入甲醇将其淬灭并在室温下搅拌。将白色沉淀物通过过滤收集,用甲醇和乙醚洗涤,然后干燥,得到白色固体产物(158mg,74%)。
化合物550的制备
N-(1-苄基哌啶-4-基)-4-(3′-氨基甲酰基联苯-3-基)-N-甲基-1H-咪唑-1-甲酰胺
在室温下,将四(三苯基膦)钯复合物(0.076g,0.066mmol)加入搅拌的N-(1-苄基哌啶-4-基)-4-(3-溴苯基)-N-甲基-1H-咪唑-1-甲酰胺(0.600g,1.323mmol)、3-氨基甲酰基苯基硼酸(0.229g,1.390mmol)和2M碳酸钠溶液(0.794mL,1.588mmol)于1-丙醇(5mL)和水(1mL)的混合物中的分散物中。在90℃下,将所述反应混合物搅拌1h。加入水并将有机层用二氯甲烷/异丙醇(7∶3)混合物稀释。将有机层分离、干燥(MgSO4)、过滤并蒸发,得到橙色油。通过柱层析(二氧化硅,二氯甲烷/甲醇5%)得到产物橙色油。将所述油与石油醚/乙酸乙酯/乙醚的混合物一起研磨,得到浅褐色固体产物(123mg,17%)。
化合物485的制备
a)4-(3-氨基-4-甲氧基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺
在氩气气氛和室温下,将10%钯碳(0.16g,0.15mmol)加入搅拌的N-环己基-4-(4-甲氧基-3-硝基苯基)-N-甲基-1H-咪唑-1-甲酰胺(1.075g,3mmol)于乙酸乙酯(50mL)和甲醇(50mL)的混合物中的溶液中。使氢气鼓泡通过溶液持续1h。然后,将所述溶液过滤通过硅藻土,并用乙酸乙酯洗涤板状物。将合并的滤液蒸发,得到棕色油状固体物,其不经进一步纯化用于下一步骤。
b)N-环己基-4-(4-甲氧基-3-(甲基磺酰氨基)苯基)-N-甲基-1H-咪唑-1-甲酰胺
在室温下,将甲磺酰氯(0.247mL,3.17mmol)加入搅拌的4-(3-氨基-4-甲氧基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(1.04g,3.17mmol)和三乙胺(0.441mL,3.17mmol)的四氢呋喃(6mL)溶液中。在室温下,将所述棕色混合物搅拌过周末。加入水并将溶剂蒸发。然后,将水层酸化并将残余物用乙酸乙酯萃取。将水层用二氯甲烷/异丙醇(7∶3)混合物萃取两次。将有机层分离、干燥(MgSO4)、过滤并蒸发,得到灰白色固体物。将所述固体物自乙醇/二氯甲烷混合物中重结晶,得到灰白色固体产物(434mg,34%)。
化合物564的制备
N-环戊基-N-甲基-4-(2-氧-2,3-二氢苯并[d]噁唑-5-基)-1H-咪唑-1-甲酰胺
在室温下,将20%的光气的甲苯溶液(0.590mL,1.121mmol)滴加至搅拌的4-(3-氨基-4-羟基苯基)-N-环戊基-N-甲基-1H-咪唑-1-甲酰胺(0.259g,0.862mmol)的二氯甲烷(5mL)溶液中,并将所述灰白色悬浮物搅拌5h。加入水并将有机层用二氯甲烷/异丙醇(7∶3)混合物稀释。将有机层分离、干燥(MgSO4)、过滤并蒸发,得到灰白色固体物,将所述固体物与热的甲醇一起研磨。过滤并干燥得到灰白色固体产物(90mg,30%)。
化合物580的制备
N-环己基-N-甲基-4-(4-(氨磺酰基氨基)苯基)-1H-咪唑-1-甲酰胺
在室温下,将磺酰胺(0.089g,0.922mmol)加入搅拌的4-(4-氨基苯基)-N-环己基-N-甲基-1H-咪唑-1-甲酰胺(0.250g,0.838mmol)的二氧杂环己烷(2mL)悬浮物中。将所述悬浮物加热回流4h,得到澄清溶液,在这之后加入更多磺酰胺(0.089g,0.922mmol),将混合物继续加热回流2.5h。除去所述溶剂,将棕色残余物通过层析法(二氧化硅,二氯甲烷/甲醇,1%、2%、5%)纯化。将均质馏分合并并蒸发。将残余物与乙酸乙酯一起研磨,通过过滤除去所形成的无色固体物。将滤液蒸发,并通过制备型TLC(二氧化硅,二氯甲烷/10%甲醇)再次纯化。将所述产物用乙酸乙酯/10%甲醇混合物从二氧化硅萃取。蒸发溶剂得到清油,将所述清油与乙酸乙酯和甲醇混合物一起研磨,得到灰白色固体产物(19mg,6%)。
化合物541的制备
N-(1-(2-氰基乙基)哌啶-4-基)-4-(3-氟-4-甲氧基苯基)-N-甲基-1H-咪唑-1-甲酰胺
在室温下,将三乙胺(0.159mL,1.139mmol)加入搅拌的4-(3-氟-4-甲氧基苯基)-N-甲基-N-(哌啶-4-基)-1H-咪唑-1-甲酰胺盐酸盐(0.200g,0.542mmol)和3-氯丙腈(0.058g,0.651mmol)的悬浮物中。将所述澄清溶液搅拌回流2h,在此期间形成白色悬浮物。使所述混合物冷却至室温,用二氯甲烷/异丙醇(7∶3)混合物稀释,然后用水洗涤。将有机层干燥(MgSO4)、过滤并蒸发,得到无色固体物,将所述固体物与乙醇一起研磨,得到产物(142mg,64%)。
化合物505的制备
a)(1H-苯并[d][1,2,3]三唑-5-基)(4-环己基哌嗪-1-基)甲酮
在氮气气氛下,将1H-苯并[d][1,2,3]三唑-5-羧酸(510mg,3.126mmol)加入100mL圆底烧瓶中的无水四氢呋喃(10mL)中,得到棕色悬浮物。将CDI(558mg,3.439mmol)分几份加入,并在室温下将所述混合物搅拌1.5h。然后,将1-环己基哌嗪(658mg,3.908mmol)分几份加入,并在室温下将所生成的棕色溶液继续搅拌30分钟。将所述溶剂蒸发,并使棕色油在30%异丙醇/二氯甲烷/水中进行分配。分离各相,将有机相用水和盐水洗涤,然后干燥(MgSO4)、过滤并蒸发。将所生成的浅褐色泡沫通过层析法(硅胶H;二氯甲烷,2%、3%、5%甲醇/二氯甲烷)纯化。将含有纯净产物的馏分蒸发,并将浅橙色泡沫与庚烷一起研磨。将所述固体物过滤并干燥,得到浅褐色固体物(605mg,54%)。
b)(4-环己基哌嗪-1-基)(2-(4,4-二甲基噁唑烷-3-羰基)-2H-苯并[d][1,2,3]三唑-5-基)甲酮草酸盐
将(1H-苯并[d][1,2,3]三唑-5-基)(4-环己基哌嗪-1-基)甲酮(612mg,1.953mmol)加入100mL圆底烧瓶中的四氢呋喃(15mL)和N,N-二甲基甲酰胺(3mL)中,得到浅黄色溶液。将该溶液冷却至0℃,加入60%的氢化钠的矿物油分散体(70.3mg,2.93mmol)。将所生成的浅粉色溶液升温至室温并搅拌45分钟。然后,将所述混合物再次冷却至0℃,滴加4,4-二甲基噁唑烷-3-碳酰氯(351mg,2.148mmol)的四氢呋喃(2.5mL)溶液。将所生成的浅黄色溶液升温至室温并搅拌4h。将溶剂蒸发,并将水加入残余物中,用甲苯萃取。将有机相用水和盐水洗涤,然后干燥(MgSO4)、过滤并蒸发。将所生成的黄色油通过层析法(硅胶H;二氯甲烷,2%甲醇/二氯甲烷)纯化。将含有纯净产物的馏分合并,并蒸发,得到浅黄色泡沫(690mg,80%)。
在室温下,将(4-环己基哌嗪-1-基)(2-(4,4-二甲基噁唑烷-3-羰基)-2H-苯并[d][1,2,3]三唑-5-基)甲酮(300mg,0.681mmol)加入50mL梨形烧瓶中的甲醇(5mL)中,得到黄色溶液。一次性加入草酸二水合物(86mg,0.681mmol),在室温下将所述溶液搅拌2h。将所述溶剂蒸发,并将所生成的浅黄色泡沫自异丙醇中重结晶。在过滤并干燥后,得到白色固体产物(150mg,39%)。
化合物595的制备
a)N-(1-氰基哌啶-4-基)-4-(4-甲氧基苯基)-N-甲基-1H-咪唑-1-甲酰胺
向4-(4-甲氧基苯基)-N-甲基-N-(哌啶-4-基)-1H-咪唑-1-甲酰胺盐酸盐(287mg,0.818mmol)的DMF(5mL)溶液中加入叔丁醇钾(184mg,1.636mmol),在室温下将所述混合物搅拌30分钟,在这之后将其在冰/水浴中冷却,并经10-15分钟滴加溴化氰(0.818mL,2.454mmol,3N二氯甲烷溶液)。将所述反应混合物经1h缓慢升温至室温,然后使其在水和二氯甲烷/异丙醇(7∶3)之间进行分配。分离各层,并将有机相用水和盐水进一步洗涤,然后干燥(Na2SO4)、过滤并在减压下除去溶剂。将所述残余物溶解于最小体积的氯仿中,通过过滤除去不溶性物质。将所述滤液浓缩,得到灰白色固体物(345mg,67%)。
b)N-(1-(2H-四唑-5-基)哌啶-4-基)-4-(4-甲氧基苯基)-N-甲基-1H-咪唑-1-甲酰胺
向N-(1-氰基哌啶-4-基)-4-(4-甲氧基苯基)-N-甲基-1H-咪唑-1-甲酰胺(151mg,0.445mmol)的甲苯(10mL)悬浮物中加入二丁基锡烷酮(13.84mg,0.056mmol),然后加入叠氮基三甲基硅烷(0.207mL,1.557mmol)。将所述反应混合物加热回流5h,在这之后将其趁热过滤,将所生成的粉色固体物相继用甲苯、二氯甲烷洗涤,之后最终用乙醚洗涤。将所述固体自甲醇中重结晶,得到浅粉色固体产物(100mg,56%)。
2.实例化合物
上述本发明化合物可通过如下所述的熔点和NMR表征。NMR光谱记录在Bruker Avance DPX400光谱仪上,以所用溶剂作为内标。13C光谱在100MHz下记录,1H光谱在400MHz下记录。按如下顺序报告数据:近似化学位移(ppm)、质子数、多重性(br,宽峰;d,双峰;m,多峰;s,单峰;t,三峰)和耦合常数(Hz)。
化合物编号1(MP:89-91).NMR溶剂:DMSO
13C:150.4,137.1,128.9,118.6,65.7,46.1
1H:8.04(1H,s),7.48(1H,s),7.03(1H,s),3.65(4H,m,J=5.0Hz),3.50(4H,m,J=5.0Hz)
化合物编号2(MP:58).NMR溶剂:CDCl3
13C:150.2,142.9,137.7,130.3,129,128,125.9,118.4,40.1
1H:7.57(1H,s),7.39(2H,t,J=7.7Hz),7.32(1H,t,J=7.3Hz),7.13(2H,d,J=7.7Hz),6.85(1H,s),6.81(1H,s),3.50(3H,s)
化合物编号3(MP:97-99).NMR溶剂:CDCl3
13C:150.8,142.7,136.9,132.7,128.7,127.7,125.2,112.8,66.5,46.8
1H:7.92(1H,s),7.79(2H,d,J=7.8Hz),7.47(1H,s),7.41(2H,t,J=7.6Hz),7.30(1H,m,J=7.6Hz),3.78(4H,m),3.68(4H,m)
化合物编号4(MP:104-105).NMR溶剂:CDCl3
13C:150.1,142.9,141.4,137.7,132.8,130.4,128.5,128.2,127.4,126,125,113.5,40.2
1H:7.60(2H,d,J=7.7Hz),7.53(1H,s),7.40(2H,t,J=7.7Hz),7.34(1H,m),7.32(2H,t,J=7.6Hz),7.25(1H,m),7.19(2H,m),7.18(1H,s),3.52(3H,s)
化合物编号5(MP:117).NMR溶剂:CDCl3
13C:154.2,146.9,136.6,131.7,129.9,129.2,129.1,128.8,126.3,124.7,119.8,106.7
1H:9.19(1H,s),8.36(1H,d,J=2.7Hz),7.91(2H,d,J=8.0Hz),7.67(2H,d,J=7.8Hz),7.49(2H,m,J=7.2Hz),7.43(3H,m),7.19(1H,t,J=7.4Hz),6.79(1H,d,J=2.7Hz)
化合物编号6(MP:98-99).NMR溶剂:CDCl3
13C:156.7,154.1,147.2,131.8,129.9,129.5,129.1,128.8,126.2,121.7,114.4,106.5,55.5
1H:9.05(1H,s),8.34(1H,d,J=2.8Hz),7.89(2H,m,J=8.4Hz),7.55(2H,m,J=8.8Hz),7.47(2H,t,J=7.7Hz),7.41(1H,t,J=7.3Hz),6.94(2H,m,J=8.8Hz),6.76(1H,d,J=2.8Hz),3.83(3H,s)
化合物编号7(MP:62).NMR溶剂:CDCl3
13C:151.7,149.1,145.7,143.1,129.6,127.7,125.8,40.5
1H:8.64(1H,s),7.73(1H,s),7.37(2H,t,J=7.7Hz),7.30(1H,t,J=7.3Hz),7.13(2H,d,J=7.8Hz),3.56(3H,s)
化合物编号8(MP:64-65).NMR溶剂:CDCl3
13C:151.7,144.6,141.8,131.1,129.3,126.6,125.4,107.3,40.41H:8.01(1H,d br,J=2.7Hz),7.40(1H,br),7.33(2H,m,J=8.1Hz),7.23(1H,m,J=7.6Hz),7.11(2H,m,J=8.3Hz),6.25(1H,d d,J=1.7,2.7Hz),3.55(3H,s)
化合物编号9(MP:71-72).NMR溶剂:CDCl3
13C:146.8,142.3,136.6,129.2,128.7,124.7,119.6,109
1H:9.13(1H,s),8.33(1H,d d,J=0.6,2.7Hz),7.69(1H,d d,J=0.6,1.6Hz),7.63(2H,m,J=8.7Hz),7.40(2H,m,J=8.0Hz),7.18(1H,m,J=7.5Hz),6.47(1H,d d,J=1.6,2.7Hz)
化合物编号10(MP:125-126).NMR溶剂:CDCl3
13C:157.4,154.3,154,147.1,132,131.7,130,129.8,129.2,128.8,126.3,123.2,121.6,119.7,118.6,106.6
1H:9.14(1H,s),8.36(1H,d,J=2.8Hz),7.91(2H,d,J=8.0Hz),7.62(2H,d,J=9.0Hz),7.49(2H,t,J=7.6Hz),7.43(1H,t,J=7.2Hz),7.36(2H,t,J=8.0Hz),7.12(1H,t,J=7.5Hz),7.08(2H,d,J=9.0Hz),7.04(2H,d,J=8.2Hz),6.80(1H,d,J=2.8Hz)
化合物编号11(MP:110).NMR溶剂:CDCl3
13C:155.9,154.1,147.1,136.8,131.8,129.9,129.8,129.1,128.8,128.6,128,127.5,126.2,121.7,115.4,106.5,70.3
1H:9.06(1H,s),8.35(1H,d,J=2.7Hz),7.90(2H,d,J=8.3Hz),7.56(2H,m,J=9.0Hz),7.47(2H,m),7.45(2H,m),7.43(1H,m),7.40(2H,m),7.34(1H,m),7.03(2H,m,J=9.0Hz),6.78(1H,d,J=2,7Hz),5.09(2H,s)
化合物编号12(MP:79).NMR溶剂:CDCl3
13C:153,151.3,144.9,132.3(2sig.),129.2,128.5(2sig.),126.7,125.9,125.9,104.7,40.5
1H:8.11(1H,d,J=2.5Hz),7.40(2H,m),7.36(2H,t,J=7.5Hz),7.28(4H,m),7.17(2H,d,J=7.8Hz),6.55(1H,d,J=2.5Hz),3.59(3H,s)
化合物编号13(MP:79-80).NMR溶剂:CDCl3
13C:153.7,151,133.3,132.1,128.8,128.7,126,104.9,66.8,47
1H:8.19(1H,d,J=2.8Hz),7.83(2H,d,J=8.4Hz),7.44(2H,t,J=7.7Hz),7.39(1H,m,J=7.2Hz),6.70(1H,d,J=2.8Hz),4.0(4H,s br),3.84(4H,m)
化合物编号14(MP:132).NMR溶剂:CDCl3
13C:150,142.9,141.4,137.9,133.5,132.8,130.4,130.1,128.2,128.2,128.1,127.6,126.2,126,125.7,123.6,123.3,114,40.2
1H:8.19(1H,s),7.85-7.77(3H,m),7.64(1H,d d,,1.8,8.7Hz),7.56(1H,d,J=1.3Hz),7.44(4H,m),7.36(1H,m,J=7.4Hz),7.34(1H,d,J=1.3Hz),7.21(2H,m,J=8.1Hz),3.54(3H,s)
化合物编号15(MP:134).NMR溶剂:丙酮
13C:154.8,148.1,141.2,138,137.9,133,131.1,129.9,129.8,129.7,128.2,128.1,127.6,127.1,121.5,107.4
1H:10.05(1H,s),8.45(1H,d,J=3.0Hz),8.03(2H,m,J=8.7Hz),7.94(2H,m,J=8.6Hz),7.72(2H,m,J=8.6Hz),7.69(2H,m,J=8.3Hz),7.49(2H,m),7.47(2H,m),7.43(1H,m),7.36(1H,m,J=7.4Hz),7.06(1H,d,J=3.0Hz)
化合物编号16(MP:119-120).NMR溶剂:CDCl3
13C:159.2,150.1,141.2,137.9,135.5,133.6,132.8,130.2,128.2,128.1,127.6,127.3,126.2,125.7,123.6,123.3,115.5,114.2,55.5,40.5
1H:8.21(1H,m),7.82-7.80(3H,m),7.67(1H,d d,J=1.7,8.6Hz),7.49(1H,d,J=1.3Hz),7.45(2H,m),7.42(1H,m),7.14(2H,m,J=9.0Hz),6.93(2H,m,J=9.0Hz),3.81(3H,s),3.50(3H,s)
化合物编号17(MP:138).NMR溶剂:CDCl3
13C:159.1,150.1,141.2,137.7,135.5,132.8,128.6,127.4,127.3,125,115.5,113.7,55.5,40.5
1H:7.64(2H,d,J=8.1Hz),7.47(1H,s),7.35(2H,t,J=7.2Hz),7.30(1H,s),7.25(1H,m,J=7.4Hz),7.11(2H,s,J=8.6Hz),6.91(2H,d,J=8.6Hz),3.81(3H,s),3.49(3H,s)
化合物编号18(MP:123-124).NMR溶剂:CDCl3
13C:150.9,143.4,142.7,141.5,132.4,130.3,127.6,125.4,124.8,123.9,120.2,114,39.7
1H:7.95(1H,d,J=7.8Hz),7.69(1H,d,J=8.0Hz),7.54(1H,s),7.38(1H,m),7.33(2H,m),7.32(1H,m),7.25(1H,m),7.12(2H,d,J=7.8Hz),3.58(3H,s)
化合物编号19(MP:104).NMR溶剂:CDCl3
13C:149.4,145.3,133.1,129.5,125.4,119.9,113.6,66.7,48.2,45.6
1H:8.10(1H,d,J=8.3Hz),8.01(1H,d,J=8.4Hz),7.62(1H,t,J=7.9Hz),7.47(1H,t,J=7.6Hz),3.96(4H,s br),3.89(4H,s br)
化合物编号20(MP:181-183).NMR溶剂:DMSO
13C:153,147.4,140.6,139.5,137.4,130.8,130.7,129,128.8,127.8,127,126.8,126.7,124.4,121,106.8
1H:10.36(1H,s),8.51(1H,d,J=2.6Hz),8.18(2H,d,J=8.1Hz),7.82(2H,d,J=8.2Hz),7.78(2H,m),7.76(2H,d,J=8.7Hz),7.50(2H,t,J=7.8Hz),7.41(2H,m),7.39(1H,m),7.19(1H,d,J=2.6Hz),7.19(1H,m)
化合物编号21(MP:208-211).NMR溶剂:DMSO
13C:150,147.8,143.2,140.7,140,134.5,130.5,126.8,106.1,66,46.6
1H:9.35(1H,s),8.86(2H,m),8.40(1H,d,J=2.5Hz),8.02(1H,t br,J=6.3Hz),7.31(1H,d,J=2.5Hz),3.77(4H,br),3.71(4H,br)
化合物编号22(MP:168-170).NMR溶剂:DMSO
13C:159.6,153,147.3,140.6,139.5,138.6,130.8,130.7,129.6,129,127.8,127,126.9,126.7,113,109.9,106.9,106.6,55.2
1H:10.32(1H,s),8.50(1H,d,J=3.0Hz),8.18(2H,d,J=8.5Hz),7.81(2H,d,J=8.5Hz),7.76(2H,d,J=8.6Hz),7.75(1H,t,J=2.3Hz),7.50(2H,t,J=7.8Hz),7.42(1H,m),7.39(1H,m,J=7.2Hz),7.31(1H,t,J=8.5Hz),7.19(1H,d,J=3.0Hz),6.76(1H,m,J=1.0,2.4,8.3Hz),3.76(3H,s)
化合物编号23(MP:163).NMR溶剂:DMSO
13C:156.2,152.9,147.5,140.5,139.5,130.8,130.7,130.2,129,127.8,127,126.8,126.7,122.9,113.9,106.6,55.3
1H:10.25(1H,s),8.49(1H,d,J=2.6Hz),8.18(2H,d,J=8.1Hz),7.82(2H,d,J=8.1Hz),7.77(2H,d,J=7.4Hz),7.66(2H,d,J=9.0Hz),7.50(2H,t,J=7.8Hz),7.40(1H,t,J=7.3Hz),7.16(1H,d,J=2.6Hz),6.98(2H,d,J=9.0Hz),3.77(3H,s)
化合物编号24(MP:99).NMR溶剂:CDCl3
13C:150.9,150.1,149.4,147.4,144.7,133,132.6,129.3,128.1,126.9,125.9,123.4,104.6,40.5
1H:8.61(1H,s),8.50(1H,d,J=4.9Hz),8.16(1H,d,J=2.6Hz),7.65(1H,d,J=7.9Hz),7.36(2H,t,J=7.6Hz),7.29(1H,t,J=7.5Hz),7.22(1H,d d,J=4.9,7.9Hz),7.17(2H,d,J=7.8Hz),6.59(1H,d,J=2.6Hz),3.58(3H,s)
化合物编号25(MP:137).NMR溶剂:DMSO
13C:151.6,150.7,144.5,140.1,139.5,133,131,129.1,129,127.7,126.8,126.6,126.5,126.1,125.8,105.1,40
1H:8.22(1H,d,J=2.5Hz),7.69(2H,d,J=7.8Hz),7.64(2H,d,J=8.4Hz),7.59(2H,d,J=8.4Hz),7.46(2H,t,J=7.6Hz),7.37(3H,m),7.26(3H,m),6.92(1H,d,J=2.5Hz),3.48(3H,s)
化合物编号26(MP:123-125).NMR溶剂:CDCl3
13C:151.9,146.5,141.4,130.3,129.3,129,128.9,128.3,127.3,126.9,124.1,120,38.9
1H:7.43-7.24(6H,m),7.14-6.93(4H,m),6.33(2H,br),3.37(3H,sbr)
化合物编号27(MP:121).NMR溶剂:CDCl3
13C:149.9,142.8,140.3,137.8,133,131.3,130.4,128.7,128.2,126.2,126,113.7,40.2
1H:7.54(2H,m,J=8.6Hz),7.50(1H,d,J=1.3Hz),7.42(2H,m,J=7.7Hz),7.35(1H,m,J=7.4Hz),7.29(2H,m,J=8.6Hz),7.19(1H,d,J=1.3Hz),7.18(2H,m),3.52(3H,s)
化合物编号28(MP:127).NMR溶剂:CDCl3
13C:159,150.1,142.9,141.2,137.6,130.3,128.1,126.3,125.9,125.5,113.9,112.4,55.2,40.2
1H:7.53(2H,m,J=8.9Hz),7.51(1H,d,J=1.4Hz),7.41(2H,m,J=7.9Hz),7.34(1H,m,J=7.5Hz),7.19(2H,m,J=8.3Hz),7.09(1H,d,J=1.4Hz),6.87(2H,m,J=8.9Hz),3.80(3H,s),3.52(3H,s)
化合物编号29(MP:127-129).NMR溶剂:CDCl3
13C:162.2(d,J=246.0Hz),150.0,142.9,140.5,137.8,130.4,129.0(d,J=3.3Hz),128.2,126.7(d,J=8.0Hz),126.0,111.5(d,J=21.5Hz),113.2,40.2
1H:7.57(2H,m,J=5.4,9.0Hz),7.50(1H,d,J=1.3Hz),7.43(2H,t,J=7.7Hz),7.35(1H,m,J=7.3Hz),7.18(2H,m),7.15(1H,d,J=1.3Hz),7.01(2H,t,J=8.7Hz),3.52(3H,s)
化合物编号30(MP:126).NMR溶剂:CDCl3
13C:159.5(d,J=249.0Hz),150.0,142.8,137.3,135.1(d,J=2.6Hz),130.3,128.3(d,J=8.6Hz),128.2,127.7(d,J=4.0Hz),125.9,124.2(d,J=3.2Hz),120.7(d,J=12.8Hz),117.7(d,J=16.0Hz),115.4(d,J=22.0Hz),40.2
1H:8.02(1H,d t,J=2.0,7.6Hz),7.65(1H,d,J=1.3Hz),7.41(2H,m),7.34(1H,m),7.31(1H,d d,J=1.3,3.6Hz),7.19(2H,m),7.16(1H,m),7.15(1H,m,J=1.6,7.4),7.03(1H,m,J=1.5,7.8,11.4Hz),3.53(3H,s)
化合物编号31(MP:128-129).NMR溶剂:CDCl3
13C:159.8,150,142.9,141.2,137.7,134.2,130.4,129.6,128.2,126,117.4,113.8,113.6,109.9,55.2,40.2
1H:7.52(1H,d,J=1.4Hz),7.41(2H,m,J=7.8Hz),7.34(1H,m,J=7.4Hz),7.23(1H,t,J=7.8Hz),7.21(1H,m),7.19(3H,m),7.16-7.13(1H,m),6.79(1H,d d d,1.0,2.5,8.0Hz),3.81(3H,s),3.52(3H,s)
化合物编号32(MP:144-146).NMR溶剂:CDCl3
13C:149.7,143.5,143.4,136,133.4,129.6,127.6,126.4,126,120.7,113.3,40.4
1H:8.10(1H,d,J=1.6Hz),7.91(1H,d,J=8.8Hz),7.40(1H,d d,J=1.6,8.8Hz),7.34(2H,m,J=7.9Hz),7.27(1H,m),7.17(2H,d,J=7.6Hz),3.67(3H,s)
化合物编号33(MP:112).NMR溶剂:CDCl3
13C:149.7,145.6,143.4,131.5,131,130.1,129.6,127.6,125.9,119.3,114.2,40.4
1H:8.0(1H,d,J=8.9Hz),7.98(1H,d,J=1.6Hz),7.57(1H,d d,J=1.6,8.9Hz),7.34(2H,t,J=8.1Hz),7.27(1H,m),7.17(2H,d,J=7.8Hz),3.67(3H,s)
化合物编号34(MP:89-90).NMR溶剂:CDCl3
13C:150.2,145,143.6,132.8,129.5,129.3,127.4,125.9,125.1,119.9,113.2,40.3
1H:8.06(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.61(1H,m,J=7.7Hz),7.43(1H,m,J=7.7Hz),7.32(2H,t,J=7.8Hz),7.25(1H,t,J=7.5Hz),7.18(2H,d,J=7.5Hz),3.68(3H,s)
化合物编号35(MP:166-169).NMR溶剂:DMSO
13C:149.8,142.9,139.7,139.7,138.7,137.9,132.1,129.9,129,127.7,127.4,126.9,126.5,126.2,125.2,114.5,39.6
1H:7.73(2H,d,J=8.2Hz),7.69-7.61(6H,m),7.48-7.39(4H,m),7.39-7.30(4H,m),3.44(3H,s)
化合物编号36(MP:油脂).NMR溶剂:DMSO
13C:160.8(d,J=245Hz),158.6,149.9,140.2,139.3(d,J=3Hz),137.6,128.6(d,J=9Hz),126.0,125.6,116.7(d,J=23.5Hz),114.1,113.0,55.1,39.5
1H:7.69(1H,s),7.57(2H,d,J=8.7Hz),7.45(1H,s),7.41(2H,m),7.25(2H,t,J=8.7Hz),6.90(2H,d,J=8.7Hz),3.73(3H,s),3.40(3H,s)
化合物编号37(MP:162-164).NMR溶剂:CDCl3
13C:149.7,142,137.6,137.4,132.8,131.7,128.9,128.6,127.5,127.1,125.8,125.1,123,113.1,45.8,26.6,23.9
1H:7.68(1H,s),7.68(2H,d,J=7.7Hz),7.36(2H,t,J=7.7Hz),7.28(1H,s),7.26(1H,m),7.23(1H,d,J=7.5Hz),7.11(1H,t,J=7.6Hz),7.03(1H,t,J=7.7Hz),6.75(1H,d,J=8.0Hz),3.92(2H,t,J=6.6Hz),2.87(2H,t,J=6.6Hz),2.11(2H,qt,J=6.6Hz)
化合物编号38(MP:232-233).NMR溶剂:DMSO
13C:158.3,147.9,141.9,137.2,135.4,129.9,128.2,126.9,126.3,118.8,115.8,114,39.9
1H:8.79(1H,s),8.78(1H,s),7.67(1H,s),7.43(2H,m,J=8.6Hz),7.41(4H,m),7.34(1H,m),6.80(2H,m,J=8.6Hz),3.74(3H,s)
化合物编号39(MP:97-98).NMR溶剂:CDCl3
13C:159.9,149.6,141.8,137.6,137.4,134.2,131.8,129.6,128.9,127.1,125.8,123,117.5,113.7,113.4,110.1,55.3,45.8,26.6,23.9
1H:7.68(1H,d,J=1.3Hz),7.29(1H,m),7.28(1H,d,J=1.3Hz),7.24(2H,m),7.23(1H,m),7.12(1H,d t,J=1.2,7.5Hz),7.04(1H,d t,J=1.5,8.0Hz),6.83(1H,d d d,1.5,2.5,7.5Hz),6.75(1H,d br,J=8.0Hz),3.93(2H,t,J=6.7Hz),3.84(3H,s),2.88(2H,t,J=6.6Hz),2.12(2H,qt,J=6.6Hz)
化合物编号40(MP:139-141).NMR溶剂:DMSO
13C:157.6,149.7,142.8,139.9,137.7,133.9,129.9,129.7,127.7,126.2,115.5,114.3,114.2,111.5,39.6
1H:9.43(1H,s),7.68(1H,s),7.43(1H,s),7.41(2H,m),7.35(2H,m),7.32(1H,m),7.11(1H,t),7.03(1H,br),7.02(1H,m),6.62(1H,d,J=8.0Hz),3.42(3H,s)
化合物编号41(MP:152).NMR溶剂:DMSO
13C:150.6,148.8,144.7,132.5,129.6,129.1,125.5,119.6,119.5,115.9,113.4,48.3,47.1,44.8
1H:8.21(1H,d,J=8.5Hz),7.97(1H,d,J=8.3Hz),7.71(1H,m,J=7.8Hz),7.55(1H,m,J=7.6Hz),7.25(2H,t,J=7.5Hz),7.0(2H,d,J=8.2Hz),6.83(1H,t,J=7.3Hz),3.92(4H,m),3.33(4H,m)化合物编号42(MP:79-80).NMR溶剂:DMSO
13C:148.6,144.7,140,132.5,129.4,129.1,128.3,125.9,125.4,119.6,113.1,47.6,45,41.9,37.1,31.6
1H:8.18(1H,d,J=8.4Hz),7.90(1H,d,J=8.4Hz),7.68(1H,m,J=8.0Hz),7.53(1H,m,J=7.6Hz),7.29(2H,t,J=7.3Hz),7.20(2H,d,J=7.3Hz),7.19(1H,t,J=7.5Hz),4.20(2H,s br),3.13(2H,s br),2.58(2H,d,J=7.2Hz),1.88(1H,m),1.70(2H,br),1.34(2H,m,J=4.0,12.5Hz)
化合物编号43(MP:105).NMR溶剂:CDCl3
13C:161.7(d,J=250.0Hz),149.8,140.5,138.8(d,J=3.6Hz),137.7,133.1,131.2,128.8,127.8(d,J=8.4Hz),126.3,117.4(d,J=23.2Hz),113.6,40.4
1H:7.56(2H,m,J=8.8Hz),7.49(1H,d,J=1.4Hz),7.31(2H,m,J=8.8Hz),7.23(1H,d,J=1.4Hz),7.17(2H,m),7.12(2H,m),3.50(3H,s)
化合物编号44(MP:145).NMR溶剂:CDCl3
13C:162.3(d,J=246.5Hz),149.6,141.1,137.6,137.5,131.8,129.0(d,J=3.0Hz),129,127.1,126.8(d,J=8.0Hz),125.9,123,115.5(d,J=21.5Hz),112.8(d,J=1.6Hz),45.8,26.6,23.9
1H:7.65(2H,m),7.65(1H,d,J=1.3Hz),7.24(1H,m),7.23(1H,d,J=1.3Hz),7.12(1H,m),7.05(2H,m,J=8.9Hz),7.05(1H,m,J=1.2,7.5Hz),6.75(1H,m,J=8.1Hz),3.92(2H,t,J=6.6Hz),2.88(2H,t,J=6.6Hz),2.12(2H,qt,J=6.6Hz)
化合物编号45(MP:93-96).NMR溶剂:CDCl3
13C:161.7(d,J=249.5Hz),159.6(d,J=249.0Hz),150.0,138.9(d,J=3.5Hz),137.2,135.3(d,J=2.0Hz),128.4(d,J=8.3Hz),127.8(d,J=8.3Hz),127.7(d,J=4.0Hz),124.3(d,J=3.2Hz),120.6(d,J=13.0Hz),117.5(d,J=16.0Hz),117.4(d,J=23.0Hz),115.5(d,J=22.0Hz),40.3
1H:8.03(1H,d t,J=2.0,7.8Hz),7.68(1H,d,J=1.4Hz),7.30(1H,dd,J=1.4,3.5Hz),7.19(2H,m),7.16(1H,m),7.15(1H,m),7.10(2H,m),7.04(1H,d d d,J=1.4,7.9,11.3Hz),3.50(3H,s)
化合物编号46(MP:90-91).NMR溶剂:CDCl3
13C:158.9(d,J=238.0Hz),154,131.7,130.2(d,10.0Hz),127.5,114.2(d,J=9.5Hz),111.9(d,J=26.0Hz),106.3(d,J=27.5Hz),106.2,66.6,47.1
1H:7.66(1H,d d,J=4.5,9.1Hz),7.34(1H,d,J=3.5Hz),7.25(1H,d d,J=2.5,9.0Hz),7.05(1H,d t,J=2.5,9.1Hz),6.58(1H d d,J=0.7,3.5Hz),3.80(4H,m,J=5.0,6.0Hz),3.62(4H,m,J=5.0,6.0Hz)
化合物编号47(MP:112-113).NMR溶剂:CDCl3
13C:155.5,154.4,130.3,130,126.7,114,113.2,106.1,103.1,66.7,55.7,47.1
1H:7.60(1H,d,J=8.9Hz),7.30(1H,d,J=3.5Hz),7.06(1H,d br,J=2.5Hz),6.95(1H,d d,J=2.5,8.9Hz),6.55(1H,d d,J=0.7,3.5Hz),3.86(3H,s),3.79(4H,m,J=5.0Hz),3.61(4H,m,J=5.0Hz)
化合物编号48(MP:184).NMR溶剂:DMSO
13C:162.4,148.7,147.4,147,144.7,132.5,129.6,128.6,125.5,123.3,119.7,113.4,109.9,108.1,101.1,60.5,51.4,46.5,43.8
1H:8.20(1H,d,J=8.4Hz),7.93(1H,d,J=8.4Hz),7.71(1H,t,J=8.0Hz),7.54(1H,t,J=7.5Hz),6.97(1H,s br),6.91(1H,d,J=8.0Hz),6.85(1H,d d,J=1.5,8.0Hz),6.02(2H,s),3.84(4H,m),3.75(2H,s),2.80(4H,m)
化合物编号49(MP:89).NMR溶剂:DMSO
13C:158.6,148.9,147.6,144.7,137.8,132.5,129.6,125.5,119.6,113.5,113.4,107.3,46.9,44.4
1H:8.21(1H,d,J=8.4Hz),8.15(1H,d d,J=1.5,4.8Hz),7.97(1H,d,J=8.3Hz),7.71(1H,m),7.58(1H,m),7.55(1H,m),6.88(1H,d,J=8.7Hz),6.69(1H,d d,J=4.8,7.1Hz),3.88(4H,m),3.71(4H,m)
化合物编号50(MP:113-114).NMR溶剂:DMSO
13C:149.2,144.7,134.4,132.6,129.5,128.6,128.6,126.8,126.5,126.3,125.5,119.6,113.5,48.6,46.7,45.5,42.8,28.8,27.2
1H:8.21(1H,d t,J=0.8,8.3Hz),7.95(1H,d,J=8.3Hz),7.70(1H,t,J=7.8Hz),7.54(1H,d d d,J=1.0,7.1,8.3Hz),7.24(4H,br),4.94(2H,br),3.96(2H,t,J=6.0Hz),3.04(2H,t,J=6.0Hz)
化合物编号51(MP:188).NMR溶剂:CDCl3
13C:158.6,150.8,142.6,138.8,138.6,134.8,133.7,130.8,130,127.8,127,124.1,117.6,115.8,114.9,113,47.1,27.5,24.9
1H:7.76(1H,d,J=1.4Hz),7.36(1H,d,J=1.4Hz),7.28(1H,d br,J=7.7Hz),7.15(1H,t,J=7.8Hz),7.13(1H,t),7.09(1H,m),7.07(1H,m),7.04(1H,d t,J=1.5,8.0Hz),6.79(1H,d br,J=8.2Hz),6.69(1H,d d d,J=1.1,2.5,8.0Hz),3.91(2H,t,J=6.5Hz),2.90(2H,t,J=6.5Hz),2.10(2H,qt,J=6.5Hz)
化合物编号52(MP:174).NMR溶剂:DMSO
13C:153.5,152.6,130.2,129.1,127.3,113.8,112.9,105.1,105,65.9,46.5
1H:9.09(1H,s),7.47(1H,d,J=9.0Hz),7.44(1H,d,J=3.5Hz),6.91(1H,d,J=2.0Hz),6.74(1H,d d,J=2.0,9.0Hz),6.50(1H,d,J=3.5Hz),3.67(4H,m),3.47(4H,m)
化合物编号53(MP:油脂).NMR溶剂:CDCl3
13C:150.9,145.3,135.7,133.2,129.4,128.8,128.1(br),128.0,125.2,119.8,113.7,55.3,53.8,37.7
1H:8.11(1H,d,J=8.2Hz),8.06(1H,d,J=8.2Hz),7.63(1H,t,J=7.4Hz),7.48(1H,t,J=7.8Hz),7.40(5H,br),4.94(2H,br),3.31(3H,br)
化合物编号54(MP:218-220).NMR溶剂:CDCl3
13C:161.8(d,J=251.0Hz),159,146.3,136.7(d,J=4.0Hz),136,134.3,127.9(d,J=9.0Hz),127,117.2(d,J=23.0Hz),115.9,115.6,113.6,40.1
1H:8.89(1H,m),7.18(2H,m),7.09(2H,m,J=8.7Hz),7.05(1H,m),6.95(2H,m,J=8.6Hz),6.65(2H,m,J=8.7Hz),3.35(3H,s)
化合物编号55(MP:116).NMR溶剂:CDCl3
13C:149.3,145.3,133.2,129.3,125.2,119.8,113.5,106.6,64.6,46.1,43.6,35.3
1H:8.09(1H,d,J=8.5Hz),7.99(1H,d,J=8.3Hz),7.61(1H,t,J=8.1Hz),7.46(1H,t,J=7.4Hz),4.03(4H,s),3.98(4H,br),1.93(4H,t,J=6.0Hz)
化合物编号56(MP:134).NMR溶剂:CDCl3
13C:157.1,154.5,146.6,146.5,131.6,131.3,130.3,129.8,125.7,123.4,121.9,120.2,119.7,118.7,114
1H:9.15(1H,s),8.35(1H,d,J=8.4Hz),8.15(1H,d,J=8.3Hz),7.69(1H,t,J=7.6Hz),7.65(2H,m,J=9.2Hz),7.52(1H,t,J=7.7Hz),7.37(2H,t,J=8.1Hz),7.14(1H,t,J=7.3Hz),7.10(2H,m,J=9.2Hz),7.05(2H,m,J=8.5Hz)
化合物编号57(MP:156-157).NMR溶剂:CDCl3
13C:157.2,146.6,146.4,131.6,130.2,128.9,125.6,122,120.2,114.5,114,55.5
1H:9.06(1H,s),8.34(1H,d,J=8.5Hz),8.14(1H,d,J=8.3Hz),7.67(1H,m,J=7.5Hz),7.59(2H,m,J=9.1Hz),7.51(1H,m,J=7.8Hz),6.97(2H,m,J=9.1Hz),3.85(3H,s)
化合物编号58(MP:101-102).NMR溶剂:CDCl3
13C:150.4,145.2,133.2,129.1,125,119.7,113.5,57.1,32.4,30.4,29.7,25.5,25.3
1H:8.09(1H,d,J=8.3Hz),7.98(1H,d,J=8.5Hz),7.60(1H,m,J=7.8Hz),7.45(1H,m,J=7.6Hz),4.26(1H,br),3.18(3H,s),2.0(2H,dbr,J=11.0Hz),1.87(2H,br),1.67(1H,br),1.63(2H,m,J=3.0,12.3Hz),1.43(2H,m),1.16(1H,m)
化合物编号59(MP:148-150).NMR溶剂:CDCl3
13C:160.6(d d,J=11.5,248.0Hz),153.4(d d,J=12.0,249.0Hz),146.5,146.4,131.5,130.5,125.9,122.7(d d,J=2.0,9.3Hz),121.0(d d,J=3.7,11.0Hz),120.4,113.8,111.6(d d,J=4.0,22.5Hz),104.2(d d,J=22.5,27.0Hz)
1H:9.28(1H,s),8.32(1H,m,J=8.3Hz),8.27(1H,m,J=6.0,8.9Hz),8.17(1H,m,J=8.3Hz),7.70(1H,m,J=8.2Hz),7.53(1H,m,J=8.1Hz),7.0(2H,m)
化合物编号60(MP:142-143).NMR溶剂:CDCl3
13C:146.5,146.4,136.1,131.6,130.3,129.4,125.7,125.3,120.2,120,114
1H:9.19(1H,s),8.35(1H,d,J=8.3Hz),8.15(1H,d,J=8.4Hz),7.70(2H,d,J=8.0Hz),7.69(1H,m),7.52(1H,t,J=7.8Hz),7.45(2H,t,J=8.0Hz),7.25(1H,t,J=7.4Hz)
化合物编号61(MP:109).NMR溶剂:CDCl3
13C:149.2,146.3,136.9,131.6,130,128.9,128,127.8,125.5,120,113.9,44.4
1H:8.32(1H,d,J=8.4Hz),8.11(1H,d,J=8.4Hz),7.67(1H,m),7.65(1H,t,J=7.8Hz),7.49(1H,t,J=8.0Hz),7.43(2H,m),7.40(2H,t,J=7.7Hz),7.34(1H,m),4.75(2H,d,J=6.0Hz)
化合物编号62(MP:195-197).NMR溶剂:CDCl3
13C:146.5,146.3,134.7,131.5,130.4(2sig.),129.4,125.9,121.2,120.3,113.9
1H:9.19(1H,s),8.34(1H,d,J=8.3Hz),8.16(1H,d,J=8.5Hz),7.70(1H,t,J=7.9Hz),7.66(2H,d,J=8.8Hz),7.53(1H,t,J=7.5Hz),7.42(2H,d,J=8.8Hz)
化合物编号63(MP:62).NMR溶剂:CDCl3
13C:150,145,142.2,133.1,132.8,129.7,129.5,127.3,125.3,119.9,113.3,40.3
1H:8.06(1H,d,J=8.5Hz),8.02(1H,d,J=8.3Hz),7.62(1H,t,J=7.9Hz),7.45(1H,t,J=7.7Hz),7.30(2H,d,J=8.6Hz),7.13(2H,d,J=8.6Hz),3.65(3H,s)
化合物编号64(MP:84-85).NMR溶剂:CDCl3
13C:161.9,160.9,149.1,146.3,143.5,129.5,128,127.5,126.1,122.4,113.8,55.2,40.4
1H:8.66(1H,s),7.71(2H,d,J=8.5Hz),7.39(2H,t,J=7.9Hz),7.32(1H,t,J=7.2Hz),7.19(2H,d,J=7.9Hz),6.87(2H,d,J=8.5Hz),3.82(3H,s),3.58(3H,s)
化合物编号65(MP:105-106).NMR溶剂:CDCl3
13C:162.6,161.2,148.8,147.3,128.3,122.3,114.1,66.6,55.3,46.9
1H:8.81(1H,s),8.06(2H,d,J=8.9Hz),6.98(2H,d,J=8.9Hz),3.98(4H,br),3.87(3H,s),3.83(4H,m br)
化合物编号66(MP:116).NMR溶剂:CDCl3
13C:162.1,161.5(d,J=248.0Hz),161,149.1,146.5,139.5(d,J=3.5Hz),128.1(d,J=9.0Hz),128,122.3,116.3(d,J=22.5Hz),113.9,55.3,40.7
1H:8.74(1H,s),7.72(2H,d,J=8.4Hz),7.20(2H,m,J=5.0,9.0Hz),7.09(2H,t,J=8.8Hz),6.89(2H,d,J=8.9Hz),3.83(3H,s),3.56(3H,s)
化合物编号67(MP:91).NMR溶剂:CDCl3
13C:161.2,148.8,146.5,143.3,135.8,129.5,128.7,128.3,127.8,127.7,126.1,40.5
1H:8.69(1H,s),7.69(2H,m,J=8.3Hz),7.39(2H,t,J=7.8Hz),7.32(1H,m),7.31(2H,m,J=,8.3Hz),7.19(2H,d,J=8.0Hz),3.58(3H,s)
化合物编号68(MP:120-121).NMR溶剂:CDCl3
13C:161.9,148.5,147.6,136.2,129,128.2,128.1,66.6,47.5,461H:8.84(1H,s),8.06(2H,d,J=8.7Hz),7.44(2H,d,J=8.7Hz),3.98(4H,br),3.84(4H,s br)
化合物编号69(MP:127-128).NMR溶剂:CDCl3
13C:161.6(d,J=248.5Hz),161.4,148.8,146.7,139.3(d,J=3.3Hz),135.9,128.8,128.2,128.1(d,J=8.5Hz),127.8,116.3(d,J=23.0Hz),40.7
1H:8.76(1H,s),7.71(2H,d,J=7.0Hz),7.35(2H,d,J=8.0Hz),7.19(2H,m),7.09(2H,t,J=8.5Hz),3.56(3H,s)
化合物编号70(MP:91-92).NMR溶剂:CDCl3
13C:161.8(d d,J=11.5,251.0Hz),157.7(d d,J=12.5,252.0Hz),150.1,144.9,132.7,129.6,129.3(d d,J=1.5,10.0Hz),127.7(d d,J=5.0,12.0Hz),125.4,119.9,113.5,112.1(d d,J=4.0,23.0Hz),105.1(dd,J=24.0,26.5Hz),39.7
1H:8.10(1H,d,J=8.4Hz),8.01(1H,d,J=8.1Hz),7.63(1H,m,J=7.8Hz),7.45(1H,t,J=7.7Hz),7.30(1H,m),6.88(1H,m),6.84(1H,m),3.60(3H,s)
化合物编号71(MP:65-66).NMR溶剂:CDCl3
13C:146.1,145.3,132.8,129.4,125.5,119.8,114.4,82.5,79.6,62.2,231H:8.23(1H,d,J=8.4Hz),8.10(1H,d,J=8.3Hz),7.62(1H,t,J=7.8Hz),7.48(1H,t,J=7.7Hz),5.54(2H,s),3.90(2H,s),1.69(6H,s)化合物编号72(MP:85).NMR溶剂:CDCl3
13C:152,142.2,138.9,130.1,124.2,122.8,119.8,115.2,67.1,47.2
1H:8.09(1H,d,J=8.6Hz),7.69(1H,d,J=8.2Hz),7.58(1H,t,J=7.5Hz),7.36(1H,t,J=7.5Hz),3.87(4H,br),3.80(4H,br)
化合物编号73(MP:80).NMR溶剂:CDCl3
13C:162.8,148.7,147.4,130.2,129.6,128.7,126.7,66.6,47.3,46.2
1H:8.85(1H,s),8.12(2H,m),7.47(3H,m),4.02(4H,br),3.84(4H,m)
化合物编号74(MP:114).NMR溶剂:CDCl3
13C:162.4,162.0(d d,J=15.0,251.0Hz),158.0(d d,J=13.0,252.0Hz),148.9,146.7,130.0,129.6,129.2(d d,J=2.0,10.0Hz),128.6,127.6(m,J=13.0Hz),126.5,111.8(d d,J=4.0,22.5Hz),104.8(t,J=25.0Hz),39.9
1H:8.86(1H,s),7.74(2H,br),7.38(3H,m br),7.28(1H,m),6.95(1H,m),6.92(1H,m),3.52(3H,s)
化合物编号75(MP:油脂).NMR溶剂:CDCl3
13C:150.5,145.2,133.2,129.2,125.1,119.7,113.6,51.7,50.4,38.0,35.7,30.1,29.0,19.8,13.8
1H:8.10(1H,d,J=8.4Hz),8.0(1H,d,J=8.3Hz),7.59(1H,t,J=7.8Hz),7.45(1H,t,J=7.6Hz),3.67(2H,br),3.31(3H,m br),1.78(2H,m),1.45-1.30(2H,m br),1.0-0.9(3H,m br)
化合物编号76(MP:130).NMR溶剂:CDCl3
13C:150.3,150.1,144.9,135.3,132.8,129.2,126.8,125,119.8,115.8,113.2,66.7,48.7,40.5
1H:8.04(1H,d,J=8.4Hz),8.0(1H,d,J=8.2Hz),7.60(1H,t,J=7.9Hz),7.42(1H,t,J=7.6Hz),7.08(2H,d,J=7.7Hz),6.80(2H,d,J=8.7Hz),3.83(4H,m),3.63(3H,s),3.13(4H,m)
化合物编号77(MP:163-138).NMR溶剂:CDCl3
13C:161.2,150.1,145.2,145,132.8,129.3,125.1,119.8,113.2,104.4,99.1,55.4,40.3
1H:8.05(1H,d,J=8.7Hz),8.02(1H,d,J=8.9Hz),7.61(1H,t,J=7.7Hz),7.44(1H,t,J=7.7Hz),6.34(1H,t,J=2.0Hz),6.31(2H,d,J=2.0Hz),3.70(6H,s),3.65(3H,s)
化合物编号78(MP:155-157).NMR溶剂:CDCl3
13C:163.8(d d,J=12.0,253.0Hz),160.8(d d,J=12.0,258.0Hz),158.4(d,J=6.0Hz),148.4,146.9,131.5(d d,J=4.0,10.0Hz),114.3(dd,J=4.0,11.5Hz),111.8(d d,J=4.0,21.5Hz),105.0(t,J=25.0Hz),66.6,47.9,45.9
1H:8.87(1H,s),8.12(1H,m,J=6.7,8.5Hz),7.0(1H,m),6.95(1H,m),4.10(4H,br),3.83(4H,s br)
化合物编号79(MP:86).NMR溶剂:CDCl3
13C:163.8(d d,J=12.0,253.0Hz),160.8(d d,J=12.5,259.0Hz),158.2(d,J=5.5Hz),148.5,146.7,139.7,131.5(d d,J=4.0,10.0Hz),129,128.3,126.1,114.6(d d,J=4.0,11.0Hz),111.7(d d,J=4.5,21.0Hz),105.0(t,J=26.0Hz),47.7,46.2,42.8,38,31.9
1H:8.83(1H,s),8.13(1H,m,J=6.8,8.3Hz),7.31(2H,t,J=7.5Hz),7.23(1H,m,J=7.3Hz),7.17(2H,d,J=7.8Hz),7.0(1H,m),6.96(1H,m),4.62(2H,m br),3.02(2H,br),2.61(2H,d,J=6.9Hz),1.87(1H,m),1.81(2H,d br,J=14.0Hz),1.43(2H,m,J=4.0,13.0Hz)
化合物编号80(MP:91).NMR溶剂:CDCl3
13C:163.7(d d,J=12,253.5Hz),162.1(d d,J=11.0,250.5Hz),160.7(d d,J=12.0,260.0Hz),158.2,157.9(d d,J=12.5,251.5Hz),148.8,146.2,131.2(d d,J=4.0,10.0Hz),129.0(d br,J=10.5Hz),126.4(d d,J=4.5,13.0Hz),114.2(d d,J=4.0,12.0Hz),111.8(d d,J=3.0,22.5Hz),111.6(d d,J=4.0,21.5Hz),104.9(t,J=25.3Hz,2Carbons),40.0
1H:8.89(1H,s),7.84(1H,br),7.26(1H,m),6.98-6.77(4H,m),3.51(3H,s)
化合物编号81(MP:99-100).NMR溶剂:CDCl3
13C:150.4,149.4,144.9,132.9,132.2,129,126.7,124.9,119.7,113.1,112.5,40.5,40.4
1H:8.03(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.59(1H,m,J=7.8Hz),7.41(1H,t,7.6Hz),7.03(2H,br),6.59(2H,d br,J=8.0Hz),3.62(3H,s),2.92(6H,s)
化合物编号82(MP:179-182(分解)).NMR溶剂:DMSO
13C:148.6,144.7,132.5,129.6,125.5,119.7,113.4,61.7,49,46,43.5,25.8,22.5,21.6
1H:10.52(1H,s br),8.20(1H,d,J=8.3Hz),7.93(1H,d,J=8.4Hz),7.71(1H,t,J=7.7Hz),7.55(1H,t,J=7.7Hz),4.43(2H,d br,J=13.5Hz),3.52(1H,m),3.41(2H,d br,J=11.5Hz),3.23(2H,t br),2.94(2H,m,J=12.0Hz),2.25(2H,br),1.88(2H,br),1.86(4H,m),1.71(1H,m,J=14.0Hz),1.40(1H,m)
化合物编号83(MP:259-261(分解)).NMR溶剂:DMSO
13C:148.8,144.8,132.5,129.8,125.7,119.7,113.6,51.9,43.3,421H:11.59(1H,s br),8.22(1H,d,J=8.3Hz),7.96(1H,d,J=8.3Hz),7.73(1H,t,J=7.8Hz),7.56(1H,t,J=7.6Hz),4.47(2H,m),3.71(2H,m),3.52(2H,m),3.29(2H,m),2.81(3H,s)
化合物编号84(MP:92).NMR溶剂:CDCl3
13C:155.9,150.4,148.7,145.2,138.4,132.6,129.5,125.3,121.8,119.9,119.5,113.5,37.8
1H:8.32(1H,d d,J=1.6,5.0Hz),8.12(1H,d,J=8.3Hz),8.02(1H,d,J=8.3Hz),7.69(1H,d t,J=1.9,7.9Hz),7.63(1H,t,J=7.8Hz),7.45(1H,t,J=7.7Hz),7.18(1H,d,J=8.1Hz),7.15(1H,d d,J=5.0,7.5Hz),3.74(3H,s)
化合物编号85(MP:66).NMR溶剂:CDCl3
13C:149.2,146.2,141.8,131.6,129.9,128.4(2sig.),125.9,125.4,120,113.9,40.3,35.4,29.1,28.5
1H:8.29(1H,m,J=8.3Hz),8.10(1H,m,J=8.4Hz),7.63(1H,m,J=1.0,7.1Hz),7.47(1H,m,J=1.0,7.1Hz),7.33(1H,br),7.30(2H,m),7.20(2H,m),7.19(1H,m),3.58(2H,m),2.71(2H,m,J=7.0Hz),1.77(4H,m)
化合物编号86(MP:60).NMR溶剂:CDCl3
13C:149.2,146.3,131.6,129.9,125.3,119.9,114,40.5,31.9,29.6,29.6,29.5,29.5,29.3,29.2,26.8,22.7,14.1
1H:8.29(1H,d,J=8.3Hz),8.10(1H,d,J=8.4Hz),7.63(1H,m,J=1.0,7.1Hz),7.47(1H,m,J=1.0,7.1Hz),7.33(1H,t br,J=5.0Hz),3.55(2H,m),1.71(2H,m),1.50-1.15(18H,m),0.88(3H,t,J=7.1Hz)化合物编号87(MP:73).NMR溶剂:CDCl3
13C:148.4,146.3,131.7,129.8,125.3,119.9,114,49.8,33,25.3,24.7
1H:8.28(1H,d,J=8.4Hz),8.09(1H,d,J=8.4Hz),7.63(1H,t,J=7.8Hz),7.47(1H,t,J=7.6Hz),7.21(1H,d,J=7.5Hz),3.95(1H,m),2.11(2H,m),1.83(2H,m),1.69(1H,m),1.43(4H,m),1.29(1H,m)
化合物编号88(MP:186-188).NMR溶剂:CDCl3
13C:146.5,146.4,140.2,138.2,135.3,131.6,130.3,128.8,128,127.4,126.9,125.8,120.3,120.2,114
1H:9.24(1H,s),8.37(1H,d,J=8.3Hz),8.16(1H,d,J=8.5Hz),7.78(2H,d,J=8.6Hz),7.69(1H,m),7.68(2H,d,J=8.6Hz),7.62(2H,d,J=7.7Hz),7.53(1H,t,J=7.8Hz),7.47(2H,t,J=7.7Hz),7.37(1H,t,J=7.6Hz)
化合物编号89(MP:167(分解)).NMR溶剂:CDCl3
13C:148.1,146.8,129.3,129,128.8,125.9,120.9,66.6,48.5,45.8
1H:8.38(1H,s),7.88(2H,d,J=8.2Hz),7.47(2H,t,J=7.7Hz),7.39(1H,m,J=7.5Hz),4.04(2H,m br),3.84(6H,m)
化合物编号90(MP:230-231(分解)).NMR溶剂:DMSO
13C:148.6,144.7,132.5,129.6,125.6,119.7,113.4,63.3,61.9,48.3,45.6,43.6,25.8
1H:11.53(1H,s br),8.20(1H,d,J=8.3Hz),7.93(1H,d,J=8.2Hz),7.71(1H,m,J=7.5Hz),7.55(1H,m,J=7.6Hz),4.44(2H,d br,J=12.5Hz),3.98(2H,d br,J=11.5Hz),3.90(2H,t,J=12.0Hz),3.54(1H,m),3.45(2H,d br,J=12.0Hz),3.22(2H,br),3.11(2H,m),2.28(2H,br),1.90(2H,m,J=4.0,12.3Hz)
化合物编号91(MP:143).NMR溶剂:DMSO
13C:152.5,148.7,145.1,144.7,137.5,132.6,129.6,128.4,127.8,127.6,125.5,119.7,118,115.4,113.4,69.4,49.8,47.5,44.9
1H:8.21(1H,d,J=8.4Hz),7.96(1H,d,J=8.4Hz),7.71(1H,t,J=7.6Hz),7.55(1H,t,J=7.5Hz),7.43(2H,d,J=8.0Hz),7.38(2H,t,J=7.7Hz),7.31(1H,m,J=7.1Hz),6.94(4H,m),5.03(2H,s),3.90(4H,m),3.19(4H,br)
化合物编号92(MP:218-220(分解)).NMR溶剂:DMSO
13C:148.7,144.8,132.5,129.6,125.5,119.7,113.4,60.2,50.5,45.7,43.2,27.9,22.7
1H:11.24(1H,s),8.20(1H,d,J=8.2Hz),7.93(1H,d,J=8.3Hz),7.70(1H,t,J=7.7Hz),7.54(1H,t,J=7.4Hz),4.40(2H,d br,J=13.0Hz),3.49(2H,br),3.45(1H,m),3.22(2H,m br),3.08(2H,br),2.20(2H,br),1.96(4H,m),1.89(2H,m)
化合物编号93(MP:254-256(分解)).NMR溶剂:DMSO
13C:148.8,144.8,132.5,131.5,129.8,129.6,129.4,128.8,125.7,119.7,113.6,58.6,50.1,43.6,42.1
1H:11.97(1H,s br),8.21(1H,d,J=8.4Hz),7.95(1H,d,J=8.3Hz),7.67(2H,m),7.56(1H,t,J=7.7Hz),7.47(3H,m),7.33(1H,t,J=7.6Hz),4.47(2H,d br,J=15.0Hz),4.39(2H,s),3.79(2H,m),3.43(2H,m),3.28(2H,m)
化合物编号94(MP:109-111).NMR溶剂:CDCl3
13C:149.4,145.4,144.7,133.2,129.3,128.6,126.8,126.6,125.2,119.8,113.5,48.8,46.1,42.6,33.2
1H:8.12(1H,m,J=8.3Hz),8.02(1H,m,J=8.4Hz),7.63(1H,m,J=1.0,7.1Hz),7.47(1H,m,J=1.0,7.1Hz),7.35(2H,m,J=7.7Hz),7.27(2H,m),7.25(1H,m),4.70(2H,d br,J=13.5Hz),3.29(2H,br),2.89(1H,m),2.01(4H,m)
化合物编号95(MP:157).NMR溶剂:CDCl3
13C:150.2,145.9,141.5,136.4,133.2,131.8,131.1,131,129.9,128.7,118.6,118,114.4,113.2,58.6,57.2,32.6,30.8,29.7,25.5,25.3
1H:8.25(1H,br),8.09(1H,d,J=8.6Hz),7.90(1H,d br,J=7.9Hz),7.80(1H,d d,J=1.6,8.7Hz),7.70(1H,d,J=7.6Hz),7.62(1H,t,J=7.7Hz),4.29(1H,m br),3.21(3H,s),2.02(2H,m br),1.90(2H,m br),1.73(1H,br),1.64(2H,m),1.46(2H,m),1.17(1H,m)
化合物编号96(MP:146-147).NMR溶剂:CDCl3
13C:162.6(d,J=247.0Hz),150.3,146,137.9,136.3(d,J=3.0Hz),132.7,129.1(d,J=8.4Hz),129.0,117.4,115.9(d,J=22.0Hz),113.8,58.6,57.2,32.7,30.4,29.6,25.5,25.3
1H:8.21(1H,br),8.03(1H,d,J=8.5Hz),7.80(1H,d d,J=1.5,8.5Hz),7.62(2H,m d,J=5.3,8.7Hz),7.19(2H,t,J=8.5Hz),4.27(1H,mbr),3.20(3H,s br),2.01(2H,m),1.89(2H,m),1.73(1H,m),1.64(2H,m),1.44(2H,m),1.17(1H,m)
化合物编号97(MP:158).NMR溶剂:CDCl3
13C:149.9,146.3,132.4,132.3,122.4,118.3,114.9,58.8,57.1,32.6,30.9,29.5,25.5,25.3
1H:8.25(1H,br,J=2.0Hz),7.89(1H,d,J=8.8Hz),7.68(1H,d d,J=2.0,8.8Hz),4.27(1H,m br),3.18(3H,s),1.98(2H,m),1.89(2H,m),1.70(1H,m),1.61(2H,m),1.45(2H,m),1.17(1H,m)
化合物编号98(MP:93-94).NMR溶剂:CDCl3
13C:148.8,145.1,133,129.2,125.2,119.7,114.3,50.3,48.5,26.6,24
1H:8.18(1H,m,J=8.4Hz),8.09(1H,m,J=8.3Hz),7.60(1H,m,J=1.0,7.0Hz),7.46(1H,m,J=1.0,7.0Hz),4.08(2H,m),3.81(2H,m),2.04(4H,m)
化合物编号99(MP:139-141).NMR溶剂:CDCl3
13C:154.7,149.4,145.4,133.2,130.7,130.1,129.3,125.2,119.8,116.2,113.5,70.9,44.4,41.9,30.4,20.5
1H:8.11(1H,d,J=8.3Hz),8.0(1H,d,J=8.4Hz),7.62(1H,t,J=7.8Hz),7.46(1H,t,J=7.6Hz),7.12(2H,m,J=8.5Hz),6.87(2H,m,J=8.5Hz),4.66(1H,m),4.0(4H,m),2.31(3H,s),2.10(4H,m)
化合物编号100(MP:80).NMR溶剂:CDCl3
13C:149.3,145.3,142.1,133.2,129.2,128.4,128.3,125.8,125.1,119.8,113.4,48.4,45.8,38,35.4,32.8,32.2
1H:8.10(1H,d,J=8.2Hz),7.98(1H,d,J=8.3Hz),7.61(1H,t,J=8.0Hz),7.46(1H,t,J=7.8Hz),7.31(2H,t,J=7.1Hz),7.21(1H,m),7.20(2H,d,J=7.9Hz),4.53(2H,d br,J=12.0Hz),3.15(2H,br),2.69(2H,m,J=7.5Hz),1.93(2H,br),1.49(2H,br),1.67(3H,m)
化合物编号101(MP:134).NMR溶剂:CDCl3
13C:150.7,150.5,142.6,137,132.8,129.3,128.7,127.7,125.2,121.1,116.9,112.9,49.5,46.5
1H:7.91(1H,s),7.82(2H,d,J=7.9Hz),7.51(1H,s),7.42(2H,t,J=7.8Hz),7.32(3H,m),6.96(3H,m),3.83(4H,m,J=5.0Hz),3.29(4H,m,J=5.0Hz)
化合物编号102(MP:122).NMR溶剂:CDCl3
13C:150.6,142.4,137.1,137,132.8,129.1,128.7,128.4,127.6,127.4,125.1,113,62.7,52.5,46.5
1H:7.91(1H,d,J=1.3Hz),7.80(2H,d,J=8.0Hz),7.47(1H,d,J=1.3Hz),7.41(2H,t,J=7.8Hz),7.34(4H,m),7.32(1H,m),7.29(1H,m),3.67(4H,m,J=5.0Hz),3.58(2H,s),2.55(4H,m,J=5.0Hz)
化合物编号103(MP:154).NMR溶剂:CDCl3
13C:151.3,142.1,136.9,133,128.7,127.5,125.1,113.2,57.5,31.3,30,25.4,25.2
1H:7.92(1H,d,J=1.0Hz),7.81(2H,d,J=8.2Hz),7.50(1H,d,J=1.0Hz),7.41(2H,t,J=8.0Hz),7.29(1H,t,J=7.5Hz),3.96(1H,m),2.99(3H,s),1.86(4H,m),1.70(1H,d br,J=13.5Hz),1.58(2H,m,J=3.5,13.1Hz),1.38(2H,m),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号104(MP:83).NMR溶剂:CDCl3
13C:150,145.2,133.3,129,125,119.7,113.5,58.9,40,31.2,25.7,25.3,15.1
1H:8.10(1H,d,J=8.3Hz),7.97(1H,d,J=8.3Hz),7.59(1H,m,J=1.0,7.1Hz),7.45(1H,m,J=1.0,7.1Hz),4.17(1H,m),3.63(2H,m,J=6.6Hz),2.02(2H,d br,J=12.0Hz),1.85(2H,d br,J=12.0Hz),1.69(3H,br),1.31(5H,br),1.17(1H,m)
化合物编号105(MP:204).NMR溶剂:CDCl3
13C:149.2,145.3,133,129.3,125.2,119.7,113.4,53.5,53.1,48,45.4,33.5,31.7(2sig.),23.3
1H:12.38(1H,s br),8.07(1H,d,J=8.3Hz),7.94(1H,d,J=8.4Hz),7.59(1H,t,J=7.7Hz),7.44(1H,t,J=7.5Hz),4.52(2H,d br,J=12.0Hz),3.79(2H,br),3.15(2H,br),3.12(2H,m),2.79(2H,m br),2.24(2H,m br),2.08(2H,m br),1.90(5H,m br),1.50(2H,m br)
化合物编号106(MP:油脂).NMR溶剂:CDCl3
13C:162.9(d,J=248Hz),150.5,144.6,141.7,136.3(d,J=3Hz),133.9,129.4(d,J=8Hz),125.1,119.9,115.8(d,J=21.5Hz),111.5,58.9(br),57.0(br),32.6(br),30.6(br),29.7(br),25.5,25.3
1H:8.12(2H,m),7.66-7.62(3H,m),7.17(2H,m,J=8.7Hz),4.28(1H,br),3.19(3H,s br),2.0(2H,m br),1.88(2H,br),1.76-1.56(3H,br),1.44(2H,br),1.18(1H,m br)
化合物编号107(MP:232-233).NMR溶剂:DMSO
13C:167.2,149.6,145.5,139.7,136.9,132.3,131.8,131.7,129.5,128.9,128.6,127.9,117.3,113.9,56.9,32.5,30.2,29,25.2,24.8
1H:13.19(1H,s br),8.49(1H,s),8.29(1H,s),8.06(1H,m),7.98(3H,m),7.65(1H,t,J=7.8Hz),4.09(1H,m br),3.08(3H,s),1.88(2H,m),1.80(2H,m),1.67(2H,m),1.60(1H,m),1.33(2H,m),1.16(1H,br)
化合物编号108(MP:183).NMR溶剂:CDCl3
13C:169.2,150.3,145.9,140.8,137.7,134.1,132.9,131,129.3,129,126.7,126.3,117.7,114,58.8,57.1,32.6,30.7,29.6,25.5,25.31H:8.27(1H,s br),8.15(1H,s br),8.04(1H,d,J=8.5Hz),7.85(1H,br),7.83(1H,m),7.81(1H,m),7.56(1H,t,J=7.8Hz),6.42(1H,s br),6.12(1H,s b),4.30(1H,br),3.22(3H,s),2.03(2H,m),1.91(2H,m),1.76(1H,m),1.67(2H,m),1.47(2H,m),1.20(1H,m)
化合物编号109(MP:209-210).NMR溶剂:DMSO
13C:167.7,149.7,144.2,140.9,139.3,135.2,133.4,130.3,129.3,127.4,126.5,125.2,120,111,58.3,57.2,32.3,29.6,28.8,25.2,24.8
1H:8.28(1H,d,J=8.6Hz),8.26(1H,s br),8.22(1H,s br),8.17(1H,br),7.94(2H,m),7.91(1H,m),7.61(1H,t,J=7.7Hz),7.53(1H,s br),4.03(1H,br),3.09(3H,s),1.89(2H,m),1.80(2H,m),1.60(1H,m),1.36(2H,m),1.67(2H,m),1.16(1H,m)
化合物编号110(MP:66-67).NMR溶剂:CDCl3
13C:149.3,145.3,142.3,133.1,129.2,128.3,128.3,125.7,125.1,119.8,113.4,48.4,45.8,36,35.9,35.8,32.2,28.5
1H:8.10(1H,d,J=8.4Hz),7.97(1H,d,J=8.3Hz),7.60(1H,t,J=7.5Hz),7.45(1H,t,J=7.7Hz),7.30(2H,t,J=7.8Hz),7.20(1H,m),7.19(2H,d,J=7.8Hz),4.51(2H,m,br),3.14(2H,br),2.64(2H,t,J=7.6Hz),1.86(2H,m),1.69(2H,m),1.64(1H,m),1.43(2H,m),1.38(2H,m)
化合物编号111(MP:83).NMR溶剂:DMSO
13C:161.4,150.6,148.4,148.1,130.2,129.7,129.1,129,126.4,119.5,115.9,48.2,45.7
1H:9.17(1H,s),8.09(2H,m,J=1.5,7.2Hz),7.53(3H,m),7.25(2H,t,J=7.6Hz),6.99(2H,d,J=8.1Hz),6.83(1H,t,J=7.2Hz),3.90(4H,br),3.30(4H,m)
化合物编号112(MP:203).NMR溶剂:DMSO
13C:167.6,149.9,140.1,137.9,137.7,136,132.6,128.9,128.3,128,127.1,124.4,115.6,61.7,52.1,45.9
1H:8.13(1H,d,J=1.2Hz),8.09(1H,d,J=1.2Hz),7.98(1H,s br),7.91(4H,m br),7.36(1H,s br),7.33(4H,m),7.26(1H,m),3.56(4H,m,J=5.5Hz),3.53(2H,s),2.47(4H,m,J=5.5Hz)
化合物编号113(MP:231-233(分解)).NMR溶剂:DMSO
13C:167.6,149.7,142.8,139.3,138,135.7,132.6,129.9,128,127.7,126.2,124.2,115.6,39.6
1H:7.95(1H,s br),7.84(2H,d,J=8.5Hz),7.74(1H,d,J=1.0Hz),7.72(2H,d,J=8.5Hz),7.60(1H,d,J=1.0Hz),7.41(2H,t,J=7.6Hz),7.35(1H,s br),7.35(2H,m),7.31(1H,t,J=7.1Hz),3.43(3H,s)
化合物编号114(MP:135-136).NMR溶剂:DMSO
13C:153.8,149.8,148.7,144.7,132.6,129.5,125.4,122.4,119.6,113.3,47.7,45.2,40.5,31.8
1H:8.50(2H,m,J=5.0Hz),8.20(1H,d,J=8.5Hz),7.95(1H,d,J=8.3Hz),7.71(1H,t,J=7.9Hz),7.54(1H,t,J=7.7Hz),7.34(2H,m,J=5.0Hz),4.39(2H,br),3.32(2H,br),2.96(1H,m),1.95(2H,br),1.82(2H,m,J=4.0,12.3Hz)
化合物编号115(MP:油脂).NMR溶剂:CDCl3
13C:150.5,145.2,138.1,133.2,129.1,128.7,128.6,126.6,125.1,119.7,113.8,53.1(br),38.2(very broad),34.3(br)
1H:8.08(1H,d,J=8.3Hz),7.91(1H,br),7.57(1H,t,J=7.7Hz),7.44(1H,t,J=7.7Hz),7.23(5H,br),3.96(2H,br),3.31(3H,s),3.10(2H,m,J=7.2Hz)
化合物编号116(MP:147).NMR溶剂:CDCl3
13C:181.1,166.4,152.1,149.4,148.6,145.4,134.7,133.1,129.5,125.3,123.7,122.9,119.9,113.5,46.9,44.8,34,29.2
1H:9.32(1H,d,J=1.7Hz),8.76(1H,d d,J=1.6,4.9Hz),8.37(1H,d t,J=2.0,8.0Hz),8.12(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.63(1H,t,J=7.9Hz),7.48(1H,t,J=7.9Hz),7.45(1H,d d,J=4.9,8.0Hz),4.56(2H,d br),3.57(2H,br),3.46(1H,m),2.37(2H,m),2.27(2H,m)
化合物编号117(MP:138-139).NMR溶剂:CDCl3
13C:155.4,149.4,145.4,133.1,129.6,129.4,126.2,125.2,119.9,117.4,113.5,71.2,44.4,42,30.4
1H:8.11(1H,d,J=8.4Hz),7.99(1H,d,J=8.2Hz),7.62(1H,t,J=7.8Hz),7.47(1H,t,J=7.8Hz),7.27(2H,m,J=9.0Hz),6.89(2H,m,J=9.0Hz),4.67(1H,m),4.01(4H,s br),2.15(2H,m),2.06(2H,m)
化合物编号118(MP:油脂).NMR溶剂:CDCl3
13C:150.5,142.5,141.0,133.2,129.2,128.5,128.2,126.1,125.1,119.8,113.6,51.4,50.4,38.1,35.8,32.9,29.6,28.6
1H:8.10(1H,d,J=8.5Hz),8.01(1H,d,J=8.2Hz),7.61(1H,t,J=7.9Hz),7.46(1H,t,J=7.7Hz),7.24(5H,br),3.71(2H,m,J=7.2Hz),3.31(3H,br),2.71(2H,br),2.15(2H,m,J=7.5Hz)
化合物编号119(MP:油脂).NMR溶剂:CDCl3
13C:160.1,151.0,145.3,137.4,133.3,129.9,129.3,125.2,120.3,119.9,113.7(2sig.),113.4,55.3,54.2,37.5
1H:8.11(1H,d,J=8.2Hz),8.06(1H,d,J=8.3Hz),7.62(1H,t,J=7.8Hz),7.47(1H,t,J=7.5Hz),7.30(1H,t,J=7.7Hz),6.96(2H,br),6.87(1H,d,J=8.2),4.89(2H,br),3.81(3H,s),3.29(3H,br)
化合物编号120(MP:70-71).NMR溶剂:CDCl3
13C:156.9,149.4,145.4,133.2,129.7,129.3,125.2,121.3,119.8,116.1,113.5,70.6,44.4,42,30.4
1H:8.11(1H,d,J=8.3Hz),8.0(1H,d,J=8.3Hz),7.62(1H,t,J=7.8Hz),7.47(1H,t,J=7.6Hz),7.33(2H,m,J=8.0Hz),7.0(1H,t,J=7.4Hz),6.97(2H,d,J=8.3Hz),4.72(1H,m),4.01(4H,s br),2.16(2H,m),2.10(2H,m)
化合物编号121(MP:115).NMR溶剂:CDCl3
13C:162.1(d,J=245.0Hz),149.3,145.3,133.1,133.1,130.6(d,J=8.0Hz),129.4,125.2,119.8,115.2(d,J=21.0Hz),113.5,61.9,52.7,48.1,45.2
1H:8.10(1H,m,J=8.3Hz),7.99(1H,m,J=8.4Hz),7.61(1H,m,J=1.0,7.0,8.2Hz),7.46(1H,m,J=1.0,7.0,8.2Hz),7.32(2H,m d,J=5.6,8.7Hz),7.06(2H,m t,J=8.3Hz),3.93(4H,s br),3.56(2H,s),2.63(4H,s br)
化合物编号122(MP:188(分解)).NMR溶剂:DMSO
13C:148.6,144.7,132.5,129.5,125.4,119.6,113.3,59.7,52.9,46.5,45.6,44.1,42.1,27.9
1H:10.72(1H,br),8.19(1H,d,J=8.4Hz),7.91(1H,d,J=8.3Hz),7.70(1H,t,J=7.9Hz),7.53(1H,t,J=7.8Hz),4.28(2H,s br),3.21(4H,m br),2.96(4H,m br),2.68(6H,m),1.90(2H,m br),1.57(2H,mbr)
化合物编号123(MP:油脂).NMR溶剂:CDCl3
13C:151.0,145.2,137.9,134.7,133.2,130.1,129.5,128.2,127.9,126.2,125.3,119.9,113.7,54.8,53.4,37.8
1H:8.11(1H,d,J=8.5Hz),8.07(1H,d,J=8.3Hz),7.63(1H,d d d,J=1,7.1,8.2Hz),7.48(1H,d d d,J=1,7.0,8.2Hz),7.42(1H,br),7.32(3H,br),4.90(2H,br),3.28(3H,br)
化合物编号124(MP:258-259(分解)).NMR溶剂:DMSO
13C:161.6,148.4,148.3,131.5,130.3,129.6,129.5,129.1,129,128.8,126.5,58.6,50,42.6
1H:12.03(1H,s br),9.16(1H,s),8.07(2H,m),7.67(2H,m),7.51(3H,m),7.45(3H,m),4.55(2H,m),4.38(2H,s),3.73(2H,m,J=12.0Hz),3.41(2H,br,J=11.7Hz),3.24(2H,m)
化合物编号125(MP:232(分解)).NMR溶剂:DMSO
13C:161.4,159.9,148.4,148.2,136.8,131.5,129.6,129.5,128.8,128.5,128.1,128,127.9,122.2,115.2,69.4,58.6,50,42.6
1H:11.97(1H,s),9.12(1H,s),8.0(2H,d,J=8.6Hz),7.66(2H,m),7.45(5H,m),7.40(2H,t,J=7.5Hz),7.33(1H,t,J=7.2Hz),7.15(2H,d,J=8.6Hz),5.17(2H,s),4.55(2H,m),4.37(2H,s),3.70(2H,m,J=12.0Hz),3.41(2H,m),3.24(2H,m)
化合物编号126(MP:135).NMR溶剂:CDCl3
13C:147.3,146.3,131.6,129.7,125.2,119.9,114.1,52.8,41.6,36.1,29.4
1H:8.27(1H,d,J=8.4Hz),8.09(1H,d,J=8.4Hz),7.61(1H,m,J=1.0,7.0,8.0Hz),7.45(1H,m,J=1.0,7.0,8.0Hz),7.17(1H,s),2.20(9H,s),1.76(6H,s)
化合物编号127(MP:101).NMR溶剂:DMSO
13C:148.6,144.7,132.5,129.5,125.5,119.7,113.3,62.6,48.4,45.2,28.3,25.9,25.4
1H:8.18(1H,d,J=8.2Hz),7.91(1H,d,J=8.5Hz),7.69(1H,t,J=7.8Hz),7.56(1H,t,J=7.6Hz),3.71(4H,m),2.63(4H,s br),2.30(1H,m),1.76(2H,m),1.73(2H,m),1.56(1H,d,J=12.4Hz),1.20(4H,m),1.07(1H,m)
化合物编号128(MP:油脂).NMR溶剂:CDCl3
13C:149.4,145.3,138.4,133.1,129.3,128.5,127.7,127.4,125.1,119.8,113.5,72.5,70.1,44.9,42.3,30.9
1H:8.10(1H,d,J=8.4Hz),7.98(1H,d,J=8.4Hz),7.61(1H,d d d,J=1,7.1,8.2Hz),7.46(1H,d d d,J=1,7.1,8.2Hz),7.40-7.28(5H,m),4.62(2H,s),4.06(2H,m),3.81(3H,m),2.08(2H,m),1.94(2H,br)
化合物编号129(MP:油脂).NMR溶剂:CDCl3
13C:150.5,145.2,142.3,133.2,129.2,128.4,128.3,125.7,125.1,119.7,113.6,51.8,50.6,38.0,35.8,31.1,28.0,26.8,26.2
1H:8.11(1H,d,J=8.3Hz),8.0(1H,d,J=8.4Hz),7.61(1H,d d d,J=1.0,7.0,8.2Hz),7.46(1H,d d d,J=1.0,7.0,8.2Hz),7.27(2H,t,J=7.7Hz),7.17(3H,m),3.66(2H,m),3.31(3H,br),2.64(2H,br),1.82(2H,m,J=7.7Hz),1.71(2H,br),1.47-1.31(2H,very broad)
化合物编号130(MP:油脂).NMR溶剂:CDCl3
13C:162.4(d,J=247Hz),150.9,145.2,133.2,131.5(d,J=3Hz),129.9,129.4,125.3,119.9,115.8(d,J=22Hz),113.6,54.5,53.2,37.6
1H:8.11(1H,d,J=8.4Hz),8.05(1H,d,J=8.3Hz),7.63(1H,d d d,J=1.0,7.1,8.2Hz),7.48(1H,d d d,J=1.0,7.1,8.2Hz),7.41(2H,br),7.08(2H,t,J=8.1Hz),4.88(2H,br),3.24(3H,br)
化合物编号131(MP:油脂).NMR溶剂:CDCl3
13C:150.9,145.2,133.9,133.2,130.9,129.4,128.9,126.8,126.1,125.3(2signa Hzs),123.1,119.9,113.6,53.1,51.7,37.5
1H:8.24-8.06(3H,m),7.98-7.82(2H,m),7.65(1H,d d d,J=1.1,7.0,8.0Hz),7.60-7.45(4H,m,br),7.48(1H,d d d,J=1.0,7.0,8.0Hz),5.38(2H,m br),3.28(3H,s br)
化合物编号132(MP:129-130(分解)).NMR溶剂:DMSO
13C:161.3,154.6,150.6,148.5,147.6,130,129.6,127.4,120.8,115.9,115.5,71.1,51.8,44.7,43,41.9,30.3,20.1
1H:11.17(1H,s),9.05(1H,s),7.92(2H,d,J=7.8Hz),7.11(2H,d,J=7.8Hz),7.08(2H,d,J=7.6Hz),6.89(2H,d,J=7.6Hz),4.64(1H,mbr),3.95(2H,m),3.93(2H,m),3.61(2H,m),3.48(2H,m),3.17(4H,m),2.79(3H,s),2.22(3H,s),2.05(2H,s br),1.74(2H,br)
化合物编号133(MP:140).NMR溶剂:DMSO
13C:161.7,152.1,148.6,147.7,138,129,128.3,127.4,127.1,119.5,114.7,65.9,62,52.4,47.4,46.2
1H:9.04(1H,s),7.88(2H,d,J=8.2Hz),7.33(4H,br),7.27(1H,br),7.02(2H,d,J=8.2Hz),3.75(4H,m br),3.70(4H,m br),3.52(2H,br),3.23(4H,br),2.50(4H,br)
化合物编号134(MP:油脂).NMR溶剂:DMSO
13C:163.1(d d,J=13.5,251.5Hz),160.1(d d,J=13.0,257.5Hz),157.1(d,J=6Hz),154.6,148.2,147.4,131.6(d d,J=4.5,10.5Hz),130.0,129.6,116.0,114.6(d d,J=4.0,11.5Hz),112.3(d d,J=4.0,22.0Hz),105.3(t,J=25.5Hz),71.1,43.1(br),30.3,20.1
1H:9.17(1H,s),8.12(1H,d t,J=6.7,8.6Hz),7.43(1H,d d d,J=2.5,9.4,11.5Hz),7.26(1H,d t,J=2.5,8.5Hz),7.08(2H,d,J=8.4Hz),6.89(2H,d,J=8.4Hz),4.64(1H,m,J=3.7Hz),3.93(2H,m br),3.61(2H,m br),2.22(3H,s br),2.05(2H,m),1.73(2H,m)
化合物编号135(MP:油脂).NMR溶剂:CDCl3
13C:149.4,145.3,141.8,133.1,129.3,128.4,128.3,125.8,125.1,119.8,113.4,73.0,67.3,45.0,42.4,32.3,31.5,30.9
1H:8.11(1H,d,J=8.4Hz),7.98(1H,d,J=8.3Hz),7.61(1H,t,J=7.7Hz),7.46(1H,t,J=7.5Hz),7.30(2H,t,J=7.9Hz),7.21(3H,m),4.04(2H,m),3.77(2H,m),3.66(1H,m,J=3.4Hz),3.50(2H,t,J=6.3Hz),2.74(2H,t,J=7.9Hz),2.02(2H,m),1.94(2H,m),1.85(2H,m)
化合物编号136(MP:197-198).NMR溶剂:DMSO
13C:151.5,148.7,144.7,143.7,132.6,129.6,125.5,119.7,118.6,115.6,113.4,50.3,47.4,45.2
1H:8.95(1H,s),8.20(1H,d,J=8.3Hz),7.95(1H,d,J=8.4Hz),7.71(1H,t,J=7.7Hz),7.55(1H,t,J=7.7Hz),6.85(2H,m,J=9.0Hz),6.68(2H,m,J=9.0Hz),3.89(4H,m br),3.12(4H,m)
化合物编号137(MP:100-101).NMR溶剂:CDCl3
13C:154.4,150.8,149.4,145.4,133.1,129.3,125.2,119.8,117.8,114.8,113.5,72,55.7,44.5,41.9,30.5
1H:8.11(1H,d,J=8.5Hz),8.0(1H,d,J=8.6Hz),7.62(1H,d,J=7.6Hz),7.47(1H,m,J=7.8Hz),6.92(2H,m,J=9.2Hz),6.86(2H,m,J=9.2Hz),4.57(1H,m),3.99(4H,m br),3.79(3H,s),2.09(4H,m)
化合物编号138(MP:187-188).NMR溶剂:DMSO
13C:161.5,151.9,150.9,149.8,147.4,129,127.4,120,119.3,115.7,115,48.2,47.5,37.8
1H:9.02(1H,s),7.92(2H,m,J=9.0Hz),7.25(2H,d d,J=7.3,8.5Hz),7.11(2H,m,J=9.0Hz),7.0(2H,d,J=8.5Hz),6.81(1H,t,J=7.3Hz),3.38(4H,m),3.29(4H,m),3.16(6H,s br)
化合物编号139(MP:161-162).NMR溶剂:DMSO
13C:161.7,152,148.6,147.7,127.4,119.5,114.7,65.9,54.4,47.2,46.3,45.7
1H:9.04(1H,s),7.89(2H,m,J=9.0Hz),7.03(2H,m,J=9.0Hz),3.75(4H,br),3.70(4H,m),3.23(4H,m,J=5.0Hz),2.47(4H,m,J=5.0Hz),2.23(3H,s)
化合物编号140(MP:167-168).NMR溶剂:CDCl3
13C:161.8,161,156.4,149.8,147.2,134.2,128.8,126.9,120.3,118.7,118.4,106.3,39.3,38.6
1H:8.84(1H,s),8.19(2H,d,J=8.8Hz),7.64(2H,d,J=9.0Hz),7.15(2H,d,J=8.8Hz),7.08(2H,d,J=9.0Hz),3.41(3H,s),3.23(3H,s)
化合物编号141(MP:144-145).NMR溶剂:CDCl3
13C:162,160.9,156.6,148.6,147.6,134.2,128.9,126.5,120.3,118.7,118.4,106.4,66.6,46.6
1H:8.85(1H,s),8.17(2H,d,J=8.8Hz),7.64(2H,d,J=8.9Hz),7.15(2H,d,J=8.8Hz),7.08(2H,d,J=8.9Hz),4.0(8H,s br)
化合物编号142(MP:202-203).NMR溶剂:DMSO
13C:149,145.5,131.4,130.2,125.8,119.9,113.6,49.6,45.7,45.4,45,24.7,21.4,17.2
1H:10.72(1H,s br),9.55(1H,d,J=6.8Hz),8.23(1H,d,J=8.3Hz),8.18(1H,d,J=8.2Hz),7.74(1H,m,J=8.0Hz),7.57(1H,m,J=7.6Hz),4.41(1H,m),3.66(1H,t,J=11.5Hz),3.40(1H,m),3.20(4H,m),2.30(1H,m),2.12(1H,m),1.94(1H,m),1.74(1H,m)
化合物编号143(MP:108-109).NMR溶剂:CDCl3
13C:150.6,145.2,133.2,129.2,125.1,119.8,113.5,96.3,70.3,70,57.9,55.8,32.6,31,30.2,26.1,24.8,22.6
1H:8.10(1H,d,J=8.3Hz),7.98(1H,d,J=8.4Hz),7.61(1H,t,J=7.5Hz),7.46(1H,t,J=7.6Hz),4.37(1H,br),3.53(4H,s),3.18(3H,s),2.41(2H,br),1.91(4H,m),1.53(2H,br),0.99(6H,s)
化合物编号144(MP:67-68).NMR溶剂:CDCl3
13C:153.8,152.9,149.3,145.3,133.1,129.2,125.1,119.8,115.3,114.6,113.4,65.6,55.7,48.4,45.8,35.6,32.9,32.1
1H:8.11(1H,m,J=8.4Hz),7.98(1H,d,J=8.4Hz),7.61(1H,m,J=1.0,7.1,8.1Hz),7.46(1H,m,J=1.0,7.1,8.1Hz),6.85(4H,s),4.55(2H,d br,J=13.0Hz),4.01(2H,t,J=6.2Hz),3.78(3H,s),3.19(2H,s br),1.96(3H,m),1.81(2H,q,J=6.2Hz),1.52(2H,m)
化合物编号145(MP:179-180(分解)).NMR溶剂:DMSO
13C:160.8,160.4,156.2,148.3,148.2,147.9,134.8,129.4,128.6,126.3,122.8,120.4,118.7,117.7(2sig.),105.7,50,44.9
1H:9.19(1H,s),8.15(2H,d,J=8.6Hz),7.88(2H,d,J=8.4Hz),7.35(2H,t,J=7.3Hz),7.29(2H,br),7.28(2H,d,J=8.6Hz),7.19(2H,d,J=8.4Hz),7.05(1H,t,J=7.0Hz),4.05(4H,br),3.46(4H,m br)
化合物编号146(MP:192-193).NMR溶剂:DMSO
13C:167.1,160.8,158.8,157.4,149.7,147.7,129.9,129.6,128.4,125.6,119.5,118.1,37.8
1H:9.10(1H,s),8.10(2H,d,J=8.8Hz),7.97(1H,s br),7.93(2H,d,J=8.9Hz),7.35(1H,s br),7.20(2H,d,J=8.8Hz),7.11(2H,d,J=8.9Hz),3.16(6H,s br)
化合物编号147(MP:220-221).NMR溶剂:DMSO
13C:167.1,160.9,158.7,157.5,148.5,148.1,129.9,129.6,128.5,125.5,119.5,118,65.9,46.2
1H:9.13(1H,s),8.10(2H,d,J=8.8Hz),7.98(1H,s br),7.93(2H,d,J=8.9Hz),7.36(1H,s br),7.20(2H,d,J=8.8Hz),7.11(2H,d,J=8.9Hz),3.75-3.70(8H,m)
化合物编号148(MP:187-188).NMR溶剂:DMSO
13C:167.1,161,158.7,157.5,150.6,148.4,148.1,129.9,129.6,129.1,128.5,125.5,119.5,119.5,118.1,115.9,48.2,45.6
1H:9.16(1H,s),8.12(2H,d,J=8.5Hz),7.98(1H,s br),7.94(2H,d,J=8.6Hz),7.36(1H,s br),7.25(2H,t,J=8.0Hz),7.21(2H,d,J=8.5Hz),7.11(2H,d,J=8.5Hz),6.98(2H,d,J=8.2Hz),6.82(1H,t,J=7.5Hz),3.90(4H,m),3.29(4H,m)
化合物编号149(MP:191-192).NMR溶剂:DMSO
13C:167.1,160.3,158.6,157.4,148.7,147.4,143.2,129.8,129.6,129.3,128.1,127.3,126.1,125.4,119.2,118.2,39.9
1H:8.95(1H,s),7.97(1H,s br),7.92(2H,d,J=8.6Hz),7.75(2H,d,J=8.2Hz),7.37(2H,t,J=7.5Hz),7.35(1H,s br),7.32(2H,d,J=8.0Hz),7.28(1H,t,J=7.0Hz),7.08(2H,d,J=8.7Hz),7.07(2H,d,J=8.7Hz),3.49(3H,s)
化合物编号150(MP:91-92).NMR溶剂:CDCl3
13C:162.3(d,J=246.5Hz),151.8,141.5,137,135.2,129.1,129.0(d,J=3.3Hz),128.2,127.5,126.8(d,J=8.0Hz),115.6(d,J=21.5Hz),112.8,54.1,36.5
1H:7.96(1H,d,J=1.3Hz),7.73(2H,d d,J=5.3,8.9Hz),7.49(1H,d,J=1.3Hz),7.43(2H,m,J=7.5Hz),7.37(1H,m,J=7.2Hz),7.32(2H,m,J=8.1Hz),7.08(2H,m t,J=8.9Hz),4.69(2H,s),3.09(3H,s)
化合物编号151(MP:143-144).NMR溶剂:DMSO
13C:167,160.9,158.6,157.3,149.7,147.7,136.2,129.6,129.6,128.5,128.2,127.5,127.4,125.4,119.2,117.9,53.3,36.3
1H:9.14(1H,s),8.05(2H,d br,J=8.0Hz),7.93(2H,d,J=8.5Hz),7.87(1H,s br),7.40(4H,m),7.33(1H,m),7.21(1H,s br),7.17(2H,d,J=8.0Hz),7.10(2H,d,J=8.5Hz),4.82(2H,s),3.14(3H,s)
化合物编号152(MP:95-96).NMR溶剂:CDCl3
13C:150.5,145.2,138.7,133.2,129.2,128.4,127.5,127.5,125.1,119.8,113.5,76.1,70.1,56.3,32.6,31,27.5
1H:8.10(1H,d,J=8.4Hz),7.98(1H,d,J=8.3Hz),7.60(1H,t,J=7.6Hz),7.46(1H,t,J=8.0Hz),7.40-7.33(4H,m),7.30(1H,m),4.58(2H,s),4.30(1H,m),3.36(1H,m),3.16(3H,s),2.24(2H,d br,J=10.0Hz),2.06(2H,d br,J=12.0Hz),1.72(2H,m,J=1.8,13.0Hz),1.51(2H,s br)
化合物编号153(MP:75).NMR溶剂:CDCl3
13C:160.8,160,149.4,145.4,133.2,129.9,129.3,125.2,119.8,113.5,106.5,106.4,100.9,71.8,55.3,48.1,45.4,36.1,29
1H:8.11(1H,m,J=1.0,8.3Hz),7.99(1H,m,J=1.0,8.3Hz),7.61(1H,m,J=1.0,7.1Hz),7.47(1H,m,J=1.0,7.1Hz),7.20(1H,t,J=8.3Hz),6.55-6.49(2H,m),6.48(1H,t,J=2.5Hz),4.62(2H,m br,J=13.5Hz),3.88(2H,d,J=6.5Hz),3.81(3H,s),3.24(2H,br),2.20(1H,m),2.04(2H,br),1.66(2H,m)
化合物编号154(MP:129-130).NMR溶剂:DMSO
13C:148.6,144.7,132.5,129.6,125.5,119.7,113.3,66.4,51.4,47.7,44.9,29.8,23.7
1H:8.19(1H,d,J=8.4Hz),7.91(1H,m,J=8.4Hz),7.69(1H,m,J=1.0,7.0,8.0Hz),7.53(1H,m,J=1.0,7.0,8.0Hz),3.73(4H,m),2.51(1H,m),2.50(4H,m),1.79(2H,m),1.61(2H,m),1.49(2H,m),1.34(2H,m)
化合物编号155(MP:108).NMR溶剂:CDCl3
13C:158.9,150.7,148.4,147.4,132.4,129.3,127.9,127.8,127.7,120.8,116.7,49.4,46.4
1H:8.83(1H,s),7.79(1H d d,J=1.2,3.7Hz),7.44(1H,d d,J=1.2,5.1Hz),7.33(2H,d d,J=7.3,8.8Hz),7.15(1H,d d,J=3.7,5.1Hz),6.98(2H,m d,J=8.8Hz),6.95(1H,m,J=7.3Hz),4.11(4H,br),3.34(4H,m,J=5.2Hz)
化合物编号156(MP:66-67).NMR溶剂:CDCl3
13C:150.9,145.2,137.8,133.2,129.2,128.4,127.7,127.5,125.1,119.7,113.6,73.2,68.2,51.5,51,39.7,37.1
1H:8.10(1H,d,J=8.3Hz),7.96(1H,d,J=8.0Hz),7.58(1H,t,J=8.2Hz),7.45(1H,t,J=7.9Hz),7.30(5H,m),4.53(2H,s br),3.93(2H,s br),3.85(2H,s br),3.41(3H,s br)
化合物编号157(MP:油脂).NMR溶剂:CDCl3
13C:154.1,152.3,150.9,150.8,145.2,133.2,129.3,125.2,119.8,115.3,114.6,113.7,66.9,55.7,50.9,40,37.3
1H:8.10(1H,d,J=8.3Hz),8.03(1H,d,J=8.4Hz),7.61(1H,m,J=1.0,7.1,8.3Hz),7.47(1H,m,J=1.0,7.1,8.3Hz),6.81(4H,m br),4.33(2H,t br,J=5.2Hz),4.10(2H,br),3.76(3H,s),3.55-3.42(3H,m br)
化合物编号158(MP:257-259(分解)).NMR溶剂:DMSO
13C:157.8,148.2(2sig.),132,131.5,129.6,129.4,128.8(2sig.),128.3,127.7,58.6,49.9,42.6
1H:11.94(1H,s br),9.13(1H,s),7.73(2H,d,J=4.0Hz),7.65(2H,m),7.46(3H,m),7.20(1H,t,J=4.2Hz),4.47(2H,br),4.37(2H,s),3.70(2H,m,J=12.5Hz),3.40(2H,d br,J=12.0Hz),3.22(2H,m)
化合物编号159(MP:143).NMR溶剂:CDCl3
13C:149.4,145.3,133.1,129.3,125.2,119.8,113.5,66.4,44.9,42.4,34
1H:8.10(1H,d,J=8.3Hz),7.98(1H,d,J=8.4Hz),7.61(1H,t,J=8.0Hz),7.46(1H,t,J=7.7Hz),4.16(2H,m),4.12(1H,m),3.69(2H,m),2.10(2H,m),1.80(2H,m),1.86(1H,d,J=3.8Hz)
化合物编号160(MP:78-80).NMR溶剂:CDCl3
13C:163.6,149.2,146.1,143.3,136.8,129.5,128.7,128.3,127.4,126.5,125.8,40.3,34.4
1H:8.52(1H,s),7.33(3H,m),7.21(2H,m),7.20(1H,m),7.11(2H,dbr,J=8.0Hz),7.0(2H,d br,J=7.0Hz),3.86(2H,s),3.53(3H,s)
化合物编号161(MP:89).NMR溶剂:CDCl3
13C:146.5,142.6,136.2,132.7,128.7,127.7,125.2,112,81.1,80.3,61.8,22.8
1H:7.96(1H,d,J=1.3Hz),7.79(2H,m,J=8.3Hz),7.52(1H,d,J=1.3Hz),7.41(2H,m,J=7.9Hz),7.30(1H,m,J=7.3Hz),5.13(2H,s),3.88(2H,s),1.62(6H,s)
化合物编号162(MP:119-121).NMR溶剂:CDCl3
13C:145.7,144.1,133.7,129.3,124.2,120.8,117.5,82.4,79.5,62.4,22.9
1H:8.48(1H,s br),7.96(1H,d,J=8.7Hz),7.59(1H,d d,J=1.5,8.7Hz),5.53(2H,s),3.90(2H,s),1.68(6H,s)
化合物编号163(MP:231-232).NMR溶剂:DMSO
13C:167.6,145.6,144.3,141.2,139.3,135.2,133,130.3,129.3,127.5,126.5,125.6,120.2,111.7,81.8,78.7,61.6,22.6
1H:8.37(1H,br),8.30(1H,d,J=8.5Hz),8.26(1H,br),8.22(1H,sbr),7.94(2H,m),7.93(1H,d,J=8.5Hz),7.62(1H,t,J=7.6Hz),7.52(1H,s br),5.46(2H,s),3.91(2H,s),1.60(6H,s)
化合物编号164(MP:102).NMR溶剂:CDCl3
13C:153.5,150.9,149.4,145.3,137.1,133.1,129.3,128.6,127.9,127.5,125.2,119.8,117.7,115.8,113.5,71.8,70.5,44.5,42,30.5
1H:8.11(1H,d,J=8.4Hz),8.0(1H,d,J=8.3Hz),7.62(1H,m,J=1.0,7.2,8.2Hz),7.47(1H,m,J=1.0,7.1,8.2Hz),7.44(2H,d,J=7.0Hz),7.40(2H,m,J=7.4Hz),7.34(1H,m,J=7.1Hz),6.93(4H,m),5.04(2H,s),4.58(1H,m),3.99(4H,br),2.10(4H,m br)
化合物编号165(MP:131).NMR溶剂:CDCl3
13C:153.8,152.9,149.4,145.3,133.1,129.3,125.1,119.8,115.3,114.6,113.4,72.5,55.7,48.1,45.5,36.2,29.1
1H:8.11(1H,d,J=8.3Hz),7.99(1H,d,J=8.4Hz),7.61(1H,t,J=7.8Hz),7.46(1H,t,J=7.6Hz),6.85(4H,s),4.61(2H,d br,J=13.0Hz),3.85(2H,d,J=6.4Hz),3.78(3H,s),3.23(2H,s br),2.18(1H,m),2.03(2H,m),1.62(2H,m)
化合物编号166(MP:87).NMR溶剂:CDCl3
13C:160.9,158.1,149.4,145.4,133.1,130.1,129.4,125.2,119.8,113.5,108,106.6,102.6,70.6,55.3,44.5,41.9,30.4
1H:8.11(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.62(1H,m,J=1.0,7.1,8.2Hz),7.47(1H,m,J=1.0,7.1,8.1Hz),7.22(1H,t,J=8.2Hz),6.58-6.54(2H,m),6.52(1H,t,J=2.2Hz),4.70(1H,m),4.01(4H,m),3.81(3H,s),2.12(4H,m)
化合物编号167(MP:162(分解)).NMR溶剂:CDCl3
13C:无数据
1H:8.15(2H,m),7.69(1H,m,J=1.0,7.1,8.2Hz),7.55(1H,m,J=1.0,7.1,8.2Hz),5.09(2H,s br),4.46(2H,s br),3.45(2H,t,J=7.1Hz)
化合物编号168(MP:72).NMR溶剂:CDCl3
13C:153.9,150.6,149.4,145.3,133.1,129.3,125.2,119.8,117.8,115.4,113.5,71.9,68.2,44.5,41.8,31.4,30.5,19.2,13.9
1H:8.11(1H,d,J=8.4Hz),8.0(1H,d,J=8.3Hz),7.62(1H,m,J=1.0,7.1,8.3Hz),7.47(1H,m,J=1.0,7.1,8.2Hz),6.90(2H,m,J=9.3Hz),6.85(2H,m,J=9.3Hz),4.57(1H,m),3.99(4H,br),3.93(2H,t,J=6.5Hz),2.11(2H,m),2.05(2H,m),1.76(2H,m),1.49(2H,m),0.98(3H,t,J=7.4Hz)
化合物编号169(MP:90).NMR溶剂:CDCl3
13C:151,145.1,132.9,129.6,125.4,119.9,113.5,62.2,36.4
1H:8.11(1H,d,J=8.4Hz),8.05(1H,d,J=8.4Hz),7.62(1H,m,J=1.0,7.1,8.3Hz),7.47(1H,m,J=1.0,7.1,8.2Hz),3.99(3H,s),3.55(3H,s)
化合物编号170(MP:51).NMR溶剂:CDCl3
13C:148.4,145.2,132.9,129.6,125.6,119.9,114.1,51.8,51,31.7,29.2
1H:8.14(1H,d,J=8.5Hz),8.11(1H,d,J=8.4Hz),7.63(1H,t,J=7.8Hz),7.49(1H,t,J=7.4Hz),5.0(2H,s br),4.28(2H,s br),3.19(2H,t,J=6.3Hz)
化合物编号171(MP:81).NMR溶剂:CDCl3
13C:150.1,145.1,133.1,129.1,125,119.7,113.4,51.5,49.8,26.9,26.7,25.8,25.2,24.1
1H:8.10(1H,d,J=8.3Hz),8.0(1H,d,J=8.3Hz),7.59(1H,m,J=1.1,7.1,8.1Hz),7.45(1H,m,J=1.0,7.1,8.2Hz),3.86(2H,m,J=5.3Hz),3.79(2H,m,J=5.3Hz),1.95(2H,m),1.79(2H,m),1.67(6H,m)
化合物编号172(MP:37-38).NMR溶剂:CDCl3
13C:150.5,145.1,133.2,129.1,125,119.7,113.5,50.4,49,29.1,27.4,27.3,26.6
1H:8.09(1H,m d,J=8.3Hz),8.01(1H,m d,J=8.5Hz),7.59(1H,m,J=1.0,7.0,8.2Hz),7.45(1H,m,J=1.0,7.1,8.2Hz),3.87(2H,t,J=6.0Hz),3.79(2H,t,J=6.0Hz),1.94(2H,m),1.90(2H,m),1.71(2H,m),1.68(2H,m)
化合物编号173(MP:油脂).NMR溶剂:CDCl3
13C:150.2,145.1,133.3,129,124.9,119.7,113.1,49,30.1,21.4,13.8
1H:8.10(1H,d,J=8.5Hz),7.92(1H,d,J=8.3Hz),7.59(1H,m,J=7.9Hz),7.45(1H,m,J=7.6Hz),4.78(2H,m),1.94(1H,m),1.87(2H,m),1.69(2H,d br,J=13.5Hz),1.61(1H,m),1.45(6H,d,J=7.1Hz)化合物编号174(MP:193).NMR溶剂:CDCl3
13C:148.9,145.1,136.6,134.4,133.1,129.5,127.9,127.9,125.5,122.6,122.6,119.8,114.5,56,54.8
1H:8.28(1H,d,J=8.4Hz),8.14(1H,d,J=8.3Hz),7.64(1H,t,J=7.7Hz),7.50(1H,t,J=7.6Hz),7.36(4H,m),5.53(2H,s),5.19(2H,s)
化合物编号175(MP:油脂).NMR溶剂:CDCl3
13C:150.1,149.2,145.4,133.3,129.1,125,125,119.8,113.5,113.4,54.4,52.6,42.3,39.2,31.6,27.4,18.8,18
1H:8.10(1H,d,J=8.3Hz),7.97(1H,d J=8.4Hz),7.59(1H,t,J=7.6Hz),7.44(1H,t,J=7.6Hz),4.45(1.4H,d,J=12.0Hz),3.88(0.6H,br),3.50(0.6H,br),2.63(1.4H,br),2.15(0.6H,m),1.89(1.4H,m),1.0-0.96(6H,m br),1.93,1.57,0.9(2H,m)
化合物编号176(MP:48).NMR溶剂:CDCl3
13C:173.9,149.4,145.3,133.1,129.4,125.2,119.8,113.5,60.8,47.4,44.9,40.7,28,14.2
1H:8.10(1H,d,J=8.3Hz),7.98(1H,d,J=8.3Hz),7.61(1H,m J=7.8Hz),7.46(1H,m,J=7.8Hz),4.41(2H,d t,J=4.0,13.5Hz),4.19(2H,q,J=7.1Hz),3.39(2H,s br),2.11(2H,d br,J=12.9Hz),1.98(2H,m),1.29(3H,t,J=7.1Hz)
化合物编号177(MP:75).NMR溶剂:CDCl3
13C:155.3,149.5,145.3,133.1,129.6,125.4,119.9,113.6,61.9,47.8,45.1,43.5,14.6
1H:8.11(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.63(1H,m,J=8.2Hz),7.48(1H,m,J=7.6Hz),4.20(2H,q,J=7.2Hz),3.92(4H,sbr),3.71(4H,m),1.30(3H,t,J=7.2Hz)
化合物编号178(MP:143).NMR溶剂:CDCl3
13C:169.2,149.5,145.3,133.1,129.7,125.5,120,113.6,47.8,46.3,46,41.2,21.4
1H:8.11(1H,d,J=8.3Hz),8.0(1H,d,J=8.3Hz),7.63(1H,m,J=1.0,7.1,8.2Hz),7.48(1H,m,J=1.0,7.1,8.2Hz),3.94(4H,s br),3.85(2H,m),3.71(2H,m),2.18(3H,s)
化合物编号179(MP:197(分解)).NMR溶剂:DMSO
13C:175.7,148.7,144.7,132.5,129.5,125.4,119.6,113.2,47.1,44.5,41,28.4
1H:8.19(1H,d,J=8.4Hz),7.91(1H,d,J=8.3Hz),7.70(1H,m,J=7.8Hz),7.53(1H,m,J=7.7Hz),7.38(1H,s br),6.90(1H,s br),4.23(2H,s br),3.24(2H,s br),2.47(1H,m),1.85(2H,s br),1.69(2H,m,J=4.2,12.0Hz)
化合物编号180(MP:油脂).NMR溶剂:CDCl3
13C:158.2,148.8,146.4,143.2,132.5,129.5,127.7,127.7,127.5,127.3,126.1,40.5
1H:8.63(1H,s),7.47(1H,d br,J=3.6Hz),7.39(2H,m,J=8.0Hz),7.33(1H,m,J=7.3Hz),7.31(1H,d d,J=1.2,5.0Hz),7.19(2H,m,J=8.3Hz),7.02(1H,d d,J=3.6,5.0Hz),3.58(3H,s)
化合物编号181(MP:79).NMR溶剂:CDCl3
13C:158.8,149.9,147.3,135.8,132.5,128.8,128,127.8,127.6,127.6,54.4,36.9,36.2
1H:8.86(1H,s),7.46-7.30(6H,m),7.73(1H,br),7.11(1H,t,J=4.0Hz),4.93(2H,br),3.24(3H,br)
化合物编号182(MP:87).NMR溶剂:CDCl3
13C:164.3,150.7,148.6,147.3,137,129.3,128.8,128.6,126.8,120.7,116.7,49.4,46.5,34.7
1H:8.73(1H,s),7.37-7.21(5H,m),7.32(2H,m),6.95(2H,m),6.93(1H,m),4.11(2H,s),4.03(4H,br),3.27(4H,m)
化合物编号183(MP:144).NMR溶剂:CDCl3
13C:163.8(d d,J=12.0,253.0Hz),160.8(d d,J=14.0,261.0Hz),158.5(d,J=6.0Hz),145.6,144.7,131.4(d d,J=4.2,10.0Hz),114.4(dd,J=4.0,11.5Hz),111.8(d d,J=4.0,22.0Hz),105.0(t,J=25.0Hz),82.1,79.2,62.2,22.8
1H:8.96(1H,s),8.12(1H,m,J=7.0,8.4Hz),7.0(1H,m),6.95(1H,m),5.53(2H,s),3.84(2H,s),1.62(6H,s)
化合物编号184(MP:126).NMR溶剂:CDCl3
13C:151,142.5,136.9,133.7,132.8,131.7,128.9,128.7,127.6,127.3,126.8,126.3,125.2,112.9,48.5,44.6,28.5
1H:7.99(1H,d,J=1,3Hz),7.82(2H,m,J=8.2Hz),7.55(1H,d,J=1.3Hz),7.42(2H,t,J=7.8Hz),7.31(1H,m,J=7.4Hz),7.27-7.19(3H,m),7.12(1H,m),4.80(2H,br),3.88(2H,t,J=5.8Hz),3.05(2H,t,J=5.8Hz)
化合物编号185(MP:125).NMR溶剂:DMSO
13C:160.4,148.6,147.8,134.7,134.2,132.4,129,128.6,128.4,128,126.7,126.3,126.2,47.3,44.2,28
1H:9.14(1H,s),8.10(2H,m,J=8.6Hz),7.59(2H,m,J=8.6Hz),7.23(4H,br),4.88(2H,br),3.93(2H,t,J=5.8Hz),3.02(2H,t,J=5.8Hz)
化合物编号186(MP:136).NMR溶剂:CDCl3
13C:146.3,141.6,136.2,133.3,131.3,128.9,126.4,112.3,81.1,80.4,61.9,22.8
1H:7.94(1H,d,J=1.3Hz),7.72(2H,m,J=8.7Hz),7.51(1H,d,J=1.3Hz),7.37(2H,m,J=8.7Hz),5.13(2H,s),3.89(2H,s),1.62(6H,s)化合物编号187(MP:176-177).NMR溶剂:DMSO
13C:167.1,161.1,158.7,157.5,147.1,144.6,129.8,129.6,128.5,125.5,119.5,118,81.4,78.4,61.4,22.4
1H:9.21(1H,s),8.11(2H,d,J=8.8Hz),7.98(1H,s br),7.93(2H,d,J=8.4Hz),7.36(1H,s br),7.20(2H,d,J=8.8Hz),7.11(2H,d,J=8.4Hz),5.44(2H,s),3.85(2H,s),1.52(6H,s)
化合物编号188(MP:88).NMR溶剂:CDCl3
13C:162.8,161.1,146,145,128.2,122.4,114.1,82,79.3,62.1,55.3,22.8
1H:8.90(1H,s),8.05(2H,m,J=9.0Hz),6.98(2H,m,J=9.0Hz),5.56(2H,s),3.87(3H,s),3.84(2H,s),1.62(6H,s)
化合物编号189(MP:132).NMR溶剂:CDCl3
13C:162.1,146.3,144.7,136.1,129,128.3,128,81.9,79.3,62.3,22.81H:8.93(1H,s),8.05(2H,m,J=8.6Hz),7.44(2H,m,J=8.6Hz),5.55(2H,s),3.85(2H,s),1.62(6H,s)
化合物编号190(MP:82).NMR溶剂:CDCl3
13C:162.7,150.1,147.4,136,134.1,133.1,128.8,128.7,128.4,128,127.8,127.1,126.9,126.7,126.5,123.7,54.5,36.7
1H:8.96(1H,s),8.64(1H,br),8.15(1H,br),7.90(3H,m),7.53(2H,m),7.47-7.31(5H,m),5.0(2H,br),3.28(3H,br)
化合物编号191(MP:107).NMR溶剂:DMSO
13C:161.7,150,147.3,136.3,133.6,130.6,128.7,128.6,128.5,127.6,127.1,126.1,125.8,125.4,53.6,37.3,35.8
1H:9.34(1H,s),8.87(1H,br),8.27(1H,d,J=7.2Hz),8.06(1H,d,J=8.0Hz),8.0(1H,br),7.63(1H,t,J=7.5Hz),7.55(1H,br),7.46-7.26(6H,m),4.90(2H,br),3.16(3H,s)
化合物编号192(MP:121-123(分解)).NMR溶剂:DMSO
13C:161,148.7,146.9,143.5,133.4,130.5,129.6,129.5,128.4,128.3,127.2,127,126(2sig.),125.8,125.2,40.1
1H:9.21(1H,s),8.10(1H,d d,J=J=1.2,7.2Hz),7.98(1H,d,J=8.2Hz),7.93(2H,m),7.60-7.30(8H,m),3.52(3H,s)
化合物编号193(MP:142).NMR溶剂:CDCl3
13C:149.2,145.3,133.1,129.5,125.3,119.9,113.5,71.8,53.3,50.2,18.6
1H:8.11(1H,d,J=8.3Hz),8.0(1H,d,J=8.4Hz),7.62(1H,m,J=1.0,7.1,8.1Hz),7.47(1H,m,J=1.0,7.1,8.1Hz),4.42(2H,d br,J=13.0Hz),3.83(2H,m),3.03-2.90(2H,m br),1.26(6H,s br)
化合物编号194(MP:75).NMR溶剂:CDCl3
13C:150,145.3,133.1,129.5,125.4,119.9,113.6,66.1,52.8,49.7,17.5
1H:8.11(1H,d,J=8.3Hz),8.01(1H,d,J=8.3Hz),7.63(1H,t,J=7.8Hz),7.48(1H,t,J=7.8Hz),4.22(2H,s br),4.06-3.90(2H,m br),3.66(2H,s br),1.31(6H,s br)
化合物编号195(MP:油脂).NMR溶剂:CDCl3
13C:150.9,145.3,139.1,133.3,129.3,128.7,127.9,127.3,125.2,119.8,113.6,55,32.2,16
1H:8.12(1H,m,J=8.3Hz),8.07(1H,m,J=8.4Hz),7.63(1H,m,J=1.0,7.0,8.0Hz),7.48(1H,m,J=1.0,7.1,8.3Hz),7.45(2H,br),7.41(2H,m,J=7.4Hz),7.34(1H,m J=8.0Hz),5.95(1H,q,J=6.8Hz),3.0(3H,s),1.78(3H,d,J=7.1Hz)
化合物编号196(MP:140).NMR溶剂:CDCl3
13C:150.7,150.5,142.6,141.7,140.9,137.1,133.2,129.3,129.2,128.7,127.4,127.2,126.5,124.1,124,121.1,116.9,113.2,49.5,46.5
1H:8.07(1H,t,J=1.7Hz),7.99(1H,d,J=1.2Hz),7.80(1H,d t,J=1.5,7.6Hz),7.67(2H,d,J=8.2Hz),7.57(1H,d,J=1.2Hz),7.56(1H,d t,J=1.5,7.7Hz),7.49(1H,t,J=7.5Hz),7.47(2H,m,J=7.7Hz),7.37(1H,m,J=7.2Hz),7.32(2H,m,J=8.2Hz),6.96(3H,m),3.85(4H,m,J=5.0Hz),3.30(4H,m,J=5.0Hz)
化合物编号197(MP:113).NMR溶剂:CDCl3
13C:150.5,142.2,141.3,137,133.1,131.5,128.8,128.3(2sig.),126.4,125.8,113.3,47,35.9,35.8,35.7,32.1,28.4
1H:7.88(1H,d,J=1.3Hz),7.73(2H,m),7.45(1H,d,J=1.3Hz),7.37(2H,m),7.30(2H,m,J=7.5Hz),7.20(1H,m,J=7.6Hz),7.19(2H,m,J=8.0Hz),4.14(2H,d br,J=13.2Hz),3.04(2H,d t,J=2.3,13.0Hz),2.63(2H,t,J=7.7Hz),1.83(2H,d br,J=13.5Hz),1.67(2H,m),1.58(1H,m),1.36(2H,m),1.25(2H,d q,J=4.2,13.1Hz)
化合物编号198(MP:178).NMR溶剂:CDCl3
13C:150.3,140.3,137.2,133,132.8,131.2,130.6,127,124.3,113.9,106.1,64.6,44.8,35
1H:7.90(1H,d,J=2.0Hz),7.89(1H,d,J=1.4Hz),7.61(1H,d d,J=2.1,8.4Hz),7.49(1H,d,J=1.4Hz),7.46(1H,d,J=8.4Hz),4.01(4H,s),3.73(4H,m,J=5.5Hz),1.82(4H,m,J=5.5Hz)
化合物编号199(MP:174).NMR溶剂:CDCl3
13C:150.2,145.8,143,141.7,137.5,130.3,128,126.2,125.9,123.5,115.1,111.7,40.1
1H:7.49(1H,d,J=1.2Hz),7.41(2H,m,J=8.4Hz),7.40(2H,m,J=7.5Hz),7.33(1H,m,J=7.4Hz),7.17(2H,m,J=8.4Hz),7.04(1H,d,J=1.2Hz),6.65(2H,m,J=8.4Hz),3.69(2H,s),3.51(3H,s)
化合物编号200(MP:吸湿的).NMR溶剂:DMSO
13C:157.8,149,142.4,137.5,130,129.9,127.9,126.2,118,115.4,114.4,111,62.3,54.4,48.4,39.7
1H:12.25(1H,s br),9.94(2H,s),8.04(1H,s),7.82(1H,s),7.42(2H,t,J=8.0Hz),7.39(1H,s),7.36(2H,m),7.32(1H,m),7.30(2H,m),6.92(1H,m),4.46(2H,m),3.63(6H,m),3.48(4H,m),3.45(3H,s)
化合物编号201(MP:119).NMR溶剂:CDCl3
13C:149.8(d d,J=13.0,244.5Hz),149.8,148.5(d d,J=12.5,245.0Hz),138.9,137.9,131.1(d d,J=4.0,7.0Hz),121.4(d d,J=3.0,6.5Hz),117.8(d,J=17.3Hz),115.2,113.5(d,J=18.7Hz),62.7,48.1,46.5,28.3,25.8,25.3
1H:8.12(1H,s),8.06(1H,s),7.87(1H,d d d,J=2.0,7.8,12.0Hz),7.70(1H,m),7.46(1H,d t,J=8.7,10.7Hz),3.51(4H,m),2.57(4H,m),2.29(1H,br),1.74(4H,m),1.57(1H,d br,J=12.0Hz),1.20(4H,m),1.07(1H,t br,J=10.0Hz)
化合物编号202(MP:油脂).NMR溶剂:CDCl3
13C:150.4,145.1,137.8,133.2,129.2,128.4,127.7,127.6,125.1,119.7,113.7,73.3,69.4,68.3,48.7,45.1,13.9,12.6
1H:8.09(1H,d,J=8.4Hz),7.98(1H,d,J=8.3Hz),7.58(1H,t,J=7.9Hz),7.45(1H,m,J=1.0,7.2,8.2Hz),7.31(5H,m),4.53(2H,br),3.95-3.75(6H,m),1.38(3H,t,J=6.9Hz)
化合物编号203(MP:132).NMR溶剂:DMSO
13C:157.4,148.6,142.2,137.3,136.6,129.9,128,126.5,126.3,123.2,115.2,114.3,62.4,54.4,48.4,39.7(2sig.)
1H:11.97(1H,s br),9.68(2H,s),7.88(1H,s),7.62(2H,d,J=8.8Hz),7.57(1H,s),7.42(2H,t,J=7.4Hz),7.36(2H,d,J=8.8Hz),7.32(1H,t,J=7.4Hz),7.0(2H,d,J=8.8Hz),4.42(2H,m),3.61(6H,m),3.47(4H,m),3.43(3H,s)
化合物编号204(MP:141).NMR溶剂:CDCl3
13C:161.7,148.5,147.3,136.1,128.9,128.4,128,106.5,64.6,44.7,35.1
1H:8.80(1H,s),8.07(2H,d,J=8.8Hz),7.43(2H,d,J=8.8Hz),4.02(4H,s),3.95(4H,br),1.89(4H,m)
化合物编号205(MP:74-75).NMR溶剂:CDCl3
13C:162.3,161,148.8,147,142.3,128.3(2sig.),128.2,125.7,122.6,114,55.3,47,36,35.8(2sig.),32.1,28.5
1H:8.75(1H,s),8.07(2H,d,J=7.7Hz),7.28(2H,m),7.19(3H,m),6.98(2H,d,J=7.7Hz),4.61(2H,br),3.03(2H,br),3.86(3H,s),2.62(2H,m),1.84(2H,m),1.67(2H,m),1.59(1H,m),1.30(4H,m)
化合物编号206(MP:131).NMR溶剂:DMSO
13C:161.8,150.6,148.5,147.3,133.6,130.7,130,129.1,128.7,128.4,127.3,126.4,126.3,125.8,125.4,119.5,115.9,48.2,45.8
1H:9.29(1H,s),9.03(1H,d,J=8.4Hz),8.28(1H,d d,J=1.0,7.3Hz),8.10(1H,d,J=8.1Hz),8.05-(1H,d,J=8.0Hz),7.72-7.57(3H,m),7.25(2H,t,J=7.8Hz),6.99(2H,d,J=8.3Hz),6.82(1H,t,J=7.3Hz),3.94(4H,s br),3.32(4H,m,J=5.0Hz)
化合物编号207(MP:181).NMR溶剂:DMSO
13C:167.1,160.7,158.8,156.6,148.7,148,134.2,132.6,131.7,131.1,129.9,129.7,128.6,126.8,126.4,126.3,121.8,120.8,118.2,116.1,46.9,44.9,28.2
1H:9.15(1H,s),7.98(1H,s br),7.96(2H,d,J=8.8Hz),7.90(1H,d,J=7.7Hz),7.66(1H,m br),7.59(1H,t,J=8.0Hz),7.37(1H,s br),7.24(1H,d d,J=2.4,8.2Hz),7.21(4H,m br),7.13(2H,d,J=8.8Hz),4.83(2H,m br),3.88(2H,m br),2.96(2H,t,J=5.3Hz)
化合物编号208(MP:217-218).NMR溶剂:DMSO
13C:167.2,160.7,159,156.4,150.6,148.3,148.1,131.7,131.1,129.8,129.6,129.1,122,121,119.5,117.9,116.6,115.9,48.2,45.8
1H:9.15(1H,s),7.98(1H,s br),7.94(2H,d,J=8.8Hz),7.91(1H,m),7.69(1H,m br),7.59(1H,t,J=8.0Hz),7.36(1H,s br),7.24(2H,t,J=7.7Hz),7.23(1H,m),7.11(2H,d,J=8.8Hz),6.97(2H,d,J=8.0Hz),6.82(1H,t,J=7.0Hz),3.88(4H,br),3.27(4H,br)
化合物编号209(MP:192-193).NMR溶剂:DMSO
13C:167.1,160.8,159,156.3,147.2,144.5,131.7,131.1,129.8,129.5,122.1,121,117.8,116.8,81.3,78.3,61.4,22.3
1H:9.20(1H,s),7.96(1H,s br),7.93(2H,m,J=8.8Hz),7.90(1H,m),7.69(1H,d d,J=1.8,2.4Hz),7.57(1H,t,J=8.0Hz),7.35(1H,sbr),7.22(1H,d d d,J=0.9,2.5,8.2Hz),7.09(2H,m,J=8.8Hz),5.39(2H,s),3.82(2H,s),1.50(6H,s)
化合物编号210(MP:185).NMR溶剂:DMSO
13C:167.1,160.7,158.9,156.5,148.3,148.1,131.7,131.1,129.8,129.6,122,120.9,118,116.5,65.8,46.2
1H:9.13(1H,s),7.97(1H,s br),7.93(2H,d,J=8.7Hz),7.88(1H,d,J=7.7Hz),7.65(1H,m br),7.58(1H,t,J=7.8Hz),7.35(1H,s br),7.22(1H,d d,J=1.9,7.9Hz),7.10(2H,d,J=8.7Hz),3.80-3.63(8H,m)
化合物编号211(MP:116).NMR溶剂:CDCl3
13C:162.6,161.2,157.7(d,J=240.0Hz),148.7,147.4(d,J=2.0Hz),147.3,128.3,122.3,118.7(d,J=7.8Hz),115.8(d,J=22.0Hz),114.1,55.3,50.5,46.4
1H:8.83(1H,s),8.08(2H,m),7.01(2H,t,J=9.4Hz),7.0(2H,m),6.93(2H,m),4.12(4H,br),3.88(3H,s),3.25(4H,m)
化合物编号212(MP:281(分解)).NMR溶剂:DMSO
13C:160.6,148.5,148.1,135,129.2,128.4,128.2,64.3,47.3,42.9,26.1,24.7,24.5
1H:11.29(1H,s),9.20(1H,s),8.10(2H,m,J=8.8Hz),7.60(2H,m,J=8.8Hz),4.55(2H,m br),3.75(2H,t br,J=12.0Hz),3.55(2H,d br,J=11.5Hz),3.23(3H,m),2.13(2H,d br,J=10.5Hz),1.82(2H,d br,J=12.8Hz),1.61(1H,d br,J=12.5Hz),1.43(2H,m,J=11.5Hz),1.26(2H,m,J=12.8Hz),1.10(1H,m,J=12.5Hz)
化合物编号213(MP:99).NMR溶剂:CDCl3
13C:159,146.2,144.7,132.4,127.9,127.7,127.6,82,79.2,62.2,22.81H:8.89(1H,s),7.74(1H,d,J=3.0Hz),7.41(1H,d,J=4.9Hz),7.13(1H,m),5.51(2H,s),3.84(2H,s),1.61(6H,s)
化合物编号214(MP:121).NMR溶剂:CDCl3
13C:162.1,147.0(2sig.),136.2,129,128.2,128.1,51.8,51.1,32,28.91H:8.93(1H,s),8.07(2H,m,J=8.8Hz),7.44(2H,m,J=8.8Hz),4.97(2H,m br),4.23(2H,m br),3.14(2H,br)
化合物编号215(MP:129).NMR溶剂:CDCl3
13C:150.6(d d,J=13.0,248.0Hz),149.9(d d,J=13.0,249.0Hz),149.4,140.9,137,129.9(d d,J=4.0,7.0Hz),121.2(d d,J=4.0,6.5Hz),117.6(d,J=17.7Hz),114.3(d,J=19.0Hz),113,51.3,50.9,30.51H:8.02(1H,d,J=1.4Hz),7.61(1H,d d d,J=2.0,7.7,11.5Hz),7.55(1H,d,J=1.4Hz),7.50(1H,m),7.19(1H,d t,J=8.3,10.0Hz),4.71(2H,s),3.98(2H,t,J=6.3Hz),3.14(2H,t,J=6.3Hz)
化合物编号216(MP:115).NMR溶剂:CDCl3
13C:149.3,149,144.2,136.4,135.8,121,118,114,112,109.1,80.7,79.3,61.4,55.8,55.6,22.2
1H:9.22(1H,s),8.36(1H,s),7.55(1H,d,J=1.8Hz),7.49(1H,d d,J=1.8,8.4Hz),7.05(1H,d,J=8.4Hz),5.22(2H,s),3.87(2H,s),3.83(3H,s),3.79(3H,s),1.52(6H,s)
化合物编号217(MP:154-155).NMR溶剂:CDCl3
13C:151.3,149.1,148.5,141.9,136.7,126.1,117.4,112.4,111.2,108.4,57.5,55.9(2sig.),31.4,30,25.4,25.2
1H:7.90(1H,s),7.43(1H,s),7.40(1H,s),7.31(1H,d br,J=8.6Hz),6.91(1H,d,J=8.3Hz),3.97(3H,s),3.97(1H,m),3.91(3H,s),3.0(3H,s),1.86(4H,m),1.70(1H,d br,J=13.5Hz),1.58(2H,m),1.38(2H,m),1.13(1H,m)
化合物编号218(MP:140-141).NMR溶剂:CDCl3
13C:149.2,139.9,137,133.1,132.8,131.1,130.6,126.9,124.3,113.6,48.9,25.3
1H:8.05(1H,d,J=1.3Hz),7.90(1H,d,J=2.0Hz),7.65(1H,d,J=1.3Hz),7.61(1H,d d,J=2.0,8.5Hz),7.46(1H,d,J=8.5Hz),3.68(4H,m),2.03(4H,m)
化合物编号219(MP:106).NMR溶剂:CDCl3
13C:147,143.1,139.8,131.8,124.8,124,120.7,113,81,80.6,61.5,23.1
1H:8.11(1H,s),7.82(1H,d,J=7.8Hz),7.70(1H,d,J=7.7Hz),7.40(1H,d t,J=1.5,7.4Hz),7.36(1H,d t,J=1.5,7.4Hz),5.04(2H,s),3.92(2H,s),1.67(6H,s)
化合物编号220(MP:114-115).NMR溶剂:CDCl3
13C:146.9,142.2,136.6,132.8,128.7,127.6,125.1,112.5,96.3,63.5,48.2,24.1
1H:8.06(1H,d,J=1.4Hz),7.80(2H,m,J=8.2Hz),7.62(1H,d,J=1.4Hz),7.41(2H,t,J=7.8Hz),7.30(1H,m,J=7.4Hz),4.10(2H,t,J=6.0Hz),3.84(2H,t,J=6.0Hz),1.73(6H,s)
化合物编号221(MP:120).NMR溶剂:CDCl3
13C:151.4,142.2,136.7,133,128.7,127.4,125.1,113.2,49.1,30,21.2,13.6
1H:7.87(1H,d,J=1.5Hz),7.80(2H,m,J=8.0Hz),7.46(1H,d,J=1.5Hz),7.41(2H,t,J=8.0Hz),7.29(1H,m,J=7.5Hz),4.41(2H,m),1.90(1H,m),1.77(2H,m),1.66(2H,m),1.62(1H,m),1.39(6H,d,J=7.2Hz)
化合物编号222(MP:116).NMR溶剂:CDCl3
13C:151.7,143.3,141.4,132.1,124.5,123.6,120.6,112.6,57.4,31.3,30,25.4,25.3
1H:8.16(1H,s),7.82(1H,m,J=7.8Hz),7.55(1H,m),7.38(1H,d t,J=1.5,7.3Hz),7.35(1H,d t,J=1.5,7.3Hz),4.0(1H,m,J=3.4,12.1Hz),2.96(3H,s),1.89(4H,m),1.70(1H,d br,J=13.5Hz),1.61(2H,dq,J=4.0,12.5Hz),1.38(2H,t q,J=4.0,13.5Hz),1.14(1H,t q,J=3.5,13.5Hz)
化合物编号223(MP:155).NMR溶剂:CDCl3
13C:157.9(d,J=241.0Hz),150.5,147.1(d,J=2.5Hz),141.6,137,133.3,131.3,128.9,126.4,118.9(d,J=7.7Hz),115.8(d,J=22.0Hz),113.2,50.5,46.5
1H:7.94(1H,d,J=1.2Hz),7.74(2H,m,J=8.6Hz),7.50(1H,d,J=1.2Hz),7.38(2H,m,J=8.6Hz),7.01(2H,m),6.91(2H,m),3.82(4H,m,J=5.0Hz),3.19(4H,m,J=5.0Hz)
化合物编号224(MP:201-202).NMR溶剂:DMSO
13C:156.8,149.8,143,139.8,137.7,129.9,127.7,126.5,126.3,126,114.9,113.3,62.2,54.9,52.8,39.6,22.5,21.2
1H:9.28(1H,s br),7.60(2H,d,J=8.9Hz),7.55(1H,d,J=1.0Hz),7.48(1H,d,J=1.0Hz),7.41(2H,t,J=7.4Hz),7.34(2H,d,J=7.3Hz),7.32(1H,m,J=7.2Hz),6.98(2H,d,J=8.9Hz),4.32(2H,t,J=5.0Hz),3.50(2H,br),3.48(2H,m),3.42(3H,s),3.0(2H,br),1.79(2H,br),1.69(3H,br),1.39(1H,br)
化合物编号225(MP:109).NMR溶剂:CDCl3
13C:149.8,147.8,146.5,142.5,137,136,128.5,127.8,127.2,126.4,117.4,114.1,111.3,108.9,81.1,80.4,71,61.8,56,22.9
1H:7.93(1H,d,J=1.5Hz),7.46(2H,d,J=8.0Hz),7.42(1H,d,J=1.5Hz),7.41(1H,d,J=2.0Hz),7.38(2H,t,J=7.7Hz),7.31(1H,m),7.21(1H,d d,J=2.0,8.3Hz),6.91(1H,d,J=8.3Hz),5.20(2H,s),5.12(2H,s),3.97(3H,s),3.88(2H,s),1.61(6H,s)
化合物编号226(MP:230-232(分解)).NMR溶剂:DMSO
13C:145.4,140.5,139.7,138.3,137.6,134.8,132.6,127.5,117.7,80.7,79.3,61.1,22.4
1H:9.34(1H,d,J=1.8Hz),8.97(1H,t d,J=1.5,8.2Hz),8.81(1H,dbr,J=5.2Hz),8.59(1H,d,J=1.3Hz),8.41(1H,d,J=1.3Hz),8.11(1H,d d,J=5.2,8.2Hz),5.20(2H,s),3.86(2H,s),1.50(6H,s)
化合物编号227(MP:118-119).NMR溶剂:CDCl3
13C:148.7,142.6,136.7,132.7,128.7,127.7,125.2,112.3,88,66.4,48,19.2
1H:8.08(1H,d,J=1.2Hz),7.81(2H,d,J=8.4Hz),7.62(1H,d,J=1.2Hz),7.42(2H,t,J=7.9Hz),7.31(1H,m.J=7.4Hz),5.49(1H,q,J=5.2Hz),4.27(1H,m),3.89(1H,m),3.80(2H,m),1.57(3H,d,J=5.2Hz)
化合物编号228(MP:204-205).NMR溶剂:DMSO
13C:147.7,146.3,145.9,141.3,136.6,124.8,117.5,115.6,111.9,109,80.6,79.3,60.8,55.6,22.4
1H:9.03(1H,s),8.09(1H,d,J=1.0Hz),7.87(1H,d,J=1.0Hz),7.38(1H,d,J=1.7Hz),7.26(1H,d d,J=1.7,8.1Hz),6.77(1H,d,J=8.1Hz),5.17(2H,s),3.84(2H,s),3.81(3H,s),1.50(6H,s)
化合物编号229(MP:152).NMR溶剂:CDCl3
13C:151.2,142.1,137.2,133.1,128.6,127.4,125.1,113,58.4,38.6,36.2,34.1,29.7
1H:7.92(1H,d,J=1.2Hz),7.80(2H,d,J=8.6Hz),7.48(1H,d,J=1.2Hz),7.40(2H,t,J=7.8Hz),7.29(1H,t,J=7.3Hz),2.99(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号230(MP:67-68).NMR溶剂:DMSO
13C:157.4,148.7,142.3,137.4,136.8,129.9,127.9,126.5,126.3,123.4,115.1,114.2,63.1,62.3,54.7,51.6,39.7
1H:11.54(1H,s br),8.28(1H,s),7.70(1H,s),7.66(2H,d,J=8.9Hz),7.43(2H,t,J=7.9Hz),7.40(2H,d,J=7.7Hz),7.34(1H,m,J=6.9Hz),7.03(2H,d.J=8.9Hz),4.46(2H,m),3.95(2H,d br,J=13.0Hz),3.85(2H,t br,J=11.70Hz),3.54(2H,m),3.48(2H,m),3.46(3H,s),3.19(2H,m)
化合物编号231(MP:46-47).NMR溶剂:CDCl3
13C:146.5,142.5,141.7,140.9,136.3,133.2,129.1,128.7,127.4,127.2,126.5,124.1,124,112.2,81.1,80.4,61.8,22.9
1H:8.05(1H,t,J=1.6Hz),7.99(1H,d,J=1.3Hz),7.77(1H,t d,J=1.3,7.6Hz),7.66(2H,d,J=8.2Hz),7.58(1H,d,J=1.3Hz),7.54(1H,t d,J=1.3,7.7Hz),7.48(1H,t,J=7.7Hz),7.46(2H,t,J=7.8Hz),7.37(1H,m,J=7.4Hz),5.15(2H,s),3.89(2H,s),1.63(6H,s)
化合物编号232(MP:191-192).NMR溶剂:DMSO
13C:167.9,146.2,140.7,140.1,140,137.1,135,134,129.6,129.4,129,126.7,125.8,125.7,124.2,123.2,114,80.6,79.3,60.8,22.4
1H:8.23-8.17(4H,m),8.15(1H,s br),7.88(3H,m),7.63(1H,m,J=8.1Hz),7.57(1H,t,J=7.8Hz),7.52(1H,t,J=7.8Hz),7.49(1H,s br),5.20(2H,s),3.86(2H,s),1.51(6H,s)
化合物编号233(MP:130-131).NMR溶剂:CDCl3
13C:146.5,141.2,136.7,133.3,131.4,128.9,126.4,112.8,98.6,63.6,48.8,29.2,22.3,7.6
1H:8.05(1H,d,J=1.3Hz),7.73(2H,m,J=8.6Hz),7.61(1H,d,J=1.3Hz),7.38(2H,m,J=8.6Hz),4.16(1H,m),4.06(1H,m),3.83(2H,m),2.21(1H,m),2.06(1H,m),1.70(3H,s),0.95(3H,t,J=7.4Hz)
化合物编号234(MP:135-136(分解)).NMR溶剂:CDCl3
13C:150.1,148.4,143.6,142.3,142.2,137.1,137,132.6,132.3,128.8,128.7,128,127.7,125.3,125.2,125.1,112.8,111.6,65.2,48.9,32.8,30.2,22.1
1H:8.18(1H,d,J=1.4Hz),7.98(1H,d,J=1.4Hz),7.81(2H,m,J=8.5Hz),7.77(2H,m,J=8.5Hz),7.67(1H,d,J=1.4Hz),7.57(1H,d,J=1.4Hz),7.42(2H,t,J=7.5Hz),7.40(2H,t,J=7.5Hz),7.33(1H,m),7.30(1H,m),5.61(1H,m),4.73(2H,t,J=5.3Hz),4.12(2H,t,J=5.3Hz),2.34(2H,m),2.30(2H,m),1.91(2H,qt,J=7.6Hz)
化合物编号235(MP:154-155).NMR溶剂:CDCl3
13C:147.3,141.7,136.1,133.3,131.3,128.9,126.4,112.3,88.8,78.6,62.5,24.8,22,20.7
1H:7.92(1H,d,J=1.2Hz),7.74(2H,d,J=8.6Hz),7.50(1H,d,J=1.2Hz),7.38(2H,d,J=8.6Hz),5.48(1H,q,J=5.2Hz),3.93(1H,d,J=8.6Hz),3.72(1H,d,J=8.6Hz),1.62(3H,s),1.47(3H,s),1.20(3H,d,J=5.2Hz)
化合物编号236(MP:114-115).NMR溶剂:CDCl3
13C:159.9,146.5,142.5(2sig.),141.6,136.3,133.2,129.7,129.1,126.6,124.2,124,119.7,112.8,112.8,112.3,81.1,80.4,61.9,55.3,22.9
1H:8.02(1H,t,J=1.8Hz),7.99(1H,d,J=1.5Hz),7.78(1H,t d,J=1.5,7.6Hz),7.57(1H,d,J=1.5Hz),7.53(1H,t d,J=1.5,7.7Hz),7.48(1H,t,J=7.7Hz),7.38(1H,t,J=8.1Hz),7.25(1H,d d d,J=1.0,1.5,7.6Hz),7.19(1H,d d,J=1.8,2.6Hz),6.92(1H,d d d,J=1.0,2.6,8.2Hz),5.15(2H,s),3.89(5H,s),1.63(6H,s)
化合物编号237(MP:148-149).NMR溶剂:CDCl3
13C:146.8,143.2,135.9,132.9,128.7,127.6,125.2,110.7,53.2,41.5,36.1,29.4
1H:8.10(1H,s),7.79(2H,d,J=8.0Hz),7.52(1H,s),7.40(2H,t,J=8.0Hz),7.30(1H,t,J=7.5Hz),5.39(1H,s),2.17(3H,s),2.11(6H,s),1.74(6H,s)
化合物编号238(MP:175).NMR溶剂:CDCl3
13C:169.3,151.3,141.8,141.5,140.6,137,133.8,133.7,130.7,129.3,129,126.3,126.3,126.1,124.5,124,113.6,57.5,31.4,29.9,25.4,25.2
1H:8.11(1H,t,J=1.8Hz),8.08(1H,t,J=1.6Hz),7.94(1H,d,J=1.2Hz),7.81(2H,m),7.78(1H,m),7.57(1H,d,J=1.2Hz),7.52(1H,t,J=7.6Hz),7.51(1H,m),7.48(1H,t,J=7.6Hz),6.43(1H,s br),5.93(1H,s br),3.97(1H,m),3.0(3H,s),1.88(2H,m),1.85(2H,m),1.70(1H,d br,J=13.5Hz),1.58(2H,d q,J=3.5,12.5Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.3,13.0Hz)
化合物编号239(MP:129).NMR溶剂:CDCl3
13C:151.3,142.1,141.7,141,137,133.5,129.1,128.7,127.3,127.2,126.3,124,124,113.4,57.5,31.3,30,25.4,25.2
1H:8.07(1H,t,J=1.8Hz),7.95(1H,d,J=1.3Hz),7.78(1H,t d,J=1.7,7.7Hz),7.67(2H,d,J=8.0Hz),7.56(1H,d,J=1.3Hz),7.54(1H,d t,J=1.8,7.9Hz),7.48(1H,t,J=7.7Hz),7.46(2H,t,J=7.9Hz),7.37(1H,m),3.97(1H,m),3.0(3H,s),1.89(2H,m),1.85(2H,m),1.71(1H,d br,J=13.0Hz),1.59(2H,d q,J=3.5,12.5Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号240(MP:129-130).NMR溶剂:CDCl3
13C:159.9,151.3,142.6,142,141.5,137,133.5,129.7,129.1,126.4,124.2,124,119.8,113.4,112.8,112.8,57.5,55.3,31.3,30,25.4,25.2
1H:8.04(1H,t,J=1.6Hz),7.94(1H,d,J=1.3Hz),7.79(1H,t t,J=1.5,7.5Hz),7.56(1H,d,J=1.3Hz),7.52(1H,d t,J=2.0,7.9Hz),7.48(1H,t,J=7.8Hz),7.38(1H,t,J=7.9Hz),7.25(1H,d d d,J=1.0,1.7,7.7Hz),7.19(1H,d d,J=1.8,2.5Hz),6.92(1H,d d d,J=1.0,2.6,8.2),3.97(1H,m),3.89(3H,s),3.0(3H,s),1.88(2H,m),1.85(2H,m),1.71(1H,d br,J=13.0Hz),1.59(2H,d q,J=3.5,12.3Hz),1.39(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.3,13.0Hz)
化合物编号241(MP:173-174).NMR溶剂:CDCl3
13C:149.1,141.7,136.7(2sig.),133.4,131.2,129.7,128.9,128.8,126.9,126.4,112.5,91,66.2,47.9
1H:8.01(1H,br),7.68(2H,d,J=8.3Hz),7.54(1H,br),7.51(2H,m),7.42(3H,m),7.36(2H,d,J=8.3Hz),6.39(1H,s),4.32(1H,br),4.12(1H,m),4.04(1H,m),3.94(1H,m)
化合物编号242(MP:173-174).NMR溶剂:CDCl3
13C:158.9,151.8,140.2,134.6,120.8,117,97.4,59.7,57.3,33.2,30.9,29.6,25.4,25.3
1H:8.61(1H,s br),7.94(1H,d,J=9.0Hz),7.53(1H,d,J=2.0Hz),7.06(1H,d d,J=2.0,9.0Hz),3.21(3H,s),2.0(2H,m),1.89(2H,m),1.70(2H,m),1.61(3H,m),1.18(1H,m)
化合物编号243(MP:165-166).NMR溶剂:DMSO
13C:167.7,145.6,145.5,139,137.4,135.1,131.9,130,129.2,129.1,127.1,126.1,117.3,114.5,81.8,78.7,61.6,22.6
1H:8.57(1H,d d,J=0.7,1.6Hz),8.31(1H,t,J=1.7Hz),8.21(1H,dd,J=0.7,8.8Hz),8.18(1H,s br),8.11(1H,d d,J=1.6,8.8Hz),7.98(1H,d t,J=1.5,7.8Hz),7.91(1H,d t,J=1.4,7.8Hz),7.60(1H,t,J=7.7Hz),7.51(1H,s br),5.46(2H,s),3.91(2H,s),1.60(6H,s)
化合物编号244(MP:148).NMR溶剂:CDCl3
13C:151.5,141.1,137,133.1,131.5,128.8,126.4,113.5,59.3,31.2,28.9,24.4
1H:7.91(1H,d,J=1.2Hz),7.73(2H,d,J=8.6Hz),7.50(1H,d,J=1.2Hz),7.37(2H,d,J=8.6Hz),4.44(1H,qt,J=8.2Hz),3.0(3H,s),1.95(2H,m),1.78(2H,m),1.68(2H,m),1.63(2H,m)
化合物编号245(MP:213-215).NMR溶剂:DMSO
13C:167.6,150.9,142.7,140.4,139.6,137.7,134.2,133.2,129.4,128.2,126.6,125.6,124.4,123.1,115,56.8,31.4,29,25.2,24.9
1H:8.20(1H,t,J=1.8Hz),8.18(1H,d,J=1.1Hz),8.15(1H,d,J=1.1Hz),8.07(1H,s br),8.0(2H,d,J=8.4Hz),7.90(1H,t d,J=1.4,7.7Hz),7.83(2H,d,J=8.4Hz),7.62(1H,t d,J=1.6,8.0Hz),7.51(1H,t,J=7.7Hz),7.44(1H,s br),3.84(1H,m),2.95(3H,s),1.80(4H,m),1.60(1H,m),1.57(2H,m),1.30(2H,m,J=12.7Hz),1.11(1H,m,J=13Hz)
化合物编号246(MP:118-119).NMR溶剂:CDCl3
13C:163.1(d,J=245.0Hz),151.3,143.3(d,J=8.0Hz),141.8,140.4(d,J=2.0Hz),137,133.7,130.1(d,J=8.5Hz),129.2,126.2,124.5,123.9,122.8(d,J=),114.1(d,J=22.0Hz),114.1(d,J=21.0Hz),113.5,57.6,31.4,30,25.4,25.2
1H:8.05(1H,m),7.94(1H,d,J=1.3Hz),7.79(1H,t d,J=2.0,6.7Hz),7.57(1H,d,J=1.3Hz),7.50(2H,m),7.44(2H,m),7.37(1H,d d d,J=1.7,2.5,10.5Hz),7.06(1H,m),3.98(1H,m),3.02(3H,s),1.89(2H,m),1.87(2H,m),1.71(1H,d br,J=11.5Hz),1.59(2H,d q,J=3.6,12.5Hz),1.39(2H,t q,J=3.2,13.2Hz),1.13(1H,t q,J=3.3,13.0Hz)
化合物编号247(MP:208-209).NMR溶剂:DMSO
13C:157.9,150.9,141.6,140.7,140.5,137.7,134,130,129.2,125.3,123.8,122.9,117.6,114.8,114.5,113.6,56.8,31.4,29,25.2,24.9
1H:9.56(1H,s,br),8.14(2H,s),8.08(1H,s),7.83(1H,t d,J=2.0,6.6Hz),7.47(1H,m),7.45(1H,t,J=7.7Hz),7.27(1H,t,J=8.0Hz),7.13(1H,d d d,J=1.0,1.7,7.6Hz),7.08(1H,t,J=1.9Hz),6.78(1H,dd d,1.0,2.4,8.0Hz),3.84(1H,m),2.94(3H,s),1.79(4H,m),1.60(1H,m),1.57(2H,m),1.30(2H,q,J=12.7Hz),1.13(1H,m,J=13.0Hz)
化合物编号248(MP:131-132).NMR溶剂:DMSO
13C:150.9,149(m,J=2.0Hz),142.5,140.3,138.8,137.7,134.3,130.9,129.5,126.0,125.6,124.6,123.1,120.2(q,J=256.0Hz),119.9,119.4,115.1,56.8,31.4,29,25.2,24.9
1H:8.20(1H,d,J=1.2Hz),8.17(1H,t,J=1.6Hz),8.15(1H,d,J=1.2Hz),7.91(1H,t d,J=1.4,7.8Hz),7.79(1H,d,J=7.9Hz),7.71(1H,br),7.62(1H,t,J=8.1Hz),7.61(1H,m),7.51(1H,t,J=7.7Hz),7.39(1H,d,J=8.2Hz),2.94(3H,s),3.84(1H,m),1.78(4H,m),1.60(1H,m),1.56(2H,m),1.30(2H,m,J=12.8Hz),1.11(1H,m)
化合物编号249(MP:162-163).NMR溶剂:CDCl3
13C:151.5,141.2,136.9,136.8,133.1,131.4,128.9,128.8,127.7,126.6,126.3,113.1,51.7,48.6,20.4
1H:7.91(1H,d,J=1.3Hz),7.46(1H,d,J=1.3Hz),7.64(2H,d,J=8.6Hz),7.39(2H,t,J=7.5Hz),7.34(2H,d,J=8.6Hz),7.32(1H,m),7.31(2H,d,J=8.2Hz),4.61(2H,s),4.20(1H,m,J=6.8Hz),1.37(6H,d,J=6.8Hz)
化合物编号250(MP:111).NMR溶剂:CDCl3
13C:151.7,142.3,137,136.7,132.9,128.9,128.6,127.7,127.5,126.6,125.1,112.9,51.7,48.5,20.4
1H:7.93(1H,d,J=1.3Hz),7.72(2H,d,J=8.2Hz),7.48(1H,d,J=1.3Hz),7.39(2H,m),7.37(2H,m),7.31(3H,m),7.27(1H,m),4.62(2H,s),4.21(1H,m,J=6.7Hz),1.37(6H,d,J=6.7Hz)
化合物编号251(MP:132-133).NMR溶剂:CDCl3
13C:152.2,142,138.4,136.8,133,129,128.6,127.6,127.3,126.1,125,113,59.4,51.3,28.1
1H:7.91(1H,d,J=1.4Hz),7.65(2H,d,J=8.5Hz),7.46(1H,d,J=1.4Hz),7.38(2H,t,J=7.1Hz),7.35(2H,t,J=8.0Hz),7.31(1H,m,J=7.4Hz),7.26(2H,m),7.25(1H,m),4.69(2H,s),1.52(9H,s)
化合物编号252(MP:129-130).NMR溶剂:CDCl3
13C:152.1,141,138.4,136.9,133,131.5,129,128.8,127.6,126.2,126.1,113.2,59.5,51.3,28.1
1H:7.89(1H,d,J=1.3Hz),7.57(2H,d,J=8.6Hz),7.43(1H,d,J=1.3Hz),7.38(2H,t,J=7.6Hz),7.31(1H,m),7.31(2H,d,J=8.6Hz),7.24(2H,d,J=8.0Hz),4.68(2H,s),1.52(9H,s)
化合物编号253(MP:147-148).NMR溶剂:CDCl3
13C:162.9,147.5,147.3,136.8,129.1,128.2,127.5,64.6,47.3,44.2
1H:8.95(1H,s),8.07(2H,d,J=8.7Hz),7.47(2H,d,J=8.7Hz),5.15(2H,br),4.36(2H,br),3.40(2H,t,J=6.8Hz)
化合物编号254(MP:141-142).NMR溶剂:CDCl3
13C:151.5,138.3,134.2,133.9,128.4,127.1,126.8,122.9,57.2,30.8,30.1,25.4,25.2,10.5
1H:7.68(2H,d,J=8.1Hz),7.62(1H,s),7.43(2H,t,J=7.8Hz),7.30(1H,t,J=7.4Hz),3.91(1H,m),2.91(3H,s),2.46(3H,s),1.86(2H,m),1.81(2H,m),1.70(1H,d br,J=13.0Hz),1.57(2H,m),1.36(2H,m),1.12(1H,m)
化合物编号255(MP:油脂).NMR溶剂:CDCl3
13C:159.9,151.6,142.1,137,136.7,134.3,129.7,128.9,127.7,126.6,117.5,113.7,113.2,110,55.3,51.7,48.6,20.4
1H:7.92(1H,d,J=1.0Hz),7.47(1H,d,J=1.0Hz),7.39(2H,t,J=7.2Hz),7.31(4H,m),7.28(2H,m),6.84(1H,m),4.61(2H,s),4.21(1H,m,J=6.8Hz),3.85(3H,s),1.37(6H,d,J=6.8Hz)
化合物编号256(MP:油脂).NMR溶剂:CDCl3
13C:159.8,152.2,141.8,138.5,136.8,134.4,129.6,129,127.6,126.1,117.4,113.8,113.3,109.7,59.4,55.2,51.2,28.1
1H:7.91(1H,d,J=1.2Hz),7.45(1H,d,J=1.2Hz),7.39(2H,t,J=7.6Hz),7.30(1H,m,J=7.3Hz),7.26(2H,m),7.24(2H,m),7.19(1H,m),6.81(1H,d d d,J=1.2,2.6,8.0Hz),4.69(2H,s),3.82(3H,s),1.53(9H,s)
化合物编号257(MP:138-139).NMR溶剂:CDCl3
13C:151.3,142.8,141.8,140.2,137,134.6,133.7,129.9,129.2,127.3,127.3,126.2,125.4,124.5,123.9,113.6,57.6,31.4,30,25.4,25.2
1H:8.04(1H,m),7.94(1H,d,J=1.3Hz),7.78(1H,m),7.66(1H,t,J=1.7Hz),7.57(1H,d,J=1.3Hz),7.54(1H,t d,J=1.5,7.6Hz),7.49(1H,t,J=7.7Hz),7.48(1H,m),7.39(1H,t,J=7.6Hz),7.34(1H,d d d,J=1.5,2.2,8.1Hz),3.98(1H,m),3.02(3H,s),1.89(2H,m),1.87(2H,m),1.71(1H,d br,J=13.3Hz),1.60(2H,m),1.39(2H,t q,J=3.0,12.7Hz),1.14(1H,t q,J=3.3,13.0Hz)
化合物编号258(MP:115-118).NMR溶剂:CDCl3
13C:159.2,151.3,142.5,142,141.6,137,133.5,129.7,129.1,126.4,124.1,124,119.6,113.4(2sig.),113.3,63.5,57.5,31.4,30,25.4,25.2,14.9
1H:8.04(1H,m,J=1.7Hz),7.94(1H,d,J=1.4Hz),7.78(1H,t d,J=1.7,7.5Hz),7.55(1H,d,J=1.4Hz),7.52(1H,d t,J=1.5,7.9Hz),7.47(1H,t,J=7.6Hz),7.36(1H,t,J=8.0Hz),7.24(1H,d d d,J=1.0,1.7,7.7Hz),7.19(1H,d d,J=1.7,2.5Hz),6.91(1H,d d d,J=1.0,2.5,8.2Hz),4.11(2H,q,J=7.0Hz),3.97(1H,m),3.01(3H,s),1.89(2H,m),1.86(2H,m),1.71(1H,d br,J=12.5Hz),1.59(2H,qd,J=3.5,12.5Hz),1.46(3H,t,J=7.0Hz),1.39(2H,t q,J=3.0,13.0Hz),1.13(1H,tq,J=3.5,13.0Hz)
化合物编号259(MP:137-139).NMR溶剂:CDCl3
13C:158.3(d,J=248.0Hz),151.3,141.7,137.0,135.0(d,J=1.3Hz),133.5,130.5(d,J=3.5Hz),130.4(m.J=14.0Hz),129.3(d,J=3.3Hz),128.9,128.7(d,J=8.5Hz),128.0,125.6(d,J=2.5Hz),124.9,117.4(d,J=25.0Hz),113.6,57.5,31.4,30,25.4,25.2
1H:7.97(1H,s br),7.93(1H,d,J=1.1Hz),7.82(1H,t d,J=1.7,7.2Hz),7.56(1H,d,J=1.1Hz),7.52-7.43(3H,m),7.29(1H,m),7.11(1H,t,J=9.5Hz),3.96(1H,m),3.0(3H,s),1.88(2H,m),1.85(2H,m),1.71(1H,d br,J=13.0Hz),1.59(2H,d q,J=3.5,12.5Hz),1.39(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号260(MP:190-191).NMR溶剂:DMSO
13C:156.8,146.3,141.3,136.7,126.2,124.4,115.4,111.6,80.6,79.3,60.8,22.5
1H:9.48(1H,s),8.09(1H,d,J=1.3Hz),7.80(1H,d,J=1.3Hz),7.64(2H,m d,J=8.5Hz),6.76(2H,m d,J=8.5Hz),5.14(2H,s),3.84(2H,s),1.49(6H,s)
化合物编号261(MP:197-199).NMR溶剂:DMSO
13C:156.7,151,140.9,137.3,126.1,124.4,115.4,112.5,56.8,31.3,29.1,25.2,24.9
1H:9.48(1H,s),8.05(1H,d,J=1.3Hz),7.77(1H,d,J=1.3Hz),7.64(2H,m,J=8.3Hz),6.77(2H,m,J=8.3Hz),3.80(1H,m),2.91(3H,s),1.77(4H,m),1.59(1H,m),1.55(2H,m),1.28(2H,m),1.10(1H,m)
化合物编号262(MP:170(分解)).NMR溶剂:DMSO
13C:157.9,149,137.3,135.3,130.2,129.5,116.3,116,115.9,112.3,58.7,31.5,28.2,24
1H:9.70(1H,s),9.24(1H,s),8.32(1H,s),7.29(1H,t,J=7.8Hz),7.27(1H,m),7.24(1H,m),6.83(1H,m,J=2.2,6.7Hz),4.39(1H,m),2.97(3H,s),1.89(2H,m),1.70(4H,m),1.53(2H,m)
化合物编号263(MP:89-91).NMR溶剂:CDCl3
13C:146.8,138.7,134,133.1,128.4,127.2,126.9,122.8,81.2,80.7,61,23,10.6
1H:7.66(2H,d,J=8.4Hz),7.63(1H,s),7.43(2H,t,J=7.8Hz),7.31(1H,t,J=7.4Hz),4.93(2H,s),3.90(2H,s),2.49(3H,s),1.61(6H,s)
化合物编号264(MP:118-119).NMR溶剂:CDCl3
13C:152.1,138.7,135.3,134.2,134.1,129.1,128.4,128.2,127.7,127.2,126.9,123.2,53.9,36,10.6
1H:7.69(1H,s),7.67(2H,d,J=8.3Hz),7.43(2H,t,J=7.7Hz),7.31(1H,t,J=7.4Hz),7.40-7.27(5H,m),4.66(2H,s),3.01(3H,s),2.49(3H,s)
化合物编号265(MP:178-180(分解)).NMR溶剂:DMSO
13C:157.9,149.1,137.3,136.8,135.8,130.2,129.5,128.5,127.2,126.8,116.3,116.1,115.4,112.4,51.4,47.1,20.1
1H:9.73(1H,s),9.18(1H,s),8.29(1H,s),7.36-7.28(5H,m),7.27(1H,t,J=8.0Hz),7.21(1H,m),7.18(1H,m),6.82(1H,m,J=2.5,8.1Hz),4.65(2H,s),4.16(1H,m),1.28(6H,d,J=6.7Hz)
化合物编号266(MP:油脂).NMR溶剂:CDCl3
13C:150.7,145.2,133.2,129.1,125.1,119.7,113.5,59.3,28.8,24.3
1H:8.09(1H,m d,J=8.3Hz),7.98(1H,m d,J=8.3Hz),7.59(1H,m,J=7.7Hz),7.45(1H,m,J=7.7Hz),4.78(1H,m),3.17(3H,s),2.07(2H,m),1.75(4H,m),1.63(2H,m)
化合物编号267(MP:142-143).NMR溶剂:CDCl3
13C:146.6,141.2,136.7,133.2,131.4,128.9,126.4,112.8,96.5,75.9,53.4,25.6,25.4,23.7,9.8
1H:8.03(1H,br),7.73(2H,d,J=8.5Hz),7.59(1H,br),7.37(2H,d,J=8.5Hz),4.10(1H,m),3.81(1H,d d,J=5.3,9.0Hz),3.43(1H,t,J=9.2Hz),1.74(3H,s),1.72(2H,m),1.66(3H,s),1.0(3H,t,J=7.5Hz)
化合物编号268(MP:117-118).NMR溶剂:CDCl3
13C:144.9,136.5,133.6,131.7,128.5,127.8,126.4,110.8,95.7,63.1,47.7,23.9
1H:7.96(2H,d,J=8.8Hz),7.78(1H,s),7.45(2H,t,J=8.0Hz),7.35(1H,t,J=7.5Hz),4.07(2H,t,J=6.2Hz),3.58(2H,t,J=6.2Hz),1.74(6H,s)
化合物编号269(MP:92-93).NMR溶剂:CDCl3
13C:141.6,135.3,133.9,129.4,128.8,128.1,127.5,111.0,80.6,61.3,29.7,22.7,22.5
1H:7.85(2H,d,J=8.8Hz),7.40(2H,d,J=8.8Hz),4.81(2H,s),3.84(2H,s),1.65(6H,s)
化合物编号270(MP:油脂).NMR溶剂:CDCl3
13C:146.7,142.2,136.6,132.9,128.7,127.6,125.2,112.5,96.4,75.9,53.4,25.6,25.4,23.7,9.8
1H:8.05(1H,d,J=1.3Hz),7.80(2H,d,J=8.5Hz),7.61(1H,d,J=1.3Hz),7.41(2H,t,J=8.0Hz),7.30(1H,t,J=7.4Hz),4.11(1H,m),3.81(1H,d d,J=5.2,9.0Hz),3.44(1H,t,J=9.5Hz),1.75(3H,s),1.73(3H,s),1.72(2H,m),1.0(3H,t,J=7.7Hz)
化合物编号271(MP:113-114).NMR溶剂:CDCl3
13C:156,151.7,137.4,136,128,127.6,121.7,120.9,117.2,110.6,57.5,55.2,31.1,30.1,25.4,25.2
1H:8.23(1H,d d,J=1.8,7.7Hz),7.94(1H,d,J=1.3Hz),7.82(1H,d,J=1.3Hz),7.28(1H,d t,J=2.0,7.6Hz),7.07(1H,J=1.1,7.6Hz),6.97(1H,d,J=8.3Hz),3.95(3H,s),3.95(1H,m),2.99(3H,s),1.87(4H,m),1.69(1H,d br,J=12.3Hz),1.59(2H,d q,J=3.5,12.5Hz),1.37(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.3,13.1Hz)
化合物编号272(MP:178-181).NMR溶剂:CDCl3
13C:151.0,150.5(d d,J=12.7,247Hz),149.7(d d,J=13.0,248.0Hz),140.3,137,130.3(d d,J=3.7,6.6Hz),121.0(d d,J=3.5,6.3Hz),117.5(d,J=17.5Hz),114.1(d,J=18.5Hz),113.5(d,J=1.0Hz),57.6,31.3,29.9,25.4,25.2
1H:7.88(1H,d,J=1.3Hz),7.61(1H,d d d,J=2.2,7.7,11.6Hz),7.49(1H,m),7.45(1H,d,J=1.3Hz),7.17(1H,d t,J=8.4,10.5Hz),3.93(1H,m),2.99(3H,s),1.86(4H,m),1.70(1H,d br),1.58(2H,d q,J=.3.5,12.3Hz),1.37(2H,t q,3.0,13.0Hz),1.12(1H,t q,J=3.5,13.0Hz)
化合物编号273(MP:142-143).NMR溶剂:CDCl3
13C:162.3(d,J=246Hz),151.3,141.3,136.9,129.2(d,J=3.2Hz),126.8(d,J=8.0Hz),115.6(d,J=22.0Hz),112.9,57.5,31.3,30,25.4,25.2
1H:7.89(1H,d,J=1.3Hz),7.76(2H,m,J=5.4,8.9Hz),7.74(1H,d,J=1.3Hz),7.09(2H,m,J=8.8Hz),3.95(1H,m),2.99(3H,s),1.87(4H,m),1.70(1H,d br,J=13.0Hz),1.58(2H,d q,J=3.5,12.2Hz),1.37(2H,t q,J=3.5,13.0Hz),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号274(MP:156-158).NMR溶剂:CDCl3
13C:151,140,137.1,133.2,132.8,131.1,130.6,126.9,124.3,114,57.6,31.4,29.9,25.4,25.2
1H:7.91(1H,d,J=2.0Hz),7.90(1H,d,J=1.4Hz),7.61(1H,d d,J=2.0,8.4Hz),7.51(1H,d,J=1.4Hz),7.45(1H,d,J=8.4Hz),3.94(1H,m),3.0(3H,s),1.86(4H,m),1.71(1H,m),1.58(2H,J=3.5,12.5Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号275(MP:160-162).NMR溶剂:CDCl3
13C:150.9,148.6,140,137.3,134.9,130.9,129.7,122,119.9,114.6,57.6,31.4,29.9,25.4,25.2
1H:8.61(1H,t,J=2Hz),8.14(2H,m),7.94(1H,d,J=1.3Hz),7.64(1H,d,J=1.3Hz),7.57(1H,t,J=8.0Hz),3.96(1H,m,J=12.0Hz),3.02(3H,s),1.88(4H,m),1.72(1H,m),1.60(2H,d q,J=3.5,12.5Hz),1.39(2H,t q,J=3.0,13.0Hz),1.14(1H,t q,J=3.5,13.0Hz)
化合物编号276(MP:130-131).NMR溶剂:CDCl3
13C:151.2,150.5(t,J=2.7Hz),141.1,137,130.5,126.5,119.7,115.9(t,J=259.5Hz),113.2,57.6,31.3,30,25.4,25.2
1H:7.89(1H,d,J=1.3Hz),7.79(2H,d,J=8.8Hz),7.47(1H,d,J=1.3Hz),7.15(2H,d,J=8.8Hz),6.54(1H,t,J=74Hz),3.95(1H,m,J=11.0Hz),3.0(3H,s),1.86(4H,m),1.70(1H,dbr,J=14.0Hz),1.58(2H,d q,J=3.6,12.2Hz),1.37(2H,J=3.2,13.0Hz),1.13(1H,J=3.5,13.0Hz)
化合物编号277(MP:168-169).NMR溶剂:CDCl3
13C:151.2,141.1,137,133.1,131.6,128.8,126.4,113.4,57.6,31.3,30,25.4,25.2
1H:7.90(1H,d,J=1.3Hz),7.73(2H,d.J=8.7Hz),7.49(1H,d,J=1.3Hz),7.37(2H,J=8.7Hz),3.95(1H,m,J=11.8Hz),2.99(3H,s),1.86(4H,m),1.70(1H,d,J=13.5Hz),1.58(2H,d q,J=3.5,12.3Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13Hz)
化合物编号278(MP:160).NMR溶剂:CDCl3
13C:151.5,142.3,136.9,132.8,128.7,127.6,125.1,113.1,67,54.4,31.8,29.5
1H:7.94(1H,s),7.80(2H,d,J=7.6Hz),7.51(1H,s),7.41(2H,t,J=7.6Hz),7.30(1H,t,J=7.3Hz),4.28(1H,m),4.09(2H,d d,J=4.0,11.5Hz),3.50(2H,t,J=11.5Hz),3.04(3H,s),1.94(2H,d q,J=4.5,12.3Hz),1.77(2H,d br,J=12.0Hz)
化合物编号279(MP:157-159).NMR溶剂:CDCl3
13C:152.2,145.6,140.7,133.3,128.6,127.1,125,112.4,57,30.7,30.1,25.4,25.2,14
1H:7.76(2H,d,J=8.2Hz),7.38(2H,t,J=7.9Hz),7.26(1H,t,J=7.5Hz),7.21(1H,s),3.90(1H,m br),2.88(3H,s),2.52(3H,s),1.81(4H,m),1.68(1H,d br,J=13.0Hz),1.55(2H,d q,J=3.3,12.2Hz),1.35(2H,q br,J=12.5Hz),1.11(1H,t q,J=3.0,13.0Hz)
化合物编号280(MP:137).NMR溶剂:CDCl3
13C:143.9,135.7,133.7,133.7,130.1,128.7,127.7,111.2,80.9,80.6,61.3,22.9
1H:7.90(2H,d,J=8.6Hz),7.73(1H,s),7.41(2H,s,J=8.6Hz),4.88(2H,s),3.91(2H,s),1.62(6H,s)
化合物编号281(MP:132-134).NMR溶剂:CDCl3
13C:151.7,149.1,148.5,142,136.7,126.1,117.4,112.4,111.2,108.4,59.3,55.9,55.9,31.2,28.8,24.3
1H:7.91(1H,d,J=1.3Hz),7.44(1H,d,J=1.3Hz),7.40(1H,d,J=2.0Hz),7.30(1H,d d,J=2.0,8.3Hz),6.90(1H,d,J=8.3Hz),4.44(1H,m,J=8.2Hz),3.96(3H,s),3.91(3H,s),2.99(3H,s),1.95(2H,m),1.73(4H,m),1.62(2H,m)
化合物编号282(MP:189-191).NMR溶剂:CDCl3
13C:151.5,142.2,138.1,137,132.9,129.1,128.7,128.3,127.6,127.2,125.1,113.1,62.8,55.8,52.5,31.6,28.9
1H:7.92(1H,d,J=1.3Hz),7.80(2H,m,J=8.0Hz),7.50(1H,d,J=1.3Hz),7.41(2H,t,J=7.6Hz),7.37-7.25(6H,m),4.03(1H,m),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.11(2H,t br,J=11.2Hz),1.90(2H,q br,J=12.0Hz),1.79(2H,d br,J=12.0Hz)
化合物编号283(MP:128).NMR溶剂:CDCl3
13C:162.3,149.8,147.2,130.1,129.9,128.7,126.7,57.6,30.2(2sig.),25.5,25.3
1H:8.82(1H,s),8.15(2H,m),7.48(3H,m),4.32(1H,m br),3.14(3H,s),1.93(4H,m),1.71(1H,d br,J=13.3Hz),1.59(2H,m),1.40(2H,m),1.15(1H,t q,J=3.5,13.0Hz)
化合物编号284(MP:151-153).NMR溶剂:CDCl3
13C:160.3,153.3,151,130.3,129.6,128.6,126.5,58.7,30.8,29.5,25.5,25.2,13.8
1H:8.10(2H,m,J=7.5Hz),7.45(3H,m),4.21+3.80(1H,m),3.03-2.99(3H,m),2.69(3H,s),1.88(4H,m),1.72(1H,m),1.58(2H,m),1.54(2H,m),1.12(1H,m)
化合物编号285(MP:135-138).NMR溶剂:CDCl3
13C:162.9,146.2,144.9,130.1,129.8,128.7,126.7,82,79.3,62.2,22.8
1H:8.94(1H,s),8.12(2H,m),7.47(3H,m),5.57(2H,s),3.86(2H,s),1.63(6H,s)
化合物编号286(MP:125-127).NMR溶剂:CDCl3
13C:160,157.7,146.4,129.9,129.9,128.6,126.6,82.2,79.6,61.7,22.8,15.1
1H:8.08(2H,m),7.45(3H,m),5.40(2H,s),3.85(2H,s),2.80(3H,s),1.62(6H,s)
化合物编号287(MP:222-224).NMR溶剂:DMSO
13C:167.8,150.7,140.5,140.2,140,137.8,135,134.2,129.6,129.3,129,126.7,125.8,125.6,124.1,123.1,114.7,57.5,37.9,35.9,33.8,29.2
1H:8.21(1H,m,J=1.6Hz),8.17(1H,m,J=1.6Hz),8.15(1H,s br),8.14(1H,d,J=1.3Hz),8.12(1H,d,J=1.3Hz),7.88(1H,d d,J=1.6,7.8Hz),7.88(2H,m),7.62(1H,m),7.57(1H,t,J=7.8Hz),7.51(1H,t,J=7.8Hz),7.48(1H,s br),2.94(3H,s),2.16(6H,s),2.11(3H,s),1.66(6H,s)
化合物编号288(MP:138-139).NMR溶剂:CDCl3
13C:159.2,151.2,141.9,137.2,137,134.6,129.7,128.5,127.9,127.5,117.8,114.3,113.3,111.2,69.9,58.4,38.6,36.2,34.1,29.7
1H:7.93(1H,d,J=1.3Hz),7.50(1H,m),7.47(2H,m),7.46(1H,d,J=1.3Hz),7.40(2H,m),7.38(1H,m),7.34(1H,m),7.31(1H,t,J=7.9Hz),6.92(1H,d d d,J=1.0,2.5,8.2Hz),5.14(2H,s),2.99(3H,s),2.20(9H,s),1.74(6H,s)
化合物编号289(MP:165-169(分解)).NMR溶剂:CDCl3
13C:150.9,148.4,146.7,139.1,137.6,132.4,129.1,123.6,113.8,58.5,38.5,36.2,34.1,29.6
1H:9.0(1H,d,J=1.5Hz),8.52(1H,d d,J=1.3,4.7Hz),8.11(1H,dt,J=1.8,7.8Hz),7.94(1H,s),7.55(1H,s),7.33(1H,d d,J=4.9,7.7Hz),2.99(3H,s),2.19(9H,s),1.73(6H,s)
化合物编号290(MP:149).NMR溶剂:CDCl3
13C:151.2,142,141.6,141,137.3,133.6,129.1,128.7,127.3,127.2,126.3,124,123.9,113.2,58.4,38.6,36.2,34.1,29.7
1H:8.05(1H,t br,J=1.8Hz),7.95(1H,d,J=.13Hz),7.78(1H,d t,J=1.5,7.5Hz),7.67(2H,m,J=8.5Hz),7.53(1H,d,J=1.3Hz),7.53(1H,m),7.48(1H,t,J=7.6Hz),7.46(2H,t,J=7.8Hz),7.37(1H,m,J=7.5Hz),3.0(3H,s),2.21(9H,s),1.74(6H,s)
化合物编号291(MP:208-210).NMR溶剂:CDCl3
13C:151.1,150.2,148.2,141.5,138.6,137.4,134.1,129.4,126,125.7,123.8,121.7,113.5,58.5,38.6,36.2,34.1,29.7
1H:8.67(2H,m,J=5.0Hz),8.11(1H,m,J=2.0Hz),7.95(1H,d,J=1.3Hz),7.84(1H,d t,J=1.7,7.5Hz),7.58(2H,m),7.55(1H,d,J=1.3Hz),7.55(1H,m),7.51(1H,t,J=7.6Hz),3.0(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号292(MP:75-77).NMR溶剂:CDCl3
13C:146.4,141.3,136.9,136.3,133.2,131.3,129,128.9,128.8,126.4,126.2,112.5,97,76.3,55.5,25.4,24
1H:8.05(1H,d,J=1.0Hz),7.70(2H,d,J=8.5Hz),7.56(1H,d,J=1.0Hz),7.46-7.38(5H,m),7.35(2H,d,J=8.5Hz),5.21(1H,d d,J=5.5,9.8Hz),4.10(1H,d d,J=5.5,9.3Hz),3.68(1H,t,J=9.5Hz),1.88(3H,s),1.87(3H,s)
化合物编号293(MP:164-165).NMR溶剂:CDCl3
13C:161.4,146.5,140.5,134.4,120.3,117.9,94.7,82.6,79.6,62.1,56,23
1H:7.92(1H,d d,J=0.5,9.0Hz),7.58(1H,d,J=2.5Hz),7.08(1H,d d,J=2.5,9.0Hz),5.53(1H,s),3.94(3H,s),3.90(2H,s),1.69(6H,s)
化合物编号294(MP:190-193(分解)).NMR溶剂:DMSO
13C:156.9,151,140.3,137.2,126.2,123.8,115.4,112.7,58.4,31.2,28.2,24
1H:9.53(1H,s),8.18(1H,s),7.81(1H,s),7.65(2H,d,J=8.7Hz),6.79(2H,d,J=8.7Hz),4.36(1H,m),2.92(3H,s),1.86(2H,m),1.67(4H,m),1.53(2H,m)
化合物编号295(MP:91-93).NMR溶剂:CDCl3
13C:144.0,136.6,133.6,131.6,128.5,127.9,126.5,110.9,81.0,80.6,61.3,22.9
1H:7.96(2H,d,J=8.4Hz),7.74(1H,s),7.45(2H,m,J=7.8Hz),7.35(1H,m,J=7.6Hz),4.88(2H,s),3.91(2H,s),1.62(6H,s)
化合物编号296(MP:106-110).NMR溶剂:CDCl3
13C:156.9,150.9,141.6,137.3,134,130,117.1,115.1,113.5,112.6,58.5,38.5,36.2,34.1,29.7
1H:7.95(1H,s),7.46(1H,m),7.42(1H,s),7.24(1H,m),7.23(1H,m),6.91(1H,m),2.96(3H,s),2.18(9H,s),1.72(6H,s)
化合物编号297(MP:119-121).NMR溶剂:DMSO
13C:149.8,144.6,132.6,129.3,125.3,119.6,113.3,67.9,57.6,56.1,34.2,27.2
1H:8.18(1H,d,J=8.3Hz),7.90(1H,d,J=8.3Hz),7.68(1H,t,J=7.8Hz),7.52(1H,t,J=7.6Hz),4.64(1H,s br),4.03(1H,s br),3.40(1H,s br),3.03(3H,s),1.90(2H,s br),1.82(2H,s br),1.75(2H,s br),1.26(2H,s br)
化合物编号298(MP:94-95).NMR溶剂:CDCl3
13C:146.6,142.4,136.9,136.3,132.8,129,128.9,128.7,127.6,126.2,125.2,112.3,96.9,76.3,55.5,25.4,24
1H:8.06(1H,d,J=1.3Hz),7.78(2H,m,J=8.3Hz),7.58(1H,d,J=1.3Hz),7.44(5H,m),7.39(2H,m,J=7.8Hz),7.29(1H,m,J=7.4Hz),5.21(1H,d d,J=5.5,9.8Hz),4.11(1H,d d,J=5.5,9.3Hz),3.69(1H,t,J=9.5Hz),1.89(3H,s),1.87(3H,s)
化合物编号299(MP:140-142).NMR溶剂:CDCl3
13C:146.7,141.2,136.7,133.3,131.4,128.9,126.4,112.8,96.4,63.6,48.3,24.1
1H:8.06(1H,br),7.73(2H,m,J=8.6Hz),7.61(1H,br),7.38(2H,m,J=8.6Hz),4.12(2H,t,J=6.0Hz),3.85(2H,t,J=6.0Hz),1.74(6H,s)
化合物编号300(MP:149-150).NMR溶剂:CDCl3
13C:149.1,136.3,134.3,131.9,128.5,127.7,126.4,111.6,57,30.6,29.8,25.3,25.2
1H:7.98(2H,d,J=8.2Hz),7.72(1H,br),7.45(2H,m,J=7.6Hz),7.34(1H,m,J=7.5Hz),4.24(1H,m br),2.88(3H,br),1.86(4H,m),1.70(1H,m),1.56(2H,m),1.40(2H,m),1.13(1H,m)
化合物编号301(MP:136-137).NMR溶剂:CDCl3
13C:144.3,138.8,135.2,133.8,130.5,128.6,128.1,96.1,81.1,80.7,61.3,22.9
1H:7.91(2H,d,J=8.5Hz),7.82(1H,s),7.41(2H,d,J=8.5Hz),4.84(2H,s),3.91(2H,s),1.63(6H,s)
化合物编号302(MP:108).NMR溶剂:CDCl3
13C:149.4,143.0,136.4,132.6,128.7,127.8,125.2,112.2,80.7,71.4,57.8,24.9,9.8
1H:7.98(1H,br),7.81(2H,d,J=8.2Hz),7.54(1H,br),7.42(2H,t,J=7.4Hz),7.31(1H,t,J=7.3Hz),5.13(1H,d,J=4.5Hz),5.0(1H,d,J=4.5Hz),4.32(2H,m),3.73(1H,m),1.91(1H,m),1.64(1H,m),0.98(3H,t,J=7.5Hz)
化合物编号303(MP:80-81).NMR溶剂:CDCl3
13C:150.6(d d,J=13.0,247.5Hz),149.9(d d,J=13.0,249.0Hz),149.1,141.1,136.5,129.9(d d,J=3.8,7.0Hz),121.2(d d,J=3.5,6.2Hz),117.6(d,J=17.5Hz),114.3(d,J=18.6Hz),112.5,80.7,71.5,57.8,24.9,9.8
1H:7.95(1H,d,J=1.3Hz),7.62(1H,d d d,J=2.0,7.5,11.5Hz),7.50(1H,d,J=1.3Hz),7.49(1H,m),7.19(1H,d t,J=8.4,10.2Hz),5.12(1H,d,J=4.5Hz),4.99(1H,d,J=4.5Hz),4.33(2H,m),3.74(1H,m),1.90(1H,m),1.64(1H,m),0.98(3H,t,J=7.4Hz)
化合物编号304(MP:100-101).NMR溶剂:CDCl3
13C:159.9,149.3,142.8,136.4,134,129.7,117.6,113.9,112.4,110.3,80.7,71.4,57.8,55.3,24.9,9.8
1H:7.98(1H,d,J=1.2Hz),7.52(1H,d,J=1.2Hz),7.39(1H,m),7.36(1H,d t,J=1.5,7.7Hz),7.31(1H,t,J=7.7Hz),6.88(1H,d d d,J=1.4,2.6,8.0Hz),5.13(1H,d,J=4.5Hz),5.0(1H,d,J=4.5Hz),4.32(2H,m),3.88(3H,s),3.73(1H,m),1.90(1H,m),1.63(1H,m),0.98(3H,t,J=7.5Hz)
化合物编号305(MP:131-132).NMR溶剂:CDCl3
13C:151.1,148.5,148.3,141.6,138.3,137.3,136.5,134.5,134,129.4,126.2,124.8,123.9,123.5,113.4,58.4,38.6,36.2,34.1,29.7
1H:8.91(1H,d,J=2.5Hz),8.61(1H,d d,J=1.7,4.8Hz),8.05(1H,m),7.95(1H,d,J=1.3Hz),7.95(1H,m),7.82(1H,m),7.55(1H,d,J=1.3Hz),7.51(1H,m),7.50(1H,m),7.38(1H,d d d,J=0.8,4.8,7.9Hz),3.0(3H,s),2.10(9H,s),1.73(6H,s)
化合物编号306(MP:195-196).NMR溶剂:CDCl3
13C:157.5,155,151,141.2,137.4,134.7,134.4,134.2,129.7,125.9,125.6,123.7,113.6,58.5,38.5,36.2,34.1,29.6
1H:9.22(1H,s),9.01(2H,s),8.05(1H,s),7.95(1H,s),7.85(1H,d,J=7.5Hz),7.56(1H,s),7.54(1H,t,J=7.5Hz),7.48(1H,d,J=7.5Hz),3.0(3H,s),2.19(9H,s),1.73(6H,s)
化合物编号307(MP:150-151).NMR溶剂:DMSO
13C:157.6,150.8,140.7,137.5,134.6,129.6,115.7,114.3,114.1,111.7,56.8,31.3,29.1,25.2,24.9
1H:9.43(1H,s),8.09(1H,d,J=1.0Hz),7.90(1H,d,J=1.0Hz),7.26(2H,m),7.16(1H,t,J=8.0Hz),6.65(1H,d d d,J=1.0,2.2,8.0Hz),3.80(1H,m),2.92(3H,s),1.77(4H,m),1.59(1H,m),1.55(2H,m),1.29(2H,m,J=11.5Hz),1.10(1H,q,J=13.0Hz)
化合物编号308(MP:139-140).NMR溶剂:CDCl3
13C:150.6(d d,J=13.0,248.0Hz),149.9(d d,J=13.0,249.0Hz),148.1,141.1,136.7,136.1,129.8(d d,J=3.9,6.5Hz),129.1,128.9,126.1,121.2(d d,J=3.5,6.2Hz),117.6(d,J=17.8Hz),114.3(d,J=18.5Hz),112.4,80.4,80.1,53.0
1H:8.05(1H,d,J=1.3Hz),7.62(1H,d d d,J=2.0,7.6,11.5Hz),7.56(1H,d,J=1.3Hz),7.45(1H,m),7.42-7.37(5H,m),7.18(1H,d t,J=8.3,10.0Hz),5.44(1H,d,J=4.5Hz),5.26(1H,d,J=4.5Hz),5.18(1H,d d,J=6.1,8.8Hz),4.16(1H,d d,J=6.1,10.0Hz),3.68(1H,d d,J=9.0,10.0Hz)
化合物编号309(MP:155-157).NMR溶剂:CDCl3
13C:148.4,142.9,136.6,136.2,132.5,129.0,128.9,128.7,127.8,126.1,125.2,112.1,80.4,80.0,53.0
1H:8.08(1H,br),7.80(2H,d,J=8.0Hz),7.60(1H,br),7.42(7H,m),7.31(1H,t,J=7.5Hz),5.44(1H,d,J=4.8Hz),5.27(1H,d,J=4.8Hz),5.16(1H,d d,J=6.3,8.8Hz),4.16(1H,d d,J=6.3,10.1Hz),3.68(1H,t,J=9.6Hz)
化合物编号310(MP:126-127).NMR溶剂:CDCl3
13C:148.9,142.9,136.4,132.6,128.7,127.8,125.2,112.1,80.4,73.4,52.9,17
1H:7.99(1H,d,J=1.3Hz),7.80(2H,m d,J=8.4Hz),7.54(1H,d,J=1.3Hz),7.42(2H,m t,J=7.8Hz),7.31(1H,m t,J=7.5Hz),5.14(1H,d,J=4.5Hz),5.04(1H,d,J=4.5Hz),4.39(1H,m),4.36(1H,m),3.63(1H,d d,J=6.9,8.4Hz),1.37(3H,d,J=6.0Hz)
化合物编号311(MP:127).NMR溶剂:CDCl3
13C:150.6(d d,J=12.5,247.5Hz),149.9(d d,J=13.0,248.5Hz),148.6,141.1,136.4,129.9(d d,J=3.5,7.0Hz),121.2(d d,J=3.5,6.3Hz),117.6(d,J=17.5Hz),114.3(d,J=18.6Hz),112.5,80.4,73.4,53,17.0
1H:7.96(1H,d,J=1.3Hz),7.62(1H,d d d,J=2.1,7.7,11.5Hz),7.51(1H,d,J=1.3Hz),7.49(1H,m),7.19(1H,d t,J=8.3,10.1Hz),5.13(1H,d,J=4.5Hz),5.04(1H,d,J=4.5Hz),4.39(1H,m),4.36(1H,m),3.65(1H,m),1.37(3H,d,J=6.0Hz)
化合物编号312(MP:118).NMR溶剂:CDCl3
13C:150.9,142.2,136.5,133,128.7,127.4,125.1,113,58.9,39.4,31.4,25.6,25.1,14.9
1H:7.89(1H,d,J=1.3Hz),7.81(2H,m d,J=8.3Hz),7.48(1H,d,J=1.3Hz),7.41(2H,m t,J=7.9Hz),7.30(1H,m t,J=7.5Hz),3.77(1H,t t,J=3.5,12.0Hz),3.43(2H,q,J=7.1Hz),1.82(4H,m),1.66(3H,m),1.30(2H,m),1.25(3H,t,J=7.1Hz),1.13(1H,m)
化合物编号313(MP:121-122).NMR溶剂:CDCl3
13C:150.9,149.1,148.5,142,136.2,126.2,117.3,112.3,111.2,108.4,58.9,55.9,55.9,39.4,31.4,25.6,25.1,14.9
1H:7.86(1H,d,J=1.3Hz),7.41(1H,s),7.41(1H,d,J=1.3Hz),6.91(1H,d,J=8.4Hz),7.30(1H,d d,J=2.0,8.4Hz),3.96(3H,s),3.91(3H,s),3.77(1H,t t,J=3.5,12.0Hz),3.43(2H,q,J=7.1Hz),1.84(4H,m),1.68(3H,m),1.29(2H,m),1.25(3H,t,J=7.1Hz),1.12(1H,m)
化合物编号314(MP:208).NMR溶剂:DMSO
13C:151.6(d,J=243.0Hz),150.6,146.1(d,J=11.0Hz),139.5(d,J=2.5Hz),137.2,126.8(d,J=7.0Hz),120.8(d,J=3.4Hz),114.1(d,J=2.0Hz),113.7,112.1(d,J=19.5Hz),56.8,56,31,28.9,25,24.61H:8.04(1H,d,J=1.3Hz),7.90(1H,d,J=1.3Hz),7.64(1H,d d,J=2.0,8.3Hz),7.61(1H,m),7.18(1H,t,J=9.3Hz),3.86(3H,s),3.80(1H,m),2.92(3H,s),1.79(4H,m),1.62(1H,m),1.59(2H,m),1.30(2H,m),1.12(1H,m)
化合物编号315(MP:162-163).NMR溶剂:DMSO
13C:151.6(d,J=242.5Hz),150.7,146.4(d,J=10.5Hz),138.5,137.5,125.7(d,J=7.6Hz),121.2(d,J=3.0Hz),114.3,114.1(d,J=2.0Hz),112.4(d,J=19.5Hz),58.5,56.1,31.3,28.2,24
1H:8.31(1H,s br),8.03(1H,d,J=1.2Hz),7.69(1H,d d,J=2.0,12.5Hz),7.65(1H,m),7.21(1H,t,J=8.8Hz),4.37(1H,m),3.86(3H,s),2.93(3H,s),1.88(2H,m),1.68(4H,m),1.53(2H,m)
化合物编号316(MP:205).NMR溶剂:DMSO
13C:151.6(d,J=243.5Hz),147.2(d,J=10.5Hz),144.6,136.8,136,122.9,121.8(d,J=3.3Hz),114.3,114.3,112.9(d,J=20.0Hz),80.7,79.3,61.3,56.1,22.3
1H:9.05(1H,s br),8.31(1H,d,J=1.3Hz),7.82(1H,d d,J=2.2,12.7Hz),7.74(1H,d,J=8.5Hz),7.28(1H,t,J=8.7Hz),5.21(2H,s),3.87(3H,s),3.86(2H,s),1.51(6H,s)
化合物编号317(MP:173-174).NMR溶剂:CDCl3
13C:151.3,150,142.3,141.5,137.2,133.4,129(2sig.),127.7,125.4,123,122.8,113.1,112.7,58.3,40.6,38.6,36.2,34.1,29.7
1H:8.01(1H,s),7.95(1H,s),7.69(1H,d,J=7.5Hz),7.59(2H,m,J=8.8Hz),7.51(1H,s),7.50(1H,d,J=8.0Hz),7.43(1H,t,J=7.7Hz),6.82(2H,m,J=8.8Hz),3.01(6H,s),3.0(3H,s),2.21(9H,s),1.74(6H,s)
化合物编号318(MP:181-182).NMR溶剂:CDCl3
13C:168.1,164.5,157.6,151.1,141.7,137.2,133.7,133.4,128.7,128,125.5,124.4,116.1,113.3,58.4,54.8,54.2,38.5,36.2,34.1,29.6
1H:8.31(1H,s),7.93(1H,s),7.91(1H,s),7.78(1H,d,J=7.6Hz),7.50(1H,s),7.46(1H,t,J=7.5Hz),7.40(1H,d,J=7.5Hz),4.04(3H,s),4.03(3H,s),2.99(3H,s),2.19(9H,s),1.73(6H,s)
化合物编号319(MP:109-111).NMR溶剂:CDCl3
13C:151.9(d,J=246.0Hz),151.2,147.8(d,J=11.0Hz),141.3,136.8,129.6(d,J=3.5Hz),117.3(d,J=7.0Hz),116.1(d,J=19.0Hz),113.1,110.3(d,J=1.5Hz),57.6,56.2,31.3,30,25.4,25.2
1H:7.89(1H,d,J=1.2Hz),7.50(1H,d d,J=2.0,8.2Hz),7.45(1H,d,J=1.2Hz),7.24(1H,d d d,J=2.0,4.3,8.3Hz),7.09(1H,d d,J=8.3,11.0Hz),3.96(3H,s),3.95(1H,m),2.99(3H,s),1.86(4H,m),1.70(1H,d br,J=13.0Hz),1.58(2H,d q,J=4.5,13.5Hz),1.37(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.4,13.0Hz)
化合物编号320(MP:170-171).NMR溶剂:CDCl3
13C:163.1(d,J=240.0Hz),151.1,145.9(d,J=15.0Hz),141.5,139.9(d,J=8.0Hz),137.4,137.2,134.7(d,J=4.5Hz),134.1,129.5,126.1,124.8,123.8,113.5,109.4(d,J=37.5Hz),,58.5,38.6,36.2,34.1,29.7
1H:8.49(1H,m,J=2.5Hz),8.05(1H,m,J=2.5,7.5Hz),8.02(1H,m,J=1.6Hz),7.95(1H,d,J=1.3Hz),7.81(1H,d t,J=1.5,7.5Hz),7.55(1H,d,J=1.3Hz),7.51(1H,t,J=7.5Hz),7.46(1H,d t,J=1.5,7.8Hz),7.03(1H,m,J=3.0,8.5Hz),3.0(3H,s),2.20(9H,s),1.74(6H,s)
化合物编号321(MP:100-103).NMR溶剂:CDCl3
13C:151.9(d,J=246.0Hz),151.5,147.8(d,J=11.0Hz),141.3,136.8,129.5(d,J=3.5Hz),117.3(d,J=7.0Hz),116.2(d,J=19.0Hz),113.2,110.3,59.3,56.2,31.2,28.9,24.3
1H:7.94(1H,d,J=1.0Hz),7.50(1H,d d,J=2.0,7.50Hz),7.47(1H,d,J=1.0Hz),7.24(1H,d d d,J=2.0,4.3,8.3Hz),7.09(1H,d d,J=8.3,11.0Hz),4.44(1H,qt,J=8.0Hz),3.97(3H,s),3.0(3H,s),1.96(2H,m),1.75(4H,m),1.63(2H,m)
化合物编号322(MP:216-217).NMR溶剂:CDCl3
13C:156.9,151,142.4,141.9,141.4,137.3,132.9,129.7,129,126.3,124.2,124.1,118.8,114.7,114.5,113.4,58.5,38.6,36.2,34.1,29.7
1H:8.07(1H,br),8.03(1H,d,J=1.3Hz),7.90(1H,s br),7.70(1H,dt,J=1.7,7.4Hz),7.52(1H,d,J=1.3Hz),7.44(1H,d t,J=1.8,7.8Hz),7.40(1H,t,J=7.6Hz),7.24(1H,t,J=7.9Hz),7.17(1H,s br),7.13(1H,m),6.85(1H,d d d,J=0.9,2.5,8.0Hz),3.0(3H,s),2.20(9H,s),1.74(6H,s)
化合物编号323(MP:184-185).NMR溶剂:CDCl3
13C:163.6,151.2,145,141.8,138.3,137.6,137.3,133.8,130,129.3,125.7,124,123.5,113.3,110.7,58.4,53.5,38.6,36.2,34.1,29.7
1H:8.44(1H,d d,J=0.6,2.5Hz),7.98(1H,m),7.95(1H,d,J=1.3Hz),7.87(1H,d d,J=2.5,8.6Hz),7.77(1H,d t,J=1.8,7.0Hz),7.53(1H,d,J=1.3Hz),7.48(1H,t,J=7.5Hz),7.45(1H,m),6.83(1H,d d,J=0.6,8.6Hz),3.99(3H,s),3.0(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号324(MP:138-140).NMR溶剂:CDCl3
13C:168.4,151.2,142,140.9,137.3,137.3,136.8,133.5,129.1,127.6,126,123.8,123.6,120,113.3,58.4,38.6,36.2,34.1,29.7,24.6
1H:8.01(1H,t,J=1.7Hz),7.95(1H,d,J=1.2Hz),7.74(1H,d t,J=1.7,7.3Hz),7.60(4H,br),7.52(1H,d,J=1.2Hz),7.49(1H,d t,J=1.9,7.8Hz),7.44(1H,t,J=7.6Hz),3.0(3H,s),2.20(9H,s),2.19(3H,s),1.73(6H,s)
化合物编号325(MP:150-152).NMR溶剂:CDCl3
13C:151.1,143.6,141.8,138.7,137.2,133.6,132.8,129.1,126.3,124.9,123.7,122.5,113.2,108.9,58.4,38.5,36.2,34.1,29.6
1H:7.96(1H,s),7.94(1H,s),7.81(1H,s),7.66(1H,m),7.51(1H,s),7.49(1H,m),7.40(2H,m),6.78(1H,m),2.99(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号326(MP:105-107).NMR溶剂:CDCl3
13C:159.1,151.8,142,136.8,126.4,125.8,114,112.1,59.3,55.3,31.1,28.8,24.3
1H:7.91(1H,d,J=1.2Hz),7.73(2H,d,J=8.8Hz),7.41(1H,d,J=1.2Hz),6.95(2H,d,J=8.8Hz),4.45(1H,qt,J=8.0Hz),3.85(3H,s),3.0(3H,s),1.95(2H,m),1.76(2H,m),1.67(2H,m),1.63(2H,m)
化合物编号327(MP:92-94).NMR溶剂:CDCl3
13C:159.9,151.6,142,136.9,134.4,129.7,117.5,113.6,113.5,110.1,59.3,55.3,31.2,28.9,24.3
1H:7.93(1H,d,J=1.3Hz),7.51(1H,d,J=1.3Hz),7.40(1H,d d,J=1.4,2.4Hz),7.36(1H,td,J=1.2,7.6Hz),7.32(1H,t,J=7.7Hz),6.86(1H,d d d,J=1.3,2.7,8.0Hz),4.45(1H,m),3.88(3H,s),3.0(3H,s),1.96(2H,m),1.78(2H,m),1.68(2H,m),1.60(2H,m)
化合物编号328(MP:153-154).NMR溶剂:CDCl3
13C:159.2,146.6,142.5,136.1,126.4,125.5,114.1,110.9,81.1,80.3,61.8,55.3,22.9
1H:7.93(1H,d,J=1.5Hz),7.71(2H,d,J=8.9Hz),7.41(1H,d,J=1.5Hz),6.94(2H,d,J=8.9Hz),5.13(2H,s),3.88(2H,s),3.84(3H,s),1.61(6H,s)
化合物编号329(MP:100-101).NMR溶剂:CDCl3
13C:159.9,146.4,142.4,136.1,134.1,129.7,117.5,113.8,112.3,110.2,81,80.3,61.8,55.3,22.8
1H:7.95(1H,d,J=1.3Hz),7.51(1H,d,J=1.3Hz),7.40(1H,d d,J=1.5,2.5Hz),7.34(1H,t d,J=1.5,7.6Hz),7.30(1H,t,J=7.8Hz),6.85(1H,d d d,J=1.5,2.7,7.9Hz),5.12(2H,s),3.87(2H,s),3.86(3H,s),1.61(6H,s)
化合物编号330(MP:164-166).NMR溶剂:DMSO
13C:151.2(d,J=240.0Hz),150.8,144.0(d,J=12.3Hz),139.9(d,J=2.0Hz),137.4,125.4(d,J=7.0Hz),121.0(d,J=3.0Hz),117.9(d,J=3.2Hz),113.5,112.5(d,J=19.5Hz),56.8,31.3,29,25.1,24.8
1H:9.89(1H,s),8.06(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.58(1H,d d,J=2.0,12.7Hz),7.48(1H,m,J=2.0,8.4Hz),6.95(1H,d d,J=8.4,9.0Hz),3.80(1H,m),2.91(3H,s),1.76(4H,m),1.60(1H,m),1.55(2H,m),1.29(2H,m),1.10(1H,m)
化合物编号331(MP:170-171).NMR溶剂:DMSO
13C:151.2(d,J=240.0Hz),151.2,144.0(d,J=12.5Hz),139.9(d,J=2.6Hz),137.4,125.4(d,J=6.9Hz),121.0(d,J=3.0Hz),117.9(d,J=3.3Hz),113.5,112.5(d,J=19.5Hz),58.4,31.2,28.2,24
1H:9.89(1H,s),8.06(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.58(1H,d d,J=2.0,12.7Hz),7.48(1H,d d d,J=1.0,2.0,8.4Hz),6.95(1H,d d,J=8.4,9.1Hz),4.35(1H,m),2.92(3H,s),1.87(2H,m),1.67(4H,m),1.53(2H,m)
化合物编号332(MP:194-196).NMR溶剂:DMSO
13C:151.2(d,J=240.0Hz),146.2,144.1(d,J=12.0Hz),140.2(d,J=2.3Hz),136.9,125.3(d,J=6.8Hz),121.1(d,J=3.0Hz),117.9(d,J=3.7Hz),112.5(d,J=20.0Hz),112.5,80.6,79.3,60.8,22.4
1H:9.91(1H,s),8.11(1H,d,J=1.3Hz),7.91(1H,d,J=1.3Hz),7.59(1H,d d,J=2.1,12.5Hz),7.48(1H,m,J=2.1,8.6Hz),6.95(1H,d d,J=8.6,9.1Hz),5.16(2H,s),3.84(2H,s),1.49(6H,s)
化合物编号333(MP:173-176).NMR溶剂:DMSO
13C:150.4(d,J=240.0Hz),146.1,145.0(d,J=12.5Hz),140.2,136.9,130.1(d,J=3.0Hz),116.2(d,J=18.5Hz),115.9(d,J=6.3Hz),114.3(d,J=2.7Hz),113.1,80.6,79.3,60.8,22.4
1H:9.93(1H,s),8.13(1H,d,J=1.3Hz),7.92(1H,d,J=1.3Hz),7.46(1H,d d,J=2.1,8.8Hz),7.24(1H,d d d,J=2.1,4.4,8.5Hz),7.13(1H,d d,J=8.5,11.2Hz),5.16(2H,s),3.84(2H,s),1.49(6H,s)
化合物编号334(MP:154-155).NMR溶剂:CDCl3
13C:154.6,150.9,150.7,137.8,134.3,128.9,124.2,122.9,121,114.6,110.9,101.9,57.6,31.4,29.9,25.4,25.2
1H:7.97(1H,d,J=1.3Hz),7.61(1H,d,J=1.3Hz),7.60(1H,m),7.49(1H,d,J=8.0Hz),7.28(1H,d t,J=.15,7.5Hz),7.24(1H,d t,J=1.1,7.3Hz),7.10(1H,s),3.97(1H,m),3.01(3H,s),1.87(4H,m),1.71(1H,d br,J=13.0Hz),1.59(2H,d q,J=3.5,12.5Hz),1.39(2H,q,J=13.0Hz),1.14(1H,t q,J=3.5,13.0Hz)
化合物编号335(MP:161-163).NMR溶剂:CDCl3
13C:151,148.5,146.7,139.2,137.3,132.4,129,123.6,114,57.6,31.4,30,25.4,25.2
1H:9.01(1H,d d,J=0.8,2.3Hz),8.53(1H,d d,J=1.7,4.8Hz),8.12(1H,d d d,J=1.8,2.2,8.0Hz),7.94(1H,d,J=1.3Hz),7.58(1H,d,J=1.3Hz),7.34(1H,d d d,J=0.8,4.9,8.0Hz),3.95(1H,m),3.01(3H,s),1.87(4H,m),1.71(1H,d br,J=13.5Hz),1.59(2H,d q,J=3.5,12.5Hz),1.38(2H,t q,J=3.5,13.0Hz),1.13(1H,t q,J=3.5,13.5Hz)
化合物编号336(MP:211-213).NMR溶剂:CDCl3
13C:151,150.4,148,141.4,137.4,137.3,137,135.5,134.2,129.5,126,125.1,124.2,123.8,113.6,58.5,38.6,36.2,34.1,29.7
1H:8.66(1H,d,J=2.0Hz),8.02(1H,s),7.95(1H,s),7.92(1H,d d,J=2.5,8.3Hz),7.81(1H,d,J=7.3Hz),7.55(1H,s),7.51(1H,t,J=7.51Hz),7.46(1H,d,J=8.0Hz),7.41(1H,d,J=8.3Hz),3.0(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号337(MP:油脂).NMR溶剂:CDCl3
13C:147.5,145.8,140.9,133,128.6,127.3,125,111.1,81,80.6,61,22.9,14.3
1H:7.74(2H,d,J=8.3Hz),7.38(2H,t,J=7.9Hz),7.27(1H,t,J=7.6Hz),7.20(1H,s),4.90(2H,s),3.88(2H,s),2.56(3H,s),1.61(6H,s)
化合物编号338(MP:129-130).NMR溶剂:CDCl3
13C:154.6,150.4,146.1,137.3,134.9,128.8,124.3,123,121.1,113.2,110.9,102.3,81.1,80.3,62,22.8
1H:8.04(1H,d,J=1.3Hz),7.61(1H,d,1.3Hz),7.60(1H,m),7.48(1H,m,J=7.8Hz),7.30(1H,d t,J=1.5,7.3Hz),7.24(1H,d t,J=1.2,7.4Hz),7.10(1H,s),5.16(2H,s),3.89(2H,s),1.62(6H,s)
化合物编号339(MP:154-155).NMR溶剂:CDCl3
13C:148.6,142.8,136.5,132.6,128.7,127.8,125.2,112.2,80.3,67.1,46.0
1H:8.05(1H,d,J=1.3Hz),7.80(2H,m d,J=8.4Hz),7.60(1H,d,J=1.3Hz),7.41(2H,m t,J=7.5Hz),7.31(1H,m t,J=7.3Hz),5.12(2H,s),4.15(2H,t,J=6.5Hz),3.80(2H,t,J=6.5Hz)
化合物编号340(MP:122-123).NMR溶剂:CDCl3
13C:159.9,148.4,142.8,136.6,136.2,133.9,129.7,129,128.9,126.1,117.6,113.9,112.3,110.3,80.4,80,55.3,53
1H:8.97(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.47-7.37(5H,m),7.40(1H,m),7.36(1H,m),7.31(1H,t,J=7.7Hz),6.87(1H,d d d,J=1.3,2.6,7.9Hz),5.43(1H,d,J=4.5Hz),5.26(1H,d,J=4.5Hz),5.16(1H,d d,J=6.1,8.8Hz),4.16(1H,d d,J=6.2,10.0Hz),3.87(3H,s),3.68(1H,t,J=9.5Hz)
化合物编号341(MP:164-165).NMR溶剂:CDCl3
13C:159.1,151.4,142,136.8,126.4,125.8,114,112.1,57.5,55.3,31.3,30,25.4,25.2
1H:7.89(1H,d,J=1.3Hz),7.40(1H,d,J=1.3Hz),7.33(2H,m d,J=9.0Hz),6.95(2H,m d,J=9.0Hz),3.95(1H,m),3.84(3H,s),2.99(3H,s),1.86(4H,m),1.70(1H,d br,J=13.0Hz),1.58(2H,d q,J=3.5,12.5Hz),1.37(2H,t q,J=3.2,13.0Hz),1.12(1H,t q,J=3.5,13.0Hz)
化合物编号342(MP:122-123).NMR溶剂:CDCl3
13C:159.9,151.3,141.9,136.8,134.4,129.7,117.5,113.6,113.5,110.1,57.5,55.3,31.3,30,25.4,25.2
1H:7.92(1H,d,J=1.3Hz),7.49(1H,d,J=1.3Hz),7.40(1H,d d,J=1.4,2.5Hz),7.36(1H,t d,J=1.4,7.7Hz),7.31(1H,1H,t,J=8.0Hz),6.85(1H,d d d,J=1.2,2.5,7.9Hz),3.95(1H,m),3.88(3H,s),3.0(3H,s),1.86(2H,m),1.84(2H,m),1.70(1H,d br,J=13.0Hz),1.58(2H,dq,J=4.5,13.3Hz),1.38(2H,t q,J=3.2,13.0Hz),1.13(1H,t q,J=3.5,13.0Hz)
化合物编号343(MP:150-152).NMR溶剂:DMSO
13C:150.3(d,J=240.0Hz),150.8,144.9(d,J=12.5Hz),139.9,137.5,130.2(d,J=3.5Hz),116.2(d,J=18.7Hz),115.9(d,J=6.3Hz),114.2(d,J=3.0Hz),114.1,56.8,31.3,29,25.1,24.8
1H:9.89(1H,s br),8.08(1H,s),7.89(1H,s),7.45(1H,d,J=8.3Hz),7.24(1H,s br),7.13(1H,m,J=9.0,11.0Hz),3.79(1H,s br),2.91(3H,s),1.76(4H,m),1.58(3H,m),1.29(2H,m),1.10(1H,m)
化合物编号344(MP:144-145).NMR溶剂:DMSO
13C:151.1,150.3(d,J=241.0Hz),144.9(d,J=12.5Hz),140.0,137.5,130.2(d,J=3.2Hz),116.3(d,J=18.5Hz),115.9(d,J=6.5Hz),114.2(d,J=3.0Hz),114.1,58.4,31.2,28.2,24.0
1H:9.91(1H,s),8.08(1H,s),7.88(1H,d,J=1.3Hz),7.45(1H,d d,J=2.0,8.7Hz),7.24(1H,m),7.13(1H,d d,J=8.6,11.2Hz),4.35(1H,m),2.92(3H,s),1.87(2H,m),1.68(4H,m),1.53(2H,m)
化合物编号345(MP:113-114).NMR溶剂:CDCl3
13C:150.8,150.5(t,J=3.0Hz),141.2,136.6,130.5,126.5,119.7,115.9(t,J=259.5Hz),113.1,58.9,39.4,31.4,25.6,25.1,14.9
1H:7.87(1H,d,J=1.3Hz),7.80(2H,m d,J=8.8Hz),7.45(1H,d,J=1.3Hz),7.16(2H,m d,J=8.8Hz),6.54(1H,t,J=74Hz),3.75(1H,tt,J=3.5,12.0Hz),3.43(2H,q,J=7.1Hz),1.85(4H,m),1.68(2H,m),1.64(1H,m),1.29(2H,m),1.25(3H,t,J=7.1Hz),1.12(1H,m)
化合物编号346(MP:129-131).NMR溶剂:CDCl3
13C:150.6(d d,J=13.0,247.5Hz),150.6,149.7(d d,J=12.5,248.0Hz),140.4(d,J=2.0Hz),136.6,130.3(d d,J=3.5,7.0Hz),121.0(d d,J=3.6,6.1Hz),117.5(d,J=17.5Hz),114.1(d,J=18.5Hz),113.4,59,39.5,31.4,25.6,25.1,14.9
1H:7.85(1H,d,J=1.3Hz),7.61(1H,d d d,J=2.2,7.6,11.6Hz),7.49(1H,m),7.44(1H,d,J=1.3Hz),7.18(1H,d t,J=8.4,10.2Hz),3.74(1H,t t,J=3.5,12.0Hz),3.43(2H,q,J=7.1Hz),1.85(4H,m),1.67(2H,m),1.64(1H,m),1.30(2H,m),1.25(3H,t,J=7.1Hz),1.13(1H,m)
化合物编号347(MP:144-145).NMR溶剂:DMSO
13C:157.6,146.2,141,136.9,134.6,129.6,115.7,114.2,113.4,111.7,80.6,79.3,60.8,22.4
1H:9.43(1H,s),8.13(1H,d,J=1.3Hz),7.93(1H,d,J=1.3Hz),7.26(2H,m),7.16(1H,t,J=7.8Hz),6.66(1H,d d d,J=1.5,2.0,8.0Hz),5.17(2H,s),3.83(2H,s),1.50(6H,s)
化合物编号348(MP:129-130).NMR溶剂:CDCl3
13C:146.4,141.8,136.4,132.9,130.6,128.7,128.5,125,123.1,112.4,94,81.9,81.1,80.3,65.5,61.9,31.5,22.8
1H:7.97(1H,d,J=1.3Hz),7.85(1H,br),7.74(1H,m),7.51(1H,d,J=1.3Hz),7.34(2H,m),5.12(2H,s),3.88(2H,s),1.63(6H,s),1.61(6H,s)
化合物编号349(MP:129-131).NMR溶剂:DMSO
13C:150.3,138.4,137.5,134.2,131.5,130.9,129.1,126.3,124.8,115.7,58.3,39.1,30.2,25.3,24.7,14.7
1H:8.15(1H,d,J=1.3Hz),8.11(1H,d,J=1.3Hz),8.09(1H,d,J=2.0Hz),7.84(1H,d d,J=2.0,8.4Hz),7.65(1H,d,J=8.4Hz),3.57(1H,t br,J=10.5Hz),3.38(2H,q,J=7.1Hz),1.79(2H,m),1.75(2H,m),1.64(2H,m),1.55(1H,m),1.17(2H,m),1.1(3H,t,J=7.1Hz),1.10(1H,m)
化合物编号350(MP:92-93).NMR溶剂:CDCl3
13C:159.1,151,142,136.4,126.4,125.8,114.1,111.9,58.9,55.3,39.3,31.4,25.6,25.1,14.9
1H:7.87(1H,d,J=1.3Hz),7.73(2H,m d,J=8.8Hz),7.38(1H,d,J=1.3Hz),6.85(2H,m d,J=8.8Hz),3.84(3H,s),3.77(1H,t t,J=3.5,12.0Hz),3.43(2H,t,J=7.1Hz),1.85(4H,m),1.68(2H,m),1.64(1H,m),1.30(2H,m),1.25(3H,t,J=7.1Hz),1.12(1H,m)
化合物编号351(MP:100-101).NMR溶剂:CDCl3
13C:152.0(d,J=246.5Hz),147.8(d,J=11.0Hz),146.4,141.8,136.1,129.4(d,J=3.5Hz),117.4(d,J=7.0Hz),116.2(d,J=18.5Hz),112,110.4(d,J=1.5Hz),81.1,80.3,61.9,56.2,22.8
1H:7.94(1H,d,J=1.3Hz),7.48(1H,d d,J=2.0,8.2Hz),7.47(1H,d,J=1.3Hz),7.23(1H,d d d,J=2.0,4.3,8.3Hz),7.09(1H,d d,J=8.3,11.0Hz),5.13(2H,s),3.96(3H,s),3.89(2H,s),1.61(6H,s)
化合物编号352(MP:113-114).NMR溶剂:CDCl3
13C:146.5,143.1,142.6,136.2,132.8,128.8,127.8,125.2,122.6,112,81.1,80.4,70.9,61.8,45.7,30.7,29.3,22.9
1H:7.97(1H,d,J=,1.3Hz),7.68(1H,t br,J=2.0Hz),7.58(1H,md,J=7.7Hz),7.50(1H,d,J=1.3Hz),7.32(1H,t,J=7.6Hz),7.15(1H,m d,J=7.7Hz),5.13(2H,s),3.89(2H,s),2.75(2H,m),1.84(2H,m),1.62(6H,s),1.30(6H,s)
化合物编号353(MP:192(分解)).NMR溶剂:CDCl3
13C:150.4,137.9,137.5,136.7,136,132.9,125.9,122.7,115.2,58.7,38.5,36.1,34.1,29.6
1H:8.68(1H,s),8.13(1H,d,J=6.3Hz),7.92(1H,d,J=0.9Hz),7.70(1H,d,J=8.1Hz),7.56(1H,d,J=0.9Hz),7.30(1H,d d,J=6.3,8.1Hz),2.98(3H,s),2.18(9H,m),1.72(6H,m)
化合物编号354(MP:217(分解)).NMR溶剂:CDCl3
13C:151,141.1,140.2,137.6,137.6,137.5,135.5,134.4,129.7,125.9,125.8,125.7,124.8,123.7,113.6,58.5,38.6,36.2,34.1,29.6
1H:8.54(1H,t,J=1.5Hz),8.21(1H,d d d,J=1.0,1.6,6.4Hz),8.0(1H,t,J=1.8Hz),7.95(1H,d,J=1.3Hz),7.86(1H,td,J=1.5,7.8Hz),7.56(1H,d d d,J=1.0,1.5,8.0Hz),7.55(1H,d,J=1.3Hz),7.52(1H,t,J=7.8Hz),7.44(1H,d d d,J=1.5,1.8,7.8Hz),7.36(1H,d d,J=6.5,8.0Hz),3.0(3H,s),2.20(9H,s),1.73(6H,s)
化合物编号355(MP:144-147).NMR溶剂:CDCl3
13C:160,149.9,140.6,135.9,132.5,129.9,117.6,114.5,113.5,110.3,59.2,55.5,39.7,31.3,25.5,25,14.9
1H:8.13(1H,br),7.50(1H,m),7.50(1H,d,J=1.3Hz),7.38(1H,m,J=7.7Hz),7.34(1H,t,J=7.8Hz),6.90(1H,d d d,J=1.3,2.6,8.0Hz),3.90(3H,s),3.72(1H,t t,J=3.5,12Hz),3.44(2H,q,J=7.1Hz),1.86(4H,m),1.69(2H,m),1.65(1H,m),1.30(2H,m),1.27(3H,t,J=7.1Hz),1.13(1H,m)
化合物编号356(MP:120-121).NMR溶剂:DMSO
13C:146.3,145.9,141.7,137.5,136.5,126.1,113.2,111.7,110.7,110.6,80.6,79.3,60.8,55.3,22.5
1H:8.07(1H,d,1.3Hz),7.71(1H,d,J=1.3Hz),7.14(1H,d,J=2.0Hz),7.0(1H,d d,J=2.0,8.5Hz),6.79(1H,d,J=8.5Hz),5.16(2H,s),4.72(2H,s),3.83(2H,s),3.77(3H,s),1.49(6H,s)
化合物编号357(MP:176(分解)).NMR溶剂:DMSO
13C:150.8,149.5,137.3,136.7,126.1,122,121,119.7,116.6,114.3,57,31.4,28.9,25,24.8
1H:11.13(1H,s),10.0(3H,br),8.75(1H,s br),8.05(1H,s br),7.81(1H,s br),7.70(1H,d,J=7.7Hz),7.13(1H,d,J=7.7Hz),3.85(1H,m),2.93(3H,s),1.78(4H,m),1.55(3H,m),1.30(2H,m),1.16(1H,m)
化合物编号358(MP:209(分解)).NMR溶剂:DMSO
13C:150.7,145.2,137.8,136.9,126.1,122.8,121,119.6,116.6,113.3,80.6,79.3,61.1,22.4
1H:11.08(1H,s),9.98(3H,s br),8.62(1H,s br),8.04(1H,s br),7.81(1H,d,J=2.0Hz),7.70(1H,d d,J=2.0,8.5Hz),7.11(1H,d,J=8.5Hz),5.18(2H,s),3.85(2H,s),1.50(6H,s)
化合物编号359(MP:97-98).NMR溶剂:CDCl3
13C:145.9,145.6,131.5,131.3,130.3,119.2,115.4,82.4,79.5,62.4,22.9
1H:8.18(1H,d,J=8.8Hz),8.08(1H,d,J=1.4Hz),7.58(1H,d d,J=1.4,8.8Hz),5.53(2H,s),3.90(2H,s),1.68(6H,s)
化合物编号360(MP:138-140).NMR溶剂:CDCl3
13C:163.3(d d,J=10.0,252.0Hz),152.9(d d,J=15.0,262.5Hz),145.3,135.1(d d,J=7.2,16.8Hz),132.7(d,J=19.0Hz),101.7(d d,J=20.0,30.0Hz),97.2(d d,J=5.5,29.5Hz),82.4,79.5,62.5,22.9
1H:7.75(1H,d d d,J=0.9,2.1,8.0Hz),6.97(1H,d t,J=2.1,9.4Hz),5.52(2H,s),3.90(2H,s),1.67(6H,s)
化合物编号361(MP:146-147).NMR溶剂:CDCl3
13C:146.2,144.7,143.1,140.2,133.5,128.9,128.1,127.9,125.7,119.9,112.4,82.5,79.6,62.2,23
1H:8.44(1H,d d,J=1.7,1.6Hz),8.14(1H,d d,J=0.7,8.7Hz),7.74(1H,d d,J=1.6,8.7Hz),7.71(2H,m,J=8.2Hz),7.50(2H,m,J=7.9Hz),7.42(1H,m,J=7.5Hz),5.57(2H,s),3.92(2H,s),1.70(6H,s)
化合物编号362(MP:225(分解)).NMR溶剂:DMSO
13C:150.4,138.3,137.1,135.7,134.7,132.8,126.7,121.2,117,56.8,31.4,29,25.1,24.8
1H:8.70(1H,t,J=1.5Hz),8.28(1H,s),8.20(1H,s),8.11(1H,d,J=6.5Hz),7.78(1H,d,J=8.1Hz),7.45(1H,d d,J=6.5,8.1Hz),3.80(1H,m),2.92(3H,s),1.77(4H,m),1.56(3H,m),1.30(2H,m),1.11(1H,m)
化合物编号363(MP:171).NMR溶剂:CDCl3
13C:161.6,155.2,151.1,141,137,135.5,134.1,130.5,121.8,119.3,118.9,117.9,117,113.9,105.7,57.6,31.3,29.9,25.4,25.2
1H:7.89(1H,d,J=1.3Hz),7.64(1H,t d,J=1.2,7.9Hz),7.60(2H,m d,J=8.9Hz),7.53(1H,t br,J=2.0Hz),7.51(1H,d,J=1.3Hz),7.43(1H,t,J=7.9Hz),7.05(2H,m d,J=8.9Hz),7.0(1H,d d d,J=1.0,2.5,7.9Hz),3.94(1H,m),2.99(3H,s),1.87(2H,m),1.84(2H,m),1.70(1H,d br,J=13.5Hz),1.58(2H,d q,J=3.4,12.3Hz),1.37(2H,tq,J=3.0,12.7Hz),1.12(1H,t q,J=3.2,13.2Hz)
化合物编号364(MP:173).NMR溶剂:CDCl3
13C:161.6,155.3,146.2,141.5,136.2,135.2,134.1,130.5,121.8,119.5,118.9,118,117.1,112.8,105.8,81,80.3,61.9,22.8
1H:7.93(1H,d,J=1.3Hz),7.64(1H,m),7.61(2H,m d,J=9.0Hz),7.53(1H,d,J=1.3Hz),7.52(1H,t br,J=2.0Hz),7.44(1H,t,J=8.0Hz),7.05(2H,m d,J=9.0Hz),7.0(1H,d d d,J=1.0,2.5,8.0Hz),5.11(2H,s),3.88(2H,s),1.61(6H,s)
化合物编号365(MP:154(分解)).NMR溶剂:DMSO
13C:150.6,148.4,139.9,137.4,130,125.9,118.8,114.9,113.4,111.6,56.8,55.8,31.3,29,25.2,24.8
1H:8.19(1H,s br),7.84(1H,s br),7.44(1H,d,J=2.0Hz),7.38(1H,dd,J=2.0,8.6Hz),7.01(1H,d,J=8.6Hz),3.84(3H,s),3.80(1H,br),2.92(3H,s),1.77(4H,m),1.57(3H,m br),1.29(2H,q br,J=13.0Hz),1.11(1H,q bbr,J=13.0Hz)
化合物编号366(MP:135-136).NMR溶剂:CDCl3
13C:156.8,149.5,145.4,125.7,124,123.6,82.4,79.4,62.5,22.9
1H:8.82(1H,d d,J=1.6,4.5Hz),8.60(1H,d d,J=1.6,8.4Hz),7.57(1H,d d,J=4.5,8.4Hz),5.58(2H,s),3.90(2H,s),1.68(6H,s)
化合物编号367(MP:67-68).NMR溶剂:CDCl3
13C:146.1,144,140.4,133.3,127.6,119.1,113.7,82.5,79.6,62.1,23,22
1H:8.02(1H,br),7.95(1H,d,J=8.5Hz),7.29(1H,d d,J=1.0,8.5Hz),5.53(2H,s),3.89(2H,s),2.55(3H,s),1.68(6H,s)
化合物编号368(MP:111-112).NMR溶剂:CDCl3
13C:152.2,145.9,144.3,136.8,129,121,81.9,80,62.1,22.9
1H:8.88(1H,d d,J=1.0,4.4Hz),8.46(1H,d d,J=1.0,8.3Hz),7.48(1H,d d,J=4.4,8.3Hz),5.37(2H,s),3.93(2H,s),1.72(6H,s)
化合物编号369(MP:84-85).NMR溶剂:CDCl3
13C:147.4,145.4,132.6,129.7,125.6,119.8,114.3,81.3,80.5,68.5,65.8,47.7,45.7
1H:8.24(1H,d,J=8.3Hz),8.11(1H,m,J=1.0,8.3Hz),7.63(1H,m,J=1.0,7.2,8.3Hz),7.49(1H,m,J=1.2,7.2,8.3Hz),5.50-5.30(2H,2s),4.20-3.91(4H,2s)
化合物编号370(MP:121-123).NMR溶剂:CDCl3
13C:156.4,146.2,144.4,140.7,133,131.2,129.6,129.5,128.1,120.9,118.7,114.6,111.1,82.5,79.6,62.1,55.6,23
1H:8.33(1H,m),8.09(1H,d d,J=0.7,8.5Hz),7.67(1H,d d,J=1.5,8.5Hz),7.39(1H,d,J=7.6Hz),7.38(1H,m),7.06(1H,d t,J=1.0,7.5Hz),7.02(1H,d,J=8.4Hz),5.54(2H,s),3.90(2H,s),3.83(3H,s),1.68(6H,s)
化合物编号371(MP:134-136).NMR溶剂:CDCl3
13C:145.5,144.6,134.4,128.2(q,J=33.0Hz),126.0(q,J=3.3Hz),123.7(q,J=273.0Hz),117.9(q,J=5.0Hz),115.5,82.5,79.6,62.5,22.9
1H:8.42(1H,m),8.38(1H,d,J=8.8Hz),7.85(1H,d d,J=1.5,8.8Hz),5.55(2H,s),3.92(2H,s),1.69(6H,s)
化合物编号372(MP:157-159).NMR溶剂:CDCl3
13C:162.9,151.6,146.5,135.7,133,97.8,87.1,82.6,79.6,62.1,56.2,56.1,23
1H:7.14(1H,s),6.42(1H,s),5.50(2H,s),4.05(3H,s),3.91(3H,s),3.88(2H,s),1.67(6H,s)
化合物编号373(MP:118-119).NMR溶剂:CDCl3
13C:146.5,145.1,133.1,129.4,125.4,119.8,114.3,96.5,64,49,24.2
1H:8.18(1H,m.J=8.3Hz),8.11(1H,m,J=8.3Hz),7.62(1H,m,J=7.7Hz),7.48(1H,m,J=7.7Hz),4.29(2H,m,J=6.2Hz),4.15(2H,m,J=6.2Hz),1.81(6H,s)
化合物编号374(MP:143-144).NMR溶剂:CDCl3
13C:149.8,144.5,134.9,127.8(q,J=33.0Hz),125.7(q,J=3.3Hz),123.8(q,J=272.5Hz),117.9(q,J=4.5Hz),114.7,58.9,57.2,32.5,30.7,30.2,29.5,25.5,25.3
1H:8.41(1H,m),8.12(1H,d,J=8.8Hz),7.83(1H,d d,J=1.5,8.8Hz),4.28(1H,m),3.19(3H,s),2.0(2H,d,br),1.90(2H,br),1.73(1H,br),1.64(2H,m),1.46(2H,br),1.18(1H,br)
化合物编号375(MP:102-104).NMR溶剂:CDCl3
13C:150.7,144.4,139.6,134.8,132.2,118.8,113,57.6,32.4,29.9,25.5,25.3,20.9,20.4
1H:7.81(1H,s),7.75(1H,s),4.24(1H,m),3.15(3H,s),2.43(3H,s),2.41(3H,s),1.98(2H,d br,J=11.5Hz),1.87(2H,br),1.70(1H,m),1.61(2H,d q,J=3.7,12.5Hz),1.40(2H,br),1.16(1H,m)
化合物编号376(MP:220-221(分解)).NMR溶剂:DMSO
13C:150.6,142.3,139.3,138.1,136.7,126.2,124.9,116.2,56.9,31.4,29,25.2,24.9
1H:8.19(2H,s),8.04(2H,d,J=8.5Hz),7.83(2H,d,J=8.5Hz),7.37(2H,s),3.83(1H,m br),2.95(3H,s),1.80(4H,m),1.60(3H,m),1.31(2H,m),1.14(1H,m)
化合物编号377(MP:93-95).NMR溶剂:CDCl3
13C:162.6,151.6,150.9,136.1,132.9,97.3,86.2,58.9,56.8,56.2,56,32.7,30.8,29.5,25.5,25.3
1H:6.89(1H,d,J=2.0Hz),6.39(1H,d,J=2.0Hz),4.25(1H,m),4.05(3H,s),3.88(3H,s),3.15(3H,s),1.98(2H,d br,J=12.0Hz),1.87(2H,br),1.69(1H,br),1.60(2H,d q,J=3.4,12.2Hz),1.43(2H,br),1.15(1H,m)
化合物编号378(MP:118-119).NMR溶剂:CDCl3
13C:145.4,143.8,139.8,117.1,82.4,79.6,62.3,22.6,21.1
1H:7.61(2H,s),5.41(2H,s),3.88(2H,s),2.40(6H,s),1.67(6H,s)
化合物编号379(MP:175).NMR溶剂:DMSO
13C:150.9,140.6,139.2,137.7,133.4,128.6,128.3,127.4,127.3,127.1,124.7,114.4,75.6,69.1,56.1,31.5,30.8,26.6
1H:8.12(1H,d,J=1.3Hz),8.0(1H,d,J=1.3Hz),7.85(2H,m d,J=8.5Hz),7.39(2H,t,J=7.6Hz),7.35-7.29(4H,m),7.27(1H,m),7.25(1H,m t,J=7.3Hz),4.51(2H,s),3.86(1H,m),3.33(1H,m),2.91(3H,s),2.13(2H,d br,J=11.5Hz),1.81(2H,d br,J=12.5Hz),1.68(2H,dq,J=2.5,12.5Hz),1.30(2H,q br,J=12.5Hz)
化合物编号380(MP:207).NMR溶剂:DMSO
13C:155.1,150.7,139.6,138,136.2,127.4,125.5,122.4,115.9,56.9,31.4,29,25.2,24.8
1H:16.76(1H,br),8.18(2H,m),8.07(4H,m),3.83(1H,m),2.94(3H,s),1.78(4H,m),1.60(1H,m),1.58(2H,m),1.30(2H,q br,J=13.0Hz),1.11(1H,m,J=12.9Hz)
化合物编号381(MP:102-103).NMR溶剂:CDCl3
13C:146.4,144.5,140.1,135.3,131.7,118.9,113.8,82.5,79.6,62.1,23,20.9,20.4
1H:7.99(1H,s),7.82(1H,s),5.53(2H,s),3.89(2H,s),2.44(3H,s),2.42(3H,s),1.68(6H,s)
化合物编号382(MP:112-114).NMR溶剂:CDCl3
13C:152.5,149.2,146.4,139.7,128.4,98.6,94.7,82.6,79.5,62.1,56.6,56.2,23
1H:7.63(1H,s),7.39(1H,s,),5.55(2H,s),4.04(3H,s),4.0(3H,s),3.89(2H,s),1.68(6H,s)
化合物编号383(MP:139).NMR溶剂:CDCl3
13C:151.4,142.2,137,132.8,128.7,127.6,125.1,113.1,69.6,56.4,34.1,31.7,27.4
1H:7.92(1H,d,J=1.3Hz),7.80(2H,m d,J=8.0Hz),7.49(1H,d,J=1.3Hz),7.41(2H,m t,J=7.9Hz),7.30(1H,m t,J=7.5Hz),4.01(1H,m),3.62(1H,m),2.99(3H,s),2.11(2H,d br,J=12.5Hz),1.90(2H,dbr,J=12.5Hz),1.71(2H,d q,J=3.0,12.5Hz),1.46(2H,d q,J=3.5,13.0Hz)
化合物编号384(MP:158-160).NMR溶剂:CDCl3
13C:163.3,151.7,149.2,134.4,133.9,97.6,86.7,69.5,56.3,56.2,56.1,24.3
1H:7.43(1H,s),7.13(1H,d,J=2.0Hz),6.40(1H,d,J=2.0Hz),4.05(3H,s),3.90(3H,s),3.82(2H,d,J=5.5Hz),3.34(1H,t,J=5.5Hz),1.51(6H,s)
化合物编号385(MP:224-226).NMR溶剂:DMSO
13C:167.6,146.1,140.1,137.3,136,132.6,128,124.4,114.7,80.6,79.3,60.9,22.4
1H:8.20(1H,d,J=1.3Hz),8.15(1H,d,J=1.3Hz),7.98(1H,s br),7.91(4H,m),7.36(1H,s br),5.19(2H,s),3.85(2H,s),1.50(6H,s)
化合物编号386(MP:183-185).NMR溶剂:DMSO
13C:157.8,144.5,136.6,136.3,126.9,122.5,115.2,113.8,80.7,79.3,62.5,61.3,54.6,52.6,22.3,22.3,21.3
1H:10.83(1H,s),9.05(1H,s br),8.27(1H,s),7.89(2H,d,J=8.6Hz),7.10(2H,d,J=8.6Hz),5.21(2H,s),4.48(2H,t,J=5.0Hz),3.87(2H,s),3.49(2H,m),3.45(2H,m),2.99(2H,m),1.80(4H,m),1.69(1H,d,J=15.0Hz),1.51(6H,s),1.38(1H,m)
化合物编号387(MP:172-175).NMR溶剂:DMSO
13C:157.9,144.2,136.6,135.7,127,122,115.2,114,80.7,79.3,63.2,62.4,61.3,54.7,51.7,22.3
1H:11.69(1H,s),9.18(1H,s),8.31(1H,s),7.91(2H,d,J=8.6Hz),7.12(2H,d,J=8.6Hz),5.22(2H,s),4.51(2H,t,J=5.0Hz),3.96(2H,d br,J=12.6Hz),3.87(2H,m),3.87(2H,s),3.56(2H,m),3.49(2H,dbr,J=12.4Hz),3.20(2H,m),1.51(6H,s)
化合物编号388(MP:218-220).NMR溶剂:DMSO
13C:157.6,144.6,136.6,136.6,126.8,122.9,115.3,113.7,80.7,79.3,62.4,61.3,54.5,48.5,39.5,22.3
1H:12.18(1H,br),9.89(2H,s),8.98(1H,s),8.24(1H,s),7.88(2H,d,J=8.9Hz),7.11(2H,d,J=8.9Hz),5.20(2H,s),4.48(2H,t,J=5.0Hz),3.86(2H,s),3.64(2H,t,J=5.0Hz),3.75(4H,m),2.50(4H,br),1.50(6H,s)
化合物编号389(MP:216-218).NMR溶剂:DMSO
13C:166.9,145.4,144.6,133.7,131.9,129.1,119,113.9,81.7,78.7,61.7,22.5
1H:8.71(1H,d d,J=0.8,1.3Hz),8.26(1H,s br),8.21(1H,d,J=1.3,8.6Hz),8.16(1H,d d,J=0.8,8.6Hz),7.63(1H,s br),5.43(2H,s),3.90(2H,s),1.58(6H,s)
化合物编号390(MP:245-247).NMR溶剂:DMSO
13C:167.6,150.7,139.8,137.9,136.1,132.5,128,124.3,115.6,56.8,31.3,29,25.1,24.8
1H:8.15(1H,d,J=1.3Hz),8.13(1H,d,J=1.3Hz),7.97(1H,s),7.92(2H,m),7.89(2H,m),7.35(1H,s),3.82(1H,m),2.93(3H,s),1.78(4H,m),1.59(3H,m),1.30(2H,q br,J=12.7Hz),1.11(1H,q br,J=13.0Hz)
化合物编号391(MP:165(分解)).NMR溶剂:CDCl3
13C:155.9,154.1,144.5,137.7,137.1,136.9,129.4,128.9,127.7,124.7,82.5,79.6,62.8,22.6
1H:9.21(1H,d,J=2.2Hz),8.40(1H,d,J=2.2Hz),7.68(2H,d,J=8.2Hz),7.56(2H,t,J=7.8Hz),7.50(1H,t,J=7.3Hz),5.50(2H,s),3.93(2H,s),1.71(6H,s)
化合物编号392(MP:120).NMR溶剂:CDCl3
13C:156.2,149.4,145.6,137.8,136.8,129.3,128.9,127.9,126.1,121,82.5,79.4,62.6,22.9
1H:9.07(1H,d,J=2.2Hz),8.75(1H,d,J=2.2Hz),7.71(2H,d,J=8.2Hz),7.54(2H,t,J=7.6Hz),7.49(1H,t,J=7.4Hz),5.61(2H,s),3.92(2H,s),1.70(6H,s)
化合物编号393(MP:179-180).NMR溶剂:DMSO
13C:158.9,144.2,136.5,135.9,127,121.3,115,113.7,80.7,79.3,71.4,61.3,42.6,33.1,25.1,22.2
1H:9.25(1H,d,J=11.0Hz),9.17(1H,s),8.93(1H,q,J=9.5Hz),8.29(1H,s),7.88(2H,d,J=8.6Hz),7.06(2H,d,J=8.6Hz),5.22(2H,s),3.91(2H,d,J=6.2Hz),3.88(2H,s),3.28(2H,d,J=12.0Hz),2.89(2H,q,J=11.5Hz),2.08(1H,m),1.92(2H,d,J=13.0Hz),1.54(2H,q,J=12.5Hz),1.52(6H,s)
化合物编号394(MP:189-190).NMR溶剂:DMSO
13C:157.9,148.9,137,135.5,127,122,115.2,114.7,62.5,57.2,54.6,52.6,31.5,28.8,25,24.8,22.3,21.2
1H:10.86(1H,br),9.14(1H,s),8.28(1H,s),7.91(2H,d,J=9.0Hz),7.11(2H,d,J=9.0Hz),4.49(2H,t,J=5.2Hz),3.84(1H,m),3.48(2H,m),3.46(2H,m),2.99(2H,m),2.96(3H,s),1.80(8H,m),1.69(1H,m),1.58(3H,m),1.39(1H,m),1.30(2H,m),1.12(1H,m)
化合物编号395(MP:74-76).NMR溶剂:DMSO
13C:158,148.7,136.9,134.8,127.1,121.3,115.3,115,63.2,62.5,57.2,54.7,51.7,31.5,28.8,25,24.8
1H:11.72(1H,br),9.32(1H,s),8.35(1H,s),7.94(2H,d,J=8.6Hz),7.15(2H,d,J=8.6Hz),4.53(2H,t,J=5.0Hz),3.97(2H,d br,J=13.0Hz),3.90(1H,m),3.88(2H,t br,J=11.8Hz),3.57(2H,m),3.50(2H,dbr,J=12.4Hz),3.21(2H,m),2.98(3H,s),1.80(4H,m),1.61(3H,m),1.33(2H,m,J=12.5Hz),1.14(1H,m)
化合物编号396(MP:180-181).NMR溶剂:DMSO
13C:159,144.3,136.5,136,127,121.3,115,113.6,80.7,79.4,65.3,61.4,43,34.7,30.4,28.3,22.3
1H:9.13(1H,d,J=1.3Hz),9.04(1H,m),8.82(1H,m),8.25(1H,d,J=1.3Hz),7.85(2H,d,J=9.0Hz),7.03(2H,d,J=9.0Hz),5.21(2H,s),4.06(2H,t,J=6.1Hz),3.87(2H,s),3.22(2H,d br,J=12.5Hz),2.83(2H,q br,J=11.5Hz),1.85(2H,d br,J=14.0Hz),1.76(1H,m),1.68(2H,m),1.51(6H,s),1.41(2H,d q,J=4.0,13.8Hz)
化合物编号397(MP:205-207).NMR溶剂:DMSO
13C:157.8,148.8,137,135.3,127,121.9,115.3,114.8,62.4,57.2,54.4,48.4,39.7,31.5,28.8,25,24.8
1H:12.35(1H,s br),10.02(2H,s),9.21(1H,s),8.31(1H,s),7.92(2H,d,J=8.6Hz),7.14(2H,d,J=8.6Hz),4.50(2H,t,J=4.8Hz),3.81(1H,m),3.65(2H,t,J=4.8Hz),3.50(8H,s br),2.96(3H,s),1.79(4H,m),1.59(3H,m),1.31(2H,q,J=12.5Hz),1.12(1H,q,J=13.0Hz)
化合物编号398(MP:201(分解)).NMR溶剂:DMSO
13C:156.7,151.2,141,137.3,126.1,124.5,115.3,112.5,66.3,54.1,31.5,29.1
1H:9.46(1H,s),8.06(1H,d,J=1.3Hz),7.79(1H,d,J=1.3Hz),7.64(2H,m d,J=8.8Hz),6.77(2H,m d,J=8.8Hz),4.09(1H,m),3.93(2H,d d,J=4.3,11.1Hz),3.73(2H,t br,J=12.0Hz),2.94(3H,s),1.85(2H,d q,J=4.5,12.2Hz),1.69(2H,m d,J=12.3Hz)
化合物编号399(MP:176-178).NMR溶剂:DMSO
13C:157.9,144.9,137.4,136.9,131.9,130.2,118.2,114.9,114.8,111.1,80.7,79.3,62.5,61.2,54.6,52.6,22.3,22.3,21.2
1H:10.80(1H,s),8.83(1H,s),8.35(1H,s),7.59(1H,br),7.54(1H,dbr,J=7.5Hz),7.39(1H,t,J=7.9Hz),6.96(1H,d d,J=2.0,8.2Hz),5.21(2H,s),4.50(2H,t,J=5.2Hz),3.87(2H,s),3.46(4H,m),3.0(2H,m),1.80(4H,m),1.69(1H,m),1.51(6H,s),1.38(1H,m)
化合物编号400(MP:200-202).NMR溶剂:DMSO
13C:159,148.8,136.9,135.3,127,121,115,114.6,71.4,57.2,42.6,33.1,31.5,28.8,25.1,25,24.8
1H:9.24(1H,m),9.22(1H,s),8.93(1H,m),8.29(1H,s),7.88(2H,d,J=8.9Hz),7.06(2H,d,J=8.9Hz),3.91(2H,d,J=6.3Hz),3.85(1H,m),3.27(2H,d br,J=12.4Hz),2.96(3H,s),2.88(2H,q,J=11.0Hz),2.07(1H,m),1.91(2H,d br,J=13.0Hz),1.79(4H,m),1.58(3H,m),1.55(2H,m),1.31(2H,m,J=13.0Hz),1.12(1H,m,J=13.0Hz)
化合物编号401(MP:160-162).NMR溶剂:DMSO
13C:157.8,145.1,138.1,136.9,132.5,130.1,118.2,114.7,114.6,111.1,80.6,79.3,62.4,61.1,54.4,48.5,25.5,22.3
1H:12.23(1H,s br),9.84(2H,s),8.69(1H,br),8.29(1H,s),7.58(1H,br),7.53(1H,d,J=7.6Hz),7.38(1H,t,J=7.9Hz),6.97(1H,d d,J=1.8,8.0Hz),5.20(2H,s),4.50(2H,m),3.86(2H,s),3.66(2H,m),3.50(8H,br),1.51(6H,s)
化合物编号402(MP:137-140).NMR溶剂:DMSO
13C:157.9,144.6,136.8,136.6,131.1,130.2,118.3,115.2,115.1,111.2,80.7,79.3,63.2,62.5,61.3,54.7,51.7,22.3
1H:11.70(1H,s),9.0(1H,s),8.41(1H,s),7.62(1H,br),7.56(1H,d,J=7.8Hz),7.40(1H,t,J=8.0Hz),7.0(1H,d d,J=2.0,8.2Hz),5.22(2H,s),4.54(2H,t,J=4.7Hz),3.96(2H,d br,J=13.0Hz),3.87(2H,s),3.87(2H,m),3.57(2H,m),3.51(2H,d br,J=13.0Hz),3.22(2H,m),1.51(6H,s)
化合物编号403(MP:204-206).NMR溶剂:DMSO
13C:167.9,150.8,140.1,137.7,134.7,133.5,128.6,127.3,126.1,123.9,114.9,56.8,31.4,29,25.2,24.8
1H:8.35(1H,t,J=1.5Hz),8.15(1H,d,J=1.2Hz),8.06(1H,d,J=1.2Hz),8.03(1H,s br),7.98(1H,d t,J=1.5,7.9Hz),7.75(1H,d t,J=1.5,7.9Hz),7.47(1H,t,J=7.7Hz),7.42(1H,s br),3.83(1H,m),2.94(3H,s),1.78(4H,m),1.58(3H,m),1.29(2H,m),1.11(1H,m)
化合物编号404(MP:198-200).NMR溶剂:CDCl3
13C:150.9,140.3,137.9,137.3,133.3,128.4,125.5,115.2,66.1,57.7,46,31.4,30,25.4,25.2
1H:7.97(2H,d,J=8.5Hz),7.93(1H,d,J=1.3Hz),7.78(2H,d,J=8.5Hz),7.64(1H,d,J=1.3Hz),3.95(1H,m,J=11.5Hz),3.75(4H,m,J=5.0Hz),3.02(4H,m,J=5.0Hz),3.01(3H,s),1.87(4H,m),1.72(1H,m),1.59(2H,d q,J=3.5,12.3Hz),1.38(2H,t q,J=3.3,13.0Hz),1.14(1H,t q,J=3.5,13.2Hz)
化合物编号405(MP:152-154).NMR溶剂:DMSO
13C:159,144.7,137.2,136.8,131.5,130.1,117.6,114.9,114.9,110.9,80.7,79.3,71.4,61.2,42.6,33.2,25.2,22.3
1H:9.14(1H,m),8.89(1H,s),8.85(1H,m),8.34(1H,s),7.52(1H,br),7.49(1H,m),7.35(1H,t,J=7.8Hz),6.91(1H,d d,J=2.0,8.3Hz),5.20(2H,s),3.92(2H,d,J=6.5Hz),3.86(2H,s),3.28(2H,d br,J=12.2Hz),2.89(2H,q br,J=11.5Hz),2.08(1H,m),1.93(2H,d br,J=13.0Hz),1.52(2H,m),1.51(6H,s)
化合物编号406(MP:190-191).NMR溶剂:DMSO
13C:150.8,150.6,140.2,137.7,133.9,131.8,125.6,124.4,114.8,56.8,31.3,29,25.2,24.8
1H:9.64(1H,s),8.12(1H,d,J=1.3Hz),8.04(1H,d,J=1.3Hz),7.84(2H,m d,J=8.5Hz),7.69(2H,m d,J=8.5Hz),5.82(2H,s),3.81(1H,m),2.93(3H,s),1.78(4H,m),1.59(2H,m),1.57(1H,m),1.29(2H,q br,J=12.8Hz),1.11(1H,q br,J=12.9Hz)
化合物编号407(MP:吸湿的).NMR溶剂:DMSO
13C:157.9,149.3,137.4,136.4,131.1,130.3,118.4,116,115.2,111.4,62.6,57.2,54.5,48.5,39.7,31.6,28.9,25.1,24.8
1H:12.09(1H,br),9.87(2H,s),8.97(1H,s),8.37(1H,s),7.62(1H,br),7.55(1H,d,J=8.0Hz),7.41(1H,t,J=8.0Hz),7.01(1H,d d,J=2.0,8.2Hz),4.50(2H,m),3.90(1H,m),3.70(4H,br),3.67(2H,m),3.50(4H,m),2.96(3H,s),1.79(4H,m),1.58(3H,m),1.31(2H,m),1.14(1H,m)
化合物编号408(MP:124-127).NMR溶剂:DMSO
13C:158,148.8,137.3,135.4,130.3,130.2,118.4,116.3,115.5,111.4,63.2,62.6,57.2,54.7,51.7,31.6,28.8,25,24.8
1H:11.80(1H,s),9.21(1H,s br),8.48(1H,s),7.67(1H,br),7.58(1H,d,J=7.5Hz),7.42(1H,t,J=8.0Hz),7.02(1H,d d,J=1.5,8.1Hz),4.55(2H,m),3.96(2H,d br,J=12.5Hz),3.90(1H,m),3.87(2H,t br,J=12.0Hz),3.58(2H,m),3.51(2H,d br,J=12.1Hz),3.22(2H,m),2.97(3H,s),1.79(4H,m),1.59(3H,m),1.32(2H,m),1.12(1H,m)
化合物编号409(MP:183).NMR溶剂:DMSO
13C:164,151.1,140.7,137.8,133.3,132.4,130.6,128.8,128.7,128.7,127.1,124.8,114.4,59.5,53.1,50.8,31.6,25.8
1H:8.13(1H,d,J=1.3Hz),8.0(1H,d,J=1.3Hz),7.85(2H,m d,J=8.5Hz),7.49-7.40(5H,m),7.39(2H,t,J=7.7Hz),7.26(1H,m t,J=7.5Hz),4.05(2H,s),4.05(1H,m),3.26(2H,d br,J=12.0Hz),2.94(3H,s),2.81(2H,t br,J=12.0Hz),2.08(2H,d q,J=3.3,12.7Hz),1.90(2H,d br,J=12.0Hz)
化合物编号410(MP:177-178).NMR溶剂:DMSO
13C:149.6,137.6,136.6,131.4,129.9,129.6,129.5,129,128.8,128.5,125.3,115.6,58.7,52.3,50.2,31.6,24.6
1H:11.36(1H,s br),9.0(1H,s),8.31(1H,s),7.92(2H,m d,J=8.5Hz),7.64(2H,m),7.50-7.43(5H,m),7.37(1H,m t,J=7.7Hz),4.26(2H,d,J=5.0Hz),4.20(1H,m),3.39(2H,d br,J=12.0Hz),3.09(2H,q br,J=12.0Hz),2.97(3H,s),2.43(2H,d q,J=3.3,13.0Hz),1.95(2H,d br,J=13.0Hz)
化合物编号411(MP:191-192).NMR溶剂:DMSO
13C:151.2,140.7,137.8,133.3,131.3,129.7,129,128.7,127.2,124.8,114.4,59.2,52.2,50.7,39.8,31.8,25.2
1H:9.42(1H,s br),8.14(1H,d,J=1.3Hz),8.0(1H,d.J=1.3Hz),7.85(2H,m d,J=8.3Hz),7.50(5H,m),7.39(2H,t,J=8.0Hz),7.26(1H,m t,J=7.3Hz),4.29(1H,m),4.29(2H,s br),3.44(2H,m,J=12.3Hz),3.13(2H,m),2.93(3H,s),2.35(3H,s),2.12(2H,q br,J=13.5Hz),2.0(2H,d br,J=12.5Hz)
化合物编号412(MP:178).NMR溶剂:DMSO
13C:175.7,171.4,151.1,140.7,137.7,135.7,133.4,129.7,128.7,128.5,127.9,127.2,124.8,114.4,72,60.8,54.5,51.7,43.4,31.6,27.2
1H:8.13(1H,s br),8.00(1H,s,br),7.84(2H,d,J=7.9Hz),7.43-7.30(7H,m),7.26(1H,t,J=7.5Hz),3.93(1H,m),3.73(2H,s),3.07(2H,dbr,J=11.0Hz),2.93(3H,s),2.68(2H,d br,J=15.3Hz),2.58(2H,d,J=15.3Hz),2.37(2H,t br,J=12.5Hz),1.92(2H,q br,J=12.5Hz),1.80(2H,d br,J=12.0Hz)
化合物编号413(MP:195).NMR溶剂:DMSO
13C:173.4,151,140.6,137.7,137.3,133.4,129.2,128.6,128.3,127.3,127.1,124.7,114.4,72.1,61.4,55,52,31.5,27.8
1H:8.12(1H,s),8.0(1H,s),7.84(2H,d br,J=7.7Hz),7.38(2H,t,J=7.6Hz),7.35-7.28(5H,m),7.25(1H,m t,J=7.5Hz),4.24(2H,s),3.87(1H,m),3.58(2H,s),2.96(2H,m),2.94(3H,s),2.15(2H,t br,J=11.0Hz),1.87(2H,q br,J=12.3Hz),1.76(2H,d br,J=11.0Hz)
化合物编号414(MP:192).NMR溶剂:DMSO
13C:151,140.6,137.7,136.8,133.4,129.3,128.6,128.4,127.5,127.1,124.8,114.4,61.2,54.9,51.8,31.5,27.6
1H:8.12(1H,d,J=1.3Hz),8.0(1H,d,J=1.3Hz),7.85(2H,m d,J=8.3Hz),7.39(2H,t,J=7.5Hz),7.36-7.27(5H,m),7.23(1H,m t,J=7.4Hz),3.89(1H,m),3.62(2H,s),2.99(2H,d br,J=12.0Hz),2.94(3H,s),2.21(2H,t br,J=12.0Hz),1.91(2H,d q,J=3.3,12.2Hz),1.77(2H,d br,J=11.8Hz)
化合物编号415(MP:175).NMR溶剂:CDCl3
13C:151,140.5,138.3,137.4,137.3,134.5,128.4,128.2,127.6,127.4,125.4,115,71.9,69.8,57.7,43.3,31.4,30.2,30,25.4,25.2
1H:7.95(2H,m,J=8.0Hz),7.93(1H,d,J=1.3Hz),7.78(2H,m,J=8.0Hz),7.62(1H,d,J=1.3Hz),7.34-7.21(5H,m),4.46(2H,s),3.95(1H,m),3.46(1H,m),3.29(2H,m),3.0(3H,s),2.96(2H,m),1.90(2H,m),1.87(4H,m),1.80(2H,m),1.71(1H,d br,J=13.3Hz),1.60(2H,dq,J=3.5,13.5Hz),1.38(2H,t q,J=3.5,13.3Hz),1.14(1H,t q,J=3.5,13.2Hz)
化合物编号416(MP:176-177).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,139.3,138,137.3,132.4,129.1,129,128.3,127.2,123.6,113.9,62.8,55.9,52.5,31.7,28.9
1H:9.0(1H,d d,J=0.7,2.2Hz),8.53(1H,d d,J=1.7,4.9Hz),8.12(1H,d t,J=1.7,7.9Hz),7.94(1H,d,J=1.3Hz),7.58(1H,d,J=1.3Hz),7.35(1H,m),7.34-7.24(5H,m),4.02(1H,m),3.52(2H,s),3.03(3H,s),3.0(2H,m),2.11(2H,t br,J=12.0Hz),1.94(2H,d q,J=3.5,12.0Hz),1.79(2H,d br,J=12.0Hz)
化合物编号417(MP:112-113).NMR溶剂:CDCl3
13C:151.4,148.5,146.6,139.2,137.3,132.4,129,123.6,114,59.4,31.2,28.9,24.3
1H:9.01(1H,d,J=1.7Hz),8.53(1H,d d,J=1.5,4.8Hz),8.12(1H,td,J=2.0,7.9Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.34(1H,d d,J=4.8,7.9Hz),4.44(1H,qt,J=8.2Hz),3.0(3H,s),1.96(2H,m),1.77(2H,m),1.70(2H,m),1.63(2H,m)
化合物编号418(MP:138-140).NMR溶剂:CDCl3
13C:159.9,151.5,142.1,138,136.9,134.3,129.7,129.1,128.3,127.2,117.5,113.7,113.4,110.1,62.8,55.8,55.3,52.5,31.6,28.9
1H:7.92(1H,d,J=1.3Hz),7.49(1H,d,J=1.3Hz),7.40(1H,d d,J=1.4,2.4Hz),7.38-7.24(6H,m),7.31(1H,t,J=7.6Hz),6.86(1H,d dd,J=1.2,2.5,7.9Hz),4.02(1H,m),3.88(3H,s),3.52(2H,s),3.02(3H,s),3.0(2H,m),2.10(2H,t br,J=11.5Hz),1.94(2H,d q,J=3.3,12.0Hz),1.79(2H,d br,J=12.0Hz)
化合物编号419(MP:190-191).NMR溶剂:CDCl3
13C:159.2,151.6,142.1,138,136.8,129.1,128.3,127.2,126.4,125.8,114.1,112,62.8,55.8,55.3,52.5,31.6,28.9
1H:7.90(1H,d,J=1.3Hz),7.73(2H,m d,J=9.0Hz),7.39(1H,d,J=1.3Hz),7.37-7.23(5H,m),6.85(2H,m d,J=9.0Hz),4.03(1H,m),3.84(3H,s),3.52(2H,s),3.02(3H,s),3.0(2H,m),2.10(2H,t br,J=12.0Hz),1.93(2H,d q,J=3.6,12.0Hz),1.78(2H,d br,J=13.0Hz)
化合物编号420(MP:190-191).NMR溶剂:CDCl3
13C:158.4,151.6,142.1,138,136.9,136.8,129.1,128.6,128.3,128,127.5,127.2,126.4,126,115,112.1,70,62.8,55.8,52.5,31.6,28.9
1H:7.89(1H,s),7.72(2H,m d,J=8.6Hz),7.45(2H,d,J=7.5Hz),7.40(2H,m),7.38(1H,s),7.37-7.23(6H,m),7.02(2H,m d,J=8.6Hz),5.10(2H,s),4.01(1H,m),3.52(2H,s),3.01(3H,s),2.99(2H,m),2.09(2H,t br,J=10.7Hz),1.93(2H,q br,J=12.5Hz),1.78(2H,d br,J=12.5Hz)
化合物编号421(MP:165-166).NMR溶剂:CDCl3
13C:150.9,137.6,137.6,136.9,136,132.8,125.9,122.6,115.3,59.4,31.2,28.9,24.3
1H:8.67(1H,t br,J=1.5Hz),8.13(1H,d d d,J=1.7,6.5Hz),7.98(1H,d,J=1.3Hz),7.71(1H,t d,J=1.2,8.0Hz),7.59(1H,d,J=1.3Hz),7.31(1H,d d,J=6.5,8.0Hz),4.40(1H,qt,J=8.0Hz),3.0(3H,s),1.95(2H,m),1.77(2H,m),1.69(2H,m),1.63(2H,m)
化合物编号422(MP:197).NMR溶剂:DMSO
13C:150.6,139.0,138.8,138.4,138.2,127.5,125.2,116.8,56.8,43.6,31.3,29.0,25.1,24.8
1H:8.26(1H,s),8.20(1H,s),8.11(2H,d,J=8.5Hz),7.93(2H,d,J=8.5Hz),3.81(1H,m),3.22(3H,s),2.93(3H,s),1.78(4H,m),1.58(3H,m),1.30(2H,q br,J=12.7Hz),1.12(1H,m)
化合物编号423(MP:179).NMR溶剂:DMSO
13C:164.1,150.9,140.1,138.5,137.8,133.6,133.5,128.8,128.7,128.2,127,127,125.4,123.2,114.9,61.9,55.5,52.2,31.5,28.2
1H:11.20(1H,br),9.15(1H,br),8.23(1H,br),8.15(1H,d,J=1.3Hz),8.05(1H,d,J=1.3Hz),7.95(1H,m d,J=7.8Hz),7.62(1H,d,J=7.8Hz),7.45(1H,t,J=7.7Hz),7.36-7.21(5H,m),3.83(1H,m),3.47(2H,s),2.95(3H,s),2.90(2H,d br,J=11.2Hz),2.0(2H,t br,J=11.0Hz),1.83(2H,d q,J=3.3,11.9Hz),1.73(2H,d br,J=12.3Hz)
化合物编号424(MP:176).NMR溶剂:DMSO
13C:163.8,149.2,137.8,136.1,133.6,130,129.2,127.8,126.6,124,116.1,57.1,31.5,28.8,25.1,24.8
1H:11.31(1H,br),9.0(1H,s),8.37(1H,s),8.27(1H,t br,J=1.5Hz),8.0(1H,t d,J=1.5,7.7Hz),7.73(1H,t d,J=1.4,7.8Hz),7.56(1H,t,J=7.7Hz),3.86(1H,m),2.98(3H,s),1.81(4H,m),1.60(3H,m),1.32(2H,q br,J=12.8Hz),1.13(1H,q br,J=13.0Hz)
化合物编号425(MP:140-142).NMR溶剂:CDCl3
13C:151.1,144.6,140.2,137.2,137,133.6,132.1,129,127.8,127.1,122.9,121.2,114.7,112.5,57.6,47.2,31.5,30,25.4,25.2
1H:8.61(1H,d,J=2.2Hz),8.50(1H,t,J=5.7Hz),7.90(1H,d,J=1.3Hz),7.89(1H,d d,J=2.2,9.0Hz),7.43(1H,d,J=1.3Hz),7.42-7.29(5H,m),6.89(1H,d,J=9.0Hz),4.61(2H,d,J=5.7Hz),3.96(1H,m),3.0(3H,s),1.87(4H,m),1.71(1H,d br,J=13.0Hz),1.60(2H,m),1.39(2H,q br,J=13.0Hz),1.13(1H,m,J=3.5,13.2Hz)
化合物编号426(MP:261).NMR溶剂:CDCl3
13C:155.4,151.1,141.6,137.1,136.2,130,128.8,128.4,127.7,127.3,126.8,118.5,112.6,108.6,106.4,57.6,44.5,31.5,29.9,25.4,25.2
1H:9.87(1H,s),8.17(1H,d,J=1.3Hz),7.74(1H,d,J=1.4Hz),7.45(1H,d,J=1.3Hz),7.39(1H,d d,J=1.4,8.2Hz),7.36-7.25(5H,m),6.87(1H,d,J=8.2Hz),5.10(2H,s),3.97(1H,m),3.02(3H,s),1.87(4H,m),1.70(1H,m),1.58(2H,q br,J=13.0Hz),1.38(2H,q br,J=13.0Hz),1.13(1H,q br,J=12.8Hz)
化合物编号427(MP:204-205).NMR溶剂:CDCl3
13C:150.6(d d,J=13.0,247.5Hz),151.2,149.8(d d,J=12.0,248.0Hz),140.4,138,137,130.2(d d,J=4.0,6.5Hz),129.1,128.3,127.2,121.0(d d,J=3.5,6.2Hz),117.5(d,J=17.5Hz),114.2(d,J=19.0Hz),113.5,62.8,55.9,52.5,31.7,28.9
1H:7.89(1H,d,J=1.3Hz),7.61(1H,d d d,J=2.2,7.2,11.5Hz),7.50(1H,m),7.46(1H,d,J=1.3Hz),7.37-7.25(5H,m),7.18(1H,d t,J=8.4,10.2Hz),4.02(1H,m),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.11(2H,t br,J=12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.78(2H,dbr,J=12.0Hz)
化合物编号428(MP:222-223).NMR溶剂:CDCl3
13C:151.3,141.2,138,137,133.1,131.5,129.1,128.8,128.3,127.2,126.4,113.4,62.8,55.8,52.5,31.6,28.9
1H:7.91(1H,d,J=1.3Hz),7.49(1H,d,J=1.3Hz),7.73(2H,m d,J=8.5Hz),7.37(2H,m d,J=8.5Hz),7.35-7.25(5H,m),4.02(1H,m),3.52(2H,s),3.02(3H,s),3.0(2H,m),2.10(2H,t br,J=11.5Hz),1.93(2H,J=3.5,12.0Hz),1.78(2H,d br,J=12.0Hz)
化合物编号429(MP:203-204).NMR溶剂:CDCl3
13C:151.4,150.5,141.2,138,137,130.4,129.1,128.3,127.2,126.6,119.7,115.9,113.2,62.8,55.9,52.5,31.6,28.9
1H:7.91(1H,d,J=1.3Hz),7.79(2H,m d,J=8.8Hz),7.47(1H,d,J=1.3Hz),7.37-7.25(5H,m),7.16(2H,m d,J=8.8Hz),6.54(1H,t,J=74.0Hz),4.03(1H,m),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.11(2H,t br,J=12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.79(2H,d br,J=12.5Hz)
化合物编号430(MP:211-212).NMR溶剂:CDCl3
13C:162.3(d,J=247.0Hz),151.4,141.4,138,136.9,129.2(d,J=3.5Hz),129.1,128.3,127.2,126.8(d,J=8.0Hz),115.6(d,J=21.5Hz),112.9,62.8,55.8,52.5,31.6,28.9
1H:7.90(1H,d,J=1.3Hz),7.76(2H,m,J=5.3,8.8Hz),7.45(1H,d,J=1.3Hz),7.37-7.25(5H,m),7.10(2H,m t,J=8.9Hz),4.03(1H,m),3.52(2H,s),3.02(3H,s),3.0(2H,m),2.10(2H,t br,J=12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.78(2H,d br,J=10.5Hz)
化合物编号431(MP:190-191).NMR溶剂:CDCl3
13C:159.3,151.2,148.5,146.7,139.2,137.2,132.4,129,128.7,123.6,114,113.7,103.8,56.2,55.8,52.1,48.9,31.5,29.1
1H:9.0(1H,d,J=1.8Hz),8.53(1H,d d,J=1.5,4.8Hz),8.11(1H,td,J=1.8,7.9Hz),7.92(1H,d,J=1.0Hz),7.57(1H,d,J=1.0Hz),7.34(1H,d d,J=4.8,7.9Hz),7.22(1H,t,J=8.3Hz),6.57(2H,d,J=8.3Hz),3.91(1H,m),3.81(6H,s),3.71(2H,s),3.09(2H,d br,J=12.0Hz),3.0(3H,s),2.20(2H,t br,J=11.6Hz),1.94(2H,d q,J=3.2,12.0Hz),1.72(2H,d br,J=12.0Hz)
化合物编号432(MP:190(分解)).NMR溶剂:DMSO
13C:150.4,139.1,137.9,137.7,133.4,127.8,125,116.3,63.8,56.7,43.1,32.8,31.2,29,25.1,24.8
1H:8.24(1H,d,J=1.3Hz),8.19(1H,d,J=1.3Hz),8.09(2H,m d,J=8.5Hz),7.73(2H,m d,J=8.5Hz),4.68(1H,d,J=4.0Hz),3.81(1H,m br),3.51(1H,m),3.16(2H,m),2.93(3H,s),2.71(2H,m),1.78(4H,m),1.73(2H,m),1.58(3H,m),1.42(2H,m),1.30(2H,q br,J=12.8Hz),1.12(1H,q br,J=12.5Hz)
化合物编号433(MP:161-162).NMR溶剂:CDCl3
13C:151.6,149.1,148.6,142.1,138,136.7,129.1,128.3,127.2,126.1,117.4,112.3,111.3,108.4,62.8,55.9,55.9,55.8,52.5,31.6,28.9
1H:7.90(1H,d,J=1.3Hz),7.42(1H,d,J=1.3Hz),7.40(1H,d,J=1.9Hz),7.37-7.24(5H,m),7.30(1H,d d,J=1.9,8.3Hz),6.91(1H,d,J=8.3Hz),4.03(1H,m),3.97(3H,s),3.92(3H,s),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.11(2H,t br,J=11.5Hz),1.94(2H,d q,J=3.2,11.8Hz),1.79(2H,d br,J=11.8Hz)
化合物编号434(MP:126-128).NMR溶剂:CDCl3
13C:150.7,142.2,136.8,133,128.7,127.5,125.1,113.1,56.2,42.2,35.3,31,25.9,25.4,24.4,23.7,19.9
1H:7.88(1H,s),7.81(2H,d,J=7.8Hz),7.46(1H,s),7.41(2H,t,J=7.7Hz),7.30(1H,t,J=7.4Hz),4.19(1H,s br),3.91(1H,s br),3.14(1H,t,J=12.7Hz),2.10-1.20(13H,m)
化合物编号435(MP:127-128).NMR溶剂:CDCl3
13C:151.2,145.3,140.4,139.1,137,130,123.4,123.2,118.3,112.6,57.5,42.5,31.4,29.9,25.4,25.2
1H:8.18(1H,d,J=2.2Hz),7.89(1H,d,J=1.3Hz),7.85(1H,d d,J=2.2,8.8Hz),7.43(1H,d,J=1.3Hz),7.06(1H,d,J=8.8Hz),3.95(1H,m),3.0(3H,s),2.93(6H,s),1.88(2H,m),1.85(2H,m),1.70(1H,dbr,J=13.0Hz),1.58(2H,d q,J=3.4,12.2Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13.2Hz)
化合物编号436(MP:215-217).NMR溶剂:DMSO
13C:166.6,145.3,144.6,134.6,130,128.6,121.5,114.3,81.7,78.7,61.7,22.5
1H:13.38(1H,br),8.70(1H,s),8.24(1H,d,J=9.0Hz),8.19(1H,d,J=9.0Hz),5.43(2H,s),3.90(2H,s),1.58(6H,s)
化合物编号437(MP:181).NMR溶剂:DMSO
13C:163.6,144.4,144.3,142.8,135.9,132.7,129.1,128.4,128.4,127.3,119.5,118.7,81.6,78.7,77.1,61.8,22.2
1H:12.06(1H,br),8.39(1H,s),8.11(1H,d,J=9.0Hz),7.87(1H,d,J=9.0Hz),7.49(2H,d,J=7.0Hz),7.41(3H,m),5.29(2H,s),4.98(2H,s),3.92(2H,s),1.57(6H,s)
化合物编号438(MP:194).NMR溶剂:DMSO
13C:155.6,151.2,150.8,139.6,137.7,129.3,126.7,125.6,114,112.5,112.4,56.8,56,31.4,29,25.2,24.9
1H:16.04(1H,br),8.58(1H,d,J=2.2Hz),8.13(1H,d,J=1.3Hz),8.05(1H,d,J=1.3Hz),8.04(1H,d d,J=2.2,8.9Hz),7.31(1H,d,J=8.9Hz),3.99(3H,s),3.82(1H,m),2.94(3H,s),1.78(4H,m),1.58(3H,m),1.30(2H,q,J=12.5Hz),1.11(1H,q,J=13.0Hz)
化合物编号439(MP:226-228(分解)).NMR溶剂:DMSO
13C:154.5,151.9,150.9,139.9,137.6,129.1,125.4,125.2,116.7,113.4,110.8,56.8,31.3,29,25.2,24.9
1H:16.0(1H,br),11.14(1H,br),8.48(1H,d,J=2.2Hz),8.12(1H,d,J=1.3Hz),7.95(1H,s br),7.87(1H,d d,J=2.2,8.5Hz),7.09(1H,d,J=8.5Hz),3.82(1H,m),2.94(3H,s),1.78(4H,m),1.57(3H,m),1.30(2H,q,J=12.5Hz),1.11(1H,q,J=13.0Hz)
化合物编号440(MP:104-105).NMR溶剂:DMSO
13C:163.3,144.4,144.2,142.9,133.2,127.4,119.3,118.1,81.6,78.7,61.8,22.2
1H:11.56(1H,br),9.27(1H,s br),8.39(1H,s),8.10(1H,d,J=9.1Hz),7.89(1H,d,J=9.1Hz),5.29(2H,s),3.92(2H,s),1.57(6H,s)
化合物编号441(MP:169-170).NMR溶剂:CDCl3
13C:152.2,151.2,139.9,139.6,138,137.2,130.7,129.1,128.3,127.2,126,122.3,113.8,113.3,62.8,56.6,55.9,52.5,31.7,28.8
1H:8.24(1H,d,J=2.2Hz),8.0(1H,d d,J=2.2,8.8Hz),7.91(1H,d,J=1.3Hz),7.49(1H,d,J=1.3Hz),7.37-7.25(5H,m),7.13(1H,d,J=8.8Hz),4.03(1H,m),4.0(3H,s),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.11(2H,t br,J=11.5Hz),1.93(2H,d q,J=3.5,12.0Hz),1.79(2H,dbr,J=12.0Hz)
化合物编号442(MP:162).NMR溶剂:CDCl3
13C:151.9(d,J=246.0Hz),151.4,147.8(d,J=11.2Hz),141.5,138,136.8,129.6(d,J=4.0Hz),129.1,128.3,127.2,117.3(d,J=7.0Hz),116.2(d,J=18.5Hz),113.1,110.4(d,J=1.7Hz),62.8,56.2,55.9,52.5,31.7,28.9
1H:7.90(1H,d,J=1.3Hz),7.50(1H,d d,J=1.8,8.3Hz),7.46(1H,d,J=1.3Hz),7.37-7.27(5H,m),7.24(1H,m),7.09(1H,d d,J=8.5,11.0Hz),4.03(1H,m),3.97(3H,s),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.10(2H,t br,J=11.8Hz),1.94(2H,d q,J=3.0,12.0Hz),1.79(2H,d br,J=11.5Hz)
化合物编号443(MP:188-189).NMR溶剂:CDCl3
13C:152.5(d,J=245.0Hz),151.4,147.1(d,J=11.0Hz),141.1(d,J=2.5Hz),138,136.9,129.1,128.3,127.2,126.5(d,J=7.2Hz),120.9(d,J=3.5Hz),113.5(d,J=2.5Hz),113.1(d,J=19.7Hz),112.6,62.8,56.3,55.8,52.5,31.6,28.9
1H:7.89(1H,d,J=1.3Hz),7.53(1H,m),7.50(1H,d d,J=2.5,8.5Hz),7.40(1H,d,J=1.3Hz),7.37-7.23(5H,m),6.99(1H,t,J=8.4Hz),4.02(1H,m),3.92(3H,s),3.52(2H,s),3.02(3H,s),3.0(2H,m),2.10(2H,t br,J=11.8Hz),1.93(2H,d q,J=3.5,12.0Hz),1.78(2H,m)
化合物编号444(MP:168).NMR溶剂:DMSO
13C:157.6,153.8,151.1,140.6,137.5,137.1,128.5,127.9,127.8,126.3,126.1,114.9,113.2,78.8,69.2,55.1,43,42.2,31.7,28.1(2sig.)
1H:8.09(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.77(2H,m d,J=8.7Hz),7.46(2H,d,J=8.4Hz),7.40(2H,t,J=7.4Hz),7.33(1H,t,J=7.3Hz),7.03(2H,m d,J=8.7Hz),5.12(2H,s),4.03(3H,m),2.92(3H,s),2.79(2H,br),1.76(2H,d br,J=11.5Hz),1.66(2H,d q,J=4.3,12.1Hz),1.41(9H,s)
化合物编号445(MP:170-171).NMR溶剂:CDCl3
13C:160.4,151.1,140,137.1,131.1,130.3,126.5,116.3,113,111.6,102,57.6,56.2,31.4,30,25.4,25.2
1H:7.98(1H,d d,J=2.2,8.5Hz),7.97(1H,d,J=2.2Hz),7.89(1H,d,J=1.3Hz),7.44(1H,d,J=1.3Hz),7.02(1H,d,J=8.5Hz),3.96(3H,s),3.95(1H,m),3.0(3H,s),1.87(4H,m),1.71(1H,m),1.58(2H,dq,J=3.5,12.5Hz),1.38(2H,t q,J=3.0,13.0Hz),1.13(1H,t q,J=3.5,13Hz)
化合物编号446(MP:176-177).NMR溶剂:CDCl3
13C:160.5,151.2,140.1,138,137.1,131.1,130.3,129.1,128.3,127.2,126.4,116.3,112.9,111.6,102,62.8,56.2,55.9,52.5,31.7,28.9
1H:7.98(1H,d d,J=2.2,8.5Hz),7.97(1H,d,J=2.2Hz),7.90(1H,d,J=1.3Hz),7.44(1H,d,J=1.3Hz),7.37-7.23(5H,m),7.01(1H,d,J=8.5Hz),4.01(1H,m),3.96(3H,s),3.53(2H,s),3.03(3H,s),3.01(2H,m),2.10(2H,t br,J=12.0Hz),1.94(2H,d q,J=3.5,12.0Hz),1.79(2H,d br,J=12.0Hz)
化合物编号447(MP:103-105).NMR溶剂:CDCl3
13C:151.5,142.3,141.4,140.3,136.8,128.9,119.4,115.4,112.4,112,57.5,43.6,31.3,30,25.4,25.2
1H:7.89(1H,d,J=1.3Hz),7.38(1H,d,J=1.3Hz),7.22(1H,d,J=2.2Hz),7.15(1H,d d,J=2.2,8.1Hz),7.03(1H,d,J=8.1Hz),4.03(2H,br),3.94(1H,m),2.99(3H,s),2.69(6H,s),1.85(4H,m),1.70(1H,d br,J=14.0Hz),1.58(2H,d q,J=3.5,12.5Hz),1.37(2H,m q,J=13.0Hz),1.13(1H,m q,J=13.0Hz)
化合物编号448(MP:180-182).NMR溶剂:CDCl3
13C:155.1,150.2,137.9,137.6,137.5,136.2,132.5,126,122.7,115,62.1,46.4,43.3,14.6
1H:8.68(1H,s br),8.15(1H,d,J=6.3Hz),7.94(1H,d,J=1.3Hz),7.71(1H,d,J=8.0Hz),7.57(1H,d,J=1.3Hz),7.33(1H,d d,J=6.3,8.0Hz),4.20(2H,q.J=7.2Hz),3.64(8H,m),1.30(3H,t,J=7.2Hz)
化合物编号449(MP:110-112).NMR溶剂:CDCl3
13C:150.8,137.6,137.6,136.9,136,132.7,125.9,122.7,115.3,50.6,36.4,29.3,19.8,13.7
1H:8.67(1H,t,J=1.5Hz),8.14(1H,d d d,J=1.0,1.6,6.4Hz),7.94(1H,d,J=1.3Hz),7.71(1H,t d,J=1.3,8.1Hz),7.58(1H,d,J=1.3Hz),7.32(1H,d d,J=6.4,8.1Hz),3.46(2H,t,J=7.6Hz),3.13(3H,s),1.68(2H,m),1.37(2H,m),0.97(3H,t,J=7.4Hz)
化合物编号450(MP:122-123).NMR溶剂:DMSO
13C:151.1,145.9,141.4,137.6,137.2,126.2,113.2,112.6,110.7,110.6,55.7,55.4,45.4,31.4,29.5
1H:8.03(1H,s),7.68(1H,s),7.14(1H,d,J=1.8Hz),7.0(1H,d d,J=1.8,8.2Hz),6.79(1H,d,J=8.2Hz),4.73(2H,s br),3.88(1H,m),3.76(3H,s),3.01(2H,d br,J=12.0Hz),2.93(3H,s),2.47(2H,m),1.67(4H,m)
化合物编号451(MP:170-172).NMR溶剂:DMSO
13C:157.6,150.2,138.3,137.3,131.4,129.7,129.7,129,126.7,121.6,115.7,113.3,59.1,52.3,50.6,31.9,25
1H:9.62(2H,m br),8.67(1H,s),8.0(1H,s),7.65(2H,d,J=8.2Hz),7.55(2H,m),7.49(3H,m),6.82(2H,d,J=8.2Hz),4.32(2H,m),4.18(1H,m),3.45(2H,m),3.16(2H,m),2.94(3H,s),2.19(2H,q br,J=12.0Hz),2.0(2H,d br,J=12.0Hz)
化合物编号452(MP:74-76).NMR溶剂:CDCl3
13C:150.3,137.6,137.3,136.9,136,132.7,125.9,122.8,115.1,42.8,13.2
1H:8.67(1H,t br,J=1.3Hz),8.14(1H,d,J=6.4Hz),7.93(1H,d,J=1.3Hz),7.72(1H,d,J=8.0Hz),7.57(1H,d,J=1.3Hz),7.32(1H,dd,J=6.4,8.0Hz),3.49(4H,q,J=7.2Hz),1.31(6H,t,J=7.2Hz)
化合物编号453(MP:130-132).NMR溶剂:DMSO
13C:149.6,147.8,145.7,142.8,138.2,137.1,132.2,129.9,129,127.7,126.3,124,115.6,39.6
1H:8.87(1H,d d,J=0.8,2.2Hz),8.43(1H,d d,J=1.7,4.9Hz),8.04(1H,t d,J=1.9,8.0Hz),7.81(1H,d,J=1.3Hz),7.61(1H,d,J=1.3Hz),7.45-7.28(6H,m),3.43(3H,s)
化合物编号454(MP:170-172).NMR溶剂:DMSO
13C:151.2(d,J=240.0Hz),151.1,144.0(d,J=12.2Hz),140.0(d,J=2.5Hz),137.6,131.4,129.7(2sig.),128.9,125.2(d,J=7.0Hz),121.1(d,J=2.5Hz),117.9(d,J=3.0Hz),113.5,112.5(d,J=20.0Hz),59.0,52.1,50.6,31.7,25.1
1H:9.91(1H,s),9.57(1H,m),8.10(1H,s),7.90(1H,s),7.58(1H,m),7.55(2H,m),7.48(4H,m),6.96(1H,t,J=8.8Hz),4.31(2H,s br),4.16(1H,m),3.45(2H,m),3.15(2H,m),2.92(3H,s),2.17(2H,q,J=12.5Hz),1.98(2H,d br,J=12.5Hz)
化合物编号455(MP:171-173).NMR溶剂:CDCl3
13C:145.8,137.7,137.2,136.8,136.1,132.6,126,122.7,114.3,81,80.3,62.1,22.8
1H:8.69(1H,t br,J=1.5Hz),8.14(1H,d d d,J=1.0,1.5,6.4Hz),7.96(1H,d,J=1.3Hz),7.70(1H,t d,J=1.2,8.2Hz),7.63(1H,d,J=1.3Hz),7.31(1H,d d,J=6.4,8.2Hz),5.12(2H,s),3.90(2H,d),1.62(6H,s)
化合物编号456(MP:181-182).NMR溶剂:DMSO
13C:149.4,142.6,138.3,137.1,135.2,134.6,132.4,129.9,127.7,126.6,126.2,121.1,117.1,39.6
1H:8.50(1H,t br,J=1.5Hz),8.08(1H,d d d,J=1.0,1.8,6.4Hz),7.96(1H,d,J=1.3Hz),7.61(1H,d,J=1.3Hz),7.60(1H,m),7.38(1H,m),7.50-7.29(5H,m),3.43(3H,s)
化合物编号457(MP:179(分解)).NMR溶剂:DMSO
13C:151.4,150.6,137.9,137.7,137,131.7,131.4,129.7,129.1,128.9,123.9,121,119.6,114.7,59,52.2,50.5,31.9,25
1H:11.13(1H,s br),9.59(1H,s),8.39(1H,s),8.33(1H,d,J=2.0Hz),8.14(1H,s),8.02(1H,d d,J=2.0,8.6Hz),7.55(2H,m),7.49(3H,m),7.19(1H,d,J=8.6Hz),4.32(2H,d,J=4.9Hz),4.18(1H,m),3.46(2H,d br,J=11.5Hz),3.16(2H,m),2.93(3H,s),2.18(2H,q br,J=12.5Hz),1.99(2H,d br,J=12.3Hz)
化合物编号458(MP:163-164).NMR溶剂:DMSO
13C:148.1,147.7,146.1,138.3,136.8,131.9,129.1,123.9,113.6,50,32.2,25.1,24.8
1H:9.02(1H,d d,J=0.8,2.2Hz),8.46(1H,d d,J=1.7,4.7Hz),8.38(1H,d,J=1.3Hz),8.33(1H,d br,J=7.3Hz),8.30(1H,d,J=1.3Hz),8.15(1H,t d,J=1.9,7.9Hz),7.42(1H,d d d,J=0.8,4.7,7.9Hz),3.63(1H,m),1.90(2H,m),1.75(2H,m),1.61(1H,d br,J=12.7Hz),1.32(4H,m),1.14(1H,m)
化合物编号459(MP:199-201).NMR溶剂:CDCl3
13C:150.8,137.9,137.6,137.6,136.9,136,132.7,129.1,128.3,127.2,125.9,122.6,115.3,62.8,56,52.4,31.7,28.9
1H:8.66(1H,s br),8.13(1H,d,J=6.3Hz),7.93(1H,s br),7.70(1H,d,J=8.1Hz),7.58(1H,s br),7.30(6H,m),3.99(1H,m),3.52(2H,s),3.02(3H,s),3.01(2H,m),2.10(2H,t br,J=10.9Hz),1.93(2H,m),1.78(2H,d br,J=10.9Hz)
化合物编号460(MP:148).NMR溶剂:CDCl3
13C:165.8,147.2,145.6,132.6,131.5,126.5,119.6,116.6,82.4,79.6,62.4,61.7,23,14.3
1H:8.91(1H,d d,J=0.8,1.4Hz),8.17(1H,d d,J=1.4,8.7Hz),8.12(1H,d d,J=0.8,8.7Hz),5.53(2H,s),4.45(2H,q,J=7.2Hz),3.91(2H,s),1.70(6H,s),1.44(3H,t,J=7.2Hz)
化合物编号461(MP:186).NMR溶剂:MeOD
13C:149.5,138.8,138.8,137.7,136.9,135,128.4,127.1,116.7,52.2,33.8,26.7,26.5
1H:8.75(1H,br),8.36(1H,d,J=1.2Hz),8.25(1H,m),8.24(1H,m),7.98(1H,d,J=8.2Hz),7.58(1H,d d,J=6.6,8.2Hz),3.73(1H,m),2.02(2H,m),1.87(2H,m),1.70(1H,d br,J=13.5Hz),1.45(2H,m),1.38(2H,m),1.24(1H,m)
化合物编号462(MP:125(分解)).NMR溶剂:DMSO
13C:167.1,145.8,145.4,135.3,132.2,124.9,119.4,113.9,81.7,78.7,61.6,22.5
1H:8.63(1H,s),8.34(1H,s br),8.25(1H,d,J=8.5Hz),8.01(1H,dd,J=1.5,8.7Hz),7.65(1H,s br),5.43(2H,s),3.91(2H,s),1.60(6H,s)
化合物编号463(MP:181-183).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,139.4,137.3,132.5,128.9,123.6,113.9,66.9,54.5,31.8,29.5
1H:9.00(1H,d d,J=1.0,2.2Hz),8.53(1H,d d,J=1.7,4.8Hz),8.11(1H,d d d,J=1.8,2.3,7.9Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.34(1H,d d d,J=1.0,4.8,7.9Hz),4.29(1H,m),4.09(2H,d d,J=4.6,11.5Hz),3.50(2H,d t,J=2.2,12.0Hz),3.04(3H,s),1.95(2H,m),1.78(2H,m)
化合物编号464(MP:143-144).NMR溶剂:CDCl3
13C:150.6,148.5,146.7,139.3,136.9,132.4,129.1,123.6,113.8,59,39.5,31.4,25.6,25.1,14.9
1H:9.01(1H,d,J=2.3Hz),8.53(1H,d d,J=1.7,4.8Hz),8.12(1H,td,J=2.0,8.0Hz),7.91(1H,d,J=1.3Hz),7.56(1H,d,J=1.3Hz),7.34(1H,d d d,J=0.8,4.8,8.0Hz),3.75(1H,m),3.44(2H,q,J=7.0Hz),1.84(4H,m),1.66(3H,m),1.30(2H,m,J=13.0Hz),1.26(3H,t,J=7.0Hz),1.13(1H,m,J=13.0Hz)
化合物编号465(MP:184-185).NMR溶剂:MeOD
13C:151.9,147.7,147.1,140.6,138.4,132.6,131.6,130.6,130.4,123,118.8,116.9,114.7,114.1,61.8,54.7,52.8,33.5,26.8
1H:8.64(1H,s br),7.82(1H,s br),7.58(2H,m),7.52(3H,m),7.18(1H,d,J=2.0Hz),7.11(1H,d d,J=2.0,8.3Hz),6.83(1H,d,J=8.3Hz),4.36(2H,s),4.28(1H,m),3.63(2H,d br,J=12.5Hz),3.24(2H,m,J=12.5Hz),3.06(3H,s),2.30(2H,m,J=13.0Hz),2.17(2H,d br,J=13.0Hz)
化合物编号466(MP:221-222).NMR溶剂:DMSO
13C:151.7(d,J=242.5Hz),151.0,146.2(d,J=10.8Hz),139.6(d,J=2.5Hz),137.7,126.7(d,J=7.5Hz),120.9(d,J=3.5Hz),114.1(2sig.),112.3(d,J=19.7Hz),66.3,56.0,54.2,31.6,29.1
1H:8.11(1H,d,J=1.3Hz),7.98(1H,d,J=1.3Hz),7.66(1H,m),7.63(1H,m),7.19(1H,t,J=8.7Hz),4.09(1H,m),3.93(2H,d d,J=4.5,12.3Hz),3.85(3H,s),3.38(2H,m),2.94(3H,s),1.85(2H,d q,J=4.5,12.3Hz),1.69(2H,d br,J=12.3Hz)
化合物编号467(MP:177).NMR溶剂:CDCl3
13C:151.5,142.3,140,137,132.9,128.7,128.6,128.4,127.6,126.1,125.1,113.1,60.2,55.7,52.6,33.8,31.6,28.9
1H:7.93(1H,d,J=1.3Hz),7.81(2H,m d,J=8.2Hz),7.51(1H,d,J=1.3Hz),7.41(2H,t,J=7.9Hz),7.30(3H,t,J=7.4Hz),7.22(1H,m),7.21(2H,d,J=7.4Hz),4.06(1H,m),3.13(2H,d br,J=11.8Hz),3.04(3H,s),2.82(2H,m),2.63(2H,m),2.17(2H,d t,J=2.4,12.0Hz),1.96(2H,d q,J=3.6,12.1Hz),1.85(2H,d br,J=12.0Hz)
化合物编号468(MP:186-187).NMR溶剂:DMSO
13C:151.2,145.9,141.4,137.5,137.2,126.2,113.2,112.6,110.7,110.6,66.3,55.3,54.1,31.6,29.1
1H:8.05(1H,d,J=1.3Hz),7.69(1H,d,J=1.3Hz),7.15(1H,d,J=2.2Hz),7.0(1H,d d,J=2.2,8.4Hz),6.79(1H,d,J=8.4Hz),4.73(2H,s),4.09(1H,m),3.93(2H,d d,J=4.3,11.3Hz),3.77(3H,s),3.38(2H,d t,J=1.5,12.0Hz),2.94(3H,s),1.84(2H,d q,J=4.5,12.3Hz),1.69(2H,d d,J=2.8,12.3Hz)
化合物编号469(MP:111(分解)).NMR溶剂:DMSO
13C:156.7,153.8,151.1,141,137.3,126.1,124.4,115.3,112.5,78.8,55,43,42.2,31.7,28.1,28.1
1H:9.46(1H,s),8.06(1H,s),7.78(1H,s),7.64(2H,d,J=8.7Hz),6.77(2H,d,J=8.7Hz),4.03(3H,m),2.91(3H,s),2.79(2H,s br),1.75(2H,d br,J=12.0Hz),1.66(2H,d q,J=4.1,12.2Hz),1.41(9H,s)
化合物编号470(MP:217(分解)).NMR溶剂:CDCl3
13C:150.8,137.7,137.6,137,136.1,132.7,126,122.8,115.3,66.9,54.6,31.9,29.5
1H:8.68(1H,t,J=1.3Hz),8.15(1H,d d d,J=1.0,1.6,6.4Hz),7.95(1H,d,J=1.3Hz),7.73(1H,t d,J=1.2,8.1Hz),7.60(1H,d,J=1.3Hz),7.33(1H,d d,J=6.4,8.1Hz),4.28(1H,m),4.10(2H,d d,J=4.5,11.6Hz),3.51(2H,d t,J=1.8,12.0Hz),3.04(3H,s),1.96(2H,d q,J=4.4,12.2Hz),1.79(2H,m)
化合物编号471(MP:205-207).NMR溶剂:CDCl3
13C:150.1,137.6,137.2,136.9,136,132.8,125.9,122.8,115.1,59.1,39.6,31.3,25.5,25,14.9
1H:8.67(1H,t,J=1.6Hz),8.14(1H,d d d,J=1.0,1.6,6.4Hz),7.89(1H,d,J=1.3Hz),7.72(1H,t d,J=1.3,8.1Hz),7.55(1H,d,J=1.3Hz),7.31(1H,d d,J=6.4,8.1Hz),3.69(1H,m),3.42(2H,q,J=7.0Hz),1.84(4H,m),1.68(3H,m),1.27(2H,m,J=13.0Hz),1.25(3H,t,J=7.0Hz),1.12(1H,m,J=12.8Hz)
化合物编号472(MP:153-154).NMR溶剂:CDCl3
13C:162.3(d,J=246.7Hz),151.4,141.5,136.9,129.1(d,J=3.6Hz),126.8(d,J=8.5Hz),115.6(d,J=21.7Hz),112.8,67,54.4,31.8,29.5
1H:7.91(1H,d,J=1.3Hz),7.76(2H,m,J=5.5,8.9Hz),7.46(1H,d,J=1.3Hz),7.10(2H,m t,J=8.8Hz),4.28(1H,m),4.09(2H,d d,J=4.6,11.6Hz),3.50(2H,d t,J=1.7,11.9Hz),3.04(3H,s),1.95(2H,d q,J=4.6,12.3Hz),1.77(2H,d br,J=11.0Hz)
化合物编号473(MP:146-147).NMR溶剂:CDCl3
13C:151.2,150.6(d d,J=13.1,247.3Hz),149.8(d d,J=12.8,248.2Hz),140.5,137.0,130.1(d d,J=4.0,6.5Hz),121.1(d d,J=3.8,6.3Hz),117.5(d,J=17.6Hz),114.2(d,J=18.8Hz),113.4,67.0,54.5,31.8,29.5
1H:7.91(1H,d,J=1.1Hz),7.61(1H,d d d,J=2.1,7.8,11.6Hz),7.50(1H,m),7.46(1H,s),7.18(1H,d t,J=8.5,10.0Hz),4.28(1H,m),4.09(2H,d d,J=4.5,11.5Hz),3.50(2H,d t,J=1.3,12.0Hz),3.04(3H,s),1.95(2H,d q,J=4.4,12.2Hz),1.77(2H,d br,J=13.5Hz)
化合物编号474(MP:148-149).NMR溶剂:CDCl3
13C:151.4,150.6(t,J=2.7Hz),141.3,137,130.3,126.6,119.7,115.9(t,J=260.0Hz),113.1,67,54.4,31.8,29.5
1H:7.92(1H,d,J=1.3Hz),7.79(2H,m d,J=8.8Hz),7.48(1H,d,J=1.3Hz),7.16(2H,m d,J=8.8Hz),6.54(1H,t,J=74.0Hz),4.29(1H,m),4.09(2H,d d,J=4.5,11.5Hz),3.50(2H,d t,J=2.0,12.0Hz),3.04(3H,s),1.95(2H,d q,J=4.5,12.3Hz),1.78(2H,m)
化合物编号475(MP:183-184).NMR溶剂:CDCl3
13C:159.2,151.6,142.2,136.8,126.4,125.6,114.1,112,67,55.3,54.3,31.8,29.5
1H:7.91(1H,d,J=1.3Hz),7.72(2H,m d,J=8.9Hz),7.40(1H,d,J=1.3Hz),6.94(2H,m d,J=8.9Hz),4.28(1H,m),4.08(2H,d d,J=4.4,11.5Hz),3.84(3H,s),3.50(2H,d t,J=1.9,11.8Hz),3.03(3H,s),1.94(2H,d q,J=4.5,12.2Hz),1.76(2H,m d,J=12.3Hz)
化合物编号476(MP:130).NMR溶剂:CDCl3
13C:151.5,149.1,148.6,142.2,136.7,125.9,117.4,112.3,111.2,108.4,67,55.9,55.9,54.4,31.8,29.5
1H:7.91(1H,d,J=1.3Hz),7.43(1H,d,J=1.3Hz),7.39(1H,d,J=2.0Hz),7.30(1H,d d,J=2.0,8.3Hz),6.90(1H,d,J=8.3Hz),4.29(1H,m),4.09(2H,d d,J=4.3,11.6Hz),3.96(3H,s),3.92(3H,s),3.50(2H,d t,J=1.7,12.0Hz),3.04(3H,s),1.95(2H,d q,J=4.5,12.4Hz),1.77(2H,d br,J=12.3Hz)
化合物编号477(MP:174-176).NMR溶剂:CDCl3
13C:151.3,141.3,137,133.2,131.4,128.9,126.4,113.3,67,54.4,31.8,29.5
1H:7.92(1H,s),7.73(2H,d,J=8.5Hz),7.50(1H,s),7.37(2H,d,J=8.5Hz),4.28(1H,m),4.09(2H,d d,J=4.5,11.5Hz),3.50(2H,t.J=11.5Hz),3.03(3H,s),1.95(2H,d q,J=4.5,12.2Hz),1.77(2H,d br,J=12.5Hz)
化合物编号478(MP:222-225).NMR溶剂:CDCl3
13C:166.1,146.3,145.9,137.5,132.5,125.2,120,112.4,82.5,79.5,62.4,52.1,28.8,23
1H:8.46(1H,d d,J=0.8,1.5Hz),8.10(1H,d d,J=0.8,8.7Hz),7.91(1H,d d,J=1.5,8.7Hz),6.12(1H,s),5.53(2H,s),3.91(2H,s),1.69(6H,s),1.51(9H,s)
化合物编号479(MP:193-195).NMR溶剂:CDCl3
13C:170.3,145.7,145.3,137.7,132.4,124.7,120.2,113.2,82.4,79.6,62.3,39.6,35.4,22.9
1H:8.30(1H,s br),8.14(1H,d,J=8.6Hz),7.53(1H,d d,J=1.4,8.6Hz),5.53(2H,s),3.91(2H,s),3.16(3H,s),3.0(3H,s),1.68(6H,s)
化合物编号480(MP:233-234).NMR溶剂:DMSO
13C:167,149.8,144.5,134,131.6,128.8,119,113.1,59,31.9,28.4,241H:8.71(1H,s),8.25(1H,s br),8.18(1H,d d,J=1.4,8.3Hz),7.94(1H,d,J=8.3Hz),7.61(1H,s br),4.57(1H,br),3.07(3H,s),1.93(2H,m),1.78(2H,m),1.72(2H,m),1.54(2H,m)
化合物编号481(MP:171-172).NMR溶剂:CDCl3
13C:165,145,144.6,143.5,137.6,135.9,129.1,127.5,124.9,120.4,119.9,118.7,82.4,79.6,62.7,22.6
1H:8.39(1H,s),8.21(1H,s br),7.95(2H,m),7.69(2H,d,J=7.9Hz),7.39(2H,t,J=7.9Hz),7.19(1H,t,J=7.3Hz),5.40(2H,s),3.92(2H,s),1.69(6H,s)
化合物编号482(MP:185-186).NMR溶剂:DMSO
13C:166.4,156.3,150.9,140,137.6,128.6,127.1,126,123,113.6,112.3,56.7,56,31.3,29,25.2,24.9
1H:8.25(1H,d,J=2.3Hz),8.09(1H,s br),7.95(1H,s br),7.92(1H,d d,J=2.3,8.7Hz),7.67(1H,s br),7.56(1H,s br),7.16(1H,d,J=8.7Hz),3.90(3H,s),3.81(1H,m),2.93(3H,s),1.78(4H,m),1.60(1H,m),1.56(2H,m),1.30(2H,m,J=13.0Hz),1.11(1H,m)
化合物编号483(MP:117).NMR溶剂:CDCl3
13C:150.6,145.3,133.2,129.3,125.2,119.8,113.6,67.1,54.6,29.9(2sig.)
1H:8.10(1H,m d,J=8.4Hz),7.99(1H,m d,J=8.4Hz),7.61(1H,m,J=1.0,7.0,8.2Hz),7.47(1H,m,J=1.0,7.1,8.2Hz),4.54(1H,m),4.10(2H,d br,J=11.5Hz),3.51(2H,s br),3.21(3H,s),2.03(2H,d q,J=4.6,12.3Hz),1.91(2H,d br,J=11.5Hz)
化合物编号484(MP:119-120).NMR溶剂:CDCl3
13C:151.9(d,J=246.5Hz),151.4,147.8(d,J=11.2Hz),141.5,136.8,129.5(d,J=3.8Hz),117.3(d,J=6.9Hz),116.2(d,J=18.7Hz),113,110.3(d,J=2.0Hz),67,56.2,54.4,31.8,29.5
1H:7.92(1H,d,J=1.3Hz),7.50(1H,d d,J=2.0,8.3Hz),7.47(1H,d,J=1.3Hz),7.24(1H,m),7.09(1H,d d,J=8.3,11.0Hz),4.29(1H,m),4.10(2H,d d,J=4.5,11.5Hz),3.96(3H,s),3.50(2H,d t,J=1.8,12.0Hz),3.04(3H,s),1.95(2H,d q,J=4.6,12.4Hz),1.78(2H,d br,J=12.5Hz)
化合物编号485(MP:181).NMR溶剂:DMSO
13C:153.2,148.8,137.1,135,126.4,124.2,123.2,121.1,115,112.4,57.2,56.1,40.7,31.5,28.8,25,24.8
1H:9.20(1H,s br),9.10(1H,s),8.31(1H,s),7.77(1H,d d,J=2.3,8.2Hz),7.76(1H,s),7.20(1H,d,J=8.2Hz),3.87(3H,s),3.84(1H,br),3.03(3H,s),2.96(3H,s),1.79(4H,m),1.61(1H,m),1.57(2H,m),1.32(2H,m),1.12(1H,m)
化合物编号486(MP:200-203(分解)).NMR溶剂:CDCl3
13C:164.7,145.6,145,137.7,134.5,132.8,129.2,128.6,124.9,120.4,118.8,115,82.4,79.5,62.5,23
1H:8.61(1H,s),8.30(1H,d,J=8.6Hz),8.19(1H,s br),8.15(1H,dd,J=1.3,8.6Hz),7.70(2H,d,J=8.0Hz),7.41(2H,t,J=8.3Hz),7.20(1H,t,J=7.5Hz),5.53(2H,s),3.92(2H,s),1.70(6H,s)
化合物编号487(MP:175-177).NMR溶剂:CDCl3
13C:165.7,145.7,145.1,134.2,133.8,128.4,118.3,114.6,82.5,79.5,62.4,52,28.8,23
1H:8.42(1H,d d,J=0.5,1.6Hz),8.25(1H,d d,J=0.5,8.7Hz),8.03(1H,d d,J=1.6,8.7Hz),6.09(1H,s br),5.54(2H,s),3.91(2H,s),1.69(6H,s),1.53(9H,s)
化合物编号488(MP:175).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,140,139.3,137.3,132.4,128.9,128.6,128.4,126.1,123.6,113.9,60.2,55.8,52.6,33.8,31.7,28.8
1H:9.01(1H,d d,J=0.7,2.2Hz),8.53(1H,d d,J=1.6,4.8Hz),8.12(1H,d d d,J=1.7,2.6,8.0Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.34(1H,d d d,J=1.0,4.8,8.0Hz),7.30(2H,m,J=7.5Hz),7.21(1H,m),7.20(2H,m,J=7.1Hz),4.05(1H,m),3.14(2H,d br,J=12.0Hz),3.05(3H,s),2.81(2H,m),2.63(2H,m),2.17(2H,d t,J=2.0,11.6Hz),1.97(2H,d q,J=3.7,12.0Hz),1.85(2H,d br,J=12.0Hz)
化合物编号489(MP:197).NMR溶剂:DMSO
13C:164.3,145.4,144.5,133.6,132.4,129,118.7,113.9,81.7,78.7,61.7,48.7,32.5,25.3,25,22.5
1H:8.68(1H,s),8.49(1H,d,J=8.0Hz),8.18(1H,d d,J=1.4,8.7Hz),8.15(1H,d,J=8.7Hz),5.44(2H,s),3.90(2H,s),3.80(1H,m),1.86(2H,m),1.75(2H,m),1.61(1H,m),1.58(6H,s),1.35(2H,m),1.30(2H,m),1.15(1H,m)
化合物编号490(MP:194-196).NMR溶剂:DMSO
13C:164.6,144.4,144.2,143,135.2,128,118.9,118.4,81.7,78.7,61.8,48.7,32.4,25.3,25,22.2
1H:8.52(1H,s),8.50(1H,m),8.07(1H,d,J=8.0Hz),7.97(1H,d d,J=1.4,9.0Hz),5.31(2H,s),3.92(2H,s),3.79(1H,m),1.85(2H,m),1.75(2H,m),1.62(1H,m),1.58(6H,s),1.34(2H,m),1.31(2H,m),1.15(1H,m)
化合物编号491(MP:254-256).NMR溶剂:DMSO
13C:167,149.5,144.5,134.1,131.6,128.8,119,113.1,58.4,56.8,32.3,30.1,28.9,25.1,24.8
1H:8.71(1H,s),8.24(1H,s),8.18(1H,d,J=8.8Hz),7.93(1H,d,J=8.8Hz),7.60(1H,s),4.0(1H,m br),3.06(3H,s),1.97-1.00(10H,m)
化合物编号492(MP:223-224).NMR溶剂:DMSO
13C:150,144.7,132.6,131.4,129.9,129.5,129.5,128.8,125.5,119.6,113.5,58.7,52.8,50.3,32.5,25.4
1H:11.21(1H,s br),8.19(1H,m,J=8.3Hz),7.91(1H,m d,J=8.3Hz),7.70(1H,m,J=1.0,7.0Hz),7.63(2H,m),7.54(1H,m,J=1.0,7.0Hz),7.45(3H,m),4.39(1H,m br),4.26(2H,m br),3.40(2H,m),3.06(3H,s),3.05(2H,m br),2.47(2H,m),2.05(2H,d br,J=12.0Hz)
化合物编号493(MP:140).NMR溶剂:CDCl3
13C:150.8,150.2,140.4,139.6,137.3,119.4,115.7,57.7,31.4,30,25.4,25.2
1H:8.62(2H,m),7.93(1H,d,J=1.3Hz),7.68(1H,d,J=1.3Hz),7.67(2H,m),3.94(1H,m),3.0(3H,s),1.86(4H,m),1.71(1H,d br,J=13.0Hz),1.59(2H,d q,J=3.4,12.3Hz),1.38(2H,m q,J=13.0Hz),1.13(1H,t q,J=3.4,13.0Hz)
化合物编号494(MP:193-194).NMR溶剂:CDCl3
13C:154.4,151.2,139.9,137.2,134.5,133.7,126,121,120.3,113.4,67,54.5,31.9,29.5
1H:10.61(1H,s),8.51(1H,d,J=2.2Hz),8.02(1H,d d,J=2.2,8.7Hz),7.93(1H,d,J=1.3Hz),7.52(1H,d,J=1.3Hz),7.21(1H,d,J=8.7Hz),4.29(1H,m),4.10(2H,d d,J=4.5,11.5Hz),3.51(2H,d t,J=1.8,12.0Hz),3.05(3H,s),1.95(2H,d q,J=4.6,12.4Hz),1.78(2H,dbr,J=12.5Hz)
化合物编号495(MP:185-187).NMR溶剂:DMSO
13C:151.1(d,J=241.0Hz),149.2,145.5(d,J=12.2Hz),137.2,135.3,122.0(d,J=3.0Hz),120.5,118.2(d,J=3.5Hz),114.8,113.4(d,J=20.5Hz),66.2,54.5,31.7,28.9
1H:10.36(1H,s br),9.08(1H,s),8.23(1H,s),7.74(1H,d d,J=2.0,12.4Hz),7.56(1H,d d,J=1.5,8.3Hz),7.07(1H,t,J=8.7Hz),4.11(1H,m),3.94(2H,d d,J=4.0,11.5Hz),3.39(2H,t,J=11.5Hz),2.97(3H,s),1.86(2H,d q,J=4.2,12.2Hz),1.70(2H,d br,J=12.0Hz)
化合物编号496(MP:116-118).NMR溶剂:CDCl3
13C:166.2,145.6,145.1,137.8,134.4,132.2,128.9,128.4,128,127.8,118.8,114.8,82.5,79.5,62.4,44.5,23
1H:8.52(1H,s),8.28(1H,d,J=8.8Hz),8.09(1H,d d,J=1.5,8.7Hz),7.40-7.30(5H,m),6.56(1H,t,J=5.3Hz),5.54(2H,s),4.72(2H,d,J=5.3Hz),3.91(2H,s),1.69(6H,s)
化合物编号497(MP:173(分解)).NMR溶剂:CDCl3
13C:150.6,139.3,138.2,137.5,131.5,121.8,115.4,57.7,31.4,29.9,25.4,25.1
1H:8.22(2H,d,J=7.0Hz),7.90(1H,s),7.68(2H,d,J=7.0Hz),7.61(1H,s),3.93(1H,m),3.0(3H,s),1.86(4H,m),1.71(1H,d,J=13.0Hz),1.59(2H,d q,J=2.8,12.2Hz),1.38(2H,q,J=13.0Hz),1.13(1H,q,J=13.0Hz)
化合物编号498(MP:109-110).NMR溶剂:CDCl3
13C:159.6,151.1,141.7,136.5,133.9,129.4,117.2,113.3,113,109.8,60,55.4,54.9,52.3,31.2,28.4,19.8,11.6
1H:7.92(1H,d,J=1.3Hz),7.49(1H,d,J=1.3Hz),7.39(1H,d d,J=1.4,2.6Hz),7.35(1H,d t,J=1.4,7.7Hz),7.31(1H,t,J=7.7Hz),6.85(1H,d d d,J=1.4,2.6,8.0Hz),4.02(1H,m),3.87(3H,s),3.06(2H,d br,J=11.7Hz),3.02(3H,s),2.32(2H,m),2.06(2H,t br,J=11.5Hz),1.95(2H,d q,J=3.4,12.2Hz),1.80(2H,d br,J=12.0Hz),1.52(2H,m),0.91(3H,t,J=7.4Hz)
化合物编号499(MP:170-171).NMR溶剂:DMSO
13C:171.2,160.9,149,137.2,135.4,130.8,125.9,119.6,118,115.2,114.7,57.2,31.6,28.8,25,24.8
1H:12.99(1H,s br),9.11(1H,s),8.42(1H,s),8.40(1H,d,J=2.2Hz),8.19(1H,s),8.06(1H,s),7.87(1H,d d,J=2.0,8.6Hz),7.02(1H,d,J=8.5Hz),3.86(1H,m),2.98(3H,s),1.79(4H,m),1.60(3H,m),1.33(2H,q,J=12.8Hz),1.12(1H,q,J=13.0Hz)
化合物编号500(MP:191-193(分解)).NMR溶剂:DMSO
13C:151.0,150.3(d,J=240.0Hz),144.9(d,J=12.5Hz),140.0,137.6,130.1,116.2(d,J=18.0Hz),115.9(d,J=6.3Hz),114.2(d,J=1.5Hz),114.1,66.3,54.2,31.6,29.1
1H:9.89(1H,s),8.10(1H,s),7.90(1H,s),7.46(1H,d,J=8.5Hz),7.24(1H,m),7.13(1H,m,J=9.2Hz),4.08(1H,m),3.93(2H,d br,J=10.0Hz),3.36(2H,m),2.94(3H,s),1.84(2H,d q,J=12.0Hz),1.69(2H,d br,J=11.0Hz)
化合物编号501(MP:138-140).NMR溶剂:DMSO
13C:158.5,151,140.6,137.4,126.1,126,114,113.1,55.1,55.1,44.9,31.5,28.7
1H:8.08(1H,s),7.87(1H,s),7.77(2H,d,J=8.3Hz),6.96(2H,d,J=8.3Hz),3.95(1H,m),3.77(3H,s),3.07(2H,d,J=12.0Hz),2.93(3H,s),2.56(2H,m),1.73(4H,m)
化合物编号502(MP:120-121).NMR溶剂:CDCl3
13C:159.9,151.5,142.1,136.9,134.3,129.7,117.5,113.7,113.4,110.2,55.7,55.3,52.2,52.1,31.6,28.8,12.1
1H:7.92(1H,s),7.49(1H,s),7.39(1H,t br),7.36(1H,d,J=7.6Hz),7.30(1H,t,J=7.9Hz),6.85(1H,d br,J=8.1Hz),4.03(1H,m),3.87(3H,s),3.08(2H,d br,J=11.0Hz),3.02(3H,s),2.45(2H,q,J=7.3Hz),2.05(2H,t br,J=11.4Hz),1.96(2H,d q,J=2.5,11.8Hz),1.85(2H,d br,J=11.0Hz),1.11(3H,t,J=7.3Hz)
化合物编号503(MP:158-159).NMR溶剂:CDCl3
13C:152.5(d,J=245.0Hz),151.4,147.1(d,J=11.0Hz),141.1(d,J=2.5Hz),136.9,126.4(d,J=7.0Hz),120.9(d,J=3.6Hz),113.5(d,J=2.5Hz),113.0(d,J=20.0Hz),112.6,56.3,55.7,52.2,52.1,31.6,28.7,12.1
1H:7.88(1H,d,J=1.3Hz),7.50(2H,m),7.40(1H,d,J=1.3Hz),6.99(1H,t,J=8.3Hz),4.03(1H,m),3.91(3H,s),3.09(2H,d br,J=11.5Hz),3.02(3H,s),2.45(2H,q,J=7.3Hz),2.06(2H,t,J=12.0Hz),1.96(2H,d q,J=3.5,12.0Hz),1.83(2H,d br,J=12.0Hz),1.11(3H,t,J=7.3Hz)
化合物编号504(MP:183-184).NMR溶剂:DMSO
13C:149.3,137.5,136.1,129.1,129,128.7,125.4,115.8,52.6,42.3,31.8,24.6
1H:9.33(1H,q br,J=10.0Hz),9.20(1H,d br,J=10.0Hz),9.13(1H,s),8.37(1H,s),7.94(2H,d,J=8.2Hz),7.48(2H,t,J=7.8Hz),7.39(1H,t,J=7.3Hz),4.23(1H,m),3.34(2H,d br,J=12.0Hz),3.0(2H,m),2.98(3H,s),2.19(2H,d q,J=3.5,12.8Hz),1.92(2H,d br,J=12.4Hz)
化合物编号505(MP:143-144).NMR溶剂:DMSO
13C:167.9,163.8,144.4,143.5,142.8,135.5,128,119.7,118,81.6,78.7,63.9,61.8,47.7,45.2,26.8,25.1,24.8,22.2
1H:8.16(1H,s br),8.11(1H,d,J=9.0Hz),7.59(1H,d d,J=1.2,8.9Hz),5.29(2H,s),3.92(2H,m),3.84(2H,br),3.59(2H,br),3.08(4H,br),2.93(1H,m),1.96(2H,d br,J=10.8Hz),1.80(2H,d,J=12.4Hz),1.58(1H,m),1.57(6H,s),1.29(4H,m),1.09(1H,m)
化合物编号506(MP:133-135).NMR溶剂:DMSO
13C:168,162.4,147.4,147,144.4,143.4,142.8,135.9,128.5,127.9,123.3,119.7,117.7,109.8,108.1,101.1,81.6,78.7,61.8,60.6,51.6,46.1,40.7,22.2
1H:8.10(1H,d,J=9.3Hz),8.09(1H,s),7.54(1H,d,J=9.3Hz),6.94(1H,s),6.90(1H,d,J=8.0Hz),6.83(1H,d,J=8.0Hz),6.01(2H,s),5.29(2H,s),3.92(2H,s),3.75(2H,m),3.72(2H,s),3.47(2H,m),2.69(4H,m),1.57(6H,s)
化合物编号507(MP:213-214).NMR溶剂:DMSO
13C:156.3,150.9,150.7,140.2,137.5,126.5,126.3,125.7,122.9,113.3,111.9,56.7,55.7,31.3,29,25.2,24.8
1H:9.38(1H,s),8.07(1H,d,J=1.3Hz),7.91(1H,d,J=1.3Hz),7.84(1H,d,J=2.2Hz),7.82(1H,d d,J=2.2,8.6Hz),7.08(1H,d,J=8.6Hz),5.63(2H,s),3.81(1H,m),3.81(3H,s),2.92(3H,s),1.78(4H,m),1.58(3H,m),1.29(2H,q,J=12.7Hz),1.11(1H,q,J=13.0Hz)
化合物编号508(MP:172-173).NMR溶剂:DMSO
13C:150.7,147.4,145.5,138.1,137.5,132.5,129.4,124.1,115.7,67.9,56.3,34.2,31.4,26.8
1H:9.08(1H,s),8.49(1H,d,J=4.8Hz),8.24(1H,t d,J=1.7,8.0Hz),8.19(1H,s),8.18(1H,s),7.47(1H,d d,J=5.0,8.0Hz),4.62(1H,br),3.79(1H,m),3.38(1H,m),2.92(3H,s),1.89(2H,d br,J=12.0Hz),1.80-1.60(4H,m),1.23(2H,q,J=11.3Hz)
化合物编号509(MP:137-139(分解)).NMR溶剂:DMSO
13C:150.7,148.4,138.5,138.2,135.2,131,130.3,121.6,118.9,116.3,55.6,51.9,51.4,31.5,28.1,12.2
1H:8.66(1H,t,J=1.8Hz),8.31(1H,s),8.29(1H,d t,J=1.8,8.0Hz),8.20(1H,d,J=1.3Hz),8.10(1H,d br,J=8.0Hz),7.69(1H,t,J=8.0Hz),3.83(1H,m),2.96(2H,m),2.95(3H,s),2.32(2H,q,J=7.1Hz),1.93(2H,t br,J=10.5Hz),1.82(2H,d q,J=3.0,12.0Hz),1.73(2H,dbr,J=12.0Hz),0.99(3H,t,J=10.5Hz)
化合物编号510(MP:133-134).NMR溶剂:CDCl3
13C:151.5,149.1,148.6,142.1,136.7,126,117.4,112.3,111.2,108.4,55.9,55.9,55.6,52.2,52.1,31.6,28.7,12.1
1H:7.89(1H,d,J=1.3Hz),7.42(1H,d,J=1.3Hz),7.39(1H,d,J=2.0Hz),7.30(1H,d d,J=2.0,8.4Hz),6.90(1H,d,J=8.4Hz),4.04(1H,m),3.96(3H,s),3.91(3H,s),3.08(2H,d br,J=11.5Hz),3.02(3H,s),2.44(2H,q,J=7.4Hz),2.05(2H,t br,J=11.5Hz),1.96(2H,d q,J=3.0,11.8Hz),1.82(2H,d br,J=11.8Hz),1.10(3H,t,J=7.4Hz)
化合物编号511(MP:142-144).NMR溶剂:DMSO
13C:151.6,146.7,142.3,136.8,133.9,129.6,115.5,114.4,113.1,111.9,55.7,52.2,52.1,31.6,28.7,12.1
1H:7.90(1H,s),7.45(1H,s),7.20(1H,s),7,16(1H,t,J=7.8Hz),7.13(1H,d,J=7.8Hz),6.63(1H,d,J=7.0Hz),4.03(1H,m),3.73(2H,s br),3.08(2H,d br,J=11.0Hz),3.01(3H,s),2.45(2H,t,J=7.1Hz),2.05(2H,t br,J=11.5Hz),1.96(2H,q,J=12.0Hz),1.82(2H,d br,J=12.0Hz),1.11(3H,t,J=7.1Hz)
化合物编号512(MP:153-154).NMR溶剂:CDCl3
13C:151.5,149.1,148.6,142.1,136.7,126.1,117.4,112.3,111.3,108.4,60.4,55.9,55.9,55.8,52.6,31.6,28.9,20.3,11.9
1H:7.89(1H,d,J=1.3Hz),7.42(1H,d,J=1.3Hz),7.40(1H,d,J=2.0Hz),7.30(1H,d d,J=2.0,8.3Hz),6.90(1H,d,J=8.3Hz),4.02(1H,m),3.96(3H,s),3.91(3H,s),3.04(2H,d,J=11.0Hz),3.02(3H,s),2.31(2H,m),2.05(2H,d t,J=1.8,11.8Hz),1.93(2H,d q,J=3.7,12.0Hz),1.80(2H,d br,J=12.0Hz),1.51(2H,m),0.9(3H,t,J=7.3Hz)
化合物编号513(MP:215-216(分解)).NMR溶剂:DMSO
13C:172.1,160.3,151,140.2,137.5,130.5,124.4,124.2,117.7,114.4,113.3,66.3,54.2,31.7,29.1
1H:13.02(1H,s),8.48(1H,s),8.32(1H,d,J=2.0Hz),8.14(1H,s),7.96(1H,s),7.89(1H,d d,J=2.2,8.5Hz),7.86(1H,s),6.92(1H,d,J=8.5Hz),4.11(1H,m),3.94(2H,d d,J=3.5,11.0Hz),3.38(2H,m),2.96(3H,s),1.96(2H,d q,J=4.6,12.4Hz),1.70(2H,d br,J=12.3Hz)
化合物编号514(MP:185-186).NMR溶剂:CDCl3
13C:152.5(d,J=245.0Hz),151.4,147.0(d,J=11.0Hz),141.1(d,J=2.6Hz),136.9,126.4(d,J=7.3Hz),120.9(d,J=3.5Hz),113.4(d,J=2.0Hz),113.0(d,J=20.0Hz),112.6,60.4,56.2,55.8,52.6,31.6,28.9,20.3,11.9
1H:7.88(1H,d,J=1.3Hz),7.50(2H,m),7.40(1H,d,J=1.3Hz),6.99(1H,t,J=8.4Hz),4.0(1H,m),3.91(3H,s),3.04(2H,d br,J=11.7Hz),3.01(3H,s),2.31(2H,m),2.05(2H,d t,J=2.0,12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.80(2H,d br,J=12.0Hz),1.51(2H,m),0.9(3H,t,J=7.5Hz)
化合物编号515(MP:171-172).NMR溶剂:CDCl3
13C:154.5,151.2,148.6,146.7,139.4,137.4,132.5,128.9,123.6,113.9,80,55.7,42.9,31.9,28.7,28.4
1H:9.01(1H,d,J=2.2Hz),8.54(1H,d d,J=1.7,4.8Hz),8.12(1H,d d d,J=1.7,2.2,8.0Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.35(1H,d d d,J=0.9,4.8,8.0Hz),4.28(2H,br),4.20(1H,m),3.02(3H,s),2.81(2H,br),1.88-1.69(4H,m),1.48(9H,s)
化合物编号516(MP:吸湿的).NMR溶剂:DMSO
13C:150.1,138.7,137.4,135.1,134.4,133,127.6,127.4,118.1,67.9,56.4,34.2,31.5,26.8
1H:9.0(1H,t,J=1.5Hz),8.47(1H,m d,J=6.3Hz),8.42(1H,s),8.40(1H,s),8.19(1H,m d,J=8.1Hz),7.74(1H,d d,J=6.3,8.1Hz),3.79(1H,m br),3.40(1H,m),2.91(3H,s),1.88(2H,d br,J=12.0Hz),1.70(4H,m),1.23(2H,q br,J=12.0Hz)
化合物编号517(MP:130-132).NMR溶剂:DMSO
13C:168,162.4,145.4,144.2,135.1,133,132.7,129.7,128.8,128.5,128,118.4,114.5,81.7,78.7,61.6,61,51.8,46.3,40.8,22.5
1H:8.21(1H,s),8.16(1H,d,J=8.5Hz),7.71(1H,d d,J=1.5,8.5Hz),7.40-7.25(5H,m),5.42(2H,s),3.91(2H,s),3.65(2H,s br),3.43(4H,m),2.55(4H,m),1.60(6H,s)
化合物编号518(MP:122).NMR溶剂:CDCl3
13C:152.2,151.2,149.3,142.3,137.5,136.8,122.2,119.7,115.9,57.4,31.4,29.8,25.4,25.2
1H:8.56(1H,d d d,J=1.0,1.8,4.8Hz),8.0(1H,t d,J=1.1,8.0Hz),7.97(1H,d,J=1.5Hz),7.88(1H,d,J=1.5Hz),7.75(1H,d t,J=1.9,7.7Hz),7.19(1H,d d d,J=1.2,4.8,7.6Hz),3.98(1H,m),3.0(3H,s),1.88(2H,m),1.85(2H,m),1.69(1H,d,J=13.0Hz),1.56(2H,d q,J=3.7,12.2Hz),1.38(2H,t q,J=3.0,13.0Hz),1.12(1H,t q,J=3.5,13.0Hz)
化合物编号519(MP:158-159).NMR溶剂:CDCl3
13C:150.8,137.6,137.6,136.9,136,132.7,125.9,122.8,115.3,60.4,56,52.6,31.7,28.8,20.2,11.9
1H:8.66(1H,t,J=1.6Hz),8.13(1H,d d d,J=1.0,1.7,6.4Hz),7.93(1H,d,J=1.3Hz),7.71(1H,t d,J=1.2,7.9Hz),7.59(1H,d,J=1.3Hz),7.31(1H,d d,J=6.4,7.9Hz),3.98(1H,m),3.04(2H,m d,J=12.0Hz),3.01(3H,s),2.30(2H,m),2.04(2H,d t,J=2.0,12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.80(2H,d br,J=11.5Hz),1.50(2H,m),0.9(3H,t,J=7.4Hz)
化合物编号520(MP:170).NMR溶剂:CDCl3
13C:159.2,151.6,142.1,136.8,126.4,125.7,114.1,112,60.4,55.8,55.3,52.6,31.5,28.9,20.2,11.9
1H:7.90(1H,d,J=1.3Hz),7.72(2H,m d,J=8.9Hz),7.40(1H,d,J=1.3Hz),6.94(2H,m d,J=8.9Hz),4.01(1H,m),3.84(3H,s),3.04(2H,m),3.01(3H,s),2.30(2H,m),2.04(2H,d t,J=2.0,12.0Hz),1.94(2H,d q,J=3.7,12.0Hz),1.80(2H,d br,J=12.0Hz),1.50(2H,m),0.9(3H,t,J=7.4Hz)
化合物编号521(MP:163-164).NMR溶剂:CDCl3
13C:159.1,151.6,142.1,136.8,126.4,125.7,114.1,112,55.7,55.3,52.2,52.1,31.5,28.8,12.2
1H:7.89(1H,d,J=1.3Hz),7.72(2H,m d,J=8.9Hz),7.39(1H,d,J=1.3Hz),6.94(2H,m d,J=8.9Hz),4.02(1H,m),3.84(3H,s),3.07(2H,m d,J=11.7Hz),3.01(3H,s),2.43(2H,q,J=7.3Hz),2.03(2H,dt,J=2.0,12.0Hz),1.93(2H,d q,J=3.5,12.0Hz),1.82(2H,d br,J=12.0Hz),1.09(3H,t,J=7.2Hz)
化合物编号522(MP:127).NMR溶剂:DMSO
13C:150.7,148.4,138.5,138.2,135.2,131,130.3,121.6,118.9,116.4,59.6,55.6,52.4,31.6,28.2,19.8,11.9
1H:8.66(1H,t,J=1.8Hz),8.32(1H,s),8.30(1H,d br,J=7.9Hz),8.20(1H,s),8.11(1H,d d,J=2.2,8.1Hz),7.69(1H,t,J=8.1Hz),3.82(1H,m),2.95(3H,s),2.93(2H,m),2.21(2H,t br,J=7.5Hz),1.91(2H,t br,J=11.2Hz),1.81(2H,d q,J=3.0,11.7Hz),1.72(2H,d br,J=12.0Hz),1.41(2H,m),0.84(3H,t,J=7.5Hz)
化合物编号523(MP:163-164(分解)).NMR溶剂:DMSO
13C:151,150.4(d,J=240.5Hz),144.9(d,J=12.5Hz),140,138.5,137.6,130.2(d,J=3.2Hz),128.9,128.3,127,116.3(d,J=19.0Hz),115.9(d,J=6.5Hz),114.2(d,J=2.5Hz),114.1,61.8,55.4,52.2,31.5,28.2
1H:9.20(1H,s),8.08(1H,s),7.89(1H,s),7.45(1H,d d,J=1.7,8.7Hz),7.39-7.19(6H,m),7.13(1H,d d,J=8.7,11.2Hz),3.82(1H,m br),3.47(2H,s),2.93(3H,s),2.90(2H,m br),2.0(2H,m br),1.83(2H,mbr),1.72(2H,m br)
化合物编号524(MP:124-125).NMR溶剂:DMSO
13C:151.1,148.8,141.4,137.3,133.8,129.1,113.7,113,112.8,110.4,59.6,55.6,52.4,31.4,28.2,19.8,11.9
1H:8.06(1H,d,J=1.3Hz),7.79(1H,d,J=1.3Hz),7.08(1H,t,J=2.0Hz),7.0(1H,t,J=7.6Hz),6.95(1H,t d,J=1.2,7.5Hz),6.45(1H,d d d,J=1.4,2.4,7.8Hz),5.08(2H,s),3.79(1H,m),2.95(2H,m),2.92(3H,s),2.23(2H,t,br,J=7.5Hz),1.92(2H,t br,J=11.0Hz),1.81(2H,d q,J=3.0,11.7Hz),1.71(2H,d br,J=12.0Hz),1.42(2H,m),0.84(3H,t,J=7.3Hz)
化合物编号525(MP:167-168).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,139.3,137.3,132.4,128.9,123.6,113.9,55.9,52.2,52.1,31.6,28.8,12.2
1H:9.0(1H,d d,J=1.0,2.3Hz),8.52(1H,d d,J=1.7,4.9Hz),8.11(1H,d d d,J=1.7,2.2,7.9Hz),7.94(1H,d,J=1.3Hz),7.58(1H,d,J=1.3Hz),7.34(1H,d d d,J=1.0,4.9,8.0Hz),4.03(1H,m),3.07(2H,md,J=11.5Hz),3.03(3H,s),2.43(2H,q,J=7.3Hz),2.03(2H,d t,J=2.0,11.7Hz),1.94(2H,d q,J=3.5,12.0Hz),1.83(2H,d br,J=12.0Hz),1.09(3H,t,J=7.3Hz)
化合物编号526(MP:117).NMR溶剂:DMSO
13C:167.9,151,140.5,140.2,140,137.7,135,134.1,129.6,129.4,129,126.8,125.8,125.7,124.2,123.1,115,59.3,55.2,52.2,31.6,27.9,19.5,11.8
1H:8.21(1H,t,J=1.7Hz),8.19(1H,t,J=1.7Hz),8.16(3H,m),7.88(3H,m),7.63(1H,d d d,J=1.2,2.0,7.8Hz),7.57(1H,t,J=7.7Hz),7.52(1H,t,J=7.8Hz),7.49(1H,s br),3.87(1H,m br),3.0(2H,mbr),2.96(3H,s),2.31(2H,m br),2.05(2H,m br),1.86(2H,q br,J=12.0Hz),1.46(2H,d br,J=10.5Hz),1.45(2H,m),0.85(3H,t,J=7.4Hz)
化合物编号527(MP:85-87).NMR溶剂:CDCl3
13C:154.4,150.3,148.9,132.3,129,126.2,123,58.8,56.6,31.1,30.6,29.4,25.4,25.3
1H:7.90(2H,m d,J=8.4Hz),7.56(1H,m t,J=7.3Hz),7.49(2H,mt,J=7.8Hz),4.13,3.70(1H,2s br),3.0(3H,s),1.87(4H,m),1.68(1H,d,J=12.0Hz),1.52(2H,q,J=12.0Hz),1.40(2H,s br),1.12(1H,t q,J=,3.2,13.0Hz)
化合物编号528(MP:138-140).NMR溶剂:CDCl3
13C:153.3,149.8,144.2,132.5,129.1,126.2,122.7,81,79.8,61.8,22.81H:7.87(2H,m d,J=8.7Hz),7.57(1H,m t,J=7.3Hz),7.50(2H,mt,J=7.2Hz),5.23(2H,s),3.83(2H,s),1.59(6H,s)
化合物编号529(MP:154-155).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,139.3,137.3,132.4,128.9,123.6,113.9,60.4,55.9,52.6,31.6,28.9,20.3,11.9
1H:9.0(1H,d,J=2.0Hz),8.52(1H,d d,J=1.6,4.8Hz),8.11(1H,td,J=2.0,8.1Hz),7.94(1H,d,J=1.3Hz),7.57(1H,d,J=1.3Hz),7.33(1H,d d,J=4.8,8.1Hz),4.01(1H,m),3.05(2H,m),3.02(3H,s),2.30(2H,m),2.04(2H,t br,J=11.5Hz),1.93(2H,d q,J=3.1,12.0Hz),1.81(2H,d br,J=11.2Hz),1.50(2H,m),0.9(3H,t,J=7.4Hz)
化合物编号530(MP:185-186(分解)).NMR溶剂:DMSO
13C:151,143.1,140,137.5,132.9,125.7,124.2,122.8,121.8,57.4,31.4,29.9,25.4,25.2
1H:8.87(1H,d,J=1.3Hz),3.37(1H,d d,J=2.0,8.3Hz),8.31(1H,d,J=6.0Hz),8.06(1H,d,J=1.3Hz),7.37(1H,d t,J=1.2,8.4Hz),7.17(1H,d t,J=2.2,7.1Hz),4.0(1H,m),3.0(3H,s),1.87(4H,m),1.69(1H,d,J=13.0Hz),1.57(2H,d q,J=3.5,13.0Hz),1.39(2H,m q,J=13.0Hz),1.12(1H,m q,J=13.0Hz)
化合物编号531(MP:>160缓慢分解).NMR溶剂:DMSO
13C:150.4,140.2,139.9,139,137.9,134.8,132.6,127.4,118.6,52.4,42.4,31.8,24.7
1H:9.33(1H,s),9.25(1H,q,J=10.0Hz),9.10(1H,d,J=10.0Hz),8.94(1H,d,J=8.2Hz),8.80(1H,d,J=5.3Hz),8.55(1H,s),8.38(1H,s),8.08(1H,d d,J=5.3,8.2Hz),4.22(1H,m),3.34(2H,d,J=12.0Hz),3.01(2H,q,J=13.0Hz),2.96(3H,s),2.17(2H,q,J=13.2Hz),1.92(2H,d,J=12.0Hz)
化合物编号532(MP:245-246(分解)).NMR溶剂:DMSO
13C:158.5,151.2,140.6,137.5,126.1,126,114,113.1,55.1,54.5,44.9,34.3,31.6,27.7
1H:8.10(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.77(2H,m d,J=8.9Hz),6.96(2H,m d,J=8.9Hz),3.98(1H,m),3.77(3H,s),3.66(2H,d br,J=12.0Hz),2.95(3H,s),2.88(3H,s),2.84(2H,m),1.87(4H,m)
化合物编号533(MP:259-260).NMR溶剂:DMSO
13C:150.9,148.1,146.2,138.2,137.8,131.9,129.1,123.8,115.5,54.5,44.9,34.4,31.7,27.7
1H:9.07(1H,s),8.46(1H,s),8.19(3H,m),7.42(1H,s br),3.98(1H,m br),3.66(2H,m d,J=10.0Hz),2.96(3H,s),2.88(3H,s),2.85(2H,m br),1.88(4H,m br)
化合物编号534(MP:162).NMR溶剂:DMSO
13C:151.5(d,J=243.0Hz),149.4,147.3(d,J=10.6Hz),137.4,135.4,122.4(m),121.9(d,J=2.8Hz),115.2,114.3(d,J=1.5Hz),113.0(d,J=20.2Hz),56.2,52.5,42.3,31.7,24.6
1H:8.91(2H,m),8.49(1H,s),8.11(1H,s),7.71(1H,d d,J=2.0,12.7Hz),7.67(1H,m d,J=8.8Hz),7.23(1H,t,J=8.8Hz),4.21(1H,m),3.86(3H,s),3.36(2H,d br,J=12.5Hz),3.02(2H,m br),2.95(3H,s),2.11(2H,d q,J=4.0,12.8Hz),1.92(2H,d br,J=12.8Hz)
化合物编号535(MP:141-142).NMR溶剂:CDCl3
13C:149.6,144.4,137.9,135.2,131.4,129.1,128.3,127.2,125.6,118.1,115.3,109.1,62.8,57.6,55.6,52.5,32.8,29.8,28.5
1H:8.49(1H,d d,J=1.0,1.4Hz),8.12(1H,d d,J=1.0,8.7Hz),7.82(1H,d d,J=1.4,8.7Hz),7.43-7.20(5H,m),4.32-4.20(1H,2s br),3.54(2H,s),3.21(3H,s),3.03(2H,s br),2.18(2H,s br),2.01(2H,m br),1.94(2H,m br)
化合物编号536(MP:173-174).NMR溶剂:DMSO
13C:151.2(d,J=240.0Hz),151,144(d,J=12.5Hz),139.9(d,J=2.4Hz),137.5,125.4(d,J=7.0Hz),121(d,J=3.0Hz),117.9(d,J=3.5Hz),113.4,112.5(d,J=19.4Hz),55.2,51.7,51.3,31.5,27.8,12
1H:9.88(1H,s),8.08(1H,d,J=1.3Hz),7.89(1H,d,J=1.3Hz),7.59(1H,d d,J=2.0,12.5Hz),7.48(1H,d d d,J=1.0,2.0,8.5Hz),6.95(1H,d d,J=8.5,9.2Hz),3.85(1H,m br),3.02(2H,m br),2.93(3H,s),2.40(2H,m br),1.98(2H,m br),1.85(2H,m br),1.77(2H,mbr),1.02(3H,m br)
化合物编号537(MP:144-146).NMR溶剂:CDCl3
13C:151.9(d,J=246.2Hz),151.4,147.8(d,J=11.0Hz),141.5,136.8,129.6(d,J=3.8Hz),117.3(d,J=6.8Hz),116.1(d,J=19.0Hz),113.1,110.3(d,J=1.5Hz),56.2,55.8,52.2,52.1,31.6,28.8,12.2
1H:7.90(1H,s),7.49(1H,d d,J=1.7,8.5Hz),7.45(1H,s),7.24(1H,m),7.08(1H,d d,J=8.6,11.1Hz),4.03(1H,m),3.96(3H,s),3.08(2H,d br,J=11.2Hz),3.02(3H,s),2.44(2H,q,J=7.4Hz),2.05(2H,t br,J=11.0Hz),1.95(2H,d q,J=2.6,11.9Hz),1.83(2H,d br,J=10.5Hz),1.10(3H,t,J=7.4Hz)
化合物编号538(MP:44-46).NMR溶剂:CDCl3
13C:150.7,145.2,133.1,129.3,125.2,119.8,113.6,40,381H:8.11(1H,d,J=8.4Hz),8.0(1H,d,J=8.4Hz),7.60(1H,m t,J=7.6Hz),7.46(1H,m t,J=7.7Hz),3.34(6H,2s br)
化合物编号539(MP:90-91).NMR溶剂:CDCl3
13C:156.8,149.9,149.2,126,123.9,123,40,38.3
1H:8.82(1H,d d,J=1.6,4.4Hz),8.42(1H,d d,J=1.6,8.5Hz),7.57(1H,d d,J=4.4,8.5Hz),3.49,3.31(6H,2s)
化合物编号540(MP:164).NMR溶剂:DMSO
13C:151.7(d,J=242.5Hz),151,146.2(d,J=10.5Hz),139.5(d,J=2.5Hz),137.6,126.7(d,J=7.3Hz),120.9(d,J=3.0Hz),114(2C),112.2(d,J=9.4Hz),60,58.8,56,55.5,52.8,31.5,28.2
1H:8.09(1H,d,J=1.3Hz),7.96(1H,d,J=1.3Hz),7.66(1H,d d,J=2.0,13.5Hz),7.63(1H,m),7.19(1H,t,J=8.7Hz),4.41(1H,t,J=5.3Hz),3.85(3H,s),3.80(1H,m),3.48(2H,m),2.95(2H,d br,J=11.5Hz),2.93(3H,s),2.38(2H,t,J=6.4Hz),2.01(2H,t br,J=11.5Hz),1.81(2H,d q,J=3.6,12.1Hz),1.69(2H,d br,12.0Hz)
化合物编号541(MP:220-221).NMR溶剂:CDCl3
13C:152.5(d,J=245.0Hz),151.5,147.1(d,J=10.0Hz),141.2(d,J=3.0Hz),136.9,126.4(d,J=7.0Hz),120.9(d,J=3.5Hz),118.7,113.5(d,J=2.0Hz),113.1(d,J=19.0Hz),112.6,56.3,55.3,53,52.2,31.7,28.7,16.3
1H:7.90(1H,d,J=1.3Hz),7.50(2H,m),7.40(1H,d,J=1.3Hz),7.0(1H,t,J=8.5Hz),4.04(1H,m),3.93(3H,s),3.03(3H,s),3.02(2H,m),2.71(2H,t,J=7.0Hz),2.52(2H,t,J=7.0Hz),2.22(2H,d t,J=2.0,11.5Hz),1.94(2H,d q,J=3.5,12.2Hz),1.83(2H,d br,J=12.2Hz)
化合物编号542(MP:175).NMR溶剂:CDCl3
13C:151,150.3,140.2,139.8,137.3,119.4,115.6,66.9,54.5,31.9,29.5
1H:8.63(2H,m d,J=4.6Hz),7.95(1H,d,J=1.3Hz),7.69(1H,d,J=1.3Hz),7.67(2H,m d,J=4.6Hz),4.28(1H,m),4.09(2H,d d,J=4.7,11.5Hz),3.50(2H,d t,J=2.1,12.0Hz),3.04(3H,s),1.95(2H,d q,J=4.9,12.5Hz),1.78(2H,m d,J=12.3Hz)
化合物编号543(MP:173-174(分解)).NMR溶剂:CDCl3
13C:150.8,139.3,138.5,137.5,131.3,121.8,115.3,66.9,54.6,31.9,29.5
1H:8.22(2H,d,J=6.8Hz),7.93(1H,s),7.68(2H,d,J=6.8Hz),7.62(1H,s),4.28(1H,m),4.10(2H,d d,J=4.0,11.7Hz),3.51(2H,t,J=11.7Hz),3.04(3H,s),1.95(2H,d q,J=4.5,12.2Hz),1.78(2H,d br,J=12.0Hz)
化合物编号544(MP:163-164).NMR溶剂:CDCl3
13C:159.1,158.2,151.6,149.4,142.1,136.8,136.4,126.4,125.7,123.2,122.1,114.1,112,64.3,55.6,55.3,52.8,31.6,28.8
1H:8.59(1H,m d,J=4.9Hz),7.89(1H,d,J=1.3Hz),7.72(2H,m d,J=8.9Hz),7.66(1H,d t,J=1.8,7.7Hz),7.39(1H,d,J=1.3Hz),7.36(1H,d,J=8.0Hz),7.18(1H,d d d,J=1.0,4.9,7.4Hz),6.94(2H,m d,J=8.9Hz),4.04(1H,m),3.84(3H,s),3.66(2H,s),3.02(2H,m),3.01(3H,s),2.20(2H,d t,J=1.8,12.0Hz),1.97(2H,d q,J=3.8,12.2Hz),1.78(2H,d br,J=12.0Hz)
化合物编号545(MP:127-128).NMR溶剂:CDCl3
13C:151.9(d,J=246.5Hz),151.4,147.8(d,J=11.0Hz),141.4,136.8,129.6(d,J=4.0Hz),117.3(d,J=7.0Hz),116.1(d,J=18.8Hz),113.1,110.3(d,J=2.0Hz),60.4,56.2,55.8,52.6,31.6,28.8,20.2,11.9
1H:7.89(1H,d,J=1.3Hz),7.49(1H,d d,J=2.0,8.2Hz),7.45(1H,d,J=1.3Hz),7.24(1H,m),7.09(1H,d d,J=8.3,11.0Hz),4.02(1H,m),3.96(3H,s),3.05(2H,d br,J=12.0Hz),3.02(3H,s),2.31(2H,m),2.05(2H,d t,J=2.0,12.0Hz),1.94(2H,d q,J=3.5,12.0Hz),1.80(2H,d br,J=12.0Hz),1.51(2H,m),0.91(3H,t,J=7.5Hz)
化合物编号546(MP:240-241).NMR溶剂:DMSO
13C:163.6,161.9,158.5,151.3,151.1,151,147.1,140.6,137.5,133.9,128.6,126.1,126,125,124.4,114,113.1,55.1,55,45.9,41.3,31.8,28.9,28.1
1H:9.18(1H,d,J=2.0Hz),8.71(1H,d d,J=1.6,4.9Hz),8.35(1H,td,J=1.8,7.9Hz),8.27(1H,s),8.11(1H,d,J=1.0Hz),7.90(1H,d,J=1.0Hz),7.77(2H,m d,J=8.8Hz),7.58(1H,d d,J=4.9,7.9Hz),6.96(2H,m d,J=8.8Hz),4.64(1H,d br,J=12.0Hz),4.37(1H,d br,J=12.0Hz),4.22(1H,m),3.77(3H,s),3.25(1H,m),2.97(3H,s),2.92(1H,m),1.88(4H,m)
化合物编号547(MP:204-205).NMR溶剂:CDCl3
13C:168.8,159.2,151.6,142.3,136.9,126.4,125.6,114.1,111.9,55.3(2sig.),45.5,40.7,31.9,29.1,28.4,21.4
1H:7.91(1H,d,J=1.3Hz),7.72(2H,m d,J=8.8Hz),7.40(1H,d,J=1.3Hz),6.94(2H,m d,J=8.8Hz),4.82(1H,m d,J=13.5Hz),4.27(1H,m),3.95(1H,m d,J=14.0Hz),3.84(3H,s),3.18(1H,d t,J=2.5,13.5Hz),3.0(3H,s),2.61(1H,d t,J=2.5,13.0Hz),2.13(3H,s),1.93(1H,m),1.88(1H,m),1.74(2H,m)
化合物编号548(MP:196-197).NMR溶剂:CDCl3
13C:168.8,151.2,148.6,146.7,139.4,137.4,132.5,128.8,123.6,113.8,55.4,45.4,40.6,32,29.1,28.3,21.4
1H:9.0(1H,d,J=2.0Hz),8.53(1H,d d,J=1.6,4.9Hz),8.11(1H,dd d,J=1.8,2.2,7.9Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.34(1H,d d d,J=0.9,4.9,8.0Hz),4.83(1H,m d,J=13.5Hz),4.28(1H,m),3.96(1H,m d,J=14.0Hz),3.19(1H,m t,J=2.7,13.5Hz),3.01(3H,s),2.61(1H,d t,J=2.8,13.2Hz),2.13(3H,s),1.94(1H,m),1.89(1H,m),1.75(2H,m)
化合物编号549(MP:206-207).NMR溶剂:CDCl3
13C:159.2,151.6,142.3,137.3,136.8,132.0(q,J=34.0Hz),130.7,130.1,129.7(q,J=3.8Hz),126.4,125.5,124.5(q,J=3.8Hz),123.1(q,J=273.0Hz),114.1,111.9,55.3,54.2,45.6,31.9,28.0
1H:8.03(1H,t br),7.97(1H,d,J=7.9Hz),7.90(1H,d,J=8.0Hz),7.87(1H,d,J=1.3Hz),7.73(1H,t,J=7.9Hz),7.70(2H,m d,J=8.9Hz),7.36(1H,d,J=1.3Hz),6.93(2H,m d,J=8.9Hz),4.01(3H,m),3.84(3H,s),3.02(3H,s),2.42(2H,d t,J=2.8,11.8Hz),2.0(2H,d q,J=4.0,12.3Hz),1.93(2H,d br)
化合物编号550(MP:89-101(分解)).NMR溶剂:DMSO
13C:167.9,151,140.5,140.1,140,138.5,137.7,135,134.1,129.6,129.4,129,128.8,128.2,127,126.7,125.8,125.6,124.2,123.1,114.9,61.9,55.5,52.2,31.6,28.2
1H:8.20(1H,t,J=1.6Hz),8.18(1H,t,J=1.7Hz),8.15(2H,s),8.14(1H,s br),7.88(3H,m),7.62(1H,d d d,J=1.2,1.8,7.8Hz),7.57(1H,t,J=7.8Hz),7.51(1H,t,J=7.8Hz),7.47(1H,s br),7.37-7.20(5H,m),3.85(1H,m),3.47(2H,s),2.96(3H,s),2.90(2H,d br,J=12.0Hz),2.01(2H,t br,J=12.0Hz),1.84(2H,d q,J=3.5,12.0Hz),1.73(2H,d br,J=12.0Hz)
化合物编号551(MP:258-260(分解)).NMR溶剂:DMSO
13C:160.1,157.3,150.6,139.4,138.1,137.1,126.5,125.3,121.5,116.2,56.9,31.4,29,25.2,24.8
1H:12.94(1H,s br),8.19(1H,s),8.18(1H,s),8.04(2H,m d,J=8.4Hz),7.83(2H,m d,J=8.4Hz),3.82(1H,m br),2.93(3H,s),1.78(4H,m),1.58(3H,m),1.30(2H,q,J=13.0Hz),1.11(1H,q,J=13.0Hz)
化合物编号552(MP:126(分解)).NMR溶剂:DMSO
13C:164.2,150.9,140,137.8,133.6,133.3,128.7,127.3,125.4,123.3,115,59.6,55.6,52.4,31.5,28.2,19.8,11.9
1H:11.25(1H,s br),9.09(1H,s br),8.23(1H,t,J=1.7Hz),8.15(1H,d,J=1.3Hz),8.05(1H,d,J=1.3Hz),7.97(1H,m d,J=7.9Hz),7.62(1H,m d,J=7.8Hz),7.46(1H,t,J=7.7Hz),3.81(1H,m),2.94(3H,s),2.93(2H,m),2.22(2H,m),1.91(2H,t br,J=11.0Hz),1.81(2H,d q,J=3.2,11.7Hz),1.72(2H,d br,J=11.7Hz),1.42(2H,m),0.84(3H,t,J=7.5Hz)
化合物编号553(MP:271-272).NMR溶剂:DMSO
13C:156.2,150.7,139.7,137.8,135.7,134.9,130,123.1,122.8,120.7,115.2,56.8,31.4,29,25.2,24.8
1H:10.12(1H,s),8.16(1H,s),8.10(1H,s),7.77(1H,d,J=8.0Hz),7.71(1H,t br),7.60(4H,s br),7.45(1H,t,J=7.8Hz),7.11(1H,d d,J=1.3,7.9Hz),3.81(1H,m br),2.93(3H,s),1.78(4H,m),1.58(3H,m),1.29(2H,q,J=12.5Hz),1.11(1H,q,J=13.0Hz)
化合物编号554(MP:187-188).NMR溶剂:DMSO
13C:172.1,160.3,151,140.2,137.4,130.5,124.4,124.2,117.7,114.4,113.3,59.5,55.4,52.3,31.6,28,19.7,11.9
1H:13.03(1H,s),8.50(1H,s br),8.32(1H,d,J=2.0Hz),8.12(1H,d,J=1.3Hz),7.97(1H,s br),7.88(1H,d d,J=2.0,8.5Hz),7.86(1H,d,J=1.3Hz),6.91(1H,d,J=8.5Hz),3.84(1H,m),2.98(2H,m),2.95(3H,s),2.26(2H,m),1.97(2H,br),1.84(2H,q,J=12.5Hz),1.73(2H,d,J=11.5Hz),1.44(2H,m),0.84(3H,t,J=7.3Hz)
化合物编号555(MP:219-222).NMR溶剂:DMSO
13C:158.4,149,137,135.4,127.2,118.7,115.9,114.2,52.7,42.5,32,24.8
1H:9.89(1H,br),9.3(1H,s),8.7(1H,d,J=10.5Hz),8.42(1H,q,J=10.5Hz),8.24(1H,s),7.68(2H,m d,J=8.7Hz),6.88(2H,m d,J=8.7Hz),4.22(1H,m),3.40(2H,d br,J=12.0Hz),3.06(2H,q br,J=11.5Hz),2.97(3H,s),2.09(2H,d q,J=3.5,12.5Hz),1.96(2H,d br,J=12.5Hz)
化合物编号556(MP:141).NMR溶剂:CDCl3
13C:151.7,142.4,141.4,140.3,138.1,136.8,129.1,128.8,128.3,127.1,119.4,115.4,112.3,111.9,62.8,55.8,52.5,43.5,31.6,28.9
1H:7.89(1H,d,J=1.3Hz),7.38(1H,d,J=1.3Hz),7.36-7.23(5H,m),7.21(1H,d,J=2.0Hz),7.15(1H,d d,J=2.0,8.2Hz),7.03(1H,d,J=8.2Hz),4.01(3H,m),3.52(2H,s),3.0(3H,s),2.99(2H,m),2.69(6H,s),2.09(2H,t br,J=12.0Hz),1.92(2H,d q,J=3.5,12.0Hz),1.77(2H,d br,J=12.0Hz)
化合物编号557(MP:183-184).NMR溶剂:CDCl3
13C:170.5,163.9,159.3,151.7,142.4,136.9,126.5,125.5,114.1,111.9,55.3,54.9,43.4,32.1,28.3
1H:7.93(1H,d,J=1.3Hz),7.72(2H,m d,J=8.9Hz),7.41(1H,d,J=1.3Hz),6.95(2H,m d,J=8.9Hz),4.97(2H,m d,J=13.5Hz),4.38(1H,m),3.84(3H,s),3.05(2H,d t,J=2.7,13.5Hz),3.02(3H,s),2.02(2H,d br,J=13.0Hz),1.82(2H,d q,J=4.5,12.5Hz)
化合物编号558(MP:179(分解)).NMR溶剂:DMSO
13C:169.4,150.9,148.1,146.2,138.2,137.8,131.9,129.1,123.8,115.5,58.1,54.1,51.5,31.5,26.9
1H:9.07(1H,s),8.46(1H,m),8.18(3H,m),7.43(1H,m),3.95(1H,m),3.31(2H,s),3.18(2H,m),2.96(3H,s),2.58(2H,m),2.0(2H,q br,J=12.0Hz),1.81(2H,d br,J=11.0Hz)
化合物编号559(MP:194-195).NMR溶剂:CDCl3
13C:159.1,156.1,151.2,148.6,146.7,144,139.3,137.3,132.4,128.9,123.6,118.8,113.9,110.9,55.4,54.5,52.2,51.9,31.7,28.6
1H:9.0(1H,d,J=1.8Hz),8.52(1H,d d,J=1.5,4.7Hz),8.10(1H,td,J=1.8,7.9Hz),7.93(1H,d,J=1.3Hz),7.57(1H,d,J=1.3Hz),7.33(1H,d d,J=4.9,7.9Hz),7.14(1H,d,J=3.5Hz),6.35(1H,d,J=3.5Hz),4.0(1H,m),3.88(3H,s),3.64(2H,s),3.04(2H,m),3.02(3H,s),2.21(2H,t br,J=12.0Hz),1.96(2H,d q,J=3.6,12.0Hz),1.81(2H,dbr,J=12.0Hz)
化合物编号560(MP:165).NMR溶剂:CDCl3
13C:152.1,151.5,149.3,142.6,137.6,136.9,122.4,119.8,115.8,67,54.4,31.8,29.5
1H:8.57(1H,d d d,J=1.0,2.0,4.8Hz),8.01(1H,t d,J=1.1,8.1Hz),8.0(1H,d,J=1.5Hz),7.89(1H,d,J=1.5Hz),7.76(1H,t d,J=1.8,7.7Hz),7.20(1H,d d d,J=1.1,4.8,7.4Hz),4.31(1H,m),4.09(2H,d d,J=4.7,11.6Hz),3.51(2H,d t,J=2.1,12.0Hz),3.05(3H,s),1.94(2H,d q,J=4.5,12.0Hz),1.78(2H,m d,J=12.3Hz)
化合物编号561(MP:201-202).NMR溶剂:DMSO
13C:151.1,150.4(d,J=240.5Hz),144.9(d,J=12.5Hz),140,137.7,130.1(d,J=3.5Hz),116.3(d,J=18.5Hz),116.0(d,J=6.5Hz),114.3(d,J=2.5Hz),114.1,52.1,50.9,50.2,31.8,25.3,9.2
1H:9.90(1H,s),9.36(1H,s br),8.13(1H,s),7.92(1H,s),7.46(1H,dd,J=2.0,8.7Hz),7.25(1H,m),7.14(1H,d d,J=8.5,11.3Hz),4.19(1H,m),3.58(2H,m d,J=11.5Hz),3.10(4H,m),2.94(3H,s),2.18(2H,m q,J=12.5Hz),2.0(2H,d br,J=12.5Hz),1.24(3H,t,J=7.2Hz)
化合物编号562(MP:190-192(分解)).NMR溶剂:DMSO
13C:151.3,149.5,137.2,135.8,126.5,121.4,121,119.7,116.7,114.6,58.7,31.4,28.2,24.1
1H:11.26(1H,s br),10.14(3H,br),8.96(1H,s),8.10(1H,s),7.84(1H,d,J=2.2Hz),7.74(1H,d d,J=2.2,8.5Hz),7.19(1H,d,J=8.6Hz),4.36(1H,m),2.95(3H,s),1.88(2H,m),1.69(4H,m),1.53(2H,m)
化合物编号563(MP:250-252).NMR溶剂:DMSO
13C:155.3,150.8,140.1,138.9,137.7,134.8,129.8,122.9,121.7,120.5,114.9,56.8,31.3,29,25.2,24.8
1H:8.12(1H,s),8.03(1H,s),7.63(1H,d,J=7.8Hz),7.57(1H,t br),7.37(1H,t,J=7.8Hz),7.0(3H,br),6.98(1H,d,J=8.2Hz),3.8(1H,m),2.93(3H,s),1.78(4H,m),1.58(3H,m),1.29(2H,m q,J=12.5Hz),1.11(1H,m q,J=12.5Hz)
化合物编号564(MP:250).NMR溶剂:DMSO
13C:154.7,151.1,142.6,140.3,137.6,130.8,129.6,118.6,114.2,109.6,106,58.4,31.3,28.2,24
1H:11.71(1H,br),8.10(1H,d,J=1.2Hz),8.0(1H,d,J=1.2Hz),7.59(1H,d d,J=1.7,8.3Hz),7.53(1H,d,J=1.7Hz),7.29(1H,d,J=8.3Hz),4.36(1H,m),2.93(3H,s),1.87(2H,m),1.68(4H,m),1.53(2H,m)
化合物编号565(MP:188-189).NMR溶剂:CDCl3
13C:151.5,146.7,142.2,138,136.8,133.9,129.6,129.1,128.3,127.2,115.5,114.4,113.1,111.9,62.8,55.8,52.5,31.6,28.9
1H:7.90(1H,s),7.45(1H,s),7.38-7.24(5H,m),7.21(1H,t br),7.17(1H,m),7.16(1H,m),6.63(1H,m d,J=7.5Hz),4.02(1H,m),3.74(2H,s),3.52(2H,s),3.01(3H,s),3.0(2H,m),2.10(2H,t br,J=11.5Hz),1.93(2H,d q,J=3.3,12.0Hz),1.78(2H,d br,J=11.0Hz)
化合物编号566(MP:196).NMR溶剂:DMSO
13C:163.9,149.6,137.8,136.9,133.5,130.7,129.1,127.7,126.4,123.9,115.9,67.9,56.5,34.1,31.5,26.7
1H:11.30(1H,br),8.81(1H,s),8.29(1H,s),8.25(1H,s),7.98(1H,td,J=1.4,7.9Hz),7.70(1H,t d,J=1.2,7.9Hz),7.54(1H,t,J=7.8Hz),3.85(1H,m),3.41(1H,m),2.94(3H,s),1.90(2H,d br,J=12.0Hz),7.71(4H,m),1.25(2H,q br,J=12.3Hz)
化合物编号567(MP:219-220).NMR溶剂:DMSO
13C:150.7,139,138.8,138.5,138.4,138.3,128.8,128.2,127.6,127,125.2,116.8,61.9,55.6,52.2,43.7,31.6,28.2
1H:8.25(1H,d,J=1.1Hz),8.20(1H,d,J=1.1Hz),8.10(2H,m d,J=8.7Hz),7.93(2H,m d,J=8.7Hz),7.36-7.20(5H,m),3.83(1H,m),3.46(2H,s),3.22(3H,s),2.95(3H,s),2.90(2H,m d,J=11.0Hz),2.0(2H,t br,J=11.0Hz),1.83(2H,d q,J=3.5,12.0Hz),1.72(2H,d br,J=12.0Hz)
化合物编号568(MP:193-194).NMR溶剂:DMSO
13C:158.3,148.9,137.0,136.9,135.3,131.6,131.3,130.1(q,J=33.0Hz),130.0(q,J=3.5Hz),127.1,123.8(q,J=4.2Hz),123.4(q,J=273.0Hz),118.8,115.9,114.2,54.3,45.2,31.9,27.3
1H:9.88(1H,br),9.21(1H,s),8.17(1H,s),8.14(1H,d br,J=7.8Hz),8.10(1H,d br,J=8.0Hz),7.99(1H,t br),7.92(1H,t,J=7.9Hz),7.64(2H,m d,J=8.7Hz),6.86(2H,m d,J=8.7Hz),3.91(1H,m),3.84(2H,m),2.94(3H,s),2.48(2H,m),1.86(4H,m)
化合物编号569(MP:157-158).NMR溶剂:CDCl3
13C:157.9,151.2,149.5,148.5,146.7,139.3,137.3,136.4,132.4,128.9,123.6,123.3,122.2,113.9,64.2,55.7,52.7,31.7,28.7
1H:9.0(1H,d,J=2.2Hz),8.59(1H,d d d,J=1.0,1.8,4.9Hz),8.53(1H,d d,J=1.6,4.8Hz),8.11(1H,d d d,J=1.8,2.2,7.9Hz),7.94(1H,d,J=1.3Hz),7.67(1H,d t,J=1.9,7.7Hz),7.57(1H,d,J=1.3Hz),7.37(1H,d,J=7.7Hz),7.34(1H,d d d,J=0.8,4.8,7.9Hz),7.19(1H,d d d,J=1.0,4.9,7.7Hz),4.05(1H,m),3.68(2H,s),3.04(2H,m d,J=12.0Hz),3.03(3H,s),2.23(2H,t br,J=11.5Hz),2.01(2H,d q,J=3.5,12.0Hz),1.79(2H,d br,J=12.0Hz)
化合物编号570(MP:206-207).NMR溶剂:MeOD
13C:153.2,152.8(d,J=241.0Hz),146.6(d,J=13.5Hz),142.5,139.2,131.0(d,J=3.5Hz),118.0(d,J=6.5Hz),117.3(d,J=19.3Hz),116.0(d,J=3.0Hz),115.1,60.0,55.2,53.3,33.3,27.4,19.5,11.6
1H:8.12(1H,d,J=1.4Hz),7.75(1H,d,J=1.4Hz),7.36(1H,d d,J=2.3,8.5Hz),7.22(1H,m),7.06(1H,d d,J=8.4,11.0Hz),4.22(1H,m),3.60(2H,d br,J=12.0Hz),3.07(3H,s),2.98(4H,m),2.25(2H,dq,J=3.0,13.0Hz),2.12(2H,d br,J=13.0Hz),1.76(2H,m),1.02(3H,t,J=7.5Hz)
化合物编号571(MP:182).NMR溶剂:DMSO
13C:163.7,150.3,138.1,138,134.1,131.7,131.4,129.7,129.7,129,127.5,124.8,116.1,59,52.3,50.5,31.9,25
1H:11.29(1H,br),9.65(1H,s br),8.59(1H,s),8.27(1H,s),7.93(2H,m d,J=8.5Hz),7.81(2H,m d,J=8.6Hz),7.56(2H,m),7.48(3H,m),4.32(2H,d,J=5.0Hz),4.19(1H,m),3.46(2H,d br,J=12.0Hz),3.17(2H,m),3.95(3H,s),2.21(2H,q br,J=13.0Hz),2.0(2H,d br,J=12.5Hz)
化合物编号572(MP:223).NMR溶剂:DMSO
13C:171.3,160.9,149.5,137.4,136,131.5,130.8,129.7,129.7,128.9,125.9,120,118,115.1,114.7,59,52.4,50.5,32,24.9
1H:13.0(1H,br),9.77(1H,s),9.06(1H,s),8.47(1H,s),8.44(1H,s),8.23(1H,s),8.08(1H,s),7.89(1H,d,J=8.5Hz),7.59(2H,m),7.49(3H,m),7.02(1H,d,J=8.5Hz),4.35(2H,d,J=4.0Hz),4.26(1H,m),3.48(2H,d br,J=11.0Hz),3.18(2H,m),3.0(3H,s),2.26(2H,q br,J=12.0Hz),2.02(2H,d br,J=12.5Hz)
化合物编号573(MP:173-174).NMR溶剂:CDCl3
13C:165.1,164.9,159.2,151.7,151.6,150.4,150.2,147.1,146.8,142.3,142.3,136.9,136.9,136.8,132,131.8,126.4,125.5,125.5,122.8,122.8,114.1,111.9,111.8,55.3,55.2,54.9,46.4,45.6,41,40.9,32.3,32,28.9,28.9,28.3,28.2
1H:8.48(1H,d d,J=1.8,4.8Hz),7.91(1H,m),7.71(2H,m d,J=8.8Hz),7.71和7.64(1H,2m),7.40(1H,m),7.35(1H,d d,J=4.9,7.5Hz),6.94(2H,m d,J=8.8Hz),4.98(1H,m),4.32(1H,m),3.84(3H,s),3.54(1H,m),3.34和3.15(1H,2m),3.04和3.03(3H,2s),2.89(1H,m),2.11-1.58(4H,m)
化合物编号574(MP:242-243).NMR溶剂:DMSO
13C:168.1,156.7,151.2,141,137.4,126.1,124.5,115.4,112.5,55.1,44.9,40,31.6,28.6,28,21.4
1H:9.46(1H,s),8.07(1H,s),7.79(1H,s),7.64(2H,d,J=8.0Hz),6.77(2H,d,J=8.0Hz),4.50(1H,d,J=12.5Hz),4.09(1H,m br),3.90(1H,d,J=12.5Hz),3.10(1H,m),2.91(3H,s),2.50(1H,m),2.01(3H,s),1.78(3H,m),1.61(1H,m)
化合物编号575(MP:233-234).NMR溶剂:DMSO
13C:156.2,153.3,150.9,139.8,137.6,126.6,125.2,124.2,123.1,113.8,112.8,56.8,55.9,31.3,29,25.2,24.8
1H:9.13(1H,s),8.10(1H,d,J=1.3Hz),7.97(1H,d,J=1.3Hz),7.83(1H,d d,J=2.3,8.6Hz),7.69(1H,d,J=2.3Hz),7.21(3H,s br),7.19(1H,d,J=8.6Hz),3.85(3H,s),3.80(1H,m),2.92(3H,s),1.77(4H,m),1.59(3H,m),1.29(2H,q br,J=12.5Hz),1.11(1H,q br,J=12.5Hz)
化合物编号576(MP:137-138).NMR溶剂:DMSO
13C:155.8,150.7,139.7,137.9,134.5,129.7,127.1,125.4,125.2,123.1,115.3,56.8,31.4,29,25.2,24.9
1H:8.56(1H,s br),8.19(1H,s),8.13(1H,s),8.02(1H,m d,J=7.9Hz),7.91(1H,m d,J=7.8Hz),7.61(1H,t,J=7.9Hz),3.83(1H,m),2.95(3H,s),1.79(4H,m),1.58(3H,m),1.30(2H,q br,J=13.0Hz),1.12(1H,q br,J=13.0Hz)
化合物编号577(MP:146-147).NMR溶剂:DMSO
13C:151.3,148,141.7,138.5,137.1,128.8,128.2,127,125.8,121.2,113.9,111.4,61.9,55.5,52.3,31.4,28.3
1H:8.0(1H,s),7.65(1H,s),7.49(2H,m d,J=8.5Hz),7.36-7.21(5H,m),6.56(2H,m d,J=8.5Hz),5.13(2H,s),3.80(1H,m),3.46(2H,s),2.92(3H,s),2.88(2H,d br,J=13.0Hz),1.99(2H,t br,J=11.0Hz),1.81(2H,d q,J=3.0,12.0Hz),1.70(2H,d br,J=11.5Hz)
化合物编号578(MP:167-168).NMR溶剂:DMSO
13C:150.8,142.3,139.3,138.1,136.6,129,128.7,128.3,127.1,126.2,124.9,116.2,61.8,55.4,52.1,31.6,28
1H:8.18(2H,2s),8.03(2H,m d,J=8.6Hz),7.83(2H,m d,J=8.6Hz),7.40-7.20(5H,m),7.28(2H,s br),3.86(1H,m br),3.49(2H,br),2.95(5H,m),2.02(2H,br),1.87(2H,br),1.76(2H,br)
化合物编号579(MP:168).NMR溶剂:DMSO
13C:151.1,148,141.7,137,125.8,121.3,113.9,111.4,56.8,31.3,29.1,25.2,24.9
1H:8.0(1H,d,J=1.3Hz),7.64(1H,d,J=1.3Hz),7.48(2H,m d,J=8.5Hz),6.56(2H,m d,J=8.5Hz),5.13(2H,s),3.80(1H,m),2.91(3H,s),1.77(4H,m),1.58(3H,m),1.29(2H,m,J=12.6Hz),1.11(1H,m,J=12.6Hz)
化合物编号580(MP:183-184).NMR溶剂:DMSO
13C:150.9,140.6,138.5,137.4,127.3,125.3,118,113.4,56.8,31.3,29,25.2,24.9
1H:9.55(1H,s br),8.07(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.73(2H,m d,J=8.7Hz),7.16(2H,m d,J=8.7Hz),7.13(2H,s br),3.81(1H,m),2.92(3H,s),1.78(4H,m),1.57(3H,m),1.29(2H,q br,J=12.7Hz),1.11(1H,m q,J=12.5Hz)
化合物编号581(MP:182(分解)).NMR溶剂:DMSO
13C:155.7,153,151,140.1,138.5,137.5,128.8,128.2,127,126.5,123.6(2sig.),113.5,112.6,61.9,55.7,55.5,52.2,31.5,28.2
1H:8.09(1H,d,J=1.3Hz),7.93(1H,d,J=1.3Hz),7.72(1H,d d,J=1.7,8.6Hz),7.59(1H,s br),7.36-7.21(5H,m),7.12(1H,d,J=8.6Hz),7.01(4H,br),3.81(1H,m),3.81(3H,s),3.47(2H,s),2.93(3H,s),2.90(2H,d br,J=11.5Hz),1.99(2H,t br,J=11.2Hz),1.83(2H,d q,J=3.5,12.1Hz),1.71(2H,d br,J=12.5Hz)
化合物编号582(MP:199-200).NMR溶剂:CDCl3
13C:159.3,151.7,142.4,136.9,126.5,125.5,117.4,114.1,111.8,55.3,53.8,49,32.2,27.7
1H:7.91(1H,d,J=1.3Hz),7.72(2H,m d,J=8.8Hz),7.39(1H,d,J=1.3Hz),6.95(2H,m d,J=8.8Hz),4.19(1H,m),3.85(3H,s),3.59(2H,m d,J=13.5Hz),3.19(2H,d t,J=2.9,12.9Hz),3.06(3H,s),2.0(2H,d q,J=4.4,12.3Hz),1.91(2H,d br,J=12.0Hz)
化合物编号583(MP:166-167).NMR溶剂:CDCl3
13C:159.2,151.6,142.2,136.8,126.5,125.6,114.5,114.1,112,55.3,54.5,51.5,46,31.9,28.3
1H:7.90(1H,d,J=1.3Hz),7.72(2H,m d,J=9.0Hz),7.40(1H,d,J=1.3Hz),6.94(2H,m d,J=9.0Hz),4.07(1H,m),3.84(3H,s),3.54(2H,s),3.03(3H,s),2.94(2H,m d,J=11.5Hz),2.51(2H,d t,J=3.0,11.5Hz),1.97(2H,d q,J=4.0,12.0Hz),1.90(2H,m)
化合物编号584(MP:189-191).NMR溶剂:CDCl3
13C:151.2,148.6,146.7,139.4,137.3,132.5,128.9,123.6,114.5,113.8,54.7,51.4,45.9,32,28.3
1H:9.02(1H,d,J=2.0Hz),8.55(1H,d d,J=1.7,4.9Hz),8.13(1H,td,J=1.9,8.0Hz),7.96(1H,d,J=1.3Hz),7.59(1H,d,J=1.3Hz),7.35(1H,d d,J=4.9,8.0Hz),4.08(1H,m),3.55(2H,s),3.05(3H,s),2.96(2H,d br,J=11.4Hz),2.53(2H,d t,J=3.0,11.5Hz),1.98(2H,d q,J=3.9,12.0Hz),1.92(2H,m)
化合物编号585(MP:197-198(分解)).NMR溶剂:DMSO
13C:157.8,149.8,137.6,137.1,131.1,130,116.1,115.4,115.3,112.1,57.3,52.3,50.7,31.9,25.1,17,11
1H:9.39(1H,s),8.90(1H,s),8.21(1H,s),7.26(3H,m),6.78(1H,m),4.22(1H,m),3.59(2H,d br,J=11.5Hz),3.12(2H,q br,J=11.5Hz),3.0(2H,m),2.97(3H,s),2.23(2H,d q,J=3.0,13.0Hz),2.0(2H,d br,J=12.5Hz),1.70(2H,m),0.91(3H,t,J=7.5Hz)
化合物编号586(MP:183(分解)).NMR溶剂:MeOD
13C:150.1,149.1,147.6,137.9,136.6,119.3,118.8,117.1,116,114.4,59.8,55.1,53,33.7,26.9,18.9,11.4
1H:9.31(1H,d,J=1.3Hz),8.09(1H,d,J=1.3Hz),7.17(1H,d,J=2.2Hz),7.10(1H,d d,J=2.2,8.2Hz),6.90(1H,d,J=8.2Hz),4.33(1H,m),3.74(2H,d br,J=12.5Hz),3.19(2H,d t,J=2.8,13.0Hz),3.11(3H,s),3.11(2H,m),2.36(2H,d q,J=3.2,12.8Hz),2.23(2H,dbr,J=13.5Hz),1.82(2H,m),1.04(3H,t,J=7.5Hz)
化合物编号587(MP:153-156(分解)).NMR溶剂:MeOD
13C:158.7,153.4,152.4,151.1,143.5,139.3,139,127.9,125.6,125.6,125.5,116.6,113.8,61.5,54.8,53.6,33.3,26.9
1H:8.69(1H,d,J=5.0Hz),8.11(1H,d,J=1.3Hz),7.92(1H,d t,J=1.7,7.6Hz),7.67(1H,d,J=1.3Hz),7.61(2H,m d,J=8.7Hz),7.52(1H,d,J=7.9Hz),7.47(1H,d d,J=5.0,7.6Hz),6.81(2H,m d,J=8.7Hz),4.45(2H,s),4.28(1H,m),3.65(2H,d br,J=11.5Hz),3.25(2H,m),3.09(3H,s),2.31(2H,q br,J=13.0Hz),2.14(2H,d br,J=12.5Hz),
化合物编号588(MP:184).NMR溶剂:DMSO
13C:151.1,140.6,138.5,138.5,137.4,128.8,128.2,127.3,127,125.3,118,113.3,61.9,55.5,52.2,31.5,28.2
1H:9.55(1H,s br),8.08(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.73(2H,m d,J=8.7Hz),7.36-7.20(5H,m),7.16(2H,m d,J=8.7Hz),7.13(2H,s br),3.81(1H,m),3.46(2H,s),2.94(3H,s),2.89(2H,m d,J=11.0Hz),2.0(2H,t br,J=11.0Hz),1.83(2H,d q,J=3.0,12.0Hz),1.71(2H,d br,J=12.0Hz)
化合物编号589(MP:126-129(分解)).NMR溶剂:DMSO
13C:152.8,151.1,148.9,141.1,138.5,137.5,134,129.1,128.8,128.2,127,122,119.6,117.8,114.1,61.9,55.5,52.2,31.5,28.3
1H:8.08(1H,d,J=1.3Hz),7.91(1H,d,J=1.3Hz),7.37(1H,t d,J=1.3,7.8Hz),7.33-7.23(6H,m),7.21(1H,t,J=7.7Hz),6.72(1H,d,J=7.9Hz),5.58(4H,s br),3.81(1H,m),3.46(2H,s),2.93(3H,s),2.89(2H,m d,J=11.5Hz),2.0(2H,t br,J=11.5Hz),1.82(2H,d q,J=3.3,12.0Hz),1.71(2H,d br,J=12.0Hz)
化合物编号590(MP:179-180).NMR溶剂:DMSO
13C:155.6,150.9,139.7,138,134.5,129.8,127.2,125.5,125,123.1,115.3,66.3,54.2,31.7,29.1
1H:8.57(1H,s),8.22(1H,s),8.16(1H,s),8.04(1H,d,J=7.7Hz),7.92(1H,d,J=7.8Hz),7.62(1H,t,J=7.6Hz),4.12(1H,m),3.94(2H,d d,J=3.7,11.2Hz),3.39(2H,t,J=11.5Hz),2.98(3H,s),1.87(2H,dq,J=4.3,12.2Hz),1.71(2H,d br,J=12.0Hz)
化合物编号591(MP:187-188).NMR溶剂:DMSO
13C:160.1,157.5,150.7,139.4,138,134.5,129.7,128.2,124.5,123.8,122.2,115.5,56.8,31.4,29,25.1,24.8
1H:13.0(1H,s br),8.32(1H,t,J=1.5Hz),8.19(1H,d,J=1.3Hz),8.11(1H,d,J=1.3Hz),8.06(1H,t d,J=1.5,7.8Hz),7.68(1H,t d,J=1.5,7.8Hz),7.59(1H,t,J=7.8Hz),3.83(1H,m),2.94(3H,s),1.79(4H,m),1.58(3H,m),1.30(2H,q br,J=13.5Hz),1.58(1H,m)
化合物编号592(MP:148-149).NMR溶剂:DMSO
13C:158.5,155.6,151,140.6,137.5,126.1,126,114,113.1,55.5,55.1,45.7,31.6,27.6
1H:8.31(1H,s),8.09(1H,s),7.88(1H,s),7.77(2H,m d,J=8.5Hz),6.95(2H,m d,J=8.5Hz),5.20(2H,s),3.95(1H,m br),3.78(3H,s),3.69(2H,d br,J=12.0Hz),2.92(3H,s),2.53(2H,m),1.78(2H,q br,J=12.5Hz),1.70(2H,m)
化合物编号593(MP:100-103(分解)).NMR溶剂:DMSO
13C:150.9,140.2,138.8,138.4,137.7,134.5,129.6,128.9,128.2,127,120.5,118.6,116.2,114.8,61.8,55.5,52.2,39.2,31.5,28.1
1H:9.78(1H,s),8.12(1H,d,J=1.3Hz),7.96(1H,d,J=1.3Hz),7.73(1H,t br,J=1.8Hz),7.56(1H,m d,J=8.0Hz),7.33(1H,t,J=8.0Hz),7.38-7.20(5H,m),7.11(1H,m d,J=8.0Hz),3.83(1H,m br),3.48(2H,br),3.0(3H,s),2.94(3H,s),2.90(2H,m br),2.01(2H,m br),1.84(2H,q br,J=11.0Hz),1.73(2H,d br,J=11.0Hz)
化合物编号594(MP:138-140).NMR溶剂:DMSO
13C:160.1,157.6,151,139.4,138,134.4,129.7,128.2,124.5,123.9,122.2,115.4,58.4,31.3,28.2,24
1H:13.02(1H,s br),8.32(1H,t br,J=1.6Hz),8.19(1H,d,J=1.3Hz),8.10(1H,d,J=1.3Hz),8.08(1H,m d,J=8.0Hz),7.69(1H,m d,J=8.0Hz),7.60(1H,t,J=8.0Hz),4.38(1H,m),2.94(3H,s),1.88(2H,m),1.69(4H,m),1.54(2H,m)
化合物编号595(MP:228-229).NMR溶剂:DMSO
13C:159.1,158.5,151.1,140.6,137.5,126.1,126.0,114.0,113.1,55.1,54.6,46.4,31.7,27.2
1H:14.96(1H,br),8.10(1H,d,J=1.3Hz),7.89(1H,d,J=1.3Hz),7.77(2H,m d,J=9.0Hz),6.96(2H,m d,J=9.0Hz),4.12(1H,m br),3.95(2H,m d,J=13.0Hz),3.77(3H,s),3.13(2H,d t,J=3.5,12.5Hz),2.93(3H,s),1.90(2H,m),1.86(2H,m)
化合物编号596(MP:178-180(分解)).NMR溶剂:DMSO
13C:无数据
1H:8.09(1H,d,J=1.3Hz),7.88(1H,d,J=1.3Hz),7.77(2H,m d,J=9.0Hz),6.95(2H,m d,J=9.0Hz),5.99(2H,s),4.06(2H,d br,J=13.5Hz),4.02(1H,m),3.77(3H,s),2.91(3H,s),2.71(2H,t br,J=12.0Hz),1.71(2H,m),1.64(2H,d q,J=4.0,12.0Hz)
化合物编号597(MP:162-163).NMR溶剂:DMSO
13C:无数据
1H:8.08(1H,d,J=1.3Hz),7.87(1H,d,J=1.3Hz),7.76(2H,m d,J=9.0Hz),6.95(2H,m d,J=9.0Hz),4.51(1H,s br),3.85(1H,m br),3.77(3H,s),3.51(2H,s br),3.05(2H,br),2.93(3H,s),2.48(2H,m),2.10(2H,br),1.88(2H,s br),1.75(2H,s br)
3.本发明化合物的生物效力
依照下述方案进行了体外试验。用于体外和体内的对照是不含所述测试化合物的反应混合物。因此,在下表1中测试化合物的低值表示强抑制剂。值100表示无可测量的抑制发生。
依照下述方案进行了体内试验。BRh表示在中枢神经组织中的抑制,LVh表示在外周组织中的抑制,在该情况下外周组织是肝。
体外方案
依照以下方法确定体外药物FAAH活性:
使用了自Wistar大鼠的冷冻大脑(无小脑),并将每一个大脑用PotterElvejhem(以500rpm进行8次)匀浆于15ml 1mM MgCL2,20nMHEPES pH 7.0中。在4℃下,将匀浆物以36000g离心20分钟(Beckman,70Ti rotor)。将片状沉淀物再悬浮于15ml的相同缓冲液中,在相同条件下离心。将片状沉淀物再悬浮于15ml的相同缓冲液中,在37℃下孵育15分钟,然后在4℃下以36000g离心20分钟。然后,将每一种片状沉淀物再悬浮于15ml 3mM MgCl2,1mM EDTA,50mM Tris pH 7.4,用BioRad Protein Assay(BioRad)使用BSA标准曲线(50-250μg/ml)测定蛋白质。将所述膜悬浮物等分并在-80℃下保存。
使用AEA(用3H标记该分子的乙醇胺部分)作为底物并测量所形成的3H-乙醇胺,测定FAAH活性。反应混合物(200μl的总体积)包含:2μMAEA(2μM AEA+5nM 3H-AEA)、0.1%不含脂肪酸的BSA、5μg蛋白质,在1mM EDTA、10mM Tris pH 7.6和10μM或0.1μM化合物中。测试的化合物的母液(10mM)制备在100%DMSO中,测定中的DMSO浓度为0.1%。在37℃下的15分钟预孵育期后,通过加入底物溶液(冷EAE+放射标记的EAE+BSA)开始反应。使反应进行10分钟,之后通过加入400μl活性炭悬浮物(8g炭在32ml 0.5M HCI中连续搅拌)终止。在室温搅拌下经30min孵育期后,通过在微量离心机中离心(10min,13000rpm)沉淀炭。将200μl的上清液加入之前分布在24孔板中的800μlOptiphase Supermix闪烁混合物中。在Microbeta TriLux闪烁计数器(计数10min或直至s=2)中测定每分钟计数(cpm)。
在每一个测定中有空白(无蛋白质,通常低于200cpm)和对照(无化合物)。结果以减去空白后对照的%记录在表1中。
体内方案
动物处理
用于实验的动物是获自Interfauna Ibérica(Spain)的雄性NMRI小鼠(体重27-44g)。将小鼠每笼5个保持在受控的环境条件下(12hr明/暗循环,室温22±1℃)。无限制地供给食物和自来水,实验均在白天进行。
动物经口服途径(8ml/kg;化合物悬浮于0.5%羧甲基纤维素(CMC)或溶解于水)给予30mg/kg或3mg/kg的本发明化合物,或者使用动物饲料不锈钢曲针(Perfectum,U.S.A.)给予载体(对照)。处死前十五分钟,通过腹膜内给予戊巴比妥60mg/kg麻醉动物。将一部分肝、左肺和不带小脑的大脑取出,置于含膜缓冲液(3mM MgCl2,1mM EDTA,50mM Tris HCl pH 7.4)的塑料瓶中。将组织在-30℃下保存至进行分析。
在给予化合物之前,动物一般空腹过夜,>18h的时间点除外,其中在给予当天的早晨除去食物,并在同一天的下午给予化合物。然后对动物给予水,但不给任何其他东西。
所有动物操作严格按照European Directive for Protection ofVertebrate Animals Used for Experimental and Other ScientificPurposes(86/609CEE)和Portuguese legislation(Decreto-Lei 129/92,Portarias 1005/92e 1131/97)进行。所使用的动物数量在符合现有规定和科学完整性下尽可能最少。
试剂和溶液
花生四烯酸乙醇胺[乙醇胺-1-3H-](40-60Ci/mmol)获自AmericanRadiochemicals。所有其他试剂获自Sigma-Aldrich。OptiphaseSupermix获自Perkin Elmer,活性炭获自Sigma-Aldrich。
组织制备
将组织在冰上解冻并使用Potter-Elvejhem(大脑-以500rpm进行8次)或Heidolph Diax(肝-在位置5持续20秒进行两次,间隔30秒)匀浆在10体积的膜缓冲液(3mM MgCl2,1mM EDTA,50mM TrisHCl pH 7.4)中。
以BioRad Protein Assay(BioRad)使用BSA标准曲线(50-250μg/ml)确定组织中的总蛋白。
酶法检测
反应混合物(200μl的总体积)包含:2μM AEA(2μM AEA+5nM3H-AEA)、0.1%不含脂肪酸的BSA、15μg(大脑)、5μg(肝)或50μg(肺)蛋白质,在1mM EDTA,10mM Tris pH 7.6中。在37℃下的15min预孵育后,通过加入底物溶液(冷AEA+放射标记的AEA+BSA)开始反应。使反应进行10min(大脑和肺)或7min(肝),之后通过加入400μl活性炭悬浮物(8g炭在32ml 0.5M HCI中连续搅拌)终止。在室温搅拌下30min孵育期后,通过在微量离心机中离心(10min,13000rpm)沉淀炭。将200μl的上清液加入之前分布在24孔板中的800μlOptiphase Supermix闪烁混合物中。在Microbeta TriLux闪烁计数器中测定每分钟计数(cpm)。
在每一个检测中有空白(无蛋白质)。
剩余酶活性的百分数是相对于对照并减去空白后计算。
4.本发明化合物的生物选择性
如上所述测定FAAH抑制。依照下述的方案进行单酰基甘油酯酶(MAGL)和羧酸酯酶(CE)的抑制。用于体外和体内的对照是不含所述测试化合物的反应混合物。因此,在下表2中测试化合物的低值表示强抑制剂。值100表示无可测量的抑制发生。
MAGL
MAGL活性测量是基于作为底物的[3H]2-OG(甘油标记的)的水解速率。简言之,将小脑胞质溶胶(CRBcyt)部分——之前获自成年WISTAR大鼠——在含1mM EDTA的Tris-HCl缓冲液(10mM,pH 7.2)中稀释至合适的测定蛋白质浓度,并加入含测试化合物的检测管中。将包含检测缓冲液而不是胞质溶胶样本的空白用作对照。然后,加入底物(终浓度2μM OG),并在37℃下将样本孵育10min。终测定包含0.125%wv-1不含脂肪酸的BSA。在孵育期后,通过加入400μL氯仿∶甲醇(1/1vv-1)停止反应,将管涡流混合两次并将其置于冰上。通过离心进行相分离,取200μL等分的甲醇/缓冲液相,通过液体闪烁谱测定氚含量,并进行淬灭校正。
CE
CE活性测量是基于从对硝基苯基乙酸酯形成对硝基苯酚。简言之,在96孔板中,将8μg/ml的大鼠或小鼠肝微体(LVms)用10μM FAAH抑制剂孵育15min,然后加入底物对硝基苯基乙酸酯至终浓度1mM。在加入底物后10min,使用分光光度计在405nm下读板,看对硝基苯酚的出现情况。将未加入抑制剂的微粒体提取物中羧酸酯酶活性设为对照100%,用抑制剂孵育后的剩余CE活性相对于该对照进行计算。
Claims (68)
1.一种具有式I或式II的化合物:
其中:
R1和R2可各自独立地选自H、C1-20烷基、C1-6烷氧基、芳基、杂芳基、部分或完全饱和的杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、R1a、卤素、OH、OR1a、OCOR1a、SH、SR1a、SCOR1a、NH2、NHR1a、NHSO2NH2、NHSO2R1a、NR1aCOR1b、NHCOR1a、NR1aR1b、COR1a、CSR1a、CN、COOH、COOR1a、CONH2、CONHOH、CONHR1a、CONHOR1a、SO2R1a、SO3H、SO2NH2、CONR1aR1b、SO2NR1aR1b,其中R1a和R1b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1a和R1b可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2为C1-20烷基、烷氧基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-10环烷基C1-6烷基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1c、卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-10烷基、OH、OR1c、OCOR1c、SH、SR1c、SCOR1c、NH2、NO2、NHR1c、NHSO2NH2、NHSO2R1c、NR1cCOR1d、NHC(NH)NH2、NHCOR1c、NR1cR1d、COR1c、CSR1c、CN、COOH、COOR1c、CONH2、CONHOH、CONHR1c、CONHOR1c、C(NOH)NH2、CONR1cR1d、SO2R1c、SO3H、SO2NH2、SO2NR1cR1d,其中R1c和R1d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1c和R1d可与其所连接的杂原子一起形成杂环基,
其中,当R1或R2的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C1-6烷基氨基、C1-6二烷基氨基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R1e、卤素、C1-10烷基、OH、OR1e、OCOR1e、SH、SR1e、SCOR1e、NH2、NO2、NHR1e、NHSO2NH2、NHSO2R1e、NR1eCOR1f、NHC(NH)NH2、NHCOR1e、NR1eR1f、COR1e、CSR1e、CN、COOH、COOR1e、CONH2、CONHOH、CONHR1e、CONHOR1e、C(NOH)NH2、CONR1eR1f、SO2R1e、SO3H、SO2NH2、SO2NR1eR1f,其中R1e和R1f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R1e和R1f可与其所连接的杂原子一起形成杂环基,
R1和R2均为H或均为甲基除外,
或者
R1和R2可与其所连接的N一起形成杂芳基或杂环基基团,所述基团中的每一个可任选被一个或多个氧原子或选自以下的一个或多个基团取代:芳基、杂芳基、部分或完全饱和的杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R2a、卤素、OH、OR2a、OCOR2a、SH、SR2a、SCOR2a、NH2、NO2、NHR2a、NHSO2NH2、NHSO2R2a、NR2aCOR2b、NHC(NH)NH2、NHCOR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、CONHOH、CONHR2a、CONHOR2a、C(NOH)NH2、CONR2aR2b、SO2R2a、SO3H、SO2NH2、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2a和R2b可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基为芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C3-8环烷基C1-6烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、羟基、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-4烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-6烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基、R2c、OR2c、OCOR2c、SH、SR2c、SCOR2c、NH2、NO2、NHR2c、NHSO2NH2、NHSO2R2c、NR2cCOR2d、NHC(NH)NH2、NHCOR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、CONHOH、CONHR2c、CONHOR2c、C(NOH)NH2、CONR2cR2d、SO2R2c、SO3H、SO2NH2、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,
其中,当由R1和R2一起形成的杂芳基或杂环基的取代基的取代基为C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷氧基、芳基C1-4烷氧基、杂芳基C1-4烷氧基、杂环基C1-4烷氧基、C3-8环烷基C1-4烷氧基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:C1-4烷氧基、R2e、卤素、OH、OR2e、OCOR2e、SH、SR2e、SCOR2e、NH2、NO2、NHR2e、NHSO2NH2、NHSO2R2e、NR2eCOR2f、NHC(NH)NH2、NR2eR2f、NHCOR2e、COR2e、CSR2e、CN、COOH、COOR2e、CONH2、CONHOH、CONHR2e、CONHOR2e、C(NOH)NH2、CONR2eR2f、SO2R2e、SO3H、SO2NH2、SO2NR2eR2f,其中R2e和R2f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2e和R2f可与其所连接的杂原子一起形成杂环基;
环A选自芳基、杂芳基和杂环基部分,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、Ra、C1-10烷基、OH、ORa、OCORa、SH、SRa、SCORa、NH2、NO2、NHRa、NHSO2NH2、NHSO2Ra、NRaCORb、NHCORa、NHC(NH)NH2、NRaRb、CORa、CSRa、CN、COOH、COORa、CONH2、CONHRa、CONHOH、CONHORa、C(NOH)NH2、CONRaRb、SO2Ra、SO3H、SO2NH2、SO2NRaRb,其中Ra和Rb独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Ra和Rb可与其所连接的杂原子一起形成杂环基,
其中,当环A被C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-10烷基、C3-8环烷基取代或被含一个或多个所述部分的基团取代时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、Rc、C1-10烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、OH、ORc、OCORc、SH、SRc、SCORc、NH2、NO2、NHRc、NHSO2NH2、NHSO2Rc、NRcCORd、NHCORc、NHC(NH)NH2、NRcRd、CORc、CSRc、CN、COOH、COORc、CONH2、CONHOH、CONHRc、CONHORc、C(NOH)NH2、CONRcRd、SO2Rc、SO3H、SO2NH2、SO2NRcRd,其中Rc和Rd独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者Rc和Rd可与其所连接的杂原子一起形成杂环基;
V可为N、CH或C-R3,其中R3为卤素、C1-10烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3a、OH、OR3a、SH、SR3a、OCOR3a、SCOR3a、NH2、NO2、NHR3a、NHSO2NH2、NHSO2R3a、NR3aCOR3b、NHCOR3a、NHC(NH)NH2、NR3aR3b、COR3a、CSR3a、CN、COOH、COOR3a、CONH2、CONHOH、CONHR3a、CONHOR3a、C(NOH)NH2、CONR3aR3b、SO2R3a、SO3H、SO2NH2、SO2NR3aR3b,其中R3a和R3b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3a和R3b可与其所连接的杂原子一起形成杂环基,
其中,当R3为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R3c、C1-10烷基、OH、OR3c、OCOR3c、SH、SR3c、SCOR3c、NH2、NO2、NHR3c、NHSO2NH2、NHSO2R3c、NR3cCOR3d、NHCOR3c、NHC(NH)NH2、NR3cR3d、COR3c、CSR3c、CN、COOH、COOR3c、CONH2、CONHOH、CONHR3c、CONHOR3c、C(NOH)NH2、CONR3cR3d、SO2R3c、SO3H、SO2NH2、SO2NR3cR3d,其中R3c和R3d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3c和R3d可与其所连接的杂原子一起形成杂环基,
其中,当R3的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R3e、C1-10烷基、OH、OR3e、OCOR3e、SH、SR3e、SCOR3e、NH2、NO2、NHR3e、NHSO2NH2、NHSO2R3e、NR3eCOR3f、NHCOR3e、NHC(NH)NH2、NR3eR3f、COR3e、CSR3e、CN、COOH、COOR3e、CONH2、CONHOH、CONHR3e、CONHOR3e、C(NOH)NH2、CONR3eR3f、SO2R3e、SO3H、SO2NH2、SO2NR3eR3f,其中R3e和R3f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R3e和R3f可与其所连接的杂原子一起形成杂环基;
W可为N、CH或C-R4,其中R4为卤素、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基、R4a、OH、OR4a、SH、SR4a、OCOR4a、SCOR4a、NH2、NO2、NHR4a、NHSO2NH2、NHSO2R4a、NR4aCOR4b、NHCOR4a、NHC(NH)NH2、NR4aR4b、COR4a、CSR4a、CN、COOH、COOR4a、CONH2、CONHOH、CONHR4a、CONHOR4a、C(NOH)NH2、CONR4aR4b、SO2R4a、SO3H、SO2NH2、SO2NR4aR4b,其中R4a和R4b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和条环基,或者R4a和R4b可与其所连接的杂原子一起形成杂环基,
其中,当R4为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R4c、C1-10烷基、OH、OR4c、OCOR4c、SH、SR4c、SCOR4c、NH2、NO2、NHR4c、NHSO2NH2、NHSO2R4c、NR4cCOR4d、NHCOR4c、NHC(NH)NH2、NR4cR4d、COR4c、CSR4c、CN、COOH、COOR4c、CONH2、CONHOH、CONHR4c、CONHOR4c、C(NOH)NH2、CONR4cR4d、SO2R4c、SO3H、SO2NH2、SO2NR4cR4d,其中R4c和R4d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4c和R4d可与其所连接的杂原子一起形成杂环基,
其中,当R4的取代基为C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R4e、C1-10烷基、OH、OR4e、OCOR4e、SH、SR4e、SCOR4e、NH2、NO2、NHR4e、NHSO2NH2、NHSO2R4e、NR4eCOR4f、NHCOR4e、NHC(NH)NH2、NR4eR4f、COR4e、CSR4e、CN、COOH、COOR4e、CONH2、CONHOH、CONHR4e、CONHOR4e、C(NOH)NH2、CONR4eR4f、SO2R4e、SO3H、SO2NH2、SO2NR4eR4f,其中R4e和R4f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R4e和R4f可与其所连接的杂原子一起形成杂环基;
R5可与其所连接的碳一起形成羰基基团,同时式II中的双键相应地重排,或者R5选自H、C1-6烷基、芳基、杂芳基、杂环基、C3-8环烷基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5a、卤素、OH、OR5a、SH、SR5a、OCOR5a、SCOR5a、NH2、NO2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHCOR5a、NHC(NH)NH2、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、CONR5aR5b、SO2R5a、SO3H、SO2NH2、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基,
其中,当R5为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C1-6烷基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R5c、C1-6烷基、OH、OR5c、OCOR5c、SH、SR5c、SCOR5c、NH2、NO2、NHR5c、NHSO2NH2、NHSO2R5c、NR5cCOR5d、NHCOR5c、NHC(NH)NH2、NR5cR5d、COR5c、CSR5c、CN、COOH、COOR5c、CONH2、CONHOH、CONHR5c、CONHOR5c、C(NOH)NH2、CONR5cR5d、SO2R5c、SO3H、SO2NH2、SO2NR5cR5d,其中R5c和R5d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5c和R5d可与其所连接的杂原子一起形成杂环基,
其中,当R5的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R5e、C1-6烷基、OH、OR5e、OCOR5e、SH、SR5e、SCOR5e、NH2、NO2、NHR5e、NHSO2NH2、NHSO2R5e、NR5eCOR5f、NHCOR5e、NHC(NH)NH2、NR5eR5f、COR5e、CSR5e、CN、COOH、COOR5e、CONH2、CONHOH、CONHR5e、CONHOR5e、C(NOH)NH2、CONR5eR5f、SO2R5e、SO3H、SO2NH2、SO2NR5eR5f,其中R5e和R5f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5e和R5f可与其所连接的杂原子一起形成杂环基;
X可为O(式II中的双键相应地重排)、N、CH或C-R6,其中R6选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R6a、卤素、OH、OR6a、SH、SR6a、OCOR6a、SCOR6a、NH2、NO2、NHR6a、NHSO2NH2、NHSO2R6a、NR6aCOR6b、NHCOR6a、NHC(NH)NH2、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、CONHOH、CONHR6a、CONHOR6a、C(NOH)NH2、CONR6aR6b、SO2R6a、SO3H、SO2NH2、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6a和R6b可与其所连接的杂原子一起形成杂环基,
其中,当R6为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R6为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NO2、NHR6c、NHC(NH)NH2、NHSO2NH2、NHSO2R6c、NR6cCOR6d、NHCOR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、CONHR6c、CONHOR6c、CONHOH、C(NOH)NH2、CONR6cR6d、SO2R6c、SO3H、SO2NH2、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6c和R6d可与其所连接的杂原子一起形成杂环基,
其中,当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R6的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R6e、C1-6烷基、C1-4烷氧基、OH、OR6e、OCOR6e、SH、SR6e、SCOR6e、NH2、NO2、NHR6e、NHC(NH)NH2、NHSO2NH2、NHSO2R6e、NR6eCOR6f、NHCOR6e、NR6eR6f、COR6e、CSR6e、CN、COOH、COOR6e、CONH2、CONHOH、CONHR6e、CONHOR6e、C(NOH)NH2、CONR6eR6f、SO2R6e、SO3H、SO2NH2、SO2NR6eR6f,其中R6e和R6f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6e和R6f可与其所连接的杂原子一起形成杂环基;
Y可为N、CH或C-R7,其中R7选自C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R7a、卤素、OH、OR7a、SH、SR7a、OCOR7a、SCOR7a、NH2、NO2、NHR7a、NHSO2NH2、NHSO2R7a、NR7aCOR7b、NHCOR7a、NHC(NH)NH2、NR7aR7b、COR7a、CSR7a、CN、COOH、COOR7a、CONH2、CONHOH、CONHR7a、CONHOR7a、C(NOH)NH2、CONR7aR7b、SO2R7a、SO3H、SO2NH2、SO2NR7aR7b,其中R7a和R7b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7a和R7b可与其所连接的杂原子一起形成杂环基,
其中,当R7为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且当R7为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R7c、C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、O7c、OCOR7c、SH、SR7c、SCOR7c、NH2、NO2、NHR7c、NHC(NH)NH2、NHSO2NH2、NHSO2R7c、NR7cCOR7d、NHCOR7c、NR7cR7d、COR7c、CSR7c、CN、COOH、COOR7c、CONH2、CONHR7c、CONHOR7c、CONHOH、C(NOH)NH2、CONR7cR7d、SO2R7c、SO3H、SO2NH2、SO2NR7cR7d,其中R7c和R7d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7c和R7d可与其所连接的杂原子一起形成杂环基,
其中,当R7的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,或者当R7的取代基为C1-6烷基、C1-6炔基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、芳基、杂芳基、杂环基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、C1-4烷氧基、R7e、C1-6烷基、OH、OR7e、OCOR7e、SH、SR7e、SCOR7e、NH2、NO2、NHR7e、NHSO2NH2、NHSO2R7e、NHC(NH)NH2、NR7eCOR7f、NHCOR7e、NR7eR7f、COR7e、CSR7e、CN、COOH、COOR7e、CONH2、CONHOH、CONHR7e、CONHOR7e、C(NOH)NH2、CONR7eR7f、SO2R7e、SO3H、SO2NH2、SO2NR7eR7f,其中R7e和R7f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R7e和R7f可与其所连接的杂原子一起形成杂环基;
Z可为N、CH或C-R8,其中R8选自C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、R8a、卤素、OH、OR8a、SH、SR8a、OCOR8a、SCOR8a、NH2、NO2、NHR8a、NHSO2NH2、NHSO2R8a、NR8aCOR8b、NHCOR8a、NHC(NH)NH2、NR8aR8b、COR8a、CSR8a、CN、COOH、COOR8a、CONH2、CONHOH、CONHR8a、CONHOR8a、C(NOH)NH2、CONR8aR8b、SO2R8a、SO3H、SO2NH2、SO2NR8aR8b,其中R8a和R8b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8a和R8b可与其所连接的杂原子一起形成杂环基,
其中,当R8为C1-6烷基、C1-10烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8c、C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、OH、OR8c、OCOR8c、SH、SR8c、SCOR8c、NH2、NO2、NHR8c、NHSO2NH2、NHSO2R8c、NR8cCOR8d、NHCOR8c、NHC(NH)NH2、NR8cR8d、COR8c、CSR8c、CN、COOH、COOR8c、CONH2、CONHOH、CONHR8c、CONHOR8c、C(NOH)NH2、CONR8cR8d、SO2R8c、SO3H、SO2NH2、SO2NR8cR8d,其中R8c和R8d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8c和R8d可与其所连接的杂原子一起形成杂环基,
其中,当R8的取代基为C1-6烷基、芳基、杂芳基、杂环基、C1-6烷氧基、芳氧基、杂芳氧基、杂环氧基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基、芳基C1-6烷氧基、杂芳基C1-6烷氧基、杂环基C1-6烷氧基、C3-8环烷基或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:卤素、R8e、C1-6烷基、OH、OR8e、OCOR8e、SH、SR8e、SCOR8e、NH2、NO2、NHR8e、NHSO2NH2、NHSO2R8e、NR8eCOR8f、NHCOR8e、NHC(NH)NH2、NR8eR8f、COR8e、CSR8e、CN、COOH、COOR8e、CONH2、CONHOH、CONHR8e、CONHOR8e、C(NOH)NH2、CONR8eR8f、SO2R8e、SO3H、SO2NH2、SO2NR8eR8f,其中R8e和R8f独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R8e和R8f可与其所连接的杂原子一起形成杂环基;
其中,X、Y和Z表示的原子或基团的至多两个可为N;
其中,当W为N时,CONR1R2基团可连至W,式I中的双键相应地重排;
或其可药用的盐或酯;
条件是当R1和R2一起形成式I的化合物中的哌啶基时,所述哌啶基不被以下基团取代:甲基、二甲基、乙基、异丙基、叔丁基、甲氧基羰基、三氟甲基、氯、溴或苄基,
条件是R1和R2一起在式I的化合物中不形成6,7-二甲氧基-3,4-二氢-1H-异喹啉-2-基、6-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-甲氧基-3,4-二氢-1H-异喹啉-2-基、7-氨基-3,4-二氢-1H-异喹啉-2-基、7-硝基-3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-2-基、3,4-二氢-1H-异喹啉-1-基、3,4-二氢-2H-喹啉-1-基、吡咯烷-1-基、3,6-二氢-2H吡啶-1-基、8-氮杂-螺14.5]癸-8-基、1,3-二氢异氮茚-2-基、八氢异氮茚-2-基、1,2,6-三氮杂-螺[2.5]辛-1-烯-6-基或氮杂环庚烷-1-基,
条件是当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基、或4-异硫氰酸根合丁基,
条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,在式I化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,和
条件是所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
3.权利要求1或2的化合物,其中R1选自H和C1-4烷基。
4.前述任一项权利要求的化合物,其中R1选自H、甲基和乙基。
5.前述任一项权利要求的化合物,其中R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。
6.前述任一项权利要求的化合物,其中R2选自芳基、杂芳基、杂环基和C3-10环烷基,所述基团中的每一个可为取代的或未取代的。
7.前述任一项权利要求的化合物,其中R2选自芳基、杂芳基、杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。
8.前述任一项权利要求的化合物,其中R2选自饱和杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。
9.前述任一项权利要求的化合物,其中R2为未取代的单环的C5-8环烷基。
10.前述任一项权利要求的化合物,其中R2为未取代的环己基。
11.权利要求1-8中任一项的化合物,其中R2为单环的饱和杂环基,并且其中所述杂环基的环包含单个杂原子。
12.权利要求11的化合物,其中所述杂原子是氮原子或氧原子。
13.权利要求12的化合物,其中所述杂环基是六元的,优选为哌啶基或四氢吡喃基。
14.权利要求11-13中任一项的化合物,其中所述杂原子是氧原子并且所述杂环基是未取代的。
15.权利要求11-13中一项的化合物,其中所述杂原子是氮原子,并且所述氮杂原子是取代的或未取代的。
16.权利要求11-13和15中任一项的化合物,其中所述氮杂原子被选自以下的基团取代:C1-6烷基、芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可为取代的或未取代的。
17.权利要求16的化合物,其中所述氮杂原子被选自以下的基团取代:C1-4烷基、芳基C1-4烷基、杂芳基C1-4烷基、杂环基C1-4烷基和C5-8环烷基C1-4烷基。
18.权利要求17的化合物,其中所述氮杂原子被选自芳基C1-4烷基和杂芳基C1-4烷基的基团取代,其中所述芳基和杂芳基是单环,优选为六元的。
19.权利要求18的化合物,其中所述氮杂原子被选自苯基C1-2烷基和吡啶基C1-2烷基的基团取代。
20.权利要求11-19中任一项的化合物,其中在所述杂环基基团中的杂原子位于相对于杂环基基团R2连接于脲氮位置的4位。
21.权利要求11-20中任一项的化合物,其中所述化合物具有式IIa。
22.权利要求21的化合物,其中R6是取代的或未取代的芳基或杂芳基。
23.权利要求22的化合物,其中R6是取代的或未取代的单环的芳基或杂芳基。
24.权利要求23的化合物,其中所述单环的芳基或杂芳基是六元的。
25.权利要求22-24中任一项的化合物,其中R6是未取代的苯基。
26.权利要求22-24中任一项的化合物,其中R6是取代的或未取代的吡啶基。
27.权利要求22-24和26中任一项的化合物,其中所述杂芳基被氧原子取代。
28.权利要求1或2的化合物,其中R1和R2与其所连接的N一起形成取代的或未取代的杂环基基团。
29.权利要求28的化合物,其中所述杂环基是5或6元单环,优选为5元单环。
30.权利要求28或29的化合物,其中所述杂环基包含一个或两个、优选1个另外的杂原子(即除N以外)。
31.权利要求28-30中任一项的化合物,其中所述杂环基是噁唑烷基。
32.权利要求31的化合物,其中所述噁唑烷基中的氧原子位于相对于脲氮的3位。
33.权利要求31或32的化合物,其中所述噁唑烷基被一个、两个或三个甲基或乙基取代。
34.权利要求31-33中任一项的化合物,其中所述噁唑烷基被两个甲基或乙基取代。
35.权利要求34的化合物,其中所述噁唑烷基在同一碳原子上被两个甲基取代。
36.权利要求35的化合物,其中所述噁唑烷基是4,4-二甲基噁唑烷-3-基。
37.权利要求28-36中任一项的化合物,其中所述化合物具有式Ia或式IIa。
38.权利要求37的化合物,其中所述化合物具有式IIa,并且其中R6是取代的或未取代的芳基,优选为苯基。
39.权利要求37的化合物,其中所述化合物具有式Ia,并且其中环A是未取代的或取代的苯并部分。
40.权利要求1或2的化合物,其中所述化合物具有式IIa,其中:
R1选自H和C1-4烷基,
R2选自芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基,所述基团中的每一个可任选被选自以下的一个或多个基团取代:R2a、卤素、OH、OR2a、OCOR2a、SH、SR2a、SCOR2a、NH2、NHR2a、NHSO2NH2、NHSO2R2a、NR2aCOR2b、NHC(NH)NH2、NHCOR2a、NR2aR2b、COR2a、CSR2a、CN、COOH、COOR2a、CONH2、CONHOH、CONHR2a、CONHOR2a、C(NOH)NH2、SO2R2a、SO3H、SO2NH2、CONR2aR2b、SO2NR2aR2b,其中R2a和R2b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2a和R2b可与其所连接的杂原子一起形成杂环基,
其中,当R2的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基、杂环基或含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R2c、卤素、OH、OR2c、OCOR2c、SH、SR2c、SCOR2c、NH2、NHR2c、NHSO2NH2、NHSO2R2c、NR2cCOR2d、NHC(NH)NH2、NHCOR2c、NR2cR2d、COR2c、CSR2c、CN、COOH、COOR2c、CONH2、CONHOH、CONHR2c、CONHOR2c、C(NOH)NH2、SO2R2c、SO3H、SO2NH2、CONR2cR2d、SO2NR2cR2d,其中R2c和R2d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,
R5选自H、R5a、卤素、OH、OR5a、OCOR5a、SH、SR5a、SCOR5a、NH2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHC(NH)NH2、NHCOR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基,
R6选自芳基、杂芳基、杂环基、C3-10环烷基,所述基团中的每一个可任选被选自以下的一个或多个基团取代:R6a、卤素、OH、OR6a、OCOR6a、SH、SR6a、SCOR6a、NH2、NHR6a、NHSO2NH2、NHSO2R6a、NR6aCOR6b、NHC(NH)NH2、NHCOR6a、NR6aR6b、COR6a、CSR6a、CN、COOH、COOR6a、CONH2、CONHOH、CONHR6a、CONHOR6a、C(NOH)NH2、SO2R6a、SO3H、SO2NH2、CONR6aR6b、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R6a和R6b可与其所连接的杂原子一起形成杂环基,并且其中当R6为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,
其中,当R6的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基、杂环基或含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:R6c、卤素、OH、OR6c、OCOR6c、SH、SR6c、SCOR6c、NH2、NHR6c、NHSO2NH2、NHSO2R6c、NR6cCOR6d、NHC(NH)NH2、NHCOR6c、NR6cR6d、COR6c、CSR6c、CN、COOH、COOR6c、CONH2、CONHOH、CONHR6c、CONHOR6c、C(NOH)NH2、SO2R6c、SO3H、SO2NH2、CONR6cR6d、SO2NR6cR6d,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R2c和R2d可与其所连接的杂原子一起形成杂环基,并且其中当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代,并且
R8选自H、R5a、卤素、OH、OR5a、OCOR5a、SH、SR5a、SCOR5a、NH2、NHR5a、NHSO2NH2、NHSO2R5a、NR5aCOR5b、NHC(NH)NH2、NHCOR5a、NR5aR5b、COR5a、CSR5a、CN、COOH、COOR5a、CONH2、CONHOH、CONHR5a、CONHOR5a、C(NOH)NH2、SO2R5a、SO3H、SO2NH2、CONR5aR5b、SO2NR5aR5b,其中R5a和R5b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或者R5a和R5b可与其所连接的杂原子一起形成杂环基。
41.权利要求40的化合物,其中R1选自H、甲基和乙基,R2选自芳基、杂芳基、杂环基和C3-8环烷基,所述基团中的每一个可为取代的或未取代的。
42.权利要求40或41的化合物,其中R2选自完全饱和的杂环基和C5-8环烷基,所述基团中的每一个为单环,并且可为取代的或未取代的。
43.权利要求42的化合物,其中R2为未取代的环戊基或未取代的环己基。
44.权利要求42的化合物,其中R2为完全饱和的杂环基,并且其中所述杂环基的环包含单个杂原子,例如氮或氧。
45.权利要求44的化合物,其中所述杂环基是六元的,并且所述杂环基中的杂原子位于相对于杂环基R2连接于脲氮位置的4位。
46.权利要求45的化合物,其中所述杂原子是氮杂原子,所述氮杂原子被选自以下的基团取代:CN、CONH2、C(NOH)NH2、SO2-C1-4烷基、SO2-芳基、CO-杂芳基、CO-C1-4烷基、COO-C1-4烷基、C1-4烷基、芳基C1-3烷基、杂芳基C1-3烷基、杂环基C1-3烷基、芳基、杂芳基和杂环基,其中C1-4烷基可任选被OH、CN、COOH取代,所述SO2-芳基可任选被C1-4烷基或C1-4卤代烷基取代,所述CO-杂芳基可任选被杂芳基或卤素取代,所述杂芳基C1-3烷基可任选被COO-C1-3烷基取代,所述杂芳基可任选被一个或多个卤素取代。
47.权利要求46的化合物,其中所述氮杂原子被苯基C1-3烷基取代。
48.权利要求40-47中任一项的化合物,其中R6选自单环芳基、单环杂芳基和杂环基,所述基团中的每一个可为取代的或未取代的。
49.权利要求48的化合物,其中R6是取代的芳基,并且其中所述芳基被选自以下的一个或多个基团取代:卤素、R6a、OH、OR6a、NH2、NO2、NHC(NH)NH2、NHR6a、NR6aR6b、C(NOH)NH2、COR6a、COOH、COOR6a、CONH2、CONHOH、SO2R6a、SO2NR6aR6b,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,其中R6a和R6b独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,
其中当R6的取代基为C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,或为含一个或多个所述部分的基团时,所述部分中的每一个可任选被选自以下的一个或多个基团取代:OR6c、OH和CONH2,其中R6c和R6d独立地选自C1-6烷基、取代的C1-6烷基、芳基、杂芳基、C3-8环烷基和杂环基,并且其中当R6的取代基为杂芳基或杂环基时,所述部分中的每一个可任选被一个或多个氧原子取代。
50.权利要求49的化合物,其中R6是取代的芳基,所述芳基被选自以下的一个或多个基团取代:卤素、OH、C1-4烷氧基、CONH2、C(NOH)NH2、CONHOH、SO2-C1-4烷基、杂环基和芳基,其中所述杂环基可任选被氧原子取代,所述芳基可任选被CONH2取代。
51.权利要求48的化合物,其中R6是被氧原子取代的杂环基。
52.权利要求48的化合物,其中R6是被氧原子取代的单环杂芳基。
53.权利要求1-20和28-36中任一项的化合物,其中环A被选自以下的一个或多个基团取代:卤素、OH、SH、NH2、NO2、NHC(NH)NH2、CN、COOH、CONH2、CONHOH、C(NOH)NH2、SO3H和SO2NH2。
54.权利要求1-20和28-36中任一项的化合物,其中环A被选自以下的一个部分取代:C1-6烷氧基、C1-6烷氧基C1-6烷基和C0-6烷基-CO-C0-6烷基,其中所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的部分取代,其中所述部分中的每一个可任选被以下基团取代:芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基。
55.权利要求54的化合物,其中环A被C0-6烷基-CO-C0-6烷基取代,其中所述C0-6烷基-CO-C0-6烷基被可任选被以下基团取代的杂环基取代:芳基、杂芳基、杂环基、C3-10环烷基、芳基C1-6烷基、杂芳基C1-6烷基、杂环基C1-6烷基和C3-10环烷基C1-6烷基。
56.权利要求1-20和28-36中任一项的化合物,其中R6为选自芳基、杂芳基、杂环基、C3-10环烷基的基团,其中所述R6基团被选自C1-6烷氧基、C1-6烷氧基C1-6烷基和C0-6烷基-CO-C0-6烷基的基团取代,其中所述C1-6烷氧基、C1-6烷氧基C1-6烷基或C0-6烷基-CO-C0-6烷基被选自芳基、杂芳基、杂环基和C3-10环烷基的基团取代。
57.权利要求56的化合物,其中R6为选自芳基、杂芳基、杂环基、C3-10环烷基的基团,其中所述R6基团被选自C1-6烷氧基和C1-6烷氧基C1-6烷基的基团取代,其中所述C1-6烷氧基或C1-6烷氧基C1-6烷基被杂环基取代。
58.权利要求57的化合物,其中R6是单环芳基,所述单环芳基被选自C1-6烷氧基和C1-6烷氧基C1-6烷基的基团取代,其中所述C1-6烷氧基或C1-6烷氧基C1-6烷基被杂环基取代。
59.权利要求58的化合物,其中所述杂环基是六元的单环杂环基。
60.权利要求56-59中任一项的化合物,其中所述化合物具有式IIa。
61.一种具有式I或式II的化合物:
其中:
R1、R2、R5、W、V、X、Y、Z和环A如权利要求1中所限定,并且仅有的适用条件是当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、嘧啶、取代的吡啶或取代的嘧啶,
环A不是未取代的苯并、羟基苯并、苯氧基苯并、氟氯苯并、氯苯并、溴苯并、硝基苯并、氨基苯并、氰基苯并、甲基苯并、三氟甲基苯并、三氟甲基氯苯并、苯基酮苯并、苯基羟基甲基苯并、环己基硫代苯并、甲氧基羰基苯并或甲氧基苯并,
当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且
所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
62.一种含前述任一项权利要求的化合物和一种或多种可药用赋形剂的药物组合物。
63.权利要求62的药物组合物,还包含一种或多种另外的活性药物成分。
64.权利要求1-61中任一项的化合物或者权利要求62或63的组合物,用于治疗。
65.权利要求1-61中任一项的化合物或者权利要求62或63的组合物,用于治疗或预防其发生或症状与FAAH酶的底物有关的病症,其中仅有的适用条件是i)当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、吡嗪、取代的吡啶或取代的吡嗪,ii)当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且iii)所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
66.一种治疗或预防其发生或症状与FAAH酶的底物有关的病症的方法,所述方法包括对需要所述治疗或预防的受试者给予治疗有效量的权利要求1-61任一项的化合物,其中仅有的适用条件是i)当R1和R2与其所连接的N一起形成哌啶基、哌嗪基、取代的哌啶基或取代的哌嗪基时,式I的化合物中的环A不形成吡啶、吡嗪、取代的吡啶或取代的吡嗪,ii)当R1或R2为甲基时,R1或R2的另一个不是4-氯丁基、4-叠氮丁基或4-异硫氰酸根合丁基,并且iii)所述化合物不是(4-苯基-1H-咪唑-1-基)(4-(喹啉-2-基甲基)哌嗪-1-基)甲酮。
67.权利要求65的化合物或者权利要求66的方法,其中所述病症是与内源性大麻素系统有关的紊乱。
68.权利要求67的化合物或方法,其中所述紊乱是选自食欲调节、肥胖症、代谢紊乱、恶病质、厌食症、疼痛、炎症、神经毒性、神经外伤、中风、多发性硬化症、脊髓损伤、帕金森氏病、左旋多巴诱导的运动障碍、亨丁顿疾病、Gilles de la Tourette’s综合征、迟发性运动障碍、张力障碍、肌萎缩性侧索硬化症、阿尔茨海默病、癫痫症、精神分裂症、焦虑症、抑郁症、失眠症、恶心、呕吐、酗酒恶习、药物成瘾,例如阿片、烟碱、可卡因、酒精和精神兴奋剂,高血压、循环休克、心肌再灌性损伤、动脉粥样硬化、哮喘、青光眼、视网膜病、癌症、炎性肠病、急性和慢性肝病,例如肝炎和肝硬化,关节炎和骨质疏松症。
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CN104487422B (zh) * | 2012-07-24 | 2017-07-25 | 比亚尔-珀特拉和Ca股份公司 | 脲类化合物及其作为酶抑制剂的用途 |
CN104662002A (zh) * | 2012-07-27 | 2015-05-27 | 比亚尔-珀特拉和Ca股份公司 | 取代脲类化合物的合成方法 |
CN105793247A (zh) * | 2013-07-24 | 2016-07-20 | 比亚尔-珀特拉和Ca股份公司 | 咪唑甲酰胺类及其作为faah抑制剂的用途 |
CN105793247B (zh) * | 2013-07-24 | 2018-03-16 | 比亚尔-珀特拉和Ca股份公司 | 咪唑甲酰胺类及其作为faah抑制剂的用途 |
CN105934431A (zh) * | 2014-01-24 | 2016-09-07 | 比亚尔-珀特拉和Ca股份公司 | 取代脲类化合物的制备方法 |
CN104292172A (zh) * | 2014-09-12 | 2015-01-21 | 浙江理工大学 | 一种苯并三氮唑类衍生物及其制备方法 |
CN110198944A (zh) * | 2017-01-23 | 2019-09-03 | 辉瑞大药厂 | 作为单酰基甘油脂肪酶抑制剂的杂环螺环化合物 |
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RU2011129416A (ru) | 2013-01-27 |
SG172301A1 (en) | 2011-07-28 |
JP5657566B2 (ja) | 2015-01-21 |
IL213747A (en) | 2017-01-31 |
BR122013027950A2 (pt) | 2019-12-10 |
US9353082B2 (en) | 2016-05-31 |
AU2009330821B2 (en) | 2015-06-11 |
MX2011006643A (es) | 2011-07-29 |
JP2015071622A (ja) | 2015-04-16 |
WO2010074588A8 (en) | 2011-10-06 |
EP2382012A2 (en) | 2011-11-02 |
TW201028408A (en) | 2010-08-01 |
BRPI0923819B1 (pt) | 2021-11-09 |
AU2009330821A1 (en) | 2011-06-23 |
NZ593418A (en) | 2013-10-25 |
US20120065191A1 (en) | 2012-03-15 |
KR101715190B1 (ko) | 2017-03-10 |
CA2747784A1 (en) | 2010-07-01 |
TWI469979B (zh) | 2015-01-21 |
ZA201104336B (en) | 2016-10-26 |
CN102333568B (zh) | 2016-01-20 |
RU2553451C2 (ru) | 2015-06-20 |
KR20110130388A (ko) | 2011-12-05 |
IL213747A0 (en) | 2011-07-31 |
WO2010074588A2 (en) | 2010-07-01 |
WO2010074588A3 (en) | 2011-05-19 |
BRPI0923819A2 (pt) | 2019-11-19 |
CN105399731A (zh) | 2016-03-16 |
MX342128B (es) | 2016-09-14 |
CA2747784C (en) | 2018-07-31 |
AR075111A1 (es) | 2011-03-09 |
JP2012513990A (ja) | 2012-06-21 |
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