CN115215823A - Fxr调节剂及其制备方法、药物组合物和用途 - Google Patents

Fxr调节剂及其制备方法、药物组合物和用途 Download PDF

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CN115215823A
CN115215823A CN202210404006.XA CN202210404006A CN115215823A CN 115215823 A CN115215823 A CN 115215823A CN 202210404006 A CN202210404006 A CN 202210404006A CN 115215823 A CN115215823 A CN 115215823A
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methyl
phenethylsulfamoyl
benzofuran
carboxylic acid
ethyl ester
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焦宁
豆晓东
霍童雨
苏凌宇
赵心怡
黄英杰
刘雅萌
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Beijing Best Way Management Consulting Center (L.P.)
Qingdao Ruisen Biotechnology Co ltd
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Abstract

本申请涉及医药领域，涉及可作为FXR调节剂的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，还涉及其制备方法、药物组合物和用途。

Description

FXR调节剂及其制备方法、药物组合物和用途
技术领域
本文涉及但不限于医药技术，特别涉及一种FXR调节剂，其制备方法、药物组合物以及用途。
背景技术
核受体(nuclear receptors,NRs)超家族由48个配体依赖的转录因子组成，控制特定基因的表达，调节哺乳动物的代谢、发育和繁殖等生理过程，并与多种人类疾病有关，包括炎症、癌症、生殖障碍、代谢综合征、心血管疾病等。NRs超家族的活性可通过结合亲脂性小分子配体来调节，后者进入脂质双分子层调控细胞内外的生理活动。根据配体选择性，NRs超家族通常分为三类：I类、II类和III类。I类为经典的内分泌核受体，由内分泌腺合成的类固醇激素作为它们的配体，包括雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、雄激素受体(androgen receptor,AR)、糖皮质激素受体(glucocorticoid receptor,GR)和矿物皮质激素受体(mineralocorticoid receptor,MR)，这些NRs以同源二聚体的方式与它们的靶DNA序列结合。第II类是尚未发现相应配体的孤儿NRs，它们通常以单体或同源二聚体的形式与DNA结合，如维甲酸相关孤儿受体(retinoid-related orphan receptors,RORs)和神经生长因子IB(nerve growth factorIB,Nurr77)等[9]。第III类为领养的孤儿NRs，即近期发现配体的II类孤儿核受体，包括法尼醇X受体(farnesoid X receptor,FXR)、过氧化物酶体增殖物激活受体(peroxisomeproliferator-activated receptors,PPARs)、肝脏X受体(liver X receptor,LXR)和维甲酸X受体(retinoid X receptor,RXR)等。
1995年，Seol等利用双杂交酵母系统，鉴定出一种可以与RXRα相互作用的新蛋白，并命名为RXR相互作用蛋白14(RXR-interacting protein 14,RIP14)。同年，Forman等从大鼠肝脏cDNA文库中克隆出小鼠RIP14的同源基因，并发现甲戊酸途径的中间体法尼醇(farnesol)能够在超生理浓度下激活大鼠RIP14，因此将RIP14重新命名为FXR。已知FXR有两个基因，分别为FXRα(NR1H4)和FXRβ(NR1H5)。已有的研究表明，FXRα在多种代谢稳态和疾病调节中发挥重要作用。与FXRα不同的是，FXRβ是人类和灵长类的一种假基因，在啮齿动物、兔子和狗中表达，其功能和作用尚不清楚。FXR在肝脏、肠道、肾脏和肾上腺等组织中表达较多，在脂肪组织和心脏中表达较少[19]。四种FXRα亚型均以组织特异性的方式表达，FXRα1和FXRα2主要在人肝脏中表达，FXRα3和FXRα4主要在人肾脏和结肠中表达，而在人小肠中四种亚型均有表达。
FXR的蛋白结构由486个氨基酸组成，全长晶体结构至今尚未被解析，但有多个FXR-LBD(氨基酸序列248-472)与配体结合的共晶结构被解析，为FXR配体的发现和理性药物设计提供了基础。已有研究表明，FXR通过调节胆汁酸(bile acids,BAs)、脂质、葡萄糖和能量稳态，影响人体代谢的多种过程。这使得FXR成为治疗胆汁淤积症、代谢综合症、炎性肠病、心血管疾病和肝脏再生肿瘤等疾病的一个潜在治疗靶点(Sun,L.；Cai,J.；Gonzalez,F.J.,The role of farnesoid X receptor in metabolic diseases,andgastrointestinal and liver cancer.Nat Rev Gastroenterol Hepatol 2021；Han,C.Y.,Update on FXR Biology:Promising Therapeutic Target？Int J Mol Sci 2018,19.)。
FXR调控剂包括激动剂和抑制剂(或拮抗剂)，其中，激动剂的类型如甾体类(例如初级BAs(CA和CDCA)，以及次级BAs(DCA和LCA)，INT-767，MFA-1，NIHS700，TC-100等)和非甾体类(例如1.5.1.2.1异噁唑衍生物-GW4064，氮杂
Figure BDA0003601498440000021
[4,5-b]吲哚衍生物-WAY-362450，苯并咪唑衍生物，Fexaramine类衍生物，以及邻氨基苯甲酸衍生物等)；拮抗剂的类型包括天然产物类FXR拮抗剂(如甾体衍生物、萜类衍生物、Tuberatolide衍生物、白术内酯衍生物、穿心莲内酯衍生物、查尔酮类衍生物、苯酚类衍生物等)和合成类FXR拮抗剂(如异噁唑衍生物－GW4064，1,3,4-三取代吡唑酮衍生物，2,3,4-三取代吡唑类化合物，吡唑-4-甲酰胺衍生物、苯烷基醚衍生物、3-叔丁基苯甲酸酯/酰胺衍生物、苯并咪唑衍生物、叔丁基苯衍生物、恶二唑衍生物等)。
本领域技术人员仍然渴望一种新型结构的FXR调节剂，可用于代谢相关疾病、心血管疾病、肝脏疾病、癌症、肾病、肠病、炎症等疾病的预防或治疗。
发明内容
本申请提供了可作为FXR调控剂的化合物，不仅可以作为FXR拮抗剂，而且毒性低，活性高，具有显著的降脂活性，在安全性和/或药效方面得到提高。
一方面，本申请提供了一种苯并呋喃衍生物，所述苯并呋喃衍生物如式(I)所示：
Figure BDA0003601498440000031
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(I)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基或取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
并规定，
当R1为-(CH2)n-R3，n为1，R4为苯基，R3为甲基时，R2不为羟基；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
另一方面，本申请提供了一种苯并呋喃衍生物作为FXR调节剂的用途，所述苯并呋喃衍生物如式(II)所示：
Figure BDA0003601498440000041
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(II)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基或取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
第三方面，本申请提供了一种药物组合物，所述的药物组合物包含药理学上有效剂量的所述式(I)或式(II)苯并呋喃衍生物或其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
第四方面，本发明提供了所述式(I)或式(II)苯并呋喃衍生物或其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物的制备方法，所述的制备方法包括如下步骤：
2-苯乙胺与式(III)化合物反应，得到式(IV)化合物；
Figure BDA0003601498440000051
当R1不为氢时，在得到式(IV)化合物后，还包括式(IV)化合物与X-R1反应，得到式(V)化合物；
Figure BDA0003601498440000052
任选地还包括式(IV)化合物或式(V)化合物进行基团转化，得到式(I)化合物或式(II)化合物；
Figure BDA0003601498440000061
或者，
式(III)化合物与式(VI)化合物反应，得到式(V)化合物；
Figure BDA0003601498440000062
任选地还包括式(V)化合物进行基团转化，得到式(I)化合物或式(II)化合物；
Figure BDA0003601498440000063
其中，式(III)中X为氯、溴或碘；式(III)、式(IV)和式(V)中R7为C1-C6烷基；式(V)和式(VI)中R1、以及式(III)、式(IV)和式(V)中R3如上述式(I)或式(II)中所定义。
详细描述
本申请中，“芳烃基”和“芳基”可以互换使用。在本申请的一些实施方案中，所述未取代的芳烃基或取代的芳烃基中的芳烃基为苯基、萘基、或茚。
本申请中，“杂芳基”是指至少一个(例如1、2或3个)环原子为杂原子(例如氮原子、氧原子或硫原子)的具有芳香性的环状基团。任选地，环状结构中的环原子(例如碳原子、氮原子或硫原子)可以被氧代。当含有多个杂原子时，所述杂原子可以相同或不同。杂芳基的环原子数优选为5至14，更优选为5至6或9至10。在一些实施方案中，所述杂芳基为5-6元含氮杂芳基(例如吡咯基、咪唑基、恶唑基、吡啶基、嘧啶基)。在一些实施方案中，所述杂芳基为5-6元含氧杂芳基(例如呋喃基、恶唑基或其与苯环稠合得到的基团)。在一些实施方案中，所述杂芳基为噻吩基。
在本申请的一些实施方案中，所述未取代的杂芳基或取代的杂芳基中的杂芳基为呋喃基、噻吩基、吡咯基、恶唑基、噻唑基、咪唑基、吡唑基、三唑基、四唑基、异恶唑基、异噻唑基、恶二唑基、噻二唑基、吡啶基、嘧啶基、吡嗪基、哒嗪基、三嗪基、喹啉基、异喹啉基、噌啉基、酞嗪基、喹唑啉基、喹喔啉基、萘啶基、蝶啶基、吲嗪基、氮杂吲嗪基、吲哚基、氮杂吲哚基、吲唑基、氮杂吲唑基、苯并咪唑基、氮杂苯并咪唑基、苯并三唑基、氮杂苯并三唑基、苯并恶唑基、氮杂苯并恶唑基、苯并异恶唑基、氮杂苯并异恶唑基、苯并呋喃基、氮杂苯并呋喃基、苯并噻吩基、氮杂苯并噻吩基、嘌呤基、或咔唑基等。
本申请中，“杂环基”和“杂环烷基”可以互换使用，指的是至少一个(例如1、2或3个)环原子为杂原子(例如氮原子、氧原子或硫原子)的非芳香性的环状基团。任选地，环状结构中的环原子(例如碳原子、氮原子或硫原子)可以被氧代。当含有多个杂原子时，所述杂原子可以相同或不同。杂环基的环原子数优选为3至10，例如5至7、9至10、6至8。
本申请中，杂环基可以包括单杂环基、螺杂环基、桥杂环基和稠杂环基。
本申请中，“螺杂环基”是指由两个或两个以上环状结构彼此共用一个环原子所形成的、至少一个环原子为杂原子(例如氮原子、氧原子或硫原子)的环状结构。任选地，环状结构中的环原子(例如碳原子、氮原子或硫原子)可以被氧代。螺杂环基的环原子数优选为7至14元，例如9至10元，具体实例包括但不仅限于：
Figure BDA0003601498440000071
Figure BDA0003601498440000072
Figure BDA0003601498440000073
等。在一些实施方案中，所述螺杂环基为含氮螺杂环基，例如9至10元含氮螺杂环基。
本申请中，“桥杂环基”是指由两个或两个以上环状结构彼此共用两个非相邻的环原子所形成的、至少一个环原子为杂原子(例如氮原子、氧原子或硫原子)的环状结构。任选地，环状结构中的环原子(例如碳原子、氮原子或硫原子)可以被氧代。螺杂环基的环原子数优选为6至14元，例如6至8元，具体实例包括但不仅限于：
Figure BDA0003601498440000081
Figure BDA0003601498440000082
Figure BDA0003601498440000083
等。在一些实施方案中，所述桥杂环基为含氮桥杂环基，例如6至8元含氮桥杂环基。
在一些实施方案中，所述杂环基为5-6元含氮单杂环基。在一些实施方案中，所述杂环基为5-6元含氧单杂环基。
在本申请的一些实施方案中，所述杂环烷基为氮杂环丙基基、氮杂环丁烷基、氧杂环丁烷基、硫杂环丁烷基、吡咯烷基、四氢呋喃基、四氢噻吩基、氧代恶唑烷基、四氢吡喃基、哌啶基、吗啉基、硫代吗啉基、哌嗪基、高哌啶基、氧杂环庚烷基、硫杂环庚烷基、氧氮杂
Figure BDA0003601498440000084
基、二氧杂
Figure BDA0003601498440000085
基、或硫氮杂
Figure BDA0003601498440000086
基。
本申请中，“3-6元环烷基”是指含有3-6个碳原子的饱和的环状烷基，在本申请的一些实施方案中，3-6元环烷基选自环丙烷基、环丁烷基、环戊烷基、环己烷基。
本申请中，“碳原子、氮原子或硫原子被氧代”是指形成C＝O、N＝O或S＝O的结构。
在本申请的一些实施方案中，所述卤素为氟、氯、溴、或碘。
在本申请的一些实施方案中，所述未取代的C1-C6烷基为甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、新戊基、或正己基。
在本申请的一些实施方案中，所述未取代的C2-C6烯烃基为乙烯基、1-丙烯-1-基、烯丙基、1-丁烯-1-基、1-戊烯-1-基、1,3-丁二烯-1-基、1,4-戊二烯-1-基等。
在本申请的一些实施方案中，所述未取代的C2-C6炔烃基为乙炔基、1-丙炔-1-基(即丙炔基)、1-丁炔-1-基(即丁炔基)、戊炔-1-基、1,3-丁二炔-1-基、1,4-戊二炔-1-基等。
在本申请的一些实施方案中，所述未取代的C1-C6烷氧基为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基、正戊氧基、新戊氧基、或正己氧基。
在本申请的一些实施方案中，所述卤代C1-C6烷基是指一个或多个选自氟、氯、溴或碘取代未取代的C1-C6烷基上的氢，例如三氟甲基。
在本申请的一些实施方案中，所述卤代C1-C6烷氧基是指一个或多个选自氟、氯、溴或碘取代未取代的C1-C6烷氧基上的氢，例如三氟甲氧基。
在本申请的一些实施方案中，所述C1-C6烷酰基包括(但不限于)甲酰基、乙酰基、正丙酰基、正丁酰基、异丁酰基、正戊酰基、新戊酰基等。
在本申请的一些实施方案中，所述药学上可接受的盐是指本发明的化合物与药学上可接受的无机酸或有机酸或者无机碱或有机碱反应而形成的盐，所述无机酸包括(但不限于)盐酸、氢溴酸、硫酸、磷酸等，所述有机酸包括(但不限于)三氟乙酸、柠檬酸、马来酸、富马酸、琥珀酸、酒石酸、乳酸、丙酮酸、草酸、甲酸、乙酸、苯甲酸、甲磺酸、苯磺酸、对甲苯磺酸等；所述无机碱包括(但不限于)氢氧化钠、氢氧化钾、氢氧化钙、氢氧化锂等，所述有机碱包括(但不限于)二乙胺、三乙胺、氨丁三醇、葡糖胺等。
在本申请的实施方案中，所述水合物包括(但不限于)半水合物、一水合物、二水合物、三水合物等。所述溶剂化物是指由本发明的化合物或其药学上可接受的盐与至少一种溶剂分子所形成的物质，包括(但不限于)甲醇合物、乙醇合物、丙酮合物等。
在本申请的实施方案中，所述互变异构体是指具有不同能量的可通过低能垒互相转化的结构异构体；若互变异构是可能的(如在溶液中)，则可以达到互变异构体的化学平衡。例如，质子互变异构体(或称质子转移互变异构体)包括(但不限于)通过质子迁移来进行的互相转化，如酮-烯醇异构化、亚胺-烯胺异构化、酰胺-亚胺醇异构化等。
在本申请的实施方案中，所述几何异构体是指位于双键或环系两侧的原子(或基团)因相对于参考平面的位置不同而形成的立体异构体；例如顺式或反式，或E式与Z式。
在本申请的实施方案中，所述前药是指在施用于患者后能够直接或间接地提供本发明的化合物的衍生物。
在本申请的实施方案中，所述代谢物是指本发明的化合物体内生物转化后的化合物。
第一方面，本申请提供了一种苯并呋喃衍生物，所述苯并呋喃衍生物如式(I)所述：
Figure BDA0003601498440000101
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(I)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基或取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
并规定，
当R1为-(CH2)n-R4，n为1，R4为苯基，R3为甲基时，R2不为羟基；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
在本申请的一些实施方案中，式(I)中R3为甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、或新戊基。
在本申请的一些实施方案中，式(I)中R3为甲基。
在本申请的一些实施方案中，式(I)中R2为羟基。
在本申请的一些实施方案中，式(I)中R2为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基或苄基；优选地，R2为乙氧基。
在本申请的一些实施方案中，式(I)中R2为-NR5R6；这里，R5和R6各自独立地选自氢、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、新戊基、苄基和苯乙基；优选地，R2为苯乙胺基。
在本申请的一些实施方案中，式(I)中n为0；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6烷基、卤代C1-C6烷基、卤代C1-C6烷氧基、氨甲酰基、卤代C1-C6烷硫基、C1-C6烷酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：未取代的C1-C6烷基、苯基取代的C1-C6烷基、未取代的C1-C6烷氧羰酰基、未取代的C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰，或者C1-C6烷基与吗啉基、哌嗪基、哌嗪甲基和哌啶基中的N形成季铵。
在本申请的一些实施方案中，式(I)中n为1或2；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6、卤代C1-C4烷基、卤代C1-C4烷氧基、C1-C6烷酰基、羧基取代的C1-C6烷基、C1-C6烷氧羰酰基、氨甲酰基、卤代C1-C4烷硫基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、氨甲酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：C1-C6烷基、苯基取代的C1-C6烷基、C1-C6烷氧羰酰基、C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C4烷烃磺酰基、单或双C1-C4取代胺甲酰。
在一些实施方案中，式(I)中n为0。在一些实施方案中，式(I)中n为1。在一些实施方案中，式(I)中n为2。
在一些实施方案中，式(I)中R4为苯基、萘基、吡啶基或喹啉基。
在一些实施方案中，式(I)中R4为被一个或多个选自A组基团取代的苯基。在一些实施方案中，式(I)中R4为被一个或多个选自A组基团取代的萘基。在一些实施方案中，式(I)中R4为被一个或多个选自A组基团取代的吡啶基。在一些实施方案中，式(I)中R4为被一个或多个选自A组基团取代的喹啉基。
在一些实施方案中，A组基团选自：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6烷基、卤代C1-C6烷基、卤代C1-C6烷氧基、氨甲酰基、卤代C1-C6烷硫基、C1-C6烷酰基、C1-C6烷氧基羰酰基、C1-C6烷氧基羰酰基-C1-C6亚烷基、羧基-C1-C6亚烷基、-C1-C6烷氧基羰酰基-C2-C6亚烯基、羧基-C2-C6亚烯基、吗啉基、哌嗪基、哌嗪甲基、哌啶基、苯基、苯基羰基；
在一些实施方案中，B组基团选自：氰基、未取代的C1-C6烷基、苯基取代的C1-C6烷基、未取代的C1-C6烷氧羰酰基、未取代的C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰；任选地，所述苯基被C1-C6烷基、氰基、卤素、卤代C1-C6烷基、氨基、硝基、乙酰胺基、C1-C6烷酰基取代。在一些实例中，所述如式(I)所示苯并呋喃衍生物选自下列化合物：
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(F27-S8)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-26)；
3-甲基-5-(N-3-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-31)；
3-甲基-5-(N-(4-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-32)；
3-甲基-5-(N-(4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-36)；
3-甲基-5-(N-(4-(叔丁基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-38)；
3-甲基-5-(N-(4-(甲氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-40)；
3-甲基-5-(N-(4-(2-甲氧基-2-氧乙基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-41)；
(E)-3-甲基-5-(N-(4-(3-甲氧基-3-氧代丙-1-烯-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-42)；
3-甲基-5-(N-(萘-1-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-53)；
3-甲基-5-(N-(2-氟-4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-54)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-58)；
3-甲基-5-(N-(2-三氟甲基-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-82)；
3-甲基-5-(N-((2’-氰基-[1,1’-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-85)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S26)；
3-甲基-5-(N-(3-苯氧基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S31)；
3-甲基-5-(N-(4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S32)；
3-甲基-5-(N-(4-氨甲酰苄基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S36)；
3-甲基-5-(N-(4-叔丁基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S38)；
3-甲基-5-(N-(4-羧苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S40)；
3-甲基-5-(N-(4-(羧甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S41)；
(E)-3-甲基-5-(N-(4-(2-羧基乙烯基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S42)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S53)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S58)；
3-甲基-5-(N-(2-(三氟甲基)-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S82)；
3-甲基-5-(N-(2'-氰基-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S85)；
3-甲基-5-(N-苯基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-12)；
3-甲基-5-(N,N-二苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-68)；
3-甲基-5-(N-(4-(4-苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M8-69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-71)；
3-甲基-5-(N-(4-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-78)；
3-甲基-5-(N-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-81)；
3-甲基-5-(N-苯乙基-N-(4-苯氧基苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M8-86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-88)；
3-甲基-5-(N-苯乙基-N-苯基氨磺酰)苯并呋喃-2-羧酸(F27-S10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S12)；
3-甲基-5-(N,N-二苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S68)；
3-甲基-5-(N-(4-(4-苯甲酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S71)；
3-甲基-5-(N-(4-(4-(甲磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S78)；
3-甲基-5-(N-(4-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S81)；
3-甲基-5-(N-(4-(4-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S88)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-1)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-2)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)；
3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-98)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苄基乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-100)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-101)；
3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-102)；
3-甲基-5-(N-(2-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-104)；
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-105)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S89)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S91)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S96)；
3-甲基-5-(N-(2-(哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S97)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S98)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺胺基)甲基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S100)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S101)；
3-甲基-5-(N-(2-(4-(甲磺酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S102)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S104)；和
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S105)；或者，其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
第二方面，本申请提供了一种苯并呋喃衍生物作为FXR调节剂的用途，所述苯并呋喃衍生物如式(II)所示：
Figure BDA0003601498440000241
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(II)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基或取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
在本申请的实施方案中，所述苯并呋喃衍生物作为FXR调节剂的用途，优选地，是作为FXR拮抗剂或抑制剂的用途，包括但不限于降脂活性、抗高脂血症活性、抗血脂异常活性、抗动脉粥样硬化活性、抗肥胖症活性、抗糖尿病活性。
在本申请的一些实施方案中，式(II)中R3为甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、或新戊基。
在本申请的一些实施方案中，式(II)中R3为甲基。
在本申请的一些实施方案中，式(II)中R2为羟基。
在本申请的一些实施方案中，式(II)中R2为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基或苄基；优选地，R2为乙氧基。
在本申请的一些实施方案中，式(II)中R2为-NR5R6；这里，R5和R6各自独立地选自氢、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、新戊基、苄基和苯乙基；优选地，R2为苯乙胺基。
在本申请的一些实施方案中，式(II)中n为0；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6烷基、卤代C1-C6烷基、卤代C1-C6烷氧基、氨甲酰基、卤代C1-C6烷硫基、C1-C6烷酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：未取代的C1-C6烷基、苯基取代的C1-C6烷基、未取代的C1-C6烷氧羰酰基、未取代的C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰，或者C1-C6烷基与吗啉基、哌嗪基、哌嗪甲基和哌啶基中的N形成季铵。
在本申请的一些实施方案中，式(II)中n为1或2；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6、卤代C1-C4烷基、卤代C1-C4烷氧基、C1-C6烷酰基、羧基取代的C1-C6烷基、C1-C6烷氧羰酰基、氨甲酰基、卤代C1-C4烷硫基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、氨甲酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：C1-C6烷基、苯基取代的C1-C6烷基、C1-C6烷氧羰酰基、C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C4烷烃磺酰基、单或双C1-C4取代胺甲酰。
在一些实施方案中，式(II)中n为0。在一些实施方案中，式(II)中n为1。在一些实施方案中，式(II)中n为2。
在一些实施方案中，式(II)中R4为苯基、萘基、吡啶基或喹啉基。
在一些实施方案中，式(II)中R4为被一个或多个选自A组基团取代的苯基。在一些实施方案中，式(II)中R4为被一个或多个选自A组基团取代的萘基。在一些实施方案中，式(II)中R4为被一个或多个选自A组基团取代的吡啶基。在一些实施方案中，式(II)中R4为被一个或多个选自A组基团取代的喹啉基。
在一些实施方案中，A组基团选自：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6烷基、卤代C1-C6烷基、卤代C1-C6烷氧基、氨甲酰基、卤代C1-C6烷硫基、C1-C6烷酰基、C1-C6烷氧基羰酰基、C1-C6烷氧基羰酰基-C1-C6亚烷基、羧基-C1-C6亚烷基、-C1-C6烷氧基羰酰基-C2-C6亚烯基、羧基-C2-C6亚烯基、吗啉基、哌嗪基、哌嗪甲基、哌啶基、苯基、苯基羰基；
在一些实施方案中，B组基团选自：氰基、未取代的C1-C6烷基、苯基取代的C1-C6烷基、未取代的C1-C6烷氧羰酰基、未取代的C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰；任选地，所述苯基被C1-C6烷基、氰基、卤素、卤代C1-C6烷基、氨基、硝基、乙酰胺基、C1-C6烷酰基取代。在一些实例中，所述如式(II)所示苯并呋喃衍生物选自下列化合物：
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(F27-S8)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-26)；
3-甲基-5-(N-3-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-31)；
3-甲基-5-(N-(4-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-32)；
3-甲基-5-(N-(4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-36)；
3-甲基-5-(N-(4-(叔丁基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-38)；
3-甲基-5-(N-(4-(甲氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-40)；
3-甲基-5-(N-(4-(2-甲氧基-2-氧乙基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-41)；
(E)-3-甲基-5-(N-(4-(3-甲氧基-3-氧代丙-1-烯-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-42)；
3-甲基-5-(N-(萘-1-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-53)；
3-甲基-5-(N-(2-氟-4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-54)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-58)；
3-甲基-5-(N-(2-三氟甲基-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-82)；
3-甲基-5-(N-((2’-氰基-[1,1’-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-85)；
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S26)；
3-甲基-5-(N-(3-苯氧基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S31)；
3-甲基-5-(N-(4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S32)；
3-甲基-5-(N-(4-氨甲酰苄基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S36)；
3-甲基-5-(N-(4-叔丁基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S38)；
3-甲基-5-(N-(4-羧苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S40)；
3-甲基-5-(N-(4-(羧甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S41)；
(E)-3-甲基-5-(N-(4-(2-羧基乙烯基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S42)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S53)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S58)；
3-甲基-5-(N-(2-(三氟甲基)-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S82)；
3-甲基-5-(N-(2'-氰基-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S85)；
3-甲基-5-(N-苯基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-12)；
3-甲基-5-(N,N-二苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-68)；
3-甲基-5-(N-(4-(4-苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M8-69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-71)；
3-甲基-5-(N-(4-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-78)；
3-甲基-5-(N-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-81)；
3-甲基-5-(N-苯乙基-N-(4-苯氧基苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M8-86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-88)；
3-甲基-5-(N-苯乙基-N-苯基氨磺酰)苯并呋喃-2-羧酸(F27-S10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S12)；
3-甲基-5-(N,N-二苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S68)；
3-甲基-5-(N-(4-(4-苯甲酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S71)；
3-甲基-5-(N-(4-(4-(甲磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S78)；
3-甲基-5-(N-(4-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S81)；
3-甲基-5-(N-(4-(4-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S88)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-1)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-2)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)；
3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-98)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苄基乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-100)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-101)；
3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-102)；
3-甲基-5-(N-(2-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-104)；
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-105)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S89)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S91)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S96)；
3-甲基-5-(N-(2-(哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S97)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S98)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺胺基)甲基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S100)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S101)；
3-甲基-5-(N-(2-(4-(甲磺酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S102)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S104)；和
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S105)；
或者，其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
本申请还提供了式(1)所示的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物；
Figure BDA0003601498440000391
其中，Q选自氢、6至10元芳基、5至14元杂芳基、3至6元环烷基、3至6元杂环基；任选地，所述6至10元芳基、5至14元杂芳基、3至6元环烷基、3至6元杂环基被一个或多个M取代，M选自以下基团：卤素、硝基、羟基、氰基、C1-C6烷基、C2-C6烯基、C2-C6炔基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6烷酰基、C1-C6酰胺基；
L1不存在或选自-(CH2)n-，n为选自1至6的整数；任选地，-(CH2)n-被一个或多个选自以下的基团取代：苯基、卤素、硝基、氰基、羟基、C1-C6烷基、氘、氚；
R1为-(CH2)n-R4，这里，n为0至6的整数，R4和A组基团如权利要求1-6或9任一项所定义；
B组基团选自：氰基、芳烃基取代的C1-C6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C7烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基、C1-C6烷氧基羰酰基、未取代的3-6元环烷基羰酰基、取代的3-6元环烷基羰酰基、取代的5-14元杂芳基羰酰基、未取代的5-14元杂芳基羰酰基、未取代的C2-C6烯基羰酰基、未取代的5-10元杂环基羰酰基、取代的5-10元杂环基羰酰基；
W为5-6元杂芳基；
R8选自氢、卤素、未取代的C1-C6烷基或取代的C1-C6烷基；m选自1、2、3、4；当有多个R8时，各个R8可以相同或不同；
R9选自-CH2OH或-(C＝O)R2，R2如权利要求1-6任一项所定义。
在一些实施方案中，Q选自6至10元芳基、5至8元单环杂芳基、8至14元稠杂芳基、5至6元环烷基、5至6元杂环基；任选地，所述6至10元芳基、5至8元单环杂芳基、8至14元稠杂芳基、5至6元环烷基、5至6元杂环基被一个或多个M取代。在一些实施方案中，Q选自6至10元芳基、5至8元单环杂芳基、5至6元环烷基。在一些实施方案中，Q选自苯基、噻吩基、环己烷基。在一些实施方案中，Q为苯基。
在一些实施方案中，L1不存在或选自-(CH2)n-，n为1、2或3。在一些实施方案中，L1为-(CH2)2-。
在一些实施方案中，R1为被一个或多个选自A组基团所取代的苯基。
在一些实施方案中，A为未取代的或被一个或多个B组基团所取代的杂环烷基。在一些实施方案中，所述杂环基为5-7元单杂环基、9-10元螺杂环基或6-8元桥杂环基。在一些实施方案中，所述杂环基为5-7元含氮单杂环基、9-10元含氮螺杂环基或6-8元含氮桥杂环基。在一些实施方案中，所述杂环基为哌嗪基。
在一些实施方案中，B选自：-(C＝O)-苯基、-(C＝O)-5～6元杂芳基、-(C＝O)-丙烯基、-(C＝O)-5～6元环烷基、-(C＝O)-5～6元杂环基、-(C＝O)-C1-C6烷基。任选地，所述苯基、5～6元杂芳基、5～6元环烷基、5～6元杂环基被1、2或3个选自以下的取代基所取代：C1-C6烷基(例如甲基)、甲酰胺基、乙酰胺基、C1-C6卤代烷基(例如三氟甲基)、氰基、卤素(例如氟、氯、溴)、氨基、硝基、C1-C6烷酰基(例如乙酰基)、C1-C6烷氧基(例如甲氧基)、苄基、乙炔苯基。在一些实施方案中，所述5～6元杂芳基选自吡啶基、噻吩基、呋喃基、吡咯基、咪唑基、恶唑基、噻唑基、吡唑基；任选地，所述5～6元杂芳基被一个或多个C1-C6烷基(例如甲基)或卤素(例如溴)取代。在一些实施方案中，所述5～6元杂环基为四氢噻吩基。
在一些实施方案中，B选自-(C＝O)-苯基、-(C＝O)-噻吩基。
在一些实施方案中，所述化合物如式(2)、(3)、(4)或(5)所示，
Figure BDA0003601498440000401
Figure BDA0003601498440000411
其中，X为O、S、N-R8，R8为氢或未取代的C1-C6烷基。
在一些实施方案中，式(2)、(3)、(4)或(5)中，R8为甲基；
在一些实施方案中，式(2)、(3)、(4)或(5)中，R2为羟基或未取代的C1-C6烷氧基。
在一些实施方案中，所述化合物选自：
Figure BDA0003601498440000421
Figure BDA0003601498440000431
Figure BDA0003601498440000441
Figure BDA0003601498440000451
Figure BDA0003601498440000461
第三方面，本申请提供了一种药物组合物，所述的药物组合物包含有效剂量的本发明的化合物或其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。任选地，所述药物组合物还可以包含一种或多种药学上可接受的载体或赋形剂。所述药物组合物可以制成药学上可接受的任一剂型。以口服、肠胃外、直肠或经肺给药等方式施用于需要这种治疗的患者。用于口服方式给药时，可制成常规的固体制剂，如片剂、胶囊剂、丸剂、颗粒剂等；也可制成口服液体制剂，如口服溶液剂、口服混悬剂、糖浆剂等。制成口服制剂时，可以加入适宜的填充剂、粘合剂、崩解剂、润滑剂等。用于肠胃外给药时，可制成注射剂，包括注射液、注射用无菌粉末与注射用浓溶液。制成注射剂时，可采用现有制药领域中的常规方法生产，配制注射剂时，可以不加入附加剂，也可根据药物的性质加入适宜的附加剂。用于直肠给药时，可制成栓剂等。用于经肺给药时，可制成吸入剂或喷雾剂等。本发明提供的上述药物组合物，可以是口服或非胃肠给药的制剂形式，剂量可以是0.1-1000mg/次/日。
第四方面，本发明提供了所述式(I)或式(II)苯并呋喃衍生物或其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物的制备方法，所述的制备方法包括如下步骤：
2-苯乙胺与式(III)化合物反应，得到式(IV)化合物；
Figure BDA0003601498440000471
当R1不为氢时，在得到式(IV)化合物后，还包括式(IV)化合物与X-R1反应，得到式(V)化合物；
Figure BDA0003601498440000472
任选地还包括式(IV)化合物或式(V)化合物进行基团转化，得到式(I)化合物或式(II)化合物；
Figure BDA0003601498440000473
或者，
式(III)化合物与式(VI)化合物反应，得到式(V)化合物；
Figure BDA0003601498440000481
任选地还包括式(V)化合物进行基团转化，得到式(I)化合物或式(II)化合物；
Figure BDA0003601498440000482
其中，式(III)中X为氯、溴或碘；式(III)、式(IV)和式(V)中R7为C1-C6烷基；式(V)和式(VI)中R1、以及式(III)、式(IV)和式(V)中R3如上述式(I)或式(II)中所定义。
在一些实施方案中，可以通过如下的示例来制备本发明的式(I)或式(II)苯并呋喃衍生物或其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物：
化合物F27及化合物F27-S14～F27-S62和F27-S82～F27-S85的合成路线见方案1.1。首先，邻羟基苯乙酮和溴乙酸乙酯在N,N-二甲基甲酰胺中回流环合生成中间体M1。中间体M1在氯仿中与氯磺酸反应得到中间体M2后，与2-苯基乙烷-1-胺缩合生成中间体M3。中间体M3与取代的苄溴亲核取代生成中间体M4和F27-S8。M4在强碱作用下水解得到终产物F27、F27-S14～F27-S62和F27-S82～F27-S85。
Figure BDA0003601498440000483
方案1.1化合物F27-S14～F27-S62和F27-S82～F27-S85。试剂和反应条件:(a)溴乙酸乙酯,碳酸钾,N,N-二甲基甲酰胺,加热至回流,反应3h,收率:37％；(b)氯磺酸,氯仿,0℃到室温,反应4h,收率:45％；(c)2-苯基乙烷-1-胺,碳酸钾,无水二氯甲烷,反应3h,收率:87％；(d)取代的苄溴,碳酸钾,二氯甲烷,加热至60℃,反应2-72h,收率:48-99％；(e)氢氧化钠或氢氧化锂,乙醇/水＝4:1,加热至回流,反应1h,收率:34-99％.
作为一种实施方案，设计化合物F27-S10～F27-S13、F27-S63～F27-S81和F27-S86～F27-S88的合成路线见方案1.2。首先，4-硝基苯基哌嗪与取代的酰氯缩合生成中间体M5。中间体M5在锌粉盐酸中还原生成相应的氨基中间体M6。苯乙醛或苯乙胺与取代的苯甲胺或苯甲醛通过还原胺化生成中间体M7，或(2-碘乙基)苯与取代的苯胺或苯乙胺亲核取代生成中间体M7。中间体M7与中间体M2酰胺缩合生成中间体M8后，在强碱作用下水解得到终产物F27-S10～F27-S13、F27-S63～F27-S81和F27-S86～F27-S88。
Figure BDA0003601498440000491
方案1.2化合物F27-S10～F27-13、F27-S63～F27-81和F27-S86～F27-88的合成路线。试剂和反应条件:(a)取代的酰氯,三乙胺,无水四氢呋喃,0℃至室温,反应10h,收率:87-93％；(b)锌粉,浓盐酸,室温反应11h,收率:60-99％；(c)取代苄胺或苯甲醛,氰基硼氢化钠,原甲酸三甲酯,甲醇,0℃至室温,反应10h,收率:44-94％；(d)取代苯胺或苯乙胺,碳酸钾,乙腈,加热至60℃,反应24h,收率:6-82％；(e)中间体M2,碳酸钾,二氯甲烷,加热至60℃,反应2-72h,收率:25-97％；(f)氢氧化钠,乙醇/水＝4:1,加热至回流,反应1h,收率:38-99％.
设计化合物F27-S89～F27-S105的合成路线见方案1.3。首先，中间体M8-77和M8-87在三氟乙酸中脱去Boc保护基生成中间体M9。中间体M9与取代的酸酐、酰氯或羧酸缩合生成中间体M10，或与卤代烃亲核取代生成中间体M10。中间体M10在强碱作用下水解得到终产物F27-S89～F27-S105。
Figure BDA0003601498440000501
方案1.3化合物F27-S89～F27-105的合成路线。试剂和反应条件:(a)三氟乙酸,二氯甲烷,室温反应2h,收率:98-99％；(b)取代的酸酐,二异丙基乙胺,二甲氨基吡啶,无水二氯甲烷,0℃至室温,反应5h,或取代的酰氯,三乙胺,无水二氯甲烷,0℃至室温,反应5h,或取代的羧酸,碳二亚胺盐酸盐,羟基苯并三唑,二异丙基乙胺,二甲基氨基吡啶,无水二氯甲烷,室温反应24h,或卤代烃,碳酸钾,乙腈,加热至60℃,反应24h,收率:52-99％；(c)氢氧化钠,乙醇/水＝4:1,加热至回流,反应1h,收率:28-89％.
另一方面，本申请还涉及本发明化合物、其药学上可接受的盐、其酯或它们的立体异构体在制备药物中的用途，所述药物用于预防和/或治疗受试者中与FXR相关的疾病。
本申请还提供了治疗和/或预防受试者中与FXR相关的疾病的方法，其包括将治疗和/或预防有效量的本发明的化合物、其药学上可接受的盐、其酯或它们的立体异构体或者本发明的药物组合物施用给有此需要的受试者。
本申请中，所述化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物可以作为FXR激动剂或FXR拮抗剂被使用。
本申请中，所述与FXR有关的疾病可以选自代谢相关疾病、心血管疾病、肝脏疾病、癌症、肾病、肠病、炎症或其任意组合。所述代谢相关疾病包括但不限于糖脂代谢疾病、胆固醇代谢疾病、脂质代谢疾病、胆汁酸代谢疾病或其任意组合。所述糖脂代谢疾病包括但不限于肥胖症、糖尿病(如2型糖尿病)、血脂异常、高脂血症、高胆固醇、胆汁淤积症、非酒精性脂肪肝、非酒精性脂肪性肝炎或其任意组合。所述心血管疾病包括但不限于动脉粥样硬化、心肌缺血再灌注损伤或其组合。所述肝脏疾病包括但不限于肝切除、肝损伤或其组合。所述癌症包括但不限于乳腺癌、黑色素瘤、脑膜瘤、软组织肉瘤、唾液腺肿瘤、原发性肝癌、椎管内肿瘤、纵隔肿瘤、脑癌、骨癌、阴茎癌、骨肉瘤、颅内肿瘤、舌癌、上颌窦癌、甲状腺癌、恶性淋巴瘤、多发性骨髓瘤、脑垂体腺瘤、睾丸肿瘤、非何杰金氏淋巴癌、膀胱癌、白血病、胃癌、鼻咽癌、喉癌、口腔癌、食管癌、肺癌、肾癌、宫颈癌、绒毛膜癌、外阴癌、皮肤癌、子宫内膜癌、卵巢癌、前列腺癌、胰腺癌、结肠癌、直肠癌、大肠癌、卡波西肉瘤、非黑色素瘤皮肤癌(包括鳞状细胞癌和基底细胞癌)、血管瘤、神经胶质瘤及这些疾病的继发性并发症或其任意组合。所述肾病包括但不限于肾炎、肾病综合征、动脉粥样栓塞性肾脏疾病或其任意组合。
在本申请中，受试者或者患者可以是任何动物，优选地哺乳动物，例如牛科动物、马科动物、猪科动物、犬科动物、猫科动物、啮齿类动物、灵长类动物。其中，特别优选的受试者为人。本申请的其它特征和优点将在随后的说明书中阐述，并且，部分地从说明书中变得显而易见，或者通过实施本申请而了解。本申请的其他优点可通过在说明书以及附图中所描述的方案来实现和获得。
附图说明
附图用来提供对本申请技术方案的理解，并且构成说明书的一部分，与本申请的实施例一起用于解释本申请的技术方案，并不构成对本申请技术方案的限制。
图1表示的是本发明FXR拮抗剂化合物F27-S96的降TG(甘油三酯)(A)和TC(总胆固醇)(B)活性。####p<0.001造模组与溶媒组比较，***p<0.005,****p<0.001给药组与造模组比较。图中数据为三次独立重复试验结果。
具体实施方式
为使本申请的目的、技术方案和优点更加清楚明白，下文中将对本发明的实施例进行详细说明。需要说明的是，在不冲突的情况下，本申请中的实施例及实施例中的特征可以相互任意组合。
MS的测定使用Agilent(ESI)质谱仪，生产商：Agilent,型号：Agilent 6120B制备高分辨质谱质谱采用PE SCLEX QSTAR光谱仪记录。
核磁氢谱和核磁碳谱采用用Bruker AVIII-400光谱仪记录。
薄层色谱法纯化采用的事研讨产的GF254(0.4-0.5nm)硅胶板。
反应的监测采用薄层色谱法(TLC),使用的展开剂体系包括但不限于：二氯甲烷和甲醇体系，正己烷和乙酸乙酯体系和石油醚和乙酸乙酯体系，溶剂的体积比根据化合物调节，但可以加入少量的三乙胺等进行调节。
如实施例中无特殊说明，则反应温度为室温(20-30℃)。
实例中所使用的试剂购自Acros oRganmes，Aldrich Chemical Company或者百灵威化学等公司。
如本文中使用的缩写具有以下含义：
EA：乙酸乙酯；DCM：二氯甲烷；MeOH：甲醇；EtOH：乙醇；PE：石油醚；THF：四氢呋喃；DMF：N,N二甲基甲酰胺；AcCl：乙酰氯；Ac2O：乙酸酐；DMSO：二甲基亚砜；NaOH：氢氧化钠；LiOH：氢氧化锂；。
实施例1
3-甲基苯并呋喃-2-羧酸乙酯(M1)
Figure BDA0003601498440000521
将2-羟基苯乙酮(2.72g,20mmol)，溴乙酸乙酯(5.01g,30mmol)，碳酸钾(5.52g,40mmol)，加入N,N-二甲基甲酰胺(25mL)中加热至160℃反应3h，TLC检测反应完毕后，冷却至室温，减压抽滤出固体，滤饼用乙酸乙酯(25mL)冲洗三次，滤液合并后减压蒸馏除去溶剂，加水(100mL)溶解，乙醚(100mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝15/1～10/1)得白色固体1.54g，收率38％。
实施例2
3-甲基-5-(氯磺酰基)苯并呋喃-2-羧酸乙酯(M2)
Figure BDA0003601498440000522
将3-甲基苯并呋喃-2-羧酸乙酯(3.06g,15mmol)加入三氯甲烷(45mL)中，0℃下搅拌10mins后，滴加氯磺酸(8.70g,75mmol)的三氯甲烷(45mL)溶液，室温搅拌4h，TLC检测反应完毕后，将反应液倒入冰水中，用二氯甲烷(150mL)萃取三次，合并有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经石油醚/乙酸乙酯重结晶得白色固体2.07g，收率46％。
实施例3
3-甲基-5-(N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M3)
Figure BDA0003601498440000531
将5-(氯磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(2.07g,6.86mmol)，碳酸钾(1.89g,13.72mmol)溶于无水二氯甲烷(80mL)中，室温下滴加苯乙胺(0.97g,8.23mmol)的无水二氯甲烷(20mL)溶液，室温搅拌3h，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(100mL)溶解，乙酸乙酯(100mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝10/1～5/1)得白色固体2.33g，收率88％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.8Hz,1H),7.84(dd,J＝8.8,1.9Hz,1H),7.59(d,J＝8.8Hz,1H),7.25–7.13(m,3H),7.10–6.99(m,2H),4.77(t,J＝6.2Hz,1H),4.47(q,J＝7.1Hz,2H),3.24(q,J＝6.9Hz,2H),2.77(t,J＝7.0Hz,2H),2.59(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,137.6,135.2,129.4,128.7,126.8,126.2,125.6,121.6,113.0,61.6,44.3,35.8,14.4,9.4.HRMS(ESI)[M+H]+理论值C20H22NO5S:388.1219；实测值：388.1213.
实施例5
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(F27-S8)
Figure BDA0003601498440000532
将3-甲基-5-(N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(195mg,0.5mmol)，苄溴(171mg,1.0mmol)，碳酸钾(276mg,2.0mmol)溶于无水二氯甲烷(10mL)中，60℃搅拌过夜，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(20mL)溶解，二氯甲烷(20mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝20/1～2/1)得白色固体229mg，收率96％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.5Hz,1H),7.87(dd,J＝8.8,1.7Hz,1H),7.63(d,J＝8.8Hz,1H),7.39–7.23(m,5H),7.22–7.09(m,3H),6.95(d,J＝6.8Hz,2H),4.48(q,J＝7.1Hz,2H),4.40(s,2H),3.45–3.28(m,2H),2.71–2.62(m,2H),2.60(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.3,136.0,135.6,129.4,128.7,128.7,128.5,128.5,128.0,126.5,126.2,125.6,121.5,113.1,61.6,52.2,49.5,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H28NO5S:478.1688；实测值：478.1680.
实施例6
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-14)
Figure BDA0003601498440000541
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟苄溴，其余条件均一致。得白色固体219mg，收率88％。1H NMR(400MHz,氯仿-d)δ8.10(s,1H),7.84(d,J＝8.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.44(t,J＝7.0Hz,1H),7.19(ddp,J＝28.7,21.6,7.4Hz,5H),7.00(dd,J＝12.4,8.1Hz,3H),4.50(s,2H),4.49–4.42(m,2H),3.44–3.36(m,2H),2.79–2.68(m,2H),2.59(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ160.9(d,J＝247.5Hz,1C),159.9,155.8,142.9,138.1,135.4,131.2(d,J＝3.7Hz,1C),129.8(d,J＝8.2Hz,1C),129.4,128.7,128.5,126.5,126.2,125.6,124.5(d,J＝3.6Hz,1C),123.2(d,J＝14.2Hz,1C),121.5,115.4(d,J＝21.8Hz,1C),113.0,61.6,50.0,45.1(d,J＝3.8Hz,1C),35.2,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-118.62.HRMS(ESI)[M+H]+理论值C27H27NO5FS:496.1594；实测值：496.1595.
实施例7
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-15)
Figure BDA0003601498440000542
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氯苄溴，其余条件均一致。得白色固体204mg，收率80％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.88(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.58–7.46(m,1H),7.32(dd,J＝7.3,1.6Hz,1H),7.28–7.09(m,5H),7.01(d,J＝7.0Hz,2H),4.57(s,2H),4.47(q,J＝7.1Hz,2H),3.49–3.36(m,2H),2.75–2.65(m,2H),2.61(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.1,135.3,133.9,133.3,130.5,129.5,129.4,129.1,128.7,128.5,127.2,126.5,126.2,125.6,121.6,113.1,61.6,50.5,49.3,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H27NO5SCl:512.1298；实测值：512.1292.
实施例8
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-16)
Figure BDA0003601498440000551
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-溴苄溴，其余条件均一致。得白色固体267mg，收率96％。1H NMR(400MHz,氯仿-d)δ8.15(s,1H),7.88(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.52(t,J＝7.5Hz,2H),7.29(t,J＝7.6Hz,1H),7.23–7.10(m,4H),7.01(d,J＝7.0Hz,2H),4.56(s,2H),4.47(q,J＝7.1Hz,2H),3.52–3.36(m,2H),2.76–2.65(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.0,135.5,135.3,132.8,130.5,129.4,129.4,128.7,128.5,127.8,126.5,126.2,125.6,123.3,121.6,113.1,61.6,51.8,50.5,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H27NO5SBr:556.0793；实测值：556.0785.
实施例9
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-17)
Figure BDA0003601498440000552
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-甲基苄溴，其余条件均一致。得白色固体208mg，收率85％。1H NMR(400MHz,氯仿-d)δ8.17(s,1H),7.92(d,J＝8.8Hz,1H),7.65(d,J＝8.7Hz,1H),7.18(tt,J＝13.3,7.4Hz,7H),6.88(d,J＝6.8Hz,2H),4.47(q,J＝7.1Hz,2H),4.38(s,2H),3.31–3.19(m,2H),2.61(s,3H),2.57–2.49(m,2H),2.36(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.3,137.6,134.8,133.3,130.8,129.7,129.5,128.6,128.5,128.3,126.4,126.4,126.0,125.6,121.6,113.1,61.6,51.2,49.8,35.7,19.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C28H30NO5S:492.1845；实测值：492.1835.
实施例10
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-18)
Figure BDA0003601498440000561
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-三氟甲基苄溴，其余条件均一致。得白色固体238mg，收率87％。1HNMR(400MHz,氯仿-d)δ8.20(s,1H),7.91(d,J＝8.8Hz,1H),7.81(d,J＝7.9Hz,1H),7.65(t,J＝8.1Hz,2H),7.54(t,J＝7.6Hz,1H),7.38(t,J＝7.6Hz,1H),7.15(dq,J＝14.1,6.9Hz,3H),6.97(d,J＝7.1Hz,2H),4.65(s,2H),4.48(q,J＝7.1Hz,2H),3.51–3.37(m,2H),2.67–2.59(m,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.9,143.1,137.8,135.7(d,J＝1.3Hz,1C),135.0,132.3,129.7,129.6,128.6,128.5,127.6(d,J＝30.5Hz,1C),127.6,126.6,126.1,125.8(t,J＝6.0Hz,1C),125.6,121.6,113.3,61.6,50.7,48.3(d,J＝2.2Hz,1C),34.9,14.3,9.4.19F NMR(376MHz,氯仿-d)δ-59.19.HRMS(ESI)[M+H]+理论值C28H27NO5F3S:546.1562；实测值：546.1562.
实施例11
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-19)
Figure BDA0003601498440000562
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-硝基苄溴，其余条件均一致。得白色固体238mg，收率91％。1H NMR(400MHz,氯仿-d)δ8.16(s,1H),7.98(d,J＝8.1Hz,1H),7.89(d,J＝8.8Hz,1H),7.84(d,J＝7.9Hz,1H),7.64(dd,J＝19.1,8.2Hz,2H),7.43(t,J＝7.8Hz,1H),7.18(q,J＝9.4,8.3Hz,3H),6.99(d,J＝7.3Hz,2H),4.79(s,2H),4.48(q,J＝7.1Hz,2H),3.57–3.42(m,2H),2.75–2.65(m,2H),2.62(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.9,148.2,143.1,137.7,134.8,133.6,132.9,130.2,129.6,128.5,128.4,126.6,126.2,125.5,124.8,121.6,113.3,61.6,51.1,49.3,34.9,14.3,9.4.HRMS(ESI)[M+H]+理论值C27H27N2O7S:523.1539；实测值：523.1534.
实施例12
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-20)
Figure BDA0003601498440000571
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-氟苄溴，其余条件均一致。得白色固体257mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.15(s,1H),7.87(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.27(q,J＝7.7Hz,1H),7.18(dt,J＝11.6,6.8Hz,3H),7.04(d,J＝7.7Hz,1H),6.97(t,J＝8.1Hz,4H),4.47(q,J＝7.1Hz,2H),4.38(s,2H),3.46–3.30(m,2H),2.74–2.64(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ163.0(d,J＝247.9Hz,1C),159.9,155.8,143.0,138.8(d,J＝7.1Hz,1C),138.1,135.4,130.2(d,J＝8.3Hz,1C),129.5,128.6,128.5,126.6,126.2,125.5,123.8(d,J＝2.9Hz,1C),121.5,115.2(d,J＝22.0Hz,1C),114.9(d,J＝21.2Hz,1C),113.1,61.6,51.7(d,J＝1.6Hz,1C),49.7,35.2,14.4,9.4.19FNMR(376MHz,氯仿-d)δ-112.36.HRMS(ESI)[M+H]+理论值C27H27NO5FS:496.1594；实测值：496.1593.
实施例13
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-21)
Figure BDA0003601498440000572
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-氯苄溴，其余条件均一致。得白色固体230mg，收率90％。1H NMR(400MHz,氯仿-d)δ8.13(s,1H),7.86(d,J＝8.8Hz,1H),7.61(d,J＝8.8Hz,1H),7.25–7.08(m,7H),6.96(d,J＝7.1Hz,2H),4.46(q,J＝7.1Hz,2H),4.36(s,2H),3.46–3.31(m,2H),2.72–2.63(m,2H),2.59(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,143.0,138.4,138.1,135.3,134.5,130.0,129.5,128.6,128.5,128.3,128.1,126.6,126.4,126.2,125.5,121.5,113.1,61.6,51.6,49.7,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H27NO5SCl:512.1298；实测值：512.1298.
实施例14
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-22)
Figure BDA0003601498440000581
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-溴苄溴，其余条件均一致。得白色固体265mg，收率92％。1H NMR(400MHz,氯仿-d)δ8.12(s,1H),7.85(d,J＝8.7Hz,1H),7.63(d,J＝8.7Hz,1H),7.39(d,J＝7.0Hz,1H),7.31(s,1H),7.18(dq,J＝14.9,7.1Hz,5H),6.98(d,J＝7.0Hz,2H),4.48(q,J＝7.1Hz,2H),4.35(s,2H),3.48–3.26(m,2H),2.74–2.64(m,2H),2.60(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.5,138.1,135.4,131.3,131.1,130.2,129.5,128.7,128.6,126.9,126.6,126.2,125.6,122.7,121.5,113.2,61.6,51.5,49.7,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H27NO5SBr:556.0793；实测值：556.0792.
实施例15
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-23)
Figure BDA0003601498440000582
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-甲基苄溴，其余条件均一致。得白色固体243mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.87(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.18(ddd,J＝13.0,8.4,5.8Hz,4H),7.08(d,J＝7.6Hz,1H),7.03(s,2H),6.96(d,J＝6.9Hz,2H),4.48(q,J＝7.1Hz,2H),4.36(s,2H),3.43–3.30(m,2H),2.72–2.63(m,2H),2.60(s,3H),2.28(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,142.9,138.4,135.8,135.7,129.4,129.2,128.7,128.7,128.5,128.5,126.5,126.3,125.6,125.5,121.5,113.0,61.6,52.1,49.4,35.2,21.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C28H30NO5S:492.1845；实测值：492.1844.
实施例16
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-24)
Figure BDA0003601498440000591
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-三氟甲基苄溴，其余条件均一致。得白色固体248mg，收率90％。1HNMR(400MHz,氯仿-d)δ8.16(s,1H),7.88(d,J＝8.8Hz,1H),7.63(d,J＝10.2Hz,1H),7.51(dd,J＝13.2,7.7Hz,2H),7.44(d,J＝7.4Hz,2H),7.17(q,J＝8.5,7.5Hz,3H),6.96(d,J＝7.4Hz,2H),4.54–4.40(m,4H),3.53–3.34(m,2H),2.69(t,J＝7.6Hz,2H),2.60(s,3H),1.46(t,J＝6.3Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,143.1,138.0,137.4,135.3,131.7,130.9(d,J＝32.0Hz,1C),129.5,129.2,128.6,128.5,126.6,126.2,125.5,124.9(t,J＝3.8Hz,1C),124.7(d,J＝3.7Hz,1C),123.9(d,J＝273.3Hz,1C),121.5,113.1,61.6,51.7,49.8,35.2,14.3,9.3.19F NMR(376MHz,氯仿-d)δ-62.67.HRMS(ESI)[M+H]+理论值C28H27NO5F3S:546.1562；实测值：546.1556.
实施例17
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-25)
Figure BDA0003601498440000601
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-硝基苄溴，其余条件均一致。得白色固体259mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.19(s,1H),8.05(d,J＝8.7Hz,2H),7.90(d,J＝8.7Hz,1H),7.64(dd,J＝15.4,8.2Hz,2H),7.46(t,J＝7.8Hz,1H),7.12(q,J＝10.2,8.3Hz,3H),6.95(d,J＝6.9Hz,2H),4.46(dd,J＝15.3,8.2Hz,4H),3.55–3.39(m,2H),2.81–2.67(m,2H),2.60(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.7,155.8,148.2,143.0,138.9,137.9,134.8,134.2,129.6,129.5,128.5,128.5,126.5,126.2,125.4,122.8,122.7,121.6,113.1,61.5,51.5,50.0,35.1,14.3,9.3.HRMS(ESI)[M+H]+理论值C27H27N2O7S:523.1539；实测值：523.1531.
实施例18
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-26)
Figure BDA0003601498440000602
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-苯基苄溴，其余条件均一致。得白色固体211mg，收率76％。1H NMR(400MHz,氯仿-d)δ8.20(s,1H),7.93(d,J＝10.6Hz,1H),7.61(d,J＝8.8Hz,1H),7.52(d,J＝7.8Hz,1H),7.47(d,J＝7.1Hz,2H),7.44–7.37(m,4H),7.34(t,J＝7.2Hz,1H),7.28(d,J＝7.6Hz,1H),7.18(dd,J＝13.4,7.2Hz,3H),7.03(d,J＝6.7Hz,2H),4.53(s,2H),4.49(t,J＝7.1Hz,2H),3.57–3.44(m,2H),2.85–2.73(m,2H),2.58(s,3H),1.49(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ159.9,155.8,143.0,141.5,140.4,138.4,136.6,135.8,129.5,129.2,128.8,128.7,128.6,127.5,127.4,127.0,127.0,126.7,126.5,126.3,125.6,121.5,113.1,61.6,52.1,49.5,35.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C33H32NO5S:554.2001；实测值：554.2007.
实施例19
3-甲基-5-(N-3-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-27)
Figure BDA0003601498440000611
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为3-苯氧基苄溴，其余条件均一致。得白色固体213mg，收率75％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.84(d,J＝8.8Hz,1H),7.57(d,J＝8.8Hz,1H),7.27(dt,J＝10.8,7.7Hz,3H),7.16(dq,J＝14.3,7.1Hz,3H),7.10–7.00(m,2H),6.97(d,J＝6.7Hz,2H),6.90(dd,J＝18.7,8.4Hz,4H),4.45(q,J＝7.1Hz,2H),4.36(s,2H),3.46–3.31(m,2H),2.76–2.64(m,2H),2.58(s,3H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,157.6,156.9,155.8,143.0,138.3,138.2,135.5,130.1,129.8,129.4,128.7,128.6,126.6,126.2,125.6,123.5,123.3,121.5,118.8,118.8,118.3,113.1,61.6,51.8,49.5,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C33H32NO6S:570.1950；实测值：570.1948.
实施例20
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-28)
Figure BDA0003601498440000612
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-氟苄溴，其余条件均一致。得白色固体220mg，收率89％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.86(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.25(dd,J＝8.4,5.4Hz,2H),7.21–7.11(m,3H),7.04–6.90(m,4H),4.47(q,J＝7.1Hz,2H),4.35(s,2H),3.43–3.29(m,2H),2.63(d,J＝16.1Hz,5H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ162.5(d,J＝247.6Hz,1C),159.9,155.8,143.0,138.2,135.4,131.9(d,J＝3.2Hz,1C),130.1(d,J＝8.2Hz,1C),129.5,128.6,128.5,126.5,126.2,125.5,121.5,115.6(d,J＝21.6Hz,1C),113.1,61.6,51.5,49.5,35.2,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-114.08.HRMS(ESI)[M+H]+理论值C27H27NO5FS:496.1594；实测值：496.1593.
实施例21
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-29)
Figure BDA0003601498440000621
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-氯苄溴，其余条件均一致。得白色固体222mg，收率87％。1H NMR(400MHz,氯仿-d)δ8.12(s,1H),7.86(d,J＝8.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.30–7.23(m,2H),7.22–7.11(m,5H),6.95(d,J＝6.5Hz,2H),4.48(q,J＝7.1Hz,2H),4.34(s,2H),3.43–3.29(m,2H),2.69–2.62(m,2H),2.60(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.1,135.4,134.7,133.8,129.7,129.5,128.8,128.6,128.6,126.6,126.2,125.5,121.5,113.1,61.6,51.6,49.6,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H27NO5SCl:512.1298；实测值：512.1299.
实施例22
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-30)
Figure BDA0003601498440000622
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-溴苄溴，其余条件均一致。得白色固体193mg，收率70％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.8Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.7Hz,1H),7.42(d,J＝8.3Hz,2H),7.17(dd,J＝17.6,7.7Hz,5H),6.96(d,J＝6.5Hz,2H),4.49(q,J＝7.1Hz,2H),4.34(s,2H),3.48–3.30(m,2H),2.70–2.64(m,2H),2.62(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,143.0,138.1,135.3,135.2,131.8,130.0,129.4,128.6,128.5,126.6,126.2,125.5,121.9,121.5,113.1,61.6,51.6,49.6,35.2,14.4,9.4.
实施例23
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-31)
Figure BDA0003601498440000631
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-甲基苄溴，其余条件均一致。得白色固体101mg，收率69％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.88(dd,J＝8.7,1.5Hz,1H),7.62(d,J＝8.8Hz,1H),7.24–7.07(m,7H),6.97(d,J＝7.0Hz,2H),4.48(q,J＝7.1Hz,2H),4.37(s,2H),3.42–3.31(m,2H),2.73–2.64(m,2H),2.60(s,3H),2.33(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,142.9,138.4,137.7,135.7,132.9,129.4,129.4,128.7,128.5,128.5,126.5,126.3,125.6,121.5,113.0,61.6,51.8,49.3,35.2,21.1,14.4,9.4.HRMS(ESI)[M+H]+理论值C28H30NO5S:492.1845；实测值：492.1837.
实施例24
3-甲基-5-(N-(4-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-32)
Figure BDA0003601498440000632
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-三氟甲基苄溴，其余条件均一致。得白色固体132mg，收率80％。1HNMR(400MHz,氯仿-d)δ8.19–8.12(m,1H),7.87(dd,J＝8.8,1.6Hz,1H),7.64(d,J＝8.8Hz,1H),7.55(d,J＝8.1Hz,2H),7.38(d,J＝8.0Hz,2H),7.16(t,J＝7.7Hz,3H),6.94(d,J＝6.5Hz,2H),4.48(q,J＝7.1Hz,2H),4.43(s,2H),3.48–3.32(m,2H),2.74–2.64(m,2H),2.60(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,143.1,140.4,138.0,135.2,129.5,128.6,128.6,128.5,126.6,126.1,125.6(d,J＝3.7Hz,1C),125.5,121.6,113.2,61.6,51.8,49.9,35.1,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-62.51.HRMS(ESI)[M+H]+理论值C28H27NO5F3S:546.1562；实测值：546.1567.
实施例25
3-甲基-5-(N-(4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-33)
Figure BDA0003601498440000641
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-氰基苄溴，其余条件均一致。得白色固体189mg，收率75％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.9Hz,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.63(dd,J＝22.4,8.5Hz,3H),7.39(d,J＝8.0Hz,2H),7.18(q,J＝5.7Hz,3H),6.98–6.89(m,2H),4.48(q,J＝7.1Hz,2H),4.41(s,2H),3.44–3.33(m,2H),2.63(d,J＝14.3Hz,5H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.9,143.2,141.9,137.8,135.0,132.5,129.6,128.7,128.6,128.6,126.7,126.1,125.4,121.6,118.5,113.3,111.9,61.7,52.0,50.0,35.1,14.4,9.4.
实施例26
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-34)
Figure BDA0003601498440000642
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(三氟甲氧基)苄溴，其余条件均一致。得白色固体289mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.17(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.31(d,J＝8.6Hz,2H),7.18(q,J＝8.9,7.7Hz,5H),6.95(d,J＝6.6Hz,2H),4.49(q,J＝7.1Hz,2H),4.40(s,2H),3.47–3.33(m,2H),2.72–2.65(m,2H),2.62(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,148.8,143.0,138.1,135.3,135.0,129.7,129.5,128.6,128.5,126.5,126.1,125.5,121.5,121.1,113.1,61.6,51.5,49.6,35.2,14.3,9.3.
实施例27
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-35)
Figure BDA0003601498440000651
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(三氟甲硫基)苄溴，其余条件均一致。得白色固体237mg，收率82％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.8Hz,1H),7.85(dd,J＝8.7,1.9Hz,1H),7.59(dd,J＝17.7,8.4Hz,3H),7.32(d,J＝8.1Hz,2H),7.22–7.08(m,3H),6.92(dd,J＝7.6,1.5Hz,2H),4.57–4.29(m,4H),3.47–3.31(m,2H),2.62(d,J＝25.5Hz,5H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,143.1,139.7,138.0,136.5,135.2,129.6(d,J＝309.4Hz,1C),129.5,129.3,128.6,128.5,126.6,126.2,125.5,123.8(d,J＝2.4Hz,1C),121.6,113.2,61.6,51.8,49.9,35.2,14.3,9.3.19F NMR(376MHz,氯仿-d)δ-42.65.
实施例28
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-36)
Figure BDA0003601498440000652
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-异丙基苄溴，其余条件均一致。得白色固体234mg，收率90％。1H NMR(400MHz,氯仿-d)δ8.17(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.23–7.11(m,7H),6.96(d,J＝6.8Hz,2H),4.48(q,J＝7.1Hz,2H),4.39(s,2H),3.45–3.32(m,2H),2.89(hept,J＝6.8Hz,1H),2.74–2.64(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H),1.24(d,J＝6.9Hz,6H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,148.7,142.9,138.4,135.7,133.2,129.4,128.7,128.6,128.5,126.7,126.5,126.3,125.6,121.5,113.0,61.6,51.8,49.3,35.3,33.8,24.0,14.4,9.4.
实施例29
3-甲基-5-(N-(4-(叔丁基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-37)
Figure BDA0003601498440000661
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(叔丁基)苄溴，其余条件均一致。得白色固体236mg，收率89％。1HNMR(400MHz,氯仿-d)δ8.18(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.33(d,J＝8.4Hz,2H),7.23–7.11(m,5H),7.00–6.92(m,2H),4.48(q,J＝7.1Hz,2H),4.40(s,2H),3.50–3.26(m,2H),2.75–2.65(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H),1.31(s,9H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,151.0,142.9,138.4,135.7,132.9,129.4,128.7,128.5,128.3,126.5,126.3,125.6,125.6,121.6,113.0,61.6,51.7,49.3,35.3,34.6,31.4,14.4,9.4.
实施例30
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-38)
Figure BDA0003601498440000662
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(乙酰基)苄溴，其余条件均一致。得白色固体256mg，收率98％。1HNMR(400MHz,氯仿-d)δ8.11(d,J＝1.9Hz,1H),7.95–7.76(m,3H),7.57(d,J＝8.7Hz,1H),7.33(d,J＝8.1Hz,2H),7.20–7.02(m,3H),6.97–6.84(m,2H),4.50–4.33(m,4H),3.42–3.28(m,2H),2.67–2.49(m,8H),1.40(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ198.8,159.9,155.8,142.9,142.2,138.0,136.3,135.1,129.4,128.8,128.6,128.5,128.4,126.5,126.2,125.5,121.5,113.2,61.6,51.9,49.9,35.1,26.5,14.3,9.4.HRMS(ESI)[M+H]+理论值C29H30NO6S:520.1794；实测值：520.1786.
实施例31
3-甲基-5-(N-(4-(甲氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-39)
Figure BDA0003601498440000671
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(甲氧羰基)苄溴，其余条件均一致。得白色固体188mg，收率70％。1HNMR(400MHz,氯仿-d)δ8.12(d,J＝1.9Hz,1H),7.94(d,J＝7.9Hz,2H),7.85(dd,J＝8.8,1.9Hz,1H),7.61(d,J＝8.8Hz,1H),7.32(d,J＝8.0Hz,2H),7.14(dq,J＝14.2,6.9Hz,3H),6.92(d,J＝6.7Hz,2H),4.57–4.34(m,4H),3.88(s,3H),3.48–3.29(m,2H),2.61(d,J＝25.1Hz,5H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ166.6,159.8,155.8,143.0,141.4,138.0,135.3,129.9,129.8,129.5,128.6,128.5,128.2,126.6,126.2,125.5,121.5,113.1,61.6,52.1,52.0,49.9,35.2,14.4,9.4.
实施例32
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-40)
Figure BDA0003601498440000672
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-(叔丁氧羰基)苄溴，其余条件均一致。得白色固体273mg，收率94％。1H NMR(400MHz,氯仿-d)δ8.12(d,J＝1.6Hz,1H),7.92(d,J＝8.2Hz,2H),7.87(dd,J＝8.8,1.8Hz,1H),7.62(d,J＝8.8Hz,1H),7.31(d,J＝8.2Hz,2H),7.16(p,J＝6.8Hz,3H),6.95(d,J＝6.7Hz,2H),4.43(s,4H),3.43–3.31(m,2H),2.70–2.61(m,2H),2.59(s,3H),1.59(s,9H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ165.3,159.8,155.8,143.0,140.8,138.1,135.3,131.7,129.7,129.4,128.6,128.5,128.1,126.5,126.2,125.5,121.5,113.1,81.1,61.5,51.9,49.8,35.2,28.2,14.4,9.4.
实施例33
3-甲基-5-(N-(4-(2-甲氧基-2-氧乙基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-41)
Figure BDA0003601498440000681
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-(4-(溴甲基)苯基)乙酸甲酯，其余条件均一致。得白色固体150mg，收率55％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.9Hz,1H),7.85(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.25–7.10(m,7H),6.94(d,J＝6.8Hz,2H),4.47(q,J＝7.1Hz,2H),4.37(s,2H),3.67(s,3H),3.60(s,2H),3.41–3.29(m,2H),2.62(d,J＝20.1Hz,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ171.8,159.9,155.8,143.0,138.3,135.5,134.9,133.8,129.6,129.4,128.7,128.5,126.5,126.2,125.6,121.5,113.1,61.6,52.1,51.7,49.4,40.8,35.2,14.4,9.4.
实施例34
(E)-3-甲基-5-(N-(4-(3-甲氧基-3-氧代丙-1-烯-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-42)
Figure BDA0003601498440000682
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为(E)-3-(4-(溴甲基)苯基)丙烯酸甲酯，其余条件均一致。得白色固体134mg，收率48％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.69–7.59(m,2H),7.44(d,J＝8.1Hz,2H),7.29(d,J＝8.0Hz,2H),7.22–7.10(m,3H),6.95(dd,J＝7.9,1.6Hz,2H),6.42(d,J＝16.0Hz,1H),4.47(q,J＝7.1Hz,2H),4.41(s,2H),3.80(s,3H),3.44–3.34(m,2H),2.73–2.64(m,2H),2.59(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ167.2,159.8,155.8,144.0,143.0,138.6,138.1,135.4,134.1,129.4,128.8,128.6,128.5,128.3,126.5,126.2,125.5,121.5,118.1,113.1,61.6,51.9,51.7,49.7,35.2,14.4,9.4.
实施例35
3-甲基-5-(N-(萘-1-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-43)
Figure BDA0003601498440000691
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为1-(溴甲基)萘，其余条件均一致。得白色固体220mg，收率84％。1H NMR(400MHz,氯仿-d)δ8.28(d,J＝8.1Hz,1H),8.20(s,1H),7.95(d,J＝8.5Hz,1H),7.81(t,J＝6.7Hz,2H),7.62(d,J＝8.7Hz,1H),7.50(dt,J＝15.2,6.7Hz,2H),7.36(d,J＝8.8Hz,2H),7.08(d,J＝7.3Hz,3H),6.75(d,J＝6.7Hz,2H),4.80(s,2H),4.46(q,J＝6.9Hz,2H),3.40–3.10(m,2H),2.58(s,3H),2.46–2.29(m,2H),1.44(t,J＝7.0Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.9,143.0,138.3,134.5,133.9,132.0,130.9,129.5,129.4,128.7,128.6,128.4,127.9,126.8,126.5,126.4,126.2,125.6,125.0,124.0,121.7,113.1,61.6,51.4,49.9,35.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C31H30NO5S:528.1845；实测值：528.1837.
实施例36
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-44)
Figure BDA0003601498440000701
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为8-(溴甲基)喹啉，其余条件均一致。得白色固体222mg，收率84％。1HNMR(400MHz,氯仿-d)δ8.83(d,J＝2.6Hz,1H),8.19–8.07(m,2H),7.95(d,J＝7.1Hz,1H),7.88(d,J＝10.3Hz,1H),7.71(d,J＝8.0Hz,1H),7.61–7.47(m,2H),7.36(dd,J＝8.2,4.2Hz,1H),7.11(dq,J＝14.2,7.0Hz,3H),6.94(d,J＝7.0Hz,2H),5.22(s,2H),4.46(q,J＝7.1Hz,2H),3.71–3.50(m,2H),2.91–2.66(m,2H),2.56(s,3H),1.44(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ159.9,155.6,149.5,146.2,142.8,138.4,136.4,135.7,134.8,129.7,129.2,128.7,128.4,128.1,127.7,126.5,126.3,126.3,125.6,121.4,121.2,112.8,61.5,50.8,47.5,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C30H29N2O5S:529.1797；实测值：529.1790.
实施例37
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-45)
Figure BDA0003601498440000702
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-(溴甲基)萘，其余条件均一致。得白色固体214mg，收率81％。1H NMR(400MHz,氯仿-d)δ8.15(s,1H),7.92(d,J＝8.8Hz,1H),7.82–7.69(m,3H),7.66–7.57(m,2H),7.50–7.38(m,3H),7.14(t,J＝7.5Hz,3H),6.95(d,J＝6.2Hz,2H),4.58(s,2H),4.48(q,J＝7.1Hz,2H),3.53–3.41(m,2H),2.79–2.68(m,2H),2.52(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.7,142.9,138.3,135.6,133.5,133.2,133.0,129.4,128.7,128.6,128.5,127.8,127.7,127.4,126.5,126.4,126.3,126.2,126.1,125.6,121.6,113.1,61.6,52.4,49.7,35.3,14.4,9.3.HRMS(ESI)[M+H]+理论值C31H30NO5S:528.1845；实测值：528.1853.
实施例38
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-46)
Figure BDA0003601498440000711
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,6-二氟苄溴，其余条件均一致。得白色固体203mg，收率79％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.6Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.59(d,J＝8.8Hz,1H),7.31–7.21(m,3H),7.20–7.13(m,1H),7.12–7.05(m,2H),6.85(t,J＝7.9Hz,2H),4.56(s,2H),4.48(q,J＝7.1Hz,2H),3.49–3.35(m,2H),2.94–2.80(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ161.8(dd,J＝251.5,7.8Hz,1C),159.9,155.8,142.9,138.3,135.2,130.5(t,J＝10.5Hz,1C),129.2,128.7(d,J＝20.6Hz,1C),126.4(d,J＝10.4Hz,1C),125.6,121.6,112.9,111.9,111.6(dd,J＝19.5,6.1Hz,1C),61.5,49.9,39.4(t,J＝2.9Hz,1C),35.5,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-112.91.HRMS(ESI)[M+H]+理论值C27H26NO5F2S:514.1500；实测值：514.1494.
实施例39
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-47)
Figure BDA0003601498440000712
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-6-氯苄溴，其余条件均一致。得白色固体240mg，收率91％。1H NMR(400MHz,氯仿-d)δ8.16(d,J＝1.7Hz,1H),7.91(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.25–7.13(m,5H),7.04–6.94(m,3H),4.63(s,2H),4.48(q,J＝7.1Hz,2H),3.40–3.28(m,2H),2.78–2.70(m,2H),2.62(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ162.2(d,J＝252.6Hz,1C),159.9,155.8,142.9,138.3,136.3(d,J＝5.2.Hz,1C),134.9,130.5(d,J＝10.0Hz,1C),129.3,128.7,128.5,126.5,126.4,125.8(d,J＝3.4Hz,1C),125.6,121.7,121.5(d,J＝17.0Hz,1C),114.3(d,J＝22.8Hz,1C),112.9,61.6,50.1,43.6(d,J＝2.7Hz,1C),35.9,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-110.75.HRMS(ESI)[M+H]+理论值C27H26NO5FSCl:530.1204；实测值：530.1207.
实施例40
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-48)
Figure BDA0003601498440000721
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-6-(三氟甲基)苄溴，其余条件均一致。得白色固体260mg，收率92％。1H NMR(400MHz,氯仿-d)δ8.22–8.13(m,1H),7.91(dd,J＝8.8,1.5Hz,1H),7.61(d,J＝8.8Hz,1H),7.47(d,J＝7.7Hz,1H),7.41(q,J＝7.9Hz,1H),7.14(tt,J＝22.7,8.2Hz,4H),6.88(d,J＝7.1Hz,2H),4.66(s,2H),4.44(q,J＝7.1Hz,2H),3.35–3.18(m,2H),2.58(d,J＝7.2Hz,5H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ162.4(d,J＝252.4Hz,1C),159.8,155.8,142.9,138.2,134.4,130.5(d,J＝9.5Hz,1C),129.4,128.5(d,J＝6.8Hz,1C),126.5(d,J＝13.2Hz,1C),125.5,122.4,122.0,121.8,119.9(d,J＝22.9Hz,1C),113.0,61.5,50.0,43.3,35.9,14.3,9.3.19F NMR(376MHz,氯仿-d)δ-57.85,-109.39.HRMS(ESI)[M+H]+理论值C28H26NO5F4S:564.1468；实测值：564.1466.
实施例41
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-49)
Figure BDA0003601498440000722
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,6-二氯苄溴，其余条件均一致。得白色固体254mg，收率93％。1H NMR(400MHz,氯仿-d)δ8.17(d,J＝1.5Hz,1H),7.93(dd,J＝8.8,1.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.27(d,J＝7.7Hz,2H),7.24–7.08(m,4H),6.92(d,J＝6.9Hz,2H),4.70(s,2H),4.47(q,J＝7.1Hz,2H),3.41–3.21(m,2H),2.62(d,J＝5.8Hz,5H),1.45(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ159.8,155.8,142.9,138.3,137.2,134.3,130.8,130.3,129.3,128.8,128.7,128.5,126.6,126.4,125.6,121.8,112.9,61.6,50.2,48.0,36.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H26NO5SCl2:546.0909；实测值：546.0917.
实施例42
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-50)
Figure BDA0003601498440000731
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,6-二甲基苄溴，其余条件均一致。得白色固体122mg，收率80％。1HNMR(400MHz,氯仿-d)δ8.21–8.11(m,1H),7.93(dd,J＝8.7,1.6Hz,1H),7.67(d,J＝8.7Hz,1H),7.23–7.09(m,4H),7.04(d,J＝7.5Hz,2H),6.79(d,J＝6.8Hz,2H),4.48(q,J＝7.1Hz,2H),4.42(s,2H),3.15–3.04(m,2H),2.63(s,3H),2.55–2.45(m,2H),2.34(s,6H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.5,138.5,133.9,130.9,129.5,128.8,128.6,128.5,126.4,126.3,125.6,121.7,113.0,61.6,49.9,47.6,37.0,20.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C29H32NO5S:506.2001；实测值：506.1993.
实施例43
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-51)
Figure BDA0003601498440000741
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,4-二氟苄溴，其余条件均一致。得白色固体252mg，收率98％。1H NMR(400MHz,氯仿-d)δ8.10(s,1H),7.83(d,J＝8.7Hz,1H),7.61(d,J＝8.8Hz,1H),7.44(q,J＝8.4Hz,1H),7.17(dq,J＝14.1,7.0Hz,3H),7.01(d,J＝6.9Hz,2H),6.85(t,J＝8.1Hz,1H),6.80–6.70(m,1H),4.47(dd,J＝15.5,8.3Hz,4H),3.46–3.33(m,2H),2.78–2.67(m,2H),2.60(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ163.0(dd,J＝250.8,12.2Hz,1C),160.8(dd,J＝249.8,11.9Hz,1C),159.9,155.8,143.0,138.0,135.3,132.1(dd,J＝9.7,5.4Hz,1C),129.4,128.6(d,J＝11.1Hz,1C),126.6,126.2,125.5,121.5,119.3(dd,J＝14.3,3.7Hz,1C),113.1,111.8(dd,J＝21.3,3.7Hz,1C),103.7(t,J＝25.6Hz,1C),61.6,50.0,44.8(d,J＝3.1Hz,1C),35.1,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-109.80,-114.40.HRMS(ESI)[M+H]+理论值C27H26NO5F2S:514.1500；实测值：514.1497.
实施例44
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-52)
Figure BDA0003601498440000742
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-4-氯苄溴，其余条件均一致。得白色固体252mg，收率95％。1H NMR(400MHz,氯仿-d)δ8.08(d,J＝1.5Hz,1H),7.83(dd,J＝8.8,1.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.38(t,J＝8.2Hz,1H),7.17(dq,J＝14.3,7.1Hz,3H),7.11–7.06(m,1H),7.05–6.96(m,3H),4.54–4.38(m,4H),3.47–3.34(m,2H),2.80–2.66(m,2H),2.59(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ160.9(d,J＝250.9Hz,1C),159.8,155.8,143.0,137.9,135.2,134.6(d,J＝10.2Hz,1C),131.9(d,J＝4.6Hz,1C),129.4,128.6(d,J＝10.8Hz,1C),126.6,126.2,125.5,124.9(d,J＝3.5Hz,1C),122.1(d,J＝14.4Hz,1C),121.5,116.1(d,J＝25.5Hz,1C),113.1,61.6,50.2,44.9(d,J＝3.3Hz,1C),35.1,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-115.97.HRMS(ESI)[M+H]+理论值C27H26NO5FSCl:530.1204；实测值：530.1215.
实施例45
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-53)
Figure BDA0003601498440000751
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-4-溴苄溴，其余条件均一致。得白色固体280mg，收率98％。1H NMR(400MHz,氯仿-d)δ8.07(d,J＝1.6Hz,1H),7.82(dd,J＝8.8,1.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.31(t,J＝8.1Hz,1H),7.25–7.11(m,5H),7.05–6.97(m,2H),4.52–4.38(m,4H),3.45–3.36(m,2H),2.78–2.68(m,2H),2.59(s,3H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ160.5(d,J＝251.9Hz,1C),159.8,155.8,143.0,137.9,135.2,132.2(d,J＝4.4Hz,1C),129.4,128.6(d,J＝10.6Hz,1C),127.8(d,J＝3.5Hz,1C),126.6,126.1,125.5,122.6(d,J＝14.3Hz,1C),122.1(d,J＝9.5Hz,1C),121.5,119.0(d,J＝25.1Hz,1C),113.1,61.6,50.2,44.9(d,J＝3.5Hz,1C),35.1,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-115.76.HRMS(ESI)[M+H]+理论值C27H26NO5FSBr:574.0699；实测值：574.0704.
实施例46
3-甲基-5-(N-(2-氟-4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-54)
Figure BDA0003601498440000752
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-4-氰基苄溴，其余条件均一致。得白色固体230mg，收率92％。1HNMR(400MHz,氯仿-d)δ8.12(s,1H),7.84(d,J＝8.7Hz,1H),7.62(dd,J＝11.9,8.0Hz,2H),7.40(d,J＝8.0Hz,1H),7.28(d,J＝9.1Hz,1H),7.16(t,J＝8.0Hz,3H),6.99(d,J＝7.1Hz,2H),4.47(d,J＝9.5Hz,4H),3.43(t,J＝7.7Hz,2H),2.80–2.48(m,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9(d,J＝251.0Hz,1C),159.8,155.9,143.1,137.6,134.6,131.7(d,J＝4.3Hz,1C),129.8(d,J＝14.2Hz,1C),129.5,128.6,128.4(d,J＝3.4Hz,1C),126.7,126.1,125.4,121.6,119.0(d,J＝25.4Hz,1C),117.3(d,J＝2.4Hz,1C),113.3,113.1(d,J＝9.7Hz,1C),61.6,50.6,45.3(d,J＝3.4Hz,1C),35.0,14.3,9.1106-4.19F NMR(376MHz,氯仿-d)δ-115.58.HRMS(ESI)[M+H]+理论值C28H26N2O5FS:521.1546；实测值：521.1552.
实施例47
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-55)
Figure BDA0003601498440000761
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氟-4-(三氟甲基)苄溴，其余条件均一致。得白色固体266mg，收率95％。1H NMR(400MHz,氯仿-d)δ8.02(s,1H),7.82–7.70(m,1H),7.51(dd,J＝14.2,8.1Hz,2H),7.27(d,J＝7.9Hz,1H),7.21–7.00(m,4H),6.91(d,J＝6.8Hz,2H),4.56–4.28(m,4H),3.47–3.24(m,2H),2.75–2.59(m,2H),2.51(s,3H),1.36(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ160.2(d,J＝249.7Hz,1H),159.8,155.9,143.1,137.8,134.9,131.5(d,J＝3.9Hz,1C),129.5,128.6,128.6,127.8(d,J＝14.2Hz,1C),126.6,126.1,125.5,121.6,121.4(t,J＝3.4Hz,1C),113.2,112.9(d,J＝3.9Hz,1C),112.6(d,J＝3.7Hz,1C),61.6,50.4,45.1(d,J＝3.7Hz,1C),35.1,14.3,9.3.19F NMR(376MHz,氯仿-d)δ-62.76,-116.40.HRMS(ESI)[M+H]+理论值C28H26NO5F4S:564.1468；实测值：564.1464.
实施例48
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-56)
Figure BDA0003601498440000771
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-氯-4-氟苄溴，其余条件均一致。得白色固体268mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.23–8.07(m,1H),7.87(d,J＝8.7Hz,1H),7.64(d,J＝8.8Hz,1H),7.52(dd,J＝8.5,6.2Hz,1H),7.17(dq,J＝14.2,7.0Hz,3H),7.10–6.93(m,4H),4.47(dd,J＝14.5,7.3Hz,4H),3.54–3.31(m,2H),2.83–2.65(m,2H),2.61(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ161.9(d,J＝251.4Hz,1C),159.9,155.8,143.1,137.9,135.1,133.8(d,J＝10.2,1C),131.8(d,J＝8.7,1C),130.0(d,J＝3.5,1C),129.5,128.6(d,J＝8.5,1C),126.6,126.2,125.5,121.5,116.7(d,J＝24.8,1C),114.6(d,J＝21.1,1C),113.2,61.6,50.5,48.8,35.2,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-111.97.HRMS(ESI)[M+H]+理论值C27H26NO5FSCl:530.1204；实测值：530.1206.
实施例49
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-57)
Figure BDA0003601498440000772
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-(三氟甲基)-4-氟苄溴，其余条件均一致。得白色固体238mg，收率84％。1H NMR(400MHz,氯仿-d)δ8.33–8.13(m,1H),7.91(dd,J＝8.8,1.6Hz,1H),7.81(dt,J＝11.6,5.8Hz,1H),7.65(d,J＝8.8Hz,1H),7.31(dd,J＝8.8,2.3Hz,1H),7.27–7.06(m,4H),6.96(d,J＝6.8Hz,2H),4.59(s,2H),4.46(q,J＝7.1Hz,2H),3.63–3.34(m,2H),2.63(d,J＝14.7Hz,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ161.3(d,J＝249.9Hz,1H),159.7,155.9,143.1,137.7,134.8,132.2(d,J＝7.9Hz,1C),131.6(d,J＝2.8Hz,1C),129.6,128.5(d,J＝2.2Hz,1C),126.6,126.1,125.5,121.6,119.2(d,J＝21.2Hz,1C),113.3,61.5,50.7,47.9,34.8,14.3,9.3.19F NMR(376MHz,氯仿-d)δ-59.60,-112.86.HRMS(ESI)[M+H]+理论值C28H26NO5F4S:564.1468；实测值：564.1465.
实施例50
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-58)
Figure BDA0003601498440000781
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,4-二(三氟甲基)苄溴，其余条件均一致。得白色固体270mg，收率88％。1H NMR(400MHz,氯仿-d)δ8.28–8.17(m,1H),8.03–7.85(m,3H),7.74(d,J＝8.1Hz,1H),7.65(d,J＝8.8Hz,1H),7.13(q,J＝8.4,7.3Hz,3H),6.96(d,J＝6.5Hz,2H),4.67(s,2H),4.47(q,J＝7.1Hz,2H),3.67–3.37(m,2H),2.64(d,J＝22.4Hz,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.7,155.9,143.1,140.4,137.5,134.4,130.5,130.0(d,J＝33.8Hz,1C),129.6,129.0,128.5,128.1(d,J＝31.5Hz,1C),126.6,126.1,125.4,124.8(d,J＝26.8Hz,1C),122.9,122.1(d,J＝25.1Hz,1C),121.7,113.3,61.5,51.0,48.4,34.7,14.2,9.2.19F NMR(376MHz,氯仿-d)δ-59.95,-62.92.HRMS(ESI)[M+H]+理论值C29H26NO5F6S:613.1358；实测值：614.1436.
实施例51
3-甲基-5-(N-(2-三氟甲基-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-59)
Figure BDA0003601498440000782
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-三氟甲基-4-溴苄溴，其余条件均一致。得白色固体311mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.18(d,J＝1.5Hz,1H),7.89(dd,J＝8.8,1.8Hz,1H),7.77–7.73(m,1H),7.71–7.59(m,3H),7.23–7.10(m,3H),6.96(d,J＝6.4Hz,2H),4.54(s,2H),4.47(q,J＝7.1Hz,2H),3.50–3.35(m,2H),2.71–2.56(m,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.9,143.1,137.6,135.4,135.0,134.6,131.6,129.6,129.2,128.8(t,J＝6.3Hz,1C),128.6(d,J＝1.5Hz,1C),126.6,126.1,125.5,121.6,121.4,113.4,61.6,50.9,48.1(d,J＝2.4Hz,1C),34.9,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-59.55.HRMS(ESI)[M+H]+理论值C28H26NO5F3SBr:624.0667；实测值：624.0663.
实施例52
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-60)
Figure BDA0003601498440000791
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,4-二氯苄溴，其余条件均一致。得白色固体113mg，收率69％。1H NMR(400MHz,氯仿-d)δ8.13(d,J＝1.6Hz,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.47(d,J＝8.4Hz,1H),7.31(d,J＝2.1Hz,1H),7.24–7.13(m,4H),7.05–6.98(m,2H),4.60–4.37(m,4H),3.54–3.34(m,2H),2.76–2.66(m,2H),2.61(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.9,143.1,137.8,135.0,134.2,133.7,132.7,131.3,129.5,129.2,128.7,128.6,127.5,126.6,126.2,125.5,121.6,113.2,61.6,50.7,48.9,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C27H26NO5SCl2:546.0909；实测值：546.0912.
实施例53
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-61)
Figure BDA0003601498440000792
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2-甲基-5-氟苄溴，其余条件均一致。得白色固体134mg，收率87％。1HNMR(400MHz,氯仿-d)δ8.17(d,J＝1.6Hz,1H),7.90(dd,J＝8.8,1.8Hz,1H),7.65(d,J＝8.8Hz,1H),7.17(m,3H),7.09(dd,J＝8.2,5.8Hz,1H),6.99–6.84(m,4H),4.47(q,J＝7.1Hz,2H),4.34(s,2H),3.40–3.25(m,2H),2.61(d,J＝6.1Hz,5H),2.27(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ162.4,160.0,159.9,155.9,143.0,138.1,135.7(d,J＝6.8Hz,1C),134.7,132.5(d,J＝3.3Hz,1C),132.0(d,J＝7.7Hz,1C),129.5,128.6(d,J＝4.8Hz,1C),126.5,126.3,125.6,121.6,115.9(d,J＝22.2Hz,1C),114.6(d,J＝20.7Hz,1C),113.1,61.6,50.6,50.1,35.5,18.5,14.4,9.4.19F NMR(376MHz,氯仿-d)δ-116.96.HRMS(ESI)[M+H]+理论值C28H29NO5FS:510.1750；实测值：510.1758.
实施例54
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-62)
Figure BDA0003601498440000801
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为2,6-二氟-4-氯苄溴，其余条件均一致。得白色固体243mg，收率89％。1HNMR(400MHz,氯仿-d)δ8.09(d,J＝1.5Hz,1H),7.84(dd,J＝8.8,1.8Hz,1H),7.59(d,J＝8.8Hz,1H),7.25–7.12(m,3H),7.06(d,J＝6.9Hz,2H),6.83(d,J＝7.2Hz,2H),4.46(d,J＝7.2Hz,4H),3.48–3.32(m,2H),2.90–2.78(m,2H),2.59(s,3H),1.44(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ161.5(dd,J＝254.1,9.4Hz,1C),159.8,155.8,143.0,138.1,135.5(t,J＝14.2Hz,1C),134.9,129.3,128.7,128.6,126.5,126.3,125.5,121.6,112.6(dd,J＝29.8,1.8Hz,1C),110.9(t,J＝18.9Hz,1C),61.6,50.2,39.5,35.4,14.4,9.3.19F NMR(376MHz,氯仿-d)δ-110.99.HRMS(ESI)[M+H]+理论值C27H25NO5F2SCl:548.1110；实测值：548.1105.
实施例55
3-甲基-5-(N-([1,1'-联苯]-4-基甲基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-82)
Figure BDA0003601498440000811
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4-苯基苄溴，其余条件均一致。得白色固体191mg，收率69％。1H NMR(400MHz,氯仿-d)δ8.14(s,1H),7.88(d,J＝8.8Hz,1H),7.64(d,J＝8.8Hz,1H),7.54(dd,J＝13.2,7.7Hz,4H),7.43(t,J＝7.5Hz,2H),7.33(dd,J＝17.2,7.7Hz,3H),7.18(dt,J＝12.5,6.8Hz,3H),6.98(d,J＝6.7Hz,2H),4.47(dd,J＝15.6,8.5Hz,4H),3.49–3.34(m,2H),2.80–2.67(m,2H),2.58(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,143.0,140.9,140.5,138.3,135.6,134.9,129.4,128.9,128.8,128.7,128.5,127.5,127.3,127.0,126.5,126.2,125.6,121.6,113.1,61.6,51.9,49.6,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C33H32NO5S:554.2001；实测值：546.1562.HRMS(ESI)[M+H]+理论值C33H32NO5S:5554.2001；实测值：554.2001.
实施例56
3-甲基-5-(N-((2’-氰基-[1,1’-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-83)
Figure BDA0003601498440000812
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4'-(溴甲基)-[1,1'-联苯]-2-碳腈，其余条件均一致。得白色固体270mg，收率93％。1H NMR(400MHz,氯仿-d)δ8.19(d,J＝1.5Hz,1H),7.88(dd,J＝8.8,1.8Hz,1H),7.72(d,J＝7.7Hz,1H),7.62(dd,J＝8.1,6.0Hz,2H),7.53–7.35(m,6H),7.17(t,J＝7.2Hz,2H),7.12(d,J＝7.1Hz,1H),7.02–6.95(m,2H),4.45(q,J＝7.2Hz,4H),3.51–3.38(m,2H),2.75–2.67(m,2H),2.60(s,3H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,144.7,143.0,138.2,137.8,136.8,135.4,133.8,132.9,130.0,129.4,129.1,128.7,128.5,127.8,126.5,126.3,125.6,121.6,118.6,113.1,111.2,61.6,51.8,49.7,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C34H31N2O5S:579.1954；实测值：579.1950.
实施例57
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-84)
Figure BDA0003601498440000821
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为4'-(溴甲基)-[1,1'-联苯]-2-羧酸叔丁酯，其余条件均一致。得白色固体303mg，收率93％。1H NMR(400MHz,氯仿-d)δ8.22(d,J＝1.5Hz,1H),7.92(dd,J＝8.8,1.7Hz,1H),7.79(dd,J＝7.7,1.4Hz,1H),7.66(d,J＝8.7Hz,1H),7.52–7.44(m,1H),7.43–7.37(m,1H),7.36–7.26(m,5H),7.18(dq,J＝14.3,7.1Hz,3H),7.01(d,J＝6.9Hz,2H),4.57–4.42(m,4H),3.56–3.34(m,2H),2.82–2.70(m,2H),2.63(s,3H),1.47(t,J＝7.1Hz,3H),1.27(s,9H).13C NMR(101MHz,氯仿-d)δ167.9,159.8,155.8,143.0,141.6,141.4,138.3,135.7,134.9,132.9,130.7,130.5,129.6,129.4,129.0,128.7,128.5,128.1,127.3,126.5,126.3,125.6,121.5,113.1,81.2,61.6,51.7,49.3,35.1,27.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C38H40NO7S:653.2447；实测值：654.2528.
实施例58
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-85)
Figure BDA0003601498440000822
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)所用方法，将苄溴替换为(4-(溴甲基)苯基)(苯基)甲酮，其余条件均一致。得白色固体142mg，收率49％。1H NMR(400MHz,氯仿-d)δ8.16(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.78–7.69(m,4H),7.58(dd,J＝27.2,8.1Hz,2H),7.50–7.35(m,4H),7.14(dq,J＝14.1,7.0Hz,3H),6.96(d,J＝6.9Hz,2H),4.45(dd,J＝14.9,7.8Hz,4H),3.52–3.34(m,2H),2.74–2.64(m,2H),2.58(s,3H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ196.0,159.8,155.8,143.1,141.0,138.1,137.4,137.1,135.3,132.5,130.4,130.0,129.5,128.6,128.6,128.4,128.1,126.6,126.2,125.5,121.6,113.2,61.6,51.9,49.9,35.2,14.4,9.4.
实施例59
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27)
Figure BDA0003601498440000831
将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(95mg,0.2mmol)，氢氧化钠(40mg,1.0mmol)溶于乙醇(8mL)和水(2mL)组成的混合溶液中，100℃搅拌1h，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，用1M稀盐酸调节PH值为3.0，静止5h后，减压抽滤、干燥得白色固体75mg，收率84％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.28(s,1H),7.95(d,J＝8.7Hz,1H),7.84(d,J＝8.8Hz,1H),7.33(dd,J＝16.2,3.9Hz,5H),7.24–7.05(m,3H),6.97(d,J＝7.1Hz,2H),4.43(s,2H),3.41–3.20(m,2H),2.58(s,3H),2.56–2.51(m,2H).13C NMR(101MHz,DMSO-d6)δ161.3,155.5,144.2,138.7,137.3,135.3,129.7,129.0,128.9,128.8,128.8,128.1,126.7,126.5,124.8,122.0,113.5,51.8,49.8,34.8,9.6.HRMS(ESI)[M+H]+理论值C25H24NO5S:450.1375；实测值：450.1378.
实施例61
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S14)
Figure BDA0003601498440000832
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-14，其余条件均一致。得白色固体90mg，收率96％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.06(s,1H),7.80(d,J＝10.6Hz,1H),7.71(d,J＝8.7Hz,1H),7.43(t,J＝7.7Hz,1H),7.39–7.30(m,1H),7.25–7.11(m,5H),7.01(d,J＝6.9Hz,2H),4.47(s,2H),3.38–3.27(m,2H),2.63–2.54(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ162.8,160.9(d,J＝246.5Hz,1C),154.8,138.6,133.8,131.4(d,J＝3.9Hz,1C),130.9,130.3(d,J＝8.2Hz,1C),128.9,128.8,126.8,124.9(d,J＝3.3Hz,1C),124.5,124.2(d,J＝14.3Hz,1C),120.7,117.8,115.9,115.7,112.8,50.2,45.8(d,J＝3.3Hz,1C),34.9,9.5.19F NMR(376MHz,DMSO-d6)δ-117.84.HRMS(ESI)[M-H]-理论值C25H21NO5FS:466.1124；实测值：466.1128.
实施例62
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S15)
Figure BDA0003601498440000841
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-15，其余条件均一致。得白色固体80mg，收率83％。M.p.156-157℃.1H NMR(400MHz,DMSO-d6)δ8.12(s,1H),7.84(d,J＝8.7Hz,1H),7.75(d,J＝8.7Hz,1H),7.50(s,1H),7.46–7.40(m,1H),7.37–7.29(m,2H),7.20(t,J＝7.2Hz,2H),7.14(t,J＝7.1Hz,1H),7.00(d,J＝7.0Hz,2H),4.50(s,2H),3.41–3.27(m,2H),2.56(d,J＝14.9Hz,5H).13C NMR(101MHz,DMSO-d6)δ154.9,138.5,134.8,133.8,133.0,130.9,130.8,129.8,129.8,128.9,128.8,127.7,126.8,124.8,121.0,112.9,50.5,49.7,35.0,9.5.HRMS(ESI)[M-H]-理论值C25H21NO5SCl:482.0829；实测值：482.0832.
实施例63
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S16)
Figure BDA0003601498440000842
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-16，其余条件均一致。得白色固体104mg，收率98％。M.p.170-171℃.1H NMR(400MHz,DMSO-d6)δ8.27(d,J＝1.7Hz,1H),7.95(dd,J＝8.8,1.9Hz,1H),7.85(d,J＝8.8Hz,1H),7.61(d,J＝7.0Hz,1H),7.48(d,J＝6.3Hz,1H),7.37(t,J＝7.0Hz,1H),7.28–7.17(m,3H),7.14(t,J＝7.2Hz,1H),7.02(d,J＝8.2Hz,2H),4.50(s,2H),3.42–3.34(m,2H),2.58(s,5H).13C NMR(101MHz,DMSO)δ161.4,155.5,138.5,136.3,134.6,133.1,130.9,130.1,129.8,129.0,128.3,126.8,126.4,123.2,122.0,113.5,52.2,50.6,35.0,9.6.HRMS(ESI)[M-H]-理论值C25H21NO5SBr:526.0324；实测值：526.0331.
实施例64
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S17)
Figure BDA0003601498440000851
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-17，其余条件均一致。得白色固体88mg，收率96％。M.p.199-200℃.1H NMR(400MHz,DMSO-d6)δ8.32(d,J＝1.7Hz,1H),8.00(dd,J＝8.8,1.9Hz,1H),7.88(d,J＝8.8Hz,1H),7.32(d,J＝7.4Hz,1H),7.26–7.14(m,5H),7.14–7.09(m,1H),6.89(d,J＝6.9Hz,2H),4.39(s,2H),3.28–3.18(m,2H),2.59(s,3H),2.45–2.36(m,2H),2.32(s,3H).13C NMR(101MHz,DMSO-d6)δ161.2,155.6,143.8,138.7,137.4,134.6,134.6,130.8,129.8,129.7,128.9,128.8,128.3,126.8,126.7,126.2,125.2,122.2,113.5,51.0,49.9,35.3,19.2,9.6.HRMS(ESI)[M-H]-理论值C26H24NO5S:462.1375；实测值：462.1377.
实施例65
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S18)
Figure BDA0003601498440000852
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-18，其余条件均一致。得白色固体87mg，收率84％。M.p.138-139℃.1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.93(d,J＝8.7Hz,1H),7.83(d,J＝8.7Hz,1H),7.72(d,J＝7.8Hz,1H),7.65(q,J＝7.6Hz,2H),7.49(t,J＝7.2Hz,1H),7.16(dq,J＝14.3,7.1Hz,3H),7.00(d,J＝7.0Hz,2H),4.58(s,2H),3.49–3.35(m,2H),2.58(d,J＝12.8Hz,5H).13C NMR(101MHz,DMSO-d6)δ162.0,155.4,146.6,138.4,136.4,134.1,133.1,130.2,130.0,128.9,128.8,128.3,126.3(d,J＝38.8Hz,1C),126.3(t,J＝5.8Hz,1C),126.1,125.9,122.9(d,J＝108.8Hz,1C),121.7,113.4,50.9,48.7,34.8,9.5.HRMS(ESI)[M-H]-理论值C26H21NO5F3S:516.1093；实测值：516.1095.
实施例66
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S19)
Figure BDA0003601498440000861
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-19，将氢氧化钠替换为氢氧化锂，其余条件均一致。得黄色固体31mg，收率63％。M.p.180-181℃.1HNMR(400MHz,DMSO-d6)δ8.27(d,J＝1.9Hz,1H),8.02(d,J＝8.1Hz,1H),7.95(dd,J＝8.7,1.9Hz,1H),7.86(d,J＝8.8Hz,1H),7.71(q,J＝3.6,3.1Hz,2H),7.55(td,J＝7.0,5.6,3.1Hz,1H),7.25–7.10(m,3H),7.05(d,J＝7.0Hz,2H),4.77(s,2H),3.54–3.34(m,2H),2.61(d,J＝21.8Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.5,155.6,148.5,138.5,134.4,134.0,133.2,130.3,129.9,129.1,129.0,128.8,126.8,126.4,125.1,122.1,113.6,51.2,49.3,34.8,9.5.HRMS(ESI)[M-H]-理论值C25H21N2O7S:493.1069；实测值：493.1070.
实施例67
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S20)
Figure BDA0003601498440000862
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-20，其余条件均一致。得白色固体85mg，收率91％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.08(s,1H),7.80(d,J＝8.7Hz,1H),7.72(d,J＝8.7Hz,1H),7.44–7.34(m,1H),7.19(d,J＝7.4Hz,3H),7.12(dt,J＝9.0,6.5Hz,3H),7.00(d,J＝6.9Hz,2H),4.42(s,2H),3.37–3.28(m,2H),2.61–2.54(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ163.1,162.6(d,J＝244.6Hz,1C),154.7,152.0,140.8(d,J＝7.2Hz,1C),138.7,133.8,131.1,130.8(d,J＝8.4Hz,1C),129.0,128.8,126.7,124.6(d,J＝2.6Hz,1C),124.2,120.6,116.9,115.2(d,J＝21.7Hz,1C),114.7(d,J＝21.0Hz,1C),112.7,51.3,50.1,40.4,34.7,9.5.19F NMR(376MHz,DMSO-d6)δ-113.23.HRMS(ESI)[M-H]-理论值C25H21NO5FS:466.1124；实测值：466.1127.
实施例68
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S21)
Figure BDA0003601498440000871
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-21，其余条件均一致。得白色固体82mg，收率85％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.07(d,J＝2.0Hz,1H),7.79(dd,J＝8.6,2.0Hz,1H),7.71(d,J＝8.7Hz,1H),7.43–7.27(m,4H),7.26–7.10(m,3H),7.01(d,J＝6.8Hz,2H),4.41(s,2H),3.40–3.27(m,2H),2.62–2.54(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ163.2,154.7,151.9,140.4,138.7,133.8,133.5,131.1,130.7,129.0,128.8,128.3,127.9,127.2,126.8,124.2,120.6,116.9,112.8,51.2,50.2,34.8,9.5.HRMS(ESI)[M-H]-理论值C25H21NO5SCl:482.0829；实测值：482.0829.
实施例69
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S22)
Figure BDA0003601498440000881
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-22，其余条件均一致。得白色固体93mg，收率99％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.09(s,1H),7.81(d,J＝8.7Hz,1H),7.72(d,J＝8.7Hz,1H),7.50–7.43(m,2H),7.38–7.27(m,2H),7.20(t,J＝7.2Hz,2H),7.14(dd,J＝8.7,5.8Hz,1H),7.01(d,J＝6.9Hz,2H),4.41(s,2H),3.37–3.28(m,2H),2.62–2.54(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ162.5,154.8,140.6,138.7,133.9,131.3,131.0,131.0,130.8,129.0,128.8,127.6,126.8,124.5,122.1,120.7,112.8,51.1,50.2,34.8,9.5.HRMS(ESI)[M-H]-理论值C25H21NO5SBr:526.0324；实测值：526.0326.
实施例70
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S23)
Figure BDA0003601498440000882
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-23，其余条件均一致。得白色固体93mg，收率99％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.08(d,J＝1.7Hz,1H),7.81(dd,J＝8.7,1.9Hz,1H),7.73(d,J＝8.7Hz,1H),7.21(q,J＝7.3Hz,3H),7.16–7.06(m,3H),7.04(s,1H),6.98(d,J＝6.9Hz,2H),4.36(s,2H),3.36–3.23(m,2H),2.54(d,J＝9.2Hz,5H),2.23(s,3H).13C NMR(101MHz,DMSO-d6)δ162.8,154.8,138.8,138.0,137.2,134.3,130.9,129.3,129.0,128.8,128.8,128.6,126.7,125.9,124.5,120.7,112.8,51.7,49.7,34.7,21.4,9.5.HRMS(ESI)[M-H]-理论值C26H24NO5S:462.1375；实测值：462.1376.
实施例71
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S24)
Figure BDA0003601498440000891
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-24，其余条件均一致。得白色固体89mg，收率86％。M.p.188-189℃.1H NMR(400MHz,DMSO-d6)δ8.14(s,1H),7.85(d,J＝8.7Hz,1H),7.75(d,J＝8.7Hz,1H),7.60(dq,J＝15.2,7.4Hz,4H),7.16(dq,J＝14.3,7.1Hz,3H),7.00(d,J＝6.8Hz,2H),4.52(s,2H),3.45–3.31(m,2H),2.64–2.56(m,2H),2.54(s,3H).13C NMR(101MHz,DMSO-d6)δ162.6,155.0,139.4,138.6,134.0,132.7,130.7,129.9,129.6(d,J＝31.7Hz,1C),129.0,128.7,126.7,125.9,125.0(d,J＝4.2Hz,1C),124.9,124.7,123.2,121.0,113.0,51.3,50.4,34.8,9.5.19F NMR(376MHz,DMSO-d6)δ-61.16.HRMS(ESI)[M-H]-理论值C26H21NO5F3S:516.1093；实测值：516.1095.
实施例72
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S25)
Figure BDA0003601498440000892
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-25，氢氧化钠替换为氢氧化锂，其余条件均一致。得白色固体51mg，收率52％。M.p.>380℃(分解).1HNMR(400MHz,DMSO-d6)δ13.79(s,1H),8.31(d,J＝1.5Hz,1H),8.16–8.06(m,2H),7.96(dd,J＝8.8,1.8Hz,1H),7.85(d,J＝8.8Hz,1H),7.78(d,J＝7.7Hz,1H),7.62(t,J＝7.9Hz,1H),7.23–7.06(m,3H),7.01(d,J＝6.9Hz,2H),4.57(s,2H),3.52–3.34(m,2H),2.61(d,J＝21.9Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.2,155.6,148.2,144.0,140.2,138.5,135.0,134.8,130.3,129.7,129.0,128.7,126.7,125.1,123.0,122.8,122.2,113.6,51.2,50.5,34.8,9.5.HRMS(ESI)[M-H]-理论值C25H21N2O7S:493.1069；实测值：493.1065.
实施例73
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S26)
Figure BDA0003601498440000901
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-26，其余条件均一致。得白色固体106mg，收率95％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.10(s,1H),7.81(d,J＝8.7Hz,1H),7.71(d,J＝8.6Hz,1H),7.57(d,J＝7.8Hz,1H),7.53–7.47(m,2H),7.47–7.39(m,4H),7.34(dd,J＝11.7,7.4Hz,2H),7.15(dq,J＝14.4,7.1Hz,3H),7.00(d,J＝6.8Hz,2H),4.48(s,2H),3.39–3.28(m,2H),2.66–2.56(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ163.1,154.7,140.8,140.3,138.8,138.1,134.2,131.2,129.5,129.4,129.0,128.8,128.0,127.9,127.0,127.0,126.7,126.4,124.2,120.5,116.7,112.7,51.6,49.7,34.8,9.5.HRMS(ESI)[M-H]-理论值C31H26NO5S:524.1532；实测值：524.1522.
实施例74
3-甲基-5-(N-(3-苯氧基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S27)
Figure BDA0003601498440000902
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-27，其余条件均一致。得白色固体99mg，收率91％。M.p.>183-184℃.1H NMR(400MHz,DMSO-d6)δ8.18(s,1H),7.86(d,J＝8.7Hz,1H),7.76(d,J＝8.7Hz,1H),7.36(td,J＝8.0,3.0Hz,3H),7.16(dq,J＝19.7,7.0Hz,5H),6.96(dt,J＝21.2,6.5Hz,6H),4.41(s,2H),3.48–3.22(m,2H),2.56(d,J＝9.0Hz,5H).13C NMR(101MHz,DMSO-d6)δ162.1,157.1,157.0,155.2,139.9,138.7,134.7,130.6,130.5,130.3,129.0,128.8,126.7,125.5,123.9,123.8,121.4,118.9,118.9,118.3,113.1,51.5,50.0,34.9,9.5.HRMS(ESI)[M-H]-理论值C31H26NO6S:540.1481；实测值：540.1477.
实施例75
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S28)
Figure BDA0003601498440000911
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-28，其余条件均一致。得白色固体81mg，收率87％。M.p.188-189℃.1H NMR(400MHz,DMSO-d6)δ8.17(s,1H),7.87(d,J＝10.5Hz,1H),7.78(d,J＝8.7Hz,1H),7.38(dd,J＝8.4,5.7Hz,2H),7.16(dq,J＝13.9,7.2Hz,5H),6.99(d,J＝7.0Hz,2H),4.40(s,2H),3.38–3.24(m,2H),2.55(d,J＝11.9Hz,5H).13C NMR(101MHz,DMSO-d6)δ162.1(d,J＝244.2Hz,1C),162.1,155.1,138.7,134.6,133.7(d,J＝2.9Hz,1C),130.8(d,J＝8.3Hz,1C),130.7,130.4,129.0,128.8,126.7,125.4,121.3,115.8,115.6,113.1,51.1,49.9,34.8,9.5.19F NMR(376MHz,DMSO-d6)δ-115.01.HRMS(ESI)[M-H]-理论值C25H21NO5FS:466.1124；实测值：466.1123.
实施例76
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S29)
Figure BDA0003601498440000912
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-29，其余条件均一致。得白色固体89mg，收率92％。M.p.172-173℃.1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.93(d,J＝8.8Hz,1H),7.83(d,J＝8.8Hz,1H),7.37(q,J＝8.5Hz,4H),7.19(t,J＝7.3Hz,2H),7.13(t,J＝7.2Hz,1H),7.01(d,J＝7.1Hz,2H),4.42(s,2H),3.41–3.26(m,2H),2.58(d,J＝4.6Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.3,155.5,144.4,138.6,136.6,135.1,132.6,130.5,129.7,129.0,128.9,128.8,126.7,126.5,124.6,122.0,113.5,51.1,50.1,34.8,9.5.HRMS(ESI)[M-H]-理论值C25H21NO5SCl:482.0829；实测值：482.0829.
实施例77
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S30)
Figure BDA0003601498440000921
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-30，其余条件均一致。得白色固体227mg，收率85％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.15(s,1H),7.93–7.69(m,2H),7.42(dd,J＝89.8,8.2Hz,4H),7.23–7.10(m,3H),7.00(d,J＝7.2Hz,2H),4.39(s,2H),3.39–3.27(m,2H),2.56(s,5H).13C NMR(101MHz,DMSO-d6)δ162.0,154.6,148.2,138.2,136.7,133.8,131.3,130.4,130.0,128.5,128.3,126.3,124.7,120.7,120.7,119.7,112.6,50.8,49.6,34.3,9.1.HRMS(ESI)[M-H]-理论值C25H21BrNO5S:526.0329；实测值：506.0323.
实施例78
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S31)
Figure BDA0003601498440000922
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-31，其余条件均一致。得白色固体63mg，收率68％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.15(d,J＝1.9Hz,1H),7.86(dd,J＝8.6,1.9Hz,1H),7.77(d,J＝8.7Hz,1H),7.26–7.07(m,7H),6.98(d,J＝7.2Hz,2H),4.36(s,2H),3.28(t,J＝8.0Hz,2H),2.61–2.51(m,5H),2.27(s,3H).13C NMR(101MHz,DMSO-d6)δ162.4,155.0,148.3,138.8,137.2,134.8,134.2,130.4,129.5,128.9,128.8,126.7,125.3,121.1,120.5,113.1,51.5,49.6,34.8,21.2,9.5.HRMS(ESI)[M-H]-理论值C26H24NO5S:462.1375；实测值：462.1378.
实施例79
3-甲基-5-(N-(4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S32)
Figure BDA0003601498440000931
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-32，其余条件均一致。得白色固体72mg，收率70％。M.p.>192-193℃.1H NMR(400MHz,DMSO-d6)δ8.33–8.19(m,1H),7.94(dd,J＝8.7,1.9Hz,1H),7.83(d,J＝8.8Hz,1H),7.68(d,J＝7.9Hz,2H),7.55(d,J＝7.9Hz,2H),7.14(dq,J＝14.1,7.3Hz,3H),7.00(d,J＝7.3Hz,2H),4.53(s,2H),3.37(t,J＝7.8Hz,2H),2.59(d,J＝10.2Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.6,155.4,145.2,142.7,138.6,134.7,129.9,129.2,129.0,128.7,126.7,126.2,126.1,125.7(d,J＝3.7Hz,1C),123.5(d,J＝34.9Hz,1C),121.9,113.4,51.5,50.5,34.8,9.5.19F NMR(376MHz,DMSO-d6)δ-60.94.HRMS(ESI)[M-H]-理论值C26H21NO5SF3:516.1093；实测值：516.1096.
实施例80
3-甲基-5-(N-(4-氨甲酰苄基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S33)
Figure BDA0003601498440000932
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-33，其余条件均一致。得白色固体103mg，收率43％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ13.56(s,1H),8.29(s,1H),8.03–7.89(m,2H),7.86(d,J＝8.7Hz,2H),7.50–7.41(m,1H),7.38(d,J＝11.8Hz,1H),7.16(dq,J＝14.1,7.1,6.6Hz,3H),7.01(d,J＝7.8Hz,2H),4.50(d,J＝9.7Hz,2H),3.35(q,J＝7.5Hz,2H),2.58(s,5H).13C NMR(101MHz,DMSO-d6)δ168.0,163.7,154.9,149.8,140.9,138.7,134.2,133.9,130.7,128.9,128.8,128.4,128.1,126.7,124.9,121.0,119.2,113.0,51.5,50.1,34.8,9.5.HRMS(ESI)[M-H]-理论值C26H23N2O6S:491.1282；实测值：491.1278.
实施例81
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S34)
Figure BDA0003601498440000941
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-34，其余条件均一致。得白色固体227mg，收率85％。M.p.216-217℃.1H NMR(400MHz,DMSO-d6)δ8.20(s,1H),7.92–7.74(m,2H),7.40(dd,J＝60.2,8.2Hz,4H),7.21–7.08(m,3H),6.98(d,J＝7.1Hz,2H),4.45(s,2H),3.34(t,J＝7.8Hz,2H),2.65–2.53(m,5H).13C NMR(101MHz,DMSO-d6)δ162.4,155.1,148.1,138.6,137.1,134.4,130.5,130.4,128.9,128.7,126.7,125.4,121.8,121.4,121.3,120.8,113.1,51.2,50.2,34.8,9.5.19F NMR(376MHz,DMSO)δ-56.83.HRMS(ESI)[M-H]-理论值C26H21F3NO6S:532.1047；实测值：532.1038.
实施例82
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S35)
Figure BDA0003601498440000942
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-35，其余条件均一致。得白色固体192mg，收率70％。M.p.165-166℃.1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.92(dd,J＝8.7,1.8Hz,1H),7.82(d,J＝8.8Hz,1H),7.70(d,J＝7.9Hz,2H),7.51(d,J＝7.9Hz,2H),7.17(dt,J＝13.7,6.9Hz,3H),7.00(d,J＝7.2Hz,2H),4.50(s,2H),3.36(t,J＝7.9Hz,2H),2.65–2.54(m,5H).13C NMR(101MHz,DMSO-d6)δ161.7,155.4,141.8,138.6,136.7,134.5,131.6,130.0,130.0,129.0,128.7,128.5,126.7,126.0,122.3,121.8,113.3,51.4,50.5,34.9,9.5.19F NMR(376MHz,DMSO-d6)δ-42.23.HRMS(ESI)[M-H]-理论值C26H21F3NO5S2:548.0819；实测值：548.0805.
实施例83
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S36)
Figure BDA0003601498440000951
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-36，其余条件均一致。得白色固体220mg，收率88％。M.p.206-207℃.1H NMR(400MHz,DMSO-d6)δ13.74(s,1H),8.26(d,J＝1.9Hz,1H),7.93(dd,J＝8.8,1.9Hz,1H),7.84(d,J＝8.8Hz,1H),7.19(dq,J＝16.2,9.2,8.7Hz,7H),7.02–6.94(m,2H),4.38(s,2H),3.34–3.27(m,2H),2.85(h,J＝6.8Hz,1H),2.58(s,5H),1.17(d,J＝6.9Hz,6H).13C NMR(101MHz,DMSO-d6)δ161.1,155.5,148.3,143.8,138.8,135.5,134.5,129.6,129.0,128.8,128.8,126.8,126.7,126.6,125.2,122.0,113.5,51.4,49.6,34.8,33.6,24.3,9.6.HRMS(ESI)[M-H]-理论值C28H28NO5S:490.1694；实测值：490.1684.
实施例84
3-甲基-5-(N-(4-叔丁基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S37)
Figure BDA0003601498440000952
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-37，其余条件均一致。得白色固体212mg，收率84％。M.p.206-207℃.1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.97–7.77(m,2H),7.34(d,J＝8.0Hz,2H),7.18(ddd,J＝22.9,15.8,7.5Hz,5H),6.97(d,J＝6.6Hz,2H),4.39(s,2H),3.36–3.27(m,2H),2.58(s,5H),1.25(s,9H).13C NMR(101MHz,DMSO)δ161.4,155.4,150.5,138.8,135.4,134.1,129.7,129.0,128.7,128.5,126.7,126.4,125.6,124.5,121.9,113.4,107.1,51.3,49.6,34.8,34.7,31.6,9.6.HRMS(ESI)[M-H]-理论值C29H30NO5S:504.1850；实测值：504.1838.
实施例85
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S38)
Figure BDA0003601498440000961
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-38，其余条件均一致。得白色固体48mg，收率49％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ13.75(s,1H),8.28(d,J＝1.9Hz,1H),8.00–7.80(m,4H),7.47(d,J＝8.0Hz,2H),7.21–7.09(m,3H),7.05–6.98(m,2H),4.52(s,2H),3.40–3.31(m,2H),2.57(t,J＝5.6Hz,8H).13C NMR(101MHz,DMSO-d6)δ197.9,161.1,155.6,143.7,143.1,138.6,136.5,135.1,129.6,129.0,128.8,128.8,128.7,126.7,126.7,125.3,122.1,113.6,51.6,50.3,34.8,27.2,9.5.HRMS(ESI)[M-H]-理论值C27H24NO6S:490.1324；实测值：490.1322.
实施例86
3-甲基-5-(N-(4-羧苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S39)
Figure BDA0003601498440000962
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-39，其余条件均一致。得白色固体105mg，收率43％。M.p.254–255℃.1H NMR(400MHz,DMSO-d6)δ13.36(s,2H),8.27(d,J＝1.9Hz,1H),8.01–7.81(m,4H),7.46(d,J＝8.0Hz,2H),7.22–7.09(m,3H),7.00(d,J＝7.2Hz,2H),4.51(s,2H),3.42–3.28(m,2H),2.57(s,5H).13C NMR(101MHz,DMSO-d6)δ167.5,161.2,155.5,144.0,142.7,138.6,135.1,130.4,129.9,129.7,129.0,128.8,128.6,126.7,126.6,125.0,122.1,113.5,51.6,50.4,34.8,9.5.HRMS(ESI)[M-H]-理论值C26H22NO7S:492.1122；实测值：491.1115.
实施例87
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S40)
Figure BDA0003601498440000971
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-40，其余条件均一致。得白色固体200mg，收率77％。M.p.188-189℃.1H NMR(400MHz,DMSO-d6)δ13.61(s,1H),8.21(s,1H),7.88(dd,J＝47.6,7.6Hz,4H),7.42(d,J＝8.1Hz,2H),7.15(dt,J＝16.9,7.1Hz,3H),7.01(d,J＝6.2Hz,2H),4.50(s,2H),3.37(s,2H),2.58(d,J＝19.8Hz,5H),1.52(s,9H).13C NMR(101MHz,DMSO)δ165.1,161.1,155.5,143.8,142.5,138.6,135.2,131.0,129.9,129.5,129.0,128.7,128.6,126.7,126.6,125.1,122.0,113.5,81.1,51.6,50.3,34.9,28.2,9.5.HRMS(ESI)[M-H]-理论值C30H30NO7S:548.1748；实测值：548.1738.
实施例88
3-甲基-5-(N-(4-(羧甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S41)
Figure BDA0003601498440000972
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-41，其余条件均一致。得白色固体95mg，收率34％。M.p.182-183℃.1H NMR(400MHz,DMSO-d6)δ12.92(s,2H),8.29(d,J＝1.9Hz,1H),7.94(dd,J＝8.8,1.9Hz,1H),7.85(d,J＝8.8Hz,1H),7.20(ddd,J＝42.8,17.3,7.5Hz,7H),7.03–6.94(m,2H),4.40(s,2H),3.56(s,2H),3.30(t,J＝8.0Hz,2H),2.57(d,J＝14.7Hz,5H).13C NMR(101MHz,DMSO)δ173.1,161.1,155.5,143.7,138.7,135.6,135.4,134.9,130.0,129.6,129.0,128.8,128.7,126.7,125.4,122.0,113.5,51.5,49.7,34.8,9.6.HRMS(ESI)[M-H]-理论值C27H24NO7S:507.1352；实测值：506.1267.
实施例89
(E)-3-甲基-5-(N-(4-(2-羧基乙烯基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S42)
Figure BDA0003601498440000981
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-42，其余条件均一致。得白色固体87mg，收率83％。M.p.270-271℃.1H NMR(400MHz,DMSO-d6)δ13.03(s,2H),8.28(d,J＝1.9Hz,1H),7.96(dd,J＝8.8,1.9Hz,1H),7.85(d,J＝8.7Hz,1H),7.66(d,J＝7.8Hz,2H),7.57(d,J＝16.0Hz,1H),7.37(d,J＝7.8Hz,2H),7.26–7.10(m,3H),7.06–6.94(m,2H),6.52(d,J＝16.0Hz,1H),4.46(s,2H),3.48–3.23(m,3H),2.58(s,5H).13CNMR(101MHz,DMSO-d6)δ168.0,161.1,155.6,143.9,143.7,139.7,138.7,135.3,134.0,129.6,129.1,129.0,128.8,126.7,126.7,125.3,122.1,119.7,113.6,51.5,50.1,34.8,9.5.HRMS(ESI)[M-H]-理论值C28H24NO7S:518.1273；实测值：518.1268.
实施例90
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S43)
Figure BDA0003601498440000991
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-43，其余条件均一致。得白色固体94mg，收率89％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.48–8.30(m,2H),8.06(dd,J＝8.7,1.9Hz,1H),8.01–7.86(m,3H),7.67–7.53(m,3H),7.49(t,J＝7.6Hz,1H),7.09(dq,J＝14.0,7.1Hz,3H),6.86–6.70(m,2H),4.86(s,2H),3.24(t,J＝8.2Hz,2H),2.60(s,3H),2.22(t,J＝8.2Hz,2H).13C NMR(101MHz,DMSO-d6)δ161.4,155.6,144.4,138.5,134.3,133.9,132.0,131.9,129.8,129.3,129.0,128.8,128.7,128.4,126.9,126.8,126.7,126.5,125.7,124.3,122.2,113.5,51.1,49.9,35.3,9.6.HRMS(ESI)[M-H]-理论值C29H24NO5S:498.1375；实测值：498.1376.
实施例91
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S44)
Figure BDA0003601498440000992
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-44，其余条件均一致。得白色固体103mg，收率99％。M.p.190-191℃.1H NMR(400MHz,DMSO-d6)δ8.88(s,1H),8.36(d,J＝7.9Hz,1H),8.20(s,1H),7.91(t,J＝9.1Hz,2H),7.80(d,J＝5.6Hz,2H),7.68–7.48(m,2H),7.12(dd,J＝15.3,6.9Hz,3H),6.95(d,J＝7.0Hz,2H),5.10(s,2H),3.60–3.38(m,2H),2.73–2.60(m,2H),2.54(s,3H).13C NMR(101MHz,DMSO-d6)δ161.1,155.4,150.2,145.8,143.6,138.7,137.2,135.4,135.0,129.8,129.4,129.0,128.7,128.2,126.8,126.7,125.2,122.0,121.9,113.4,50.8,47.7,35.1,9.5.HRMS(ESI)[M-H]-理论值C28H23N2O5S:499.1328；实测值：499.1321.
实施例92
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S45)
Figure BDA0003601498440001001
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-45，其余条件均一致。得白色固体101mg，收率99％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.09(s,1H),7.89(d,J＝8.1Hz,2H),7.84(d,J＝8.8Hz,3H),7.73(d,J＝8.6Hz,1H),7.58–7.43(m,3H),7.13(dq,J＝14.2,6.9Hz,3H),6.95(d,J＝6.7Hz,2H),4.57(s,2H),3.46(s,3H),3.38–3.29(m,2H),2.62–2.54(m,2H).13C NMR(101MHz,DMSO-d6)δ163.2,154.7,152.3,138.8,135.0,134.0,133.2,132.9,131.2,128.9,128.8,128.6,128.1,128.1,127.4,126.8,126.7,126.7,126.5,124.2,120.5,116.6,112.7,52.0,49.9,34.8,9.5.HRMS(ESI)[M-H]-理论值C29H24NO5S:498.1375；实测值：498.1379.
实施例93
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S46)
Figure BDA0003601498440001002
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-46，其余条件均一致。得白色固体89mg，收率92％。M.p.180-181.1H NMR(400MHz,DMSO-d6)δ8.09(d,J＝1.9Hz,1H),7.85(dd,J＝8.8,1.9Hz,1H),7.78(d,J＝8.8Hz,1H),7.40(ddd,J＝15.0,8.5,6.6Hz,1H),7.24(t,J＝7.3Hz,2H),7.16(ddd,J＝7.3,5.1,1.3Hz,1H),7.12–7.00(m,4H),4.49(s,2H),3.37–3.26(m,2H),2.72–2.63(m,2H),2.55(s,3H).13C NMR(101MHz,DMSO-d6)δ162.0,161.6(dd,J＝249.6,8.0Hz,1C),155.3,146.0,134.4,131.5(t,J＝10.6Hz,1C),129.9,128.9,128.9,126.8,125.9,122.8,121.5,113.2,112.5,112.2(dd,J＝18.9,12.0Hz,1C),112.1(d,J＝25.1Hz,1C),50.4,35.2,9.5.19F NMR(376MHz,DMSO-d6)δ-113.36.HRMS(ESI)[M-H]-理论值C25H20NO5F2S:484.1030；实测值：484.1036.
实施例94
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S47)
Figure BDA0003601498440001011
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-47，其余条件均一致。得白色固体93mg，收率94％。M.p.195-196.1H NMR(400MHz,DMSO-d6)δ8.18(d,J＝1.9Hz,1H),7.92(dd,J＝8.8,2.0Hz,1H),7.83(d,J＝8.8Hz,1H),7.39(td,J＝8.2,6.1Hz,1H),7.30(d,J＝8.0Hz,1H),7.26–7.12(m,4H),6.98(d,J＝7.0Hz,2H),4.55(s,2H),3.35–3.23(m,2H),2.56(s,5H).13C NMR(101MHz,DMSO-d6)δ162.1(d,J＝250.9Hz,1C),161.2,155.5,143.9,138.5,135.6(d,J＝5.3Hz,1C),134.5,131.6(d,J＝10.0Hz,1C),129.5,128.9(d,J＝2.2Hz,1C),126.8,126.7,126.3(d,J＝3.1Hz,1C),125.0,122.0,121.8(d,J＝16.9Hz,1C),115.2(d,J＝22.6Hz,1C),113.5,50.5,44.3(d,J＝1.9Hz,1C),35.7,9.5.19F NMR(376MHz,DMSO-d6)δ-111.00.HRMS(ESI)[M-H]-理论值C25H20NO5FSCl:500.0735；实测值：500.0743.
实施例95
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S48)
Figure BDA0003601498440001012
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-48，其余条件均一致。得白色固体98mg，收率91％。M.p.99-100.1H NMR(400MHz,DMSO-d6)δ8.17(s,1H),7.99–7.76(m,2H),7.57(dd,J＝40.4,6.1Hz,3H),7.17(dt,J＝17.0,7.2Hz,3H),6.90(d,J＝7.5Hz,2H),4.60(s,2H),3.20(t,J＝8.1Hz,2H),2.56(s,3H),2.50–2.36(m,2H).13CNMR(101MHz,DMSO-d6)δ162.3(d,J＝250.0Hz,1C),161.8,155.4,146.1,138.4,133.8,131.6(d,J＝9.7Hz,1C),130.2(d,J＝33.4Hz,1C),130.0,128.9,128.7,126.8,126.1,125.2,122.9(d,J＝41.2Hz,1C),122.5,122.1(d,J＝14.6Hz,1C),121.8,120.8(d,J＝23.3Hz,1C),113.3,50.3,43.7,35.7,9.4.19F NMR(376MHz,DMSO-d6)δ-56.89,-110.29.HRMS(ESI)[M-H]-理论值C26H20NO5F4S:534.0998；实测值：534.0999.
实施例96
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S49)
Figure BDA0003601498440001021
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-49，其余条件均一致。得白色固体84mg，收率81％。M.p.176-177℃.1H NMR(400MHz,DMSO-d6)δ8.21(s,1H),7.94(d,J＝8.6Hz,1H),7.84(d,J＝8.7Hz,1H),7.46(d,J＝7.9Hz,2H),7.42–7.32(m,1H),7.16(dt,J＝23.5,6.4Hz,3H),6.89(d,J＝7.0Hz,2H),4.62(s,2H),3.33–3.13(m,2H),2.57(s,3H),2.46(d,J＝7.9Hz,2H).13C NMR(101MHz,DMSO-d6)δ161.5,155.5,145.0,138.4,136.7,133.8,131.5,131.0,129.7,129.5,128.9,128.8,126.8,126.5,124.0,122.0,113.4,50.3,48.5,36.3,9.5.HRMS(ESI)[M-H]-理论值C25H20NO5SCl2:516.0439；实测值：516.0431.
实施例97
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S50)
Figure BDA0003601498440001022
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-50，其余条件均一致。得白色固体62mg，收率65％。M.p.211-212℃.1H NMR(400MHz,DMSO-d6)δ13.76(s,1H),8.22(s,1H),7.96(d,J＝8.7Hz,1H),7.86(d,J＝8.7Hz,1H),7.15(dt,J＝14.1,6.9Hz,4H),7.02(d,J＝7.4Hz,2H),6.77(d,J＝7.0Hz,2H),4.37(s,2H),3.15–2.98(m,2H),2.58(s,3H),2.41–2.31(m,2H),2.26(s,6H).13C NMR(101MHz,DMSO-d6)δ161.2,155.6,143.7,138.6,133.8,131.6,129.6,128.9,128.8,128.8,128.6,126.8,126.7,125.2,122.2,113.5,49.9,47.9,40.4,36.6,20.2,9.6.HRMS(ESI)[M-H]-理论值C27H26NO5S:476.1532；实测值：476.1533.
实施例98
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S51)
Figure BDA0003601498440001031
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-51，其余条件均一致。得白色固体92mg，收率95％。M.p.155-156℃.1H NMR(400MHz,DMSO-d6)δ8.15(d,J＝1.9Hz,1H),7.87(dd,J＝8.7,2.0Hz,1H),7.79(d,J＝8.8Hz,1H),7.47(q,J＝8.5Hz,1H),7.28–7.11(m,4H),7.11–6.99(m,3H),4.44(s,2H),3.41–3.28(m,2H),2.58(d,J＝20.0Hz,5H).13C NMR(101MHz,DMSO-d6)δ162.1,155.2,138.6,134.4,132.7(dd,J＝9.7,5.1Hz,1C),130.2,129.0,128.8,126.8,125.7,121.7(d,J＝2.8Hz,1C),121.4,120.6(dd,J＝14.8,3.7Hz,1C),113.2,112.0(dd,J＝21.1,3.2Hz,1C),104.3(t,J＝26.2Hz,1C),50.3,45.5(d,J＝1.4Hz,1C),35.0,9.5.19F NMR(376MHz,DMSO-d6)δ-110.70,-113.08.HRMS(ESI)[M-H]-理论值C25H20NO5SF2:484.1030；实测值：484.1037.
实施例99
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S52)
Figure BDA0003601498440001041
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-52，其余条件均一致。得白色固体90mg，收率90％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.03(d,J＝1.9Hz,1H),7.79(dd,J＝8.6,2.0Hz,1H),7.71(d,J＝8.7Hz,1H),7.44(t,J＝8.3Hz,1H),7.37(dd,J＝10.0,2.1Hz,1H),7.26(dd,J＝8.3,2.1Hz,1H),7.24–7.11(m,3H),7.03(d,J＝6.9Hz,2H),4.43(s,2H),3.39–3.28(m,2H),2.67–2.58(m,2H),2.52(s,3H).13CNMR(101MHz,DMSO-d6)δ163.1,160.6(d,J＝250.7Hz,1C),154.7,151.5,138.6,133.7,133.6,132.6(d,J＝4.8Hz,1C),131.0,129.0,128.8,126.8,125.1(d,J＝3.5Hz,1C),124.4,123.7(d,J＝14.4Hz,1C),120.6,117.3,116.4(d,J＝25.5Hz,1C),112.8,50.4,45.5(d,J＝2.2Hz,1C),34.9,9.5.19F NMR(376MHz,DMSO-d6)δ-114.61.HRMS(ESI)[M-H]-理论值C25H20NO5FSCl:500.0735；实测值：500.0736.
实施例100
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S53)
Figure BDA0003601498440001042
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-53，其余条件均一致。得白色固体98mg，收率90％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.03(d,J＝1.9Hz,1H),7.79(dd,J＝8.7,2.0Hz,1H),7.71(d,J＝8.7Hz,1H),7.53–7.46(m,1H),7.38(d,J＝5.0Hz,2H),7.26–7.11(m,3H),7.03(d,J＝6.7Hz,2H),4.42(s,2H),3.38–3.28(m,2H),2.67–2.58(m,2H),2.52(s,3H).13C NMR(101MHz,DMSO-d6)δ163.1,160.6(d,J＝251.6Hz,1C),154.7,151.8,138.6,133.5,132.9(d,J＝4.7Hz,1C),131.0,129.0,128.8,128.1(d,J＝3.4Hz,1C),126.8,124.3,124.2(d,J＝14.4Hz,1C),121.6(d,J＝9.7Hz,1C),120.6,119.2(d,J＝25.0Hz,1C),117.1,112.8,50.4,45.6(d,J＝1.7Hz,1C),34.9,9.5.19FNMR(376MHz,DMSO-d6)δ-114.52.HRMS(ESI)[M-H]-理论值C25H20NO5FSBr:544.0230；实测值：544.0230.
实施例102
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S55)
Figure BDA0003601498440001051
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-55，其余条件均一致。得白色固体82mg，收率77％。M.p.174-175℃.1H NMR(400MHz,DMSO-d6)δ8.23(d,J＝1.9Hz,1H),7.93(dd,J＝8.7,1.9Hz,1H),7.83(d,J＝8.8Hz,1H),7.62(q,J＝10.7,9.2Hz,2H),7.54(d,J＝8.0Hz,1H),7.24–7.11(m,3H),7.05(d,J＝7.0Hz,2H),4.55(s,2H),3.49–3.36(m,2H),2.72–2.63(m,2H),2.56(s,3H).13C NMR(101MHz,DMSO-d6)δ161.3,160.3(d,J＝248.9Hz,1C),155.5,144.8,138.5,134.6,132.2(d,J＝4.1Hz,1C),129.8,129.6(d,J＝14.3Hz,1C),129.0,128.8,126.7,126.4,124.6(d,J＝99.9Hz,1C),121.9,121.7(t,J＝3.5Hz,1C),113.4,113.2(d,J＝25.6Hz,1C),50.8,45.8(d,J＝3.3Hz,1C),35.0,9.5.19FNMR(376MHz,DMSO-d6)δ-61.16,-114.91.HRMS(ESI)[M-H]-理论值C26H20NO5SF4:534.0998；实测值：534.0992.
实施例103
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S56)
Figure BDA0003601498440001052
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-56，其余条件均一致。得白色固体65mg，收率65％。M.p.145-146℃.1H NMR(400MHz,DMSO-d6)δ13.82(s,1H),8.27(s,1H),8.10–7.72(m,2H),7.53(t,J＝7.5Hz,1H),7.40(d,J＝8.9Hz,1H),7.30–7.09(m,4H),7.02(d,J＝7.3Hz,2H),4.48(s,2H),3.37(t,J＝8.0Hz,2H),2.58(s,5H).13C NMR(101MHz,DMSO-d6)δ161.8(d,J＝248.6Hz,1C),161.2,155.6,144.1,138.5,134.7,133.8(d,J＝10.7Hz,1C),132.4(d,J＝8.9Hz,1C),131.2(d,J＝3.4Hz,1C),129.7,129.0,128.8,126.8,126.7,124.9,122.1,117.1(d,J＝25.1Hz,1C),114.9(d,J＝21.3Hz,1C),113.6,50.6,49.3,35.1,9.5.19F NMR(376MHz,DMSO-d6)δ-112.54.HRMS(ESI)[M-H]-理论值C25H20NO5FSCl:500.0735；实测值：500.0732.
实施例104
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S57)
Figure BDA0003601498440001061
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-57，其余条件均一致。得白色固体109mg，收率99％。M.p.156-157℃.1H NMR(400MHz,DMSO-d6)δ8.29(s,1H),7.91(dd,J＝36.9,8.4Hz,2H),7.70(s,1H),7.60(d,J＝8.1Hz,1H),7.55–7.44(m,1H),7.16,7.00(d,J＝6.0Hz,2H),4.54(s,2H),3.42(s,2H),2.58(s,5H).13C NMR(101MHz,DMSO-d6)δ161.3,161.2(d,J＝247.6,1C),160.0,155.6,144.4,138.3,134.3,132.8,132.7,129.8,128.8(d,J＝13.3,1C),126.8,126.5,124.6,122.2,120.0(d,J＝20.9,1C),114.0(d,J＝6.2,1C),113.6,50.9,48.3,34.8,9.5.19F NMR(376MHz,DMSO)δ-58.58,-113.37.HRMS(ESI)[M-H]-理论值C26H20NO5F4S:534.0998；实测值：534.0988.
实施例105
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S58)
Figure BDA0003601498440001071
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-58，其余条件均一致。得白色固体62mg，收率53％。M.p.155-156℃.1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),8.05–7.92(m,3H),7.90–7.83(m,2H),7.15(dq,J＝14.1,7.0Hz,3H),7.04(d,J＝6.9Hz,2H),4.64(s,2H),3.58–3.41(m,2H),2.74–2.61(m,2H).2.57(s,3H).13C NMR(101MHz,DMSO-d6)δ161.6,155.6,141.9,138.3,133.9,131.1,129.9,129.0,128.8,127.4(d,J＝31.4Hz,1C),126.8,126.4,125.2(d,J＝5.5Hz,1C),123.8(d,J＝3.6Hz,1C),123.1,122.5(d,J＝3.1Hz,1C),122.1,113.6,51.3,48.7,34.8,9.5.19F NMR(376MHz,DMSO-d6)δ-58.84,-61.35.HRMS(ESI)[M-H]-理论值C27H20NO5F6S:584.0966；实测值：584.0955.
实施例106
3-甲基-5-(N-(2-(三氟甲基)-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S59)
Figure BDA0003601498440001072
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-59，其余条件均一致。得白色固体75mg，收率63％。M.p.150-151℃.1H NMR(400MHz,DMSO-d6)δ13.82(s,1H),8.28(s,1H),8.10–7.72(m,4H),7.57(d,J＝8.5Hz,1H),7.38–6.87(m,5H),4.53(s,2H),3.44(t,J＝7.8Hz,2H),2.59(d,J＝15.7Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.2,155.7,144.0,138.3,136.1(d,J＝14.9Hz,1C),134.3,132.2,129.7,129.0,128.9,128.8,128.4(d,J＝31.4Hz,1C),126.7(d,J＝10.7Hz,1C),125.0(d,J＝4.3Hz,1C),122.3,121.0,113.7,51.1,48.4,34.8,9.5.19F NMR(376MHz,DMSO-d6)δ-58.57.HRMS(ESI)[M-H]-理论值C26H20NO5F3SBr:594.0198；实测值：594.0205.
实施例107
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S60)
Figure BDA0003601498440001081
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-60，其余条件均一致。得白色固体48mg，收率46％。M.p.177-178℃.1H NMR(400MHz,DMSO-d6)δ13.77(s,1H),8.27(s,1H),7.96(d,J＝8.5Hz,1H),7.85(d,J＝8.6Hz,1H),7.55(s,1H),7.48(d,J＝8.2Hz,1H),7.39(d,J＝7.9Hz,1H),7.17(dt,J＝16.7,6.5Hz,3H),7.03(d,J＝6.8Hz,2H),4.49(s,2H),3.50–3.32(m,2H),2.59(d,J＝12.3Hz,5H).13C NMR(101MHz,DMSO-d6)δ161.1,155.6,143.8,138.5,134.7,134.1,133.8,133.4,132.1,129.6,129.2,129.0,128.8,127.9,126.8,126.7,125.2,122.2,113.6,50.8,49.4,35.1,9.5.HRMS(ESI)[M-H]-理论值C25H20NO5SCl2:516.0439；实测值：516.0430.
实施例108
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S61)
Figure BDA0003601498440001082
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-61，其余条件均一致。得白色固体72mg，收率75％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.19(d,J＝2.0Hz,1H),7.89(dd,J＝8.7,2.0Hz,1H),7.79(d,J＝8.7Hz,1H),7.28–7.09(m,5H),7.02(td,J＝8.5,2.9Hz,1H),6.95(d,J＝6.8Hz,2H),4.37(s,2H),3.37–3.22(m,2H),2.56(s,3H),2.46(d,J＝7.7Hz,2H),2.26(s,3H).13C NMR(101MHz,DMSO-d6)δ162.5,161.0(d,J＝242.1Hz,1C),155.0,138.6,137.6(d,J＝6.9Hz,1C),133.6,133.0(d,J＝2.8Hz,1C),132.2(d,J＝7.9Hz,1C),130.7,128.8(d,J＝9.0Hz,1C),126.7,125.1,121.2,115.9(d,J＝22.3Hz,1C),114.4(d,J＝20.8Hz,1C),113.0,50.5,50.2,35.1,18.4,9.5.19F NMR(376MHz,DMSO-d6)δ-117.53.HRMS(ESI)[M-H]-理论值C26H23NO5SF:480.1281；实测值：480.1284.
实施例109
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S62)
Figure BDA0003601498440001091
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-62，其余条件均一致。得白色固体102mg，收率98％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.08(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.81(d,J＝8.8Hz,1H),7.24(t,J＝7.7Hz,4H),7.17(t,J＝7.3Hz,1H),7.09(d,J＝7.0Hz,2H),4.43(s,2H),3.42–3.32(m,2H),2.77–2.69(m,2H),2.55(s,3H).13C NMR(101MHz,DMSO-d6)δ161.4(dd,J＝252.4,9.9Hz,1C),161.2,155.5,144.1,138.6,134.7(t,J＝14.2Hz,1C),134.7,129.5,129.0,128.9,126.8,126.5,124.7,121.7,113.4,113.2(d,J＝29.6Hz,1C),111.8(t,J＝19.3Hz,1C),50.8,35.3,9.5.19F NMR(376MHz,DMSO-d6)δ-111.06.HRMS(ESI)[M-H]-理论值C25H19NO5F2SCl:518.0641；实测值：518.0642.
实施例110
3-甲基-5-(N-([1,1'-联苯]-4-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S82)
Figure BDA0003601498440001092
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-82，其余条件均一致。得白色固体93mg，收率84％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.96(d,J＝8.8Hz,1H),7.84(d,J＝8.8Hz,1H),7.63(dd,J＝7.6,5.2Hz,4H),7.50–7.39(m,4H),7.35(t,J＝7.3Hz,1H),7.18(t,J＝7.2Hz,2H),7.12(t,J＝7.2Hz,1H),7.02(d,J＝6.9Hz,2H),4.48(s,2H),3.41–3.34(m,2H),2.67–2.58(m,2H),2.56(s,3H).13CNMR(101MHz,DMSO-d6)δ161.3,155.5,144.1,140.1,139.9,138.7,136.5,135.4,129.7,129.4,129.3,129.0,128.8,127.9,127.1,127.1,126.7,126.6,124.9,122.0,113.5,51.4,49.9,34.8,9.5.HRMS(ESI)[M-H]-理论值C31H26NO5S:524.1532；实测值：524.1528.
实施例111
3-甲基-5-(N-(2'-氰基-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S83)
Figure BDA0003601498440001101
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-83，其余条件均一致。得白色固体96mg，收率86％。M.p.197-198℃.1H NMR(400MHz,DMSO-d6)δ8.25(d,J＝1.9Hz,1H),8.00–7.89(m,2H),7.79(dd,J＝15.5,8.1Hz,2H),7.58(dd,J＝14.5,7.9Hz,4H),7.50(d,J＝8.2Hz,2H),7.24–7.08(m,3H),7.02(d,J＝7.0Hz,2H),4.51(s,2H),3.45–3.32(m,2H),2.60(d,J＝14.5Hz,5H).13C NMR(101MHz,DMSO-d6)δ155.2,144.6,138.7,138.3,137.5,134.7,134.3,134.0,130.5,130.2,129.3,129.0,129.0,128.8,128.7,126.7,125.8,121.6,119.0,113.3,110.7,51.6,50.2,34.9,9.6.HRMS(ESI)[M-H]-理论值C32H25N2O5S:549.1484；实测值：549.1487.
实施例112
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S84)
Figure BDA0003601498440001111
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-84，其余条件均一致。得白色固体52mg，收率42％。M.p.197-198℃.1H NMR(400MHz,DMSO-d6)δ8.35–8.23(m,1H),7.95(dd,J＝8.8,1.7Hz,1H),7.83(d,J＝8.8Hz,1H),7.66(d,J＝7.6Hz,1H),7.56(t,J＝7.4Hz,1H),7.43(dd,J＝22.4,7.8Hz,3H),7.34(d,J＝7.5Hz,1H),7.27(d,J＝8.0Hz,2H),7.20(t,J＝7.2Hz,2H),7.13(t,J＝7.2Hz,1H),7.03(d,J＝7.1Hz,2H),4.51(s,2H),3.43–3.28(m,2H),2.60(d,J＝12.8Hz,5H),1.17(s,9H).13C NMR(101MHz,DMSO-d6)δ167.9,161.8,155.4,141.0,140.7,138.7,136.4,135.2,133.2,131.3,130.8,130.0,129.5,129.0,128.9,128.8,128.4,127.8,126.7,126.2,121.7,113.4,81.2,51.2,49.7,34.7,27.6,9.6.HRMS(ESI)[M-H]-理论值C36H34NO7S:624.2056；实测值：624.2044.
实施例113
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S85)
Figure BDA0003601498440001112
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M4-85，其余条件均一致。得白色固体70mg，收率63％。M.p.192-193℃.1H NMR(400MHz,DMSO-d6)δ13.70(s,1H),8.30(d,J＝1.9Hz,1H),7.97(dd,J＝8.8,2.0Hz,1H),7.86(d,J＝8.7Hz,1H),7.69(d,J＝8.0Hz,5H),7.60–7.48(m,4H),7.19(t,J＝7.3Hz,2H),7.13(t,J＝7.2Hz,1H),7.08–6.99(m,2H),4.55(s,2H),3.41(t,J＝7.9Hz,2H),2.64(t,J＝7.9Hz,2H),2.58(s,3H).13CNMR(101MHz,DMSO-d6)δ195.8,161.1,155.6,143.8,142.6,138.7,137.5,136.6,135.1,133.1,130.3,130.0,129.6,129.0,129.0,128.8,128.6,126.7,126.7,125.3,122.2,113.6,51.6,50.4,34.8,9.6.HRMS(ESI)[M-H]-理论值C32H26NO6S:552.1481；实测值：552.1484.
实施例114
3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(M5-1)
Figure BDA0003601498440001121
将4-硝基苯基哌嗪(2.07g,10mmol)，三乙胺(1.22g,12mmol)，加入无水四氢呋喃(30mL)中，0℃搅拌10mins，缓慢滴加3,3-二甲基丁酰氯(1.62g,12mmol)的无水四氢呋喃(10mL)溶液，滴完升至室温反应10h，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(100mL)，并用乙酸乙酯(100mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(DCM/MeOH＝150/1)得橙红色固体2.82g，收率92％。
实施例115
丙基-4-(4-硝基苯基)哌嗪-1-甲酸酯(M5-2)
Figure BDA0003601498440001122
按照3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(M5-1)所用方法，将3,3-二甲基丁酰氯替换为氯甲酸丙酯，其余条件均一致。得黄色固体1.35g，收率92％。1H NMR(400MHz,氯仿-d)δ8.22–7.95(m,2H),6.87–6.71(m,2H),4.06(t,J＝6.7Hz,2H),3.71–3.58(m,4H),3.49–3.35(m,4H),1.66(h,J＝7.2Hz,2H),0.94(t,J＝7.4Hz,3H).13C NMR(101MHz,氯仿-d)δ155.4,154.6,138.9,125.9,112.9,67.3,46.9,43.0,22.3,10.4.
实施例116
1-(4-(4-硝基苯基)哌嗪-1-基)乙-1-酮(M5-3)
Figure BDA0003601498440001123
按照3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(M5-1)所用方法，将3,3-二甲基丁酰氯替换为乙酰氯，其余条件均一致。得黄色固体1.08g，收率87％。
实施例117
(4-(4-硝基苯基)哌嗪-1-基)苯基甲基酮(M5-4)
Figure BDA0003601498440001131
按照3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(M5-1)所用方法，将3,3-二甲基丁酰氯替换为苯甲酰氯，其余条件均一致。得黄色固体1.45g，收率93％。
实施例118
N,N-二甲基-4-(4-硝基苯基)哌嗪-1-酰胺(M5-5)
Figure BDA0003601498440001132
按照3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(M5-1)所用方法，将3,3-二甲基丁酰氯替换为二甲氨基甲酰氯，其余条件均一致。得黄色固体2.47g，收率88％。
实施例119
3,3-二甲基-1-(4-(4-氨基苯基)哌嗪-1-基)丁-1-酮(M6-1)
Figure BDA0003601498440001133
将3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮(94mg,0.3mmol)，38％浓盐酸(0.5mL,6mmol)混合搅拌，分批加入锌粉(0.14g,2.1mmol)，室温反应11h，TLC检测反应完毕后，缓慢滴加氨水至PH＝5～6，加水(5mL)溶解，二氯甲烷(15mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，减压蒸馏除去溶剂，得白色固体90mg，收率99％。
实施例120
丙基-4-(4-氨基苯基)哌嗪-1-甲酸酯(M6-2)
Figure BDA0003601498440001134
按照3,3-二甲基-1-(4-(4-氨基苯基)哌嗪-1-基)丁-1-酮(M6-1)所用方法，将3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮替换为丙基-4-(4-硝基苯基)哌嗪-1-甲酸酯，其余条件均一致。得白色固体0.50g，收率64％。1H NMR(400MHz,氯仿-d)δ6.80(d,J＝8.8Hz,2H),6.69–6.59(m,2H),4.06(t,J＝6.7Hz,2H),3.69–3.57(m,4H),3.51(s,2H),2.96(t,J＝5.1Hz,4H),1.66(h,J＝7.1Hz,2H),0.95(t,J＝7.4Hz,3H).13C NMR(101MHz,氯仿-d)δ155.6,144.2,140.8,119.3,116.1,67.1,51.2,43.9,22.4,10.4.
实施例121
1-(4-(4-氨基苯基)哌嗪-1-基)乙-1-酮(M6-3)
Figure BDA0003601498440001141
按照3,3-二甲基-1-(4-(4-氨基苯基)哌嗪-1-基)丁-1-酮(M6-1)所用方法，将3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮替换为1-(4-(4-硝基苯基)哌嗪-1-基)乙-1-酮，其余条件均一致。得黄色固体0.39g，收率60％。
实施例122
(4-(4-氨基苯基)哌嗪-1-基)苯基甲基酮(M6-4)
Figure BDA0003601498440001142
按照3,3-二甲基-1-(4-(4-氨基苯基)哌嗪-1-基)丁-1-酮(M6-4)所用方法，将3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮替换为(4-(4-硝基苯基)哌嗪-1-基)苯基甲基酮，其余条件均一致。得黄色固体0.62g，收率74％。
实施例123
N,N-二甲基-4-(4-氨基苯基)哌嗪-1-酰胺(M6-5)
Figure BDA0003601498440001143
按照3,3-二甲基-1-(4-(4-氨基苯基)哌嗪-1-基)丁-1-酮(M6-1)所用方法，将3,3-二甲基-1-(4-(4-硝基苯基)哌嗪-1-基)丁-1-酮替换为N,N-二甲基-4-(4-硝基苯基)哌嗪-1-酰胺，其余条件均一致。得白色固体0.55g，收率74％。
实施例124
中间体M7的合成通法
方法A:将取代的苯胺或苯乙胺(1.8mmol)，2-碘代乙基苯(1.2mmol)，碳酸钾(0.25g,2.7mmol)，溶于乙腈(8mL)中加热至60℃反应24h，TLC检测反应完毕后，冷却至室温，减压蒸馏除去溶剂，加水(10mL)，并用乙酸乙酯(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离得中间体M7。
方法B:将取代的苯甲醛或苯乙醛(0.5mmol)，取代的苯胺或苯乙胺(0.5mmol)，原甲酸三甲酯(85mg,0.8mmol)溶于甲醇(10mL)中0℃搅拌，分批加入氰基硼氢化钠(38mg,0.6mmol)，室温反应10h，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)，并用乙酸乙酯(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离得中间体M7。
实施例125
N-苯乙基苯胺(M7-10)
Figure BDA0003601498440001151
方法A，得黄色油状物32mg，收率32％。
实施例126
4-苄基-N-苯乙基苯胺(M7-11)
Figure BDA0003601498440001152
方法B，得黄色油状物190mg，收率79％。1H NMR(400MHz,氯仿-d)δ7.79–7.51(m,10H),7.43(d,J＝8.4Hz,2H),6.91(d,J＝8.5Hz,2H),4.30(s,2H),3.88(s,1H),3.70(t,J＝7.1Hz,2H),3.21(t,J＝7.1Hz,2H).13C NMR(101MHz,氯仿-d)δ146.2,142.0,139.3,129.8,129.7,128.7,128.7,128.5,128.3,126.3,125.7,113.0,45.1,41.0,35.4.
实施例127
N-苯乙基-4-苯氧基苯胺(M7-12)
Figure BDA0003601498440001153
方法B，得黄色固体140mg，收率65％。
实施例128
二苯乙胺(M7-13)
Figure BDA0003601498440001154
方法A，得黄色油状物89mg，收率80％。
实施例129
4-吗啉-N-苯乙基苯胺(M7-63)
Figure BDA0003601498440001155
方法A，得黄色固体120mg，收率43％。
实施例130
4-(4-甲基哌嗪-1-基)-N-苯乙基苯胺(M7-64)
Figure BDA0003601498440001161
方法A，得黄色油状物39mg，收率13％。
实施例131
4-(4-(苯乙氨基)苯基)哌嗪-1-羧酸叔丁酯(M7-65)
Figure BDA0003601498440001162
方法A，得黄色固体340mg，收率45％。1H NMR(400MHz,氯仿-d)δ7.36(t,J＝7.3Hz,2H),7.31–7.22(m,3H),6.89(d,J＝8.0Hz,2H),6.63(s,2H),3.68–3.58(m,4H),3.39(s,2H),3.14–2.83(m,6H),1.56(s,9H).13C NMR(101MHz,氯仿-d)δ154.8,143.6,142.9,139.5,128.8,128.6,126.4,119.4,114.0,79.7,60.4,51.4,45.8,35.7,28.5.
实施例132
3,3-二甲基-1-(4-(苯乙胺基)苯基)哌嗪-1-基)丁酮(M7-66)
Figure BDA0003601498440001163
方法A，得黄色固体245mg，收率53％。1H NMR(400MHz,氯仿-d)δ7.30(t,J＝7.3Hz,2H),7.21(t,J＝8.4Hz,3H),6.83(d,J＝8.7Hz,2H),6.58(d,J＝8.6Hz,2H),3.77(t,J＝5.1Hz,2H),3.69–3.60(m,2H),3.50(s,1H),3.34(t,J＝7.0Hz,2H),2.98(q,J＝5.8Hz,4H),2.88(t,J＝7.0Hz,2H),2.29(s,2H),1.07(s,9H).13C NMR(101MHz,氯仿-d)δ170.4,143.2,143.0,139.4,128.8,128.6,126.4,119.4,114.1,51.7,51.4,46.9,45.7,44.7,41.6,35.6,31.5,30.2.
实施例133
4-(4-(苯乙氨基)苯基)哌嗪-1-羧酸丙酯(M7-67)
Figure BDA0003601498440001171
方法A，得黄色固体328mg，收率56％。1H NMR(400MHz,氯仿-d)δ7.32–7.10(m,5H),6.79(d,J＝8.3Hz,2H),6.53(d,J＝8.3Hz,2H),4.05(t,J＝6.6Hz,2H),3.57(q,J＝11.4,8.2Hz,5H),3.29(t,J＝7.1Hz,2H),2.87(dt,J＝36.4,6.0Hz,6H),1.64(h,J＝7.1Hz,2H),0.93(t,J＝7.4Hz,3H).13C NMR(101MHz,氯仿-d)δ155.6,143.5,143.1,139.5,128.9,128.6,126.4,119.5,114.0,67.1,51.3,45.8,44.0,35.7,22.5,10.6.
实施例134
1-(4-(4-(苯乙氨基)苯基)哌嗪-1-基)乙烷-1-酮(M7-68)
Figure BDA0003601498440001172
方法A，得黄色固体23mg，收率6％。1H NMR(400MHz,氯仿-d)δ7.34(t,J＝7.4Hz,2H),7.25(t,J＝8.1Hz,3H),6.87(s,2H),6.62(s,2H),3.78(t,J＝5.1Hz,2H),3.62(t,J＝5.1Hz,2H),3.39(s,2H),3.15–2.84(m,6H),2.15(s,3H).
实施例135
(4-(4-(苯乙氨基)苯基)哌嗪-1-基)(苯基)甲酮(M7-69)
Figure BDA0003601498440001173
方法A，得黄色固体257mg，收率33％。1H NMR(400MHz,氯仿-d)δ7.54–7.40(m,5H),7.35(t,J＝7.3Hz,2H),7.30–7.18(m,3H),6.88(d,J＝8.6Hz,2H),6.61(d,J＝8.5Hz,2H),3.96(s,2H),3.62(d,J＝41.1Hz,3H),3.36(t,J＝7.1Hz,2H),3.19–2.82(m,6H).13C NMR(101MHz,氯仿-d)δ170.3,143.2,143.1,139.6,136.0,129.8,128.9,128.7,128.6,127.3,126.4,119.5,114.0,51.7,48.0,45.8,42.5,35.7.
实施例136
4-(4-苄基哌嗪-1-基)-N-苯乙基苯胺(M7-70)
Figure BDA0003601498440001181
方法A，得黄色固体138mg，收率37％。1H NMR(400MHz,氯仿-d)δ7.53–7.28(m,10H),6.95(s,2H),6.68(s,2H),3.69(s,2H),3.44(s,2H),3.18(s,4H),2.97(t,J＝6.9Hz,2H),2.73(t,J＝5.0Hz,4H).13C NMR(101MHz,氯仿-d)δ143.9,142.4,139.6,138.0,129.4,129.0,128.7,128.5,127.3,126.5,118.9,114.2,63.2,53.4,51.0,46.0,35.7.
实施例137
N,N-二甲基-4-(4-(苯基乙基氨基)苯基)哌嗪-1-甲酰胺(M7-71)
Figure BDA0003601498440001182
方法A，得白色固体120mg，收率34％。1H NMR(400MHz,氯仿-d)δ7.34(t,J＝7.3Hz,2H),7.29–7.21(m,3H),6.89(d,J＝7.4Hz,2H),6.62(s,2H),3.42(t,J＝5.0Hz,6H),3.05(s,4H),2.93(t,J＝7.0Hz,2H),2.88(s,6H).13C NMR(101MHz,氯仿-d)δ164.9,139.5,128.9,128.7,126.5,119.3,114.2,51.3,47.0,38.7.
实施例138
4-(4-(甲磺酰基)哌嗪-1-基)-N-苯乙基苯胺(M7-72)
Figure BDA0003601498440001183
方法A，得黄色固体258mg，收率36％。1H NMR(400MHz,氯仿-d)δ7.26(dt,J＝35.0,7.5Hz,5H),6.83(d,J＝7.5Hz,2H),6.57(d,J＝8.3Hz,2H),3.54–3.23(m,7H),3.09(s,4H),2.88(t,J＝6.9Hz,2H),2.79(s,3H).13C NMR(101MHz,氯仿-d)δ143.4,142.8,139.4,128.8,128.6,126.5,119.7,114.0,51.1,46.1,45.7,35.6,34.2.
实施例139
4-(4-(苯乙胺基)苯基)哌啶-1-羧酸叔丁酯(M7-73)
Figure BDA0003601498440001191
方法A，得黄色固体212mg，收率20％。1H NMR(400MHz,氯仿-d)δ7.37(t,J＝7.4Hz,2H),7.29(t,J＝7.1Hz,3H),7.08(d,J＝8.4Hz,2H),6.64(d,J＝8.4Hz,2H),4.29(s,2H),3.70(s,1H),3.43(t,J＝7.0Hz,2H),2.96(t,J＝7.0Hz,2H),2.84(t,J＝11.0Hz,2H),2.59(t,J＝12.1Hz,1H),1.84(d,J＝12.6Hz,2H),1.63(dt,J＝12.6,6.2Hz,2H),1.55(s,9H).13CNMR(101MHz,氯仿-d)δ155.0,146.5,139.4,135.0,128.8,128.6,127.6,126.5,113.2,79.4,45.4,41.8,35.6,33.5,28.6.
实施例140
4-(4-(苯乙氨基)-2-(三氟甲基)苯基)哌嗪-1-羧酸叔丁酯(M7-74)
Figure BDA0003601498440001192
方法A，得黄色油状物288mg，收率64％。1H NMR(400MHz,氯仿-d)δ7.36(t,J＝7.3Hz,2H),7.28(t,J＝8.6Hz,3H),7.20(d,J＝8.6Hz,1H),6.88(d,J＝2.3Hz,1H),6.79–6.70(m,1H),4.06(s,1H),3.59(s,4H),3.41(t,J＝7.0Hz,2H),2.94(t,J＝6.9Hz,2H),2.82(t,J＝5.0Hz,4H),1.57(s,9H).13C NMR(101MHz,氯仿-d)δ155.0,145.7,141.6,139.1,128.8,128.7,127.0(q,J＝295.3Hz,1C),126.6,125.4,116.0,110.6(q,J＝4.9Hz,1C),79.6,53.6,45.1,35.4,28.5.19F NMR(376MHz,氯仿-d)δ-60.46.
实施例141
4-(5-(苯乙氨基)吡啶-2-基)哌嗪-1-羧酸叔丁酯(M7-75)
Figure BDA0003601498440001193
方法A，得棕色油状物340mg，收率45％。1H NMR(400MHz,氯仿-d)δ7.71(d,J＝2.7Hz,1H),7.29(t,J＝7.4Hz,2H),7.24–7.15(m,3H),6.90(dd,J＝8.9,2.8Hz,1H),6.59(d,J＝8.9Hz,1H),3.61–3.47(m,5H),3.32(q,J＝5.6,4.7Hz,6H),2.86(t,J＝6.9Hz,2H),1.48(s,9H).13C NMR(101MHz,氯仿-d)δ154.8,153.4,139.2,137.5,133.3,128.8,128.6,126.5,124.1,109.1,79.7,46.9,45.9,35.5,28.5.
实施例142
4-(4-(苯乙氨基)苄基)哌嗪-1-羧酸叔丁酯(M7-76)
Figure BDA0003601498440001201
方法A，得黄色油状物230mg，收率29％。1H NMR(400MHz,氯仿-d)δ7.30(dd,J＝34.6,6.5Hz,5H),7.16(d,J＝7.3Hz,2H),6.61(d,J＝7.3Hz,2H),3.89(s,1H),3.65–3.32(m,8H),2.93(s,2H),2.41(s,4H),1.53(s,9H).13C NMR(101MHz,氯仿-d)δ154.8,147.4,139.4,130.5,128.9,128.7,126.5,126.2,112.7,79.4,62.8,52.8,45.2,35.6,28.6.
实施例143
4-(2-(苯乙氨基)苯基)哌嗪-1-羧酸叔丁酯(M7-77)
Figure BDA0003601498440001202
方法A，得无色油状物314mg，收率82％。1H NMR(400MHz,氯仿-d)δ7.29(d,J＝14.8Hz,2H),7.25–7.18(m,3H),7.03(td,J＝7.8,1.4Hz,1H),6.92(dd,J＝8.0,1.4Hz,1H),6.65(ddt,J＝7.8,4.0,1.5Hz,2H),4.67(s,1H),3.71–2.44(m,12H),1.48(s,9H).13C NMR(101MHz,氯仿-d)δ154.8,143.0,139.5,138.6,128.9,128.6,126.5,125.5,119.8,116.7,110.3,79.8,51.2,44.5,35.4,28.5.
实施例144
3-(4-甲基哌嗪-1-基)-N-苯乙基苯胺(M7-78)
Figure BDA0003601498440001203
方法A，得黄色油状物33mg，收率11％。1H NMR(400MHz,氯仿-d)δ7.36(dd,J＝10.8,4.4Hz,2H),7.27(t,J＝6.7Hz,3H),7.11(td,J＝8.4,1.6Hz,1H),6.37(d,J＝8.4Hz,1H),6.21(d,J＝5.8Hz,2H),3.77(s,1H),3.43(t,J＝7.0Hz,2H),3.31–3.15(m,4H),2.95(t,J＝7.0Hz,2H),2.68–2.54(m,4H),2.39(s,3H).13C NMR(101MHz,氯仿-d)δ152.5,149.0,139.4,129.9,128.8,128.6,126.4,106.0,105.1,101.0,55.2,49.2,46.1,45.2,35.7.
实施例145
N-(4-吗啉苄基)-2-苯基乙烷-1-胺(M7-79)
Figure BDA0003601498440001211
方法B，得白色固体132mg，收率44％。
实施例146
N-(4-(4-甲基哌嗪-1-基)苄基)-2-苯基乙烷-1-胺(M7-80)
Figure BDA0003601498440001212
方法B，得白色固体270mg，收率87％。
实施例147
4-(4-((苯乙胺基)甲基)苯基)哌嗪-1-羧酸叔丁酯(M7-81)
Figure BDA0003601498440001213
方法B，得白色固体185mg，收率94％。1H NMR(400MHz,氯仿-d)δ7.23–7.15(m,2H),7.10(dd,J＝7.1,5.0Hz,5H),6.78(d,J＝8.6Hz,2H),3.63(s,2H),3.55–3.42(m,4H),3.12–2.93(m,4H),2.80(t,J＝6.8Hz,2H),2.72(t,J＝6.5Hz,2H),1.52(s,1H),1.40(s,9H).13CNMR(101MHz,氯仿-d)δ154.7,150.3,140.1,132.1,129.1,128.7,128.5,126.1,116.6,79.9,53.3,50.5,49.6,36.4,28.5.
实施例148
N-(4-苯氧基苄基)-2-苯基乙烷-1-胺(M7-86)
Figure BDA0003601498440001214
方法B，得淡黄色液体497mg，收率82％。
实施例149
4-(2-((苯乙胺基)甲基)苯基)哌嗪-1-羧酸叔丁酯(M7-87)
Figure BDA0003601498440001221
方法B，得白色固体326mg，收率83％。1H NMR(400MHz,氯仿-d)δ7.37–7.31(m,2H),7.29(d,J＝6.8Hz,1H),7.25–7.14(m,5H),7.14–7.08(m,1H),5.28(s,1H),4.18(s,2H),3.28(s,4H),3.16(t,J＝6.9Hz,2H),3.00(t,J＝6.8Hz,2H),2.66(s,4H),1.47(s,9H).13CNMR(101MHz,氯仿-d)δ154.6,151.1,136.7,131.5,130.5,129.1,128.8,127.6,127.3,125.8,121.3,80.0,53.5,52.7,49.5,48.9,33.1,28.4.
实施例150
4-(3-((苯乙胺基)甲基)苯基)哌嗪-1-羧酸叔丁酯(M7-88)
Figure BDA0003601498440001222
方法B，得白色固体200mg，收率50％。1H NMR(400MHz,氯仿-d)δ7.63(s,2H),7.30–7.13(m,5H),6.84(dd,J＝18.3,6.7Hz,2H),3.99(s,2H),3.61–3.34(m,4H),3.20–2.72(m,8H),1.95(s,1H),1.47(s,9H).13C NMR(101MHz,氯仿-d)δ154.8,151.6,136.5,132.0,129.9,128.8,128.8,127.1,120.9,117.3,116.7,80.1,51.8,48.6,48.3,32.5,28.4.
实施例151
3-甲基-5-(N-苯基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-10)
Figure BDA0003601498440001223
将3-甲基-5-(氯磺酰基)苯并呋喃-2-羧酸乙酯(91mg,0.3mmol)，N-苯乙基苯胺(59mg,0.3mmol)，碳酸钾(46mg,0.33mmol)溶于无水二氯甲烷(10mL)中，60℃搅拌过夜，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，二氯甲烷(20mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝10/1～5/1)得黄色固体90mg，收率65％。1H NMR(400MHz,氯仿-d)δ7.88(s,1H),7.63(d,J＝8.8Hz,1H),7.56(d,J＝8.7Hz,1H),7.39–7.31(m,3H),7.30–7.24(m,2H),7.23–7.18(m,1H),7.17–7.10(m,2H),7.09–7.00(m,2H),4.48(q,J＝7.1Hz,2H),3.90–3.77(m,2H),2.89–2.76(m,2H),2.54(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.9,142.9,139.0,138.0,133.6,129.2,128.9,128.8,128.5,128.2,126.8,126.6,125.6,122.0,112.6,61.5,52.2,35.2,14.4,9.3.HRMS(ESI)[M+H]+理论值C26H26NO5S:464.1532；实测值：464.1525.
实施例152
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-11)
Figure BDA0003601498440001231
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-11，其余条件均一致。得白色固体193mg，收率70％。1H NMR(400MHz,氯仿-d)δ7.85(d,J＝1.8Hz,1H),7.64(dd,J＝8.8,1.9Hz,1H),7.53(d,J＝8.8Hz,1H),7.31(t,J＝7.3Hz,2H),7.26–7.08(m,10H),7.03–6.93(m,2H),4.46(q,J＝7.1Hz,2H),3.99(s,2H),3.89–3.72(m,2H),2.88–2.73(m,2H),2.49(s,3H),1.45(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ159.9,155.8,142.9,141.4,140.5,138.1,137.0,133.6,129.6,129.1,129.0,128.9,128.9,128.8,128.6,128.5,126.8,126.6,126.4,125.6,122.1,112.6,61.5,52.2,41.5,35.2,14.4,9.3.
实施例153
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-12)
Figure BDA0003601498440001232
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-12，其余条件均一致。得白色固体123mg，收率44％。1H NMR(400MHz,氯仿-d)δ7.92(d,J＝1.9Hz,1H),7.67(dd,J＝8.8,1.9Hz,1H),7.58(d,J＝8.8Hz,1H),7.39(t,J＝7.9Hz,2H),7.28(t,J＝7.2Hz,2H),7.18(dt,J＝22.1,7.0Hz,4H),7.07(t,J＝7.8Hz,2H),7.02–6.97(m,2H),6.93(d,J＝9.0Hz,2H),4.49(q,J＝7.1Hz,2H),3.93–3.65(m,2H),2.94–2.79(m,2H),2.57(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,157.3,156.3,155.9,142.9,138.0,133.6,133.6,130.4,129.9,129.2,128.8,128.5,126.8,126.6,125.6,124.1,122.0,119.5,118.6,112.7,61.6,52.3,35.2,14.4,9.3.
实施例154
3-甲基-5-(N,N-二苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-13)
Figure BDA0003601498440001241
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-13，其余条件均一致。得白色油状物112mg，收率76％。1HNMR(400MHz,氯仿-d)δ8.16(s,1H),7.84(d,J＝8.7Hz,1H),7.60(d,J＝8.7Hz,1H),7.29(t,J＝7.2Hz,4H),7.22(t,J＝7.3Hz,2H),7.16(d,J＝7.0Hz,4H),4.49(q,J＝7.1Hz,2H),3.56–3.40(m,4H),2.96–2.82(m,4H),2.63(s,3H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.7,142.9,138.4,135.4,129.4,128.8,128.6,126.6,126.3,125.6,121.5,113.0,61.6,50.0,35.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C28H30NO5S:492.1845；实测值：492.1836.
实施例155
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-63)
Figure BDA0003601498440001251
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-63，其余条件均一致。得白色固体158mg，收率96％。1H NMR(400MHz,氯仿-d)δ7.90(s,1H),7.65–7.57(m,1H),7.54(d,J＝8.7Hz,1H),7.21(dd,J＝18.1,7.2Hz,3H),7.11(d,J＝7.1Hz,2H),6.90(d,J＝8.8Hz,2H),6.81(d,J＝8.8Hz,2H),4.46(q,J＝7.1Hz,2H),3.92–3.81(m,4H),3.79–3.69(m,2H),3.22–3.12(m,4H),2.83–2.72(m,2H),2.53(s,3H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,150.8,142.8,138.2,133.9,130.2,129.8,129.1,128.8,128.5,126.9,126.5,125.6,122.0,115.4,112.6,66.8,61.5,52.3,48.8,35.1,14.4,9.4.HRMS(ESI)[M+H]+理论值C30H33N2O6S:549.2059；实测值：549.2054.
实施例156
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-64)
Figure BDA0003601498440001252
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-64，其余条件均一致。得白色油状物56mg，收率84％。1HNMR(400MHz,氯仿-d)δ7.90(s,1H),7.63(d,J＝8.8Hz,1H),7.55(d,J＝8.7Hz,1H),7.31–7.22(m,2H),7.22–7.16(m,1H),7.15–7.07(m,2H),6.89(d,J＝9.0Hz,2H),6.82(d,J＝9.1Hz,2H),4.47(q,J＝7.1Hz,2H),3.86–3.69(m,2H),3.33–3.18(m,4H),2.84–2.74(m,2H),2.63–2.55(m,4H),2.54(s,3H),2.36(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,150.7,142.8,138.2,133.9,129.8,129.7,129.7,129.1,128.8,128.5,126.9,126.5,125.6,122.0,115.7,112.5,61.5,55.0,52.3,48.5,46.1,35.1,14.4,9.4.HRMS(ESI)[M+H]+理论值C31H36N3O5S:562.2376；实测值：562.2380.
实施例157
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-65)
Figure BDA0003601498440001261
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-65，其余条件均一致。得白色油状物288mg，收率74％。1HNMR(400MHz,氯仿-d)δ7.88(s,1H),7.60(d,J＝8.8Hz,1H),7.51(d,J＝8.8Hz,1H),7.25–7.11(m,3H),7.08(d,J＝6.9Hz,2H),6.89(d,J＝8.9Hz,2H),6.80(d,J＝9.0Hz,2H),4.43(q,J＝7.1Hz,2H),3.84–3.68(m,2H),3.61–3.50(m,4H),3.22–3.02(m,4H),2.80–2.70(m,2H),2.51(s,3H),1.48(s,9H),1.41(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,154.6,150.7,142.8,138.2,133.9,130.3,129.8,129.1,128.8,128.4,126.9,126.5,125.6,122.0,116.2,112.5,79.9,79.6,61.5,52.3,48.7,35.1,28.4,14.4,9.3.HRMS(ESI)[M+H]+理论值C35H42N3O7S:648.2743；实测值：648.2745.
实施例158
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-66)
Figure BDA0003601498440001262
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-66，其余条件均一致。得白色固体308mg，收率95％。1H NMR(400MHz,氯仿-d)δ7.85(d,J＝1.8Hz,1H),7.56(dd,J＝8.7,1.9Hz,1H),7.48(d,J＝8.8Hz,1H),7.22–7.01(m,5H),6.95–6.71(m,4H),4.40(q,J＝7.1Hz,2H),3.82–3.58(m,6H),3.23–3.07(m,4H),2.83–2.64(m,2H),2.48(s,3H),2.27(s,2H),1.38(t,J＝7.1Hz,3H),1.03(s,9H).13C NMR(101MHz,氯仿-d)δ170.4,159.8,155.8,150.4,142.8,138.1,133.8,130.4,129.8,129.1,128.8,128.4,126.9,126.5,125.5,121.9,116.1,112.5,61.5,52.2,49.0,48.8,46.3,44.6,41.1,35.1,31.4,30.1,14.4,9.4.
实施例159
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-67)
Figure BDA0003601498440001271
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-67，其余条件均一致。得白色固体308mg，收率97％。1H NMR(400MHz,氯仿-d)δ7.88(d,J＝1.8Hz,1H),7.60(dd,J＝8.8,1.8Hz,1H),7.52(d,J＝8.7Hz,1H),7.23(dd,J＝8.0,6.4Hz,2H),7.19–7.14(m,1H),7.12–7.05(m,2H),6.93–6.86(m,2H),6.84–6.77(m,2H),4.44(q,J＝7.1Hz,2H),4.07(t,J＝6.7Hz,2H),3.81–3.70(m,2H),3.66–3.58(m,4H),3.22–3.09(m,4H),2.82–2.68(m,2H),2.52(s,3H),1.67(h,J＝7.2Hz,2H),1.43(t,J＝7.1Hz,3H),0.95(t,J＝7.4Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,155.5,150.7,142.8,138.2,133.9,130.5,129.8,129.1,128.8,128.5,126.9,126.5,125.6,122.0,116.3,112.6,67.2,61.5,52.3,48.8,43.5,35.1,22.4,14.4,10.4,9.4.
实施例160
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-68)
Figure BDA0003601498440001281
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-68，其余条件均一致。得白色固体254mg，收率86％。1H NMR(400MHz,氯仿-d)δ7.82(d,J＝1.8Hz,1H),7.58–7.42(m,2H),7.21–7.08(m,3H),7.07–6.99(m,2H),6.89–6.70(m,4H),4.38(q,J＝7.1Hz,2H),3.77–3.62(m,4H),3.56(t,J＝5.1Hz,2H),3.12(dt,J＝16.2,5.3Hz,4H),2.76–2.63(m,2H),2.46(s,3H),2.07(s,3H),1.37(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ169.1,159.9,155.8,150.4,142.9,138.1,133.9,130.7,129.9,129.2,128.9,128.5,126.9,126.6,125.6,122.0,116.3,112.6,61.6,52.3,49.1,48.8,46.1,41.2,35.1,21.4,14.4,9.4.
实施例161
3-甲基-5-(N-(4-(4-苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M8-69)
Figure BDA0003601498440001282
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-69，其余条件均一致。得白色固体282mg，收率86％。1H NMR(400MHz,氯仿-d)δ7.91(d,J＝1.7Hz,1H),7.61(dd,J＝8.8,1.9Hz,1H),7.54(d,J＝8.7Hz,1H),7.44(s,5H),7.28–7.15(m,3H),7.15–7.07(m,2H),6.97–6.89(m,2H),6.87–6.79(m,2H),4.46(q,J＝7.1Hz,2H),3.92(s,2H),3.79–3.73(m,2H),3.61(s,2H),3.22(d,J＝22.6Hz,4H),2.84–2.70(m,2H),2.54(s,3H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ170.4,159.9,155.8,150.4,142.8,138.1,135.5,133.9,130.7,130.0,129.9,129.1,128.8,128.6,128.5,127.1,126.9,126.5,125.6,122.0,116.4,112.6,61.6,52.3,49.1,35.1,14.4,9.4.
实施例162
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-70)
Figure BDA0003601498440001291
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-70，其余条件均一致。得白色固体251mg，收率79％。1H NMR(400MHz,氯仿-d)δ7.93(d,J＝1.3Hz,1H),7.65(dd,J＝8.8,1.6Hz,1H),7.57(d,J＝8.7Hz,1H),7.37(q,J＝7.4Hz,4H),7.29(dd,J＝14.7,7.4Hz,3H),7.21(t,J＝7.2Hz,1H),7.15(d,J＝7.0Hz,2H),6.91(d,J＝8.9Hz,2H),6.84(d,J＝9.0Hz,2H),4.49(q,J＝7.1Hz,2H),3.84–3.75(m,2H),3.61(s,2H),3.31–3.21(m,4H),2.85–2.78(m,2H),2.68–2.61(m,4H),2.56(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,150.9,142.8,138.3,137.8,133.9,129.7,129.7,129.2,129.1,128.9,128.5,128.3,127.2,127.0,126.5,125.7,122.1,115.7,112.5,63.0,61.5,53.0,52.4,48.5,35.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C37H40N3O5S:638.2689；实测值：638.2697.
实施例163
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-71)
Figure BDA0003601498440001301
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-71，其余条件均一致。得白色固体143mg，收率92％。1H NMR(400MHz,氯仿-d)δ7.87(d,J＝1.8Hz,1H),7.58(dd,J＝8.7,1.9Hz,1H),7.51(d,J＝8.7Hz,1H),7.21(t,J＝7.2Hz,2H),7.14(dd,J＝8.6,5.9Hz,1H),7.11–7.03(m,2H),6.87(d,J＝9.0Hz,2H),6.79(d,J＝9.0Hz,2H),4.43(q,J＝7.1Hz,2H),3.82–3.67(m,2H),3.46–3.29(m,4H),3.25–3.14(m,4H),2.85(s,6H),2.80–2.70(m,2H),2.51(s,3H),1.41(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ164.6,159.9,155.8,150.7,142.8,138.2,133.9,130.2,129.8,129.1,128.8,128.4,126.9,126.5,125.6,122.0,116.0,112.5,61.5,52.3,48.5,46.6,38.4,35.1,14.4,9.4.
实施例164
3-甲基-5-(N-(4-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-72)
Figure BDA0003601498440001302
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-72，其余条件均一致。得黄色油状物275mg，收率87％。1HNMR(400MHz,氯仿-d)δ7.87(d,J＝1.8Hz,1H),7.58(dd,J＝8.8,1.9Hz,1H),7.50(d,J＝8.8Hz,1H),7.20(t,J＝7.2Hz,2H),7.13(dd,J＝8.6,5.9Hz,1H),7.07(d,J＝6.9Hz,2H),6.89(d,J＝9.0Hz,2H),6.81(d,J＝9.0Hz,2H),4.41(q,J＝7.1Hz,2H),3.79–3.69(m,2H),3.39–3.31(m,4H),3.30–3.22(m,4H),2.80(s,3H),2.77–2.68(m,2H),2.50(s,3H),1.40(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,150.2,142.8,138.1,133.8,130.9,129.9,129.1,128.8,128.5,126.9,126.5,125.5,122.0,116.6,112.6,61.5,52.2,48.7,45.7,35.0,34.5,14.4,9.4.
实施例165
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-73)
Figure BDA0003601498440001311
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-73，其余条件均一致。得白色固体309mg，收率95％。1H NMR(400MHz,氯仿-d)δ7.84(d,J＝1.5Hz,1H),7.61(dd,J＝8.8,1.8Hz,1H),7.54(d,J＝8.7Hz,1H),7.16(ddd,J＝35.7,17.1,7.2Hz,7H),6.96(d,J＝8.4Hz,2H),4.46(q,J＝7.1Hz,2H),4.25(s,2H),3.81–3.72(m,2H),2.79(q,J＝10.4,7.5Hz,4H),2.65(ddd,J＝15.1,7.6,3.6Hz,1H),2.51(s,3H),1.82(d,J＝12.4Hz,2H),1.65–1.55(m,2H),1.46(d,J＝16.9Hz,12H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,154.8,145.9,142.9,138.1,137.1,133.7,129.1,128.9,128.8,128.5,127.5,126.8,126.5,125.5,122.0,112.6,79.5,61.6,52.2,42.3,35.2,33.1,28.5,14.4,9.3.
实施例166
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-74)
Figure BDA0003601498440001312
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-74，其余条件均一致。得白色固体175mg，收率48％。1H NMR(400MHz,氯仿-d)δ7.82(d,J＝1.8Hz,1H),7.65–7.54(m,2H),7.25–7.09(m,6H),7.08–7.00(m,2H),4.44(q,J＝7.1Hz,2H),3.83–3.71(m,2H),3.55(t,J＝4.8Hz,4H),2.86(t,J＝4.8Hz,4H),2.81–2.73(m,2H),2.50(s,3H),1.45(d,J＝17.8Hz,12H).13C NMR(101MHz,氯仿-d)δ159.8,155.9,154.8,151.8,143.1,137.6,135.8,133.9,133.2,129.3,128.8,128.5,127.5(t,J＝29.6Hz,1C),127.5(d,J＝5.3Hz,1C),126.6,126.6,125.4,124.5,123.2(d,J＝274.9Hz,1C),122.0,112.8,79.8,61.6,53.3,52.1,35.2,28.4,14.3,9.2.19FNMR(376MHz,氯仿-d)δ-60.46.
实施例167
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-75)
Figure BDA0003601498440001321
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-75，其余条件均一致。得白色固体294mg，收率75％。1H NMR(400MHz,氯仿-d)δ7.90(d,J＝1.4Hz,1H),7.72(d,J＝2.5Hz,1H),7.61(dd,J＝8.8,1.7Hz,1H),7.53(d,J＝8.7Hz,1H),7.21(t,J＝7.2Hz,2H),7.18–7.11(m,2H),7.08(d,J＝6.9Hz,2H),6.54(d,J＝9.0Hz,1H),4.43(q,J＝7.1Hz,2H),3.81–3.71(m,2H),3.52(s,8H),2.81–2.73(m,2H),2.51(s,3H),1.46(s,9H),1.41(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,158.1,155.8,154.7,148.2,142.9,138.4,137.8,133.8,129.2,128.8,128.5,126.7,126.6,125.5,125.5,121.9,112.8,106.7,80.0,61.5,52.4,44.8,35.1,28.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C34H41N4O7S:649.2696；实测值：649.2701.
实施例168
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-76)
Figure BDA0003601498440001331
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-76，其余条件均一致。得白色固体247mg，收率74％。1H NMR(400MHz,氯仿-d)δ7.83(d,J＝1.4Hz,1H),7.58(dd,J＝8.8,1.7Hz,1H),7.51(d,J＝8.8Hz,1H),7.26–7.11(m,5H),7.07(d,J＝7.0Hz,2H),6.96(d,J＝8.3Hz,2H),4.43(q,J＝7.1Hz,2H),3.84–3.71(m,2H),3.48(s,2H),3.42(t,J＝5.0Hz,4H),2.83–2.72(m,2H),2.49(s,3H),2.36(t,J＝5.0Hz,4H),1.43(d,J＝9.5Hz,12H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,154.8,142.9,138.1,138.0,137.9,133.6,129.6,129.1,128.8,128.7,128.5,126.8,126.5,125.5,122.0,112.6,79.6,62.4,61.5,52.9,52.2,35.2,28.4,14.4,9.3.HRMS(ESI)[M+H]+理论值C36H44N3O7S:662.2900；实测值：662.2896.
实施例169
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-77)
Figure BDA0003601498440001332
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-77，其余条件均一致。得白色固体102mg，收率31％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.6Hz,1H),7.89(dd,J＝8.8,1.8Hz,1H),7.61(d,J＝8.8Hz,1H),7.36–7.26(m,1H),7.20–6.98(m,6H),6.93(d,J＝6.6Hz,2H),4.46(q,J＝7.1Hz,2H),4.23–3.76(m,2H),3.48(s,4H),3.16(s,2H),2.79(dd,J＝40.6,17.5Hz,2H),2.68–2.45(m,5H),1.46(d,J＝12.3Hz,12H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,154.8,151.2,143.0,138.2,136.1,133.8,130.5,129.4,129.3,128.5,128.4,126.8,126.4,125.5,124.3,122.6,122.0,112.9,79.7,61.5,51.2,34.7,28.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C35H42N3O7S:648.2743；实测值：648.2736.
实施例170
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-78)
Figure BDA0003601498440001341
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-78，其余条件均一致。得白色固体42mg，收率76％。1H NMR(400MHz,氯仿-d)δ7.92(d,J＝1.8Hz,1H),7.65(dd,J＝8.7,1.9Hz,1H),7.56(d,J＝8.7Hz,1H),7.31–7.09(m,6H),6.87(dd,J＝8.3,2.5Hz,1H),6.65(t,J＝2.2Hz,1H),6.39(dd,J＝7.7,1.9Hz,1H),4.48(q,J＝7.1Hz,2H),3.88–3.71(m,2H),3.26–3.09(m,4H),2.89–2.77(m,2H),2.62(t,J＝4.8Hz,4H),2.55(s,3H),2.41(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,151.7,142.9,139.9,138.1,133.8,129.4,129.1,128.9,128.5,126.9,126.5,125.6,122.1,118.9,117.4,115.4,112.5,61.5,54.8,52.2,48.3,45.8,35.2,14.3,9.3.HRMS(ESI)[M+H]+理论值C31H36N3O5S:562.2376；实测值：562.2380.
实施例171
3-甲基-5-(N-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-79)
Figure BDA0003601498440001342
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-79，其余条件均一致。得白色固体142mg，收率63％。1H NMR(400MHz,氯仿-d)δ8.23–8.04(m,1H),7.93–7.78(m,1H),7.60(d,J＝8.8Hz,1H),7.15(dq,J＝16.9,8.2,7.5Hz,5H),6.96(d,J＝7.1Hz,2H),6.81(d,J＝8.0Hz,2H),4.46(q,J＝7.0Hz,2H),4.32(s,2H),3.83(s,4H),3.43–3.28(m,2H),3.11(s,4H),2.74–2.53(m,5H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.7,150.9,142.9,138.5,135.8,129.6,129.3,128.7,128.5,126.9,126.4,126.3,125.6,121.5,115.5,113.0,66.8,61.5,51.5,49.2,49.1,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C31H35N2O6S:563.2216；实测值：563.2211.
实施例172
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-80)
Figure BDA0003601498440001351
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-80，其余条件均一致。得白色固体129mg，收率75％。1H NMR(400MHz,氯仿-d)δ8.10(s,1H),7.84(d,J＝8.8Hz,1H),7.59(d,J＝8.8Hz,1H),7.13(dt,J＝22.9,7.7Hz,5H),6.95(d,J＝6.9Hz,2H),6.81(d,J＝8.6Hz,2H),4.44(q,J＝7.1Hz,2H),4.30(s,2H),3.42–3.27(m,2H),3.23–3.08(m,4H),2.71–2.61(m,2H),2.57(s,3H),2.56–2.49(m,4H),2.32(s,3H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.7,151.0,142.9,138.5,135.8,129.6,129.3,128.7,128.5,126.4,126.3,126.3,125.6,121.5,115.8,113.0,61.5,55.0,51.5,49.1,48.8,46.1,35.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C32H38N3O5S:576.2532；实测值：576.2535.
实施例173
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-81)
Figure BDA0003601498440001352
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-81，其余条件均一致。得白色固体223mg，收率85％。1H NMR(400MHz,氯仿-d)δ8.11(s,1H),7.84(d,J＝8.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.15(dt,J＝15.3,7.7Hz,5H),6.95(d,J＝6.8Hz,2H),6.82(d,J＝8.6Hz,2H),4.45(q,J＝7.1Hz,2H),4.31(s,2H),3.69–3.46(m,4H),3.42–3.28(m,2H),3.21–3.04(m,4H),2.72–2.61(m,2H),2.58(s,3H),1.47(s,9H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.7,154.7,151.0,142.9,138.4,135.8,129.6,129.3,128.7,128.5,127.0,126.4,126.2,125.6,121.5,116.4,113.0,79.9,61.5,51.5,49.1,35.3,28.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H44N3O7S:662.2900；实测值：662.2891.
实施例174
3-甲基-5-(N-苯乙基-N-(4-苯氧基苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M8-86)
Figure BDA0003601498440001361
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-86，其余条件均一致。得白色固体70mg，收率25％。1H NMR(400MHz,氯仿-d)δ8.16(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.7Hz,1H),7.34(dd,J＝8.6,7.3Hz,2H),7.26–7.08(m,6H),7.03–6.91(m,6H),4.48(q,J＝7.1Hz,2H),4.38(s,2H),3.47–3.34(m,2H),2.75–2.66(m,2H),2.62(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,157.2,156.9,155.8,143.0,138.3,135.6,130.6,130.0,129.8,129.4,128.7,128.5,126.5,126.2,125.6,123.6,121.5,119.0,118.8,113.1,61.6,51.6,49.4,35.3,14.4,9.4.
实施例175
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-87)
Figure BDA0003601498440001362
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-87，其余条件均一致。得白色固体250mg，收率75％。1H NMR(400MHz,氯仿-d)δ8.07(d,J＝1.5Hz,1H),7.80(dd,J＝8.8,1.8Hz,1H),7.55(d,J＝8.8Hz,1H),7.33(d,J＝7.7Hz,1H),7.23–7.16(m,1H),7.12–6.98(m,5H),6.88–6.78(m,2H),4.49(s,2H),4.39(q,J＝7.1Hz,2H),3.45(s,4H),3.29–3.20(m,2H),2.78–2.67(m,4H),2.53(d,J＝4.4Hz,5H),1.39(d,J＝9.6Hz,12H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,154.8,151.4,143.0,138.4,135.5,130.8,130.0,129.4,128.7,128.5,128.5,126.4,126.2,125.5,124.7,121.5,120.2,113.0,79.9,61.6,52.9,49.5,46.4,34.8,28.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H44N3OS:662.2900；实测值：662.2896.
实施例176
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-88)
Figure BDA0003601498440001371
按照5-(N-苯基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M8-10)所用方法，将N-苯乙基苯胺替换为M7-88，其余条件均一致。得白色固体129mg，收率49％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.9Hz,1H),7.86(dd,J＝8.7,1.9Hz,1H),7.62(d,J＝8.7Hz,1H),7.17(dddt,J＝14.2,9.9,7.3,3.3Hz,4H),6.96(d,J＝6.7Hz,2H),6.84(d,J＝6.1Hz,2H),6.74(d,J＝7.2Hz,1H),4.47(q,J＝7.1Hz,2H),4.35(s,2H),3.62–3.50(m,4H),3.42–3.32(m,2H),3.07(t,J＝5.2Hz,4H),2.63(d,J＝25.7Hz,5H),1.47(d,J＝11.5Hz,12H).13CNMR(101MHz,氯仿-d)δ159.9,155.8,154.7,143.0,138.4,137.0,135.6,129.4,128.7,128.5,126.5,126.2,125.6,121.5,120.1,116.3,116.0,113.0,80.0,61.6,52.3,49.4,49.2,35.2,28.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H44N3O7S:662.2900；实测值：662.2904.
实施例177
3-甲基-5-(N-苯乙基-N-苯基氨磺酰)苯并呋喃-2-羧酸(F27-S10)
Figure BDA0003601498440001381
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-10，其余条件均一致。得白色固体50mg，收率76％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.73(s,1H),7.67(d,J＝8.7Hz,1H),7.44(d,J＝8.6Hz,1H),7.35(d,J＝6.8Hz,3H),7.21(dt,J＝27.5,7.2Hz,3H),7.12(d,J＝7.1Hz,2H),7.04(d,J＝7.8Hz,2H),3.82(t,J＝7.2Hz,2H),2.64(t,J＝7.2Hz,2H),2.45(s,3H).13C NMR(101MHz,DMSO-d6)δ154.9,139.2,138.7,132.2,130.6,129.4,129.2,129.0,128.7,128.3,126.8,124.9,121.0,112.5,51.5,34.6,9.4.HRMS(ESI)[M-H]-理论值C24H20NO5S:434.1062；实测值：434.1054.
实施例178
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S11)
Figure BDA0003601498440001382
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-11，其余条件均一致。得白色固体92mg，收率88％。M.p.301-302℃.1H NMR(400MHz,DMSO-d6)δ7.90–7.66(m,2H),7.56(dd,J＝8.6,1.9Hz,1H),7.34(tq,J＝15.6,6.5,5.5Hz,10H),7.21(d,J＝7.4Hz,2H),7.05(d,J＝8.0Hz,2H),4.04(s,2H),3.87(t,J＝7.3Hz,2H),2.72(t,J＝7.3Hz,2H),2.60(s,3H).13C NMR(101MHz,DMSO-d6)δ162.6,154.9,141.4,141.4,138.7,137.1,132.2,130.5,129.7,129.2,129.2,129.2,129.0,128.9,128.7,126.7,126.5,124.9,121.1,112.5,51.5,41.0,34.6,9.3.HRMS(ESI)[M-H]-理论值C31H26NO5S:524.1532；实测值：524.1533.
实施例179
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S12)
Figure BDA0003601498440001391
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-12，其余条件均一致。得白色固体85mg，收率81％。M.p.285-286℃.1H NMR(400MHz,DMSO-d6)δ7.85(d,J＝1.9Hz,1H),7.75(d,J＝8.8Hz,1H),7.54(dd,J＝8.7,1.9Hz,1H),7.46–7.38(m,2H),7.25(t,J＝7.1Hz,2H),7.22–7.11(m,4H),7.07–6.99(m,4H),6.97–6.91(m,2H),3.81(t,J＝7.2Hz,2H),2.67(t,J＝7.2Hz,2H),2.51(s,3H).13C NMR(101MHz,DMSO-d6)δ162.0,156.7,156.6,155.3,138.7,134.1,132.6,130.8,130.6,130.0,129.2,128.7,126.7,126.0,124.3,121.7,119.4,119.1,112.9,51.6,34.6,9.4.HRMS(ESI)[M-H]-理论值C30H24NO6S:526.1324；实测值：526.1316.
实施例180
3-甲基-5-(N,N-二苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S13)
Figure BDA0003601498440001392
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-13，其余条件均一致。得白色固体54mg，收率78％。M.p.212-213℃.1H NMR(400MHz,DMSO-d6)δ13.75(s,1H),8.25(s,1H),7.96–7.86(m,1H),7.82(d,J＝8.8Hz,1H),7.32–7.22(m,4H),7.18(d,J＝7.4Hz,6H),3.49–3.29(m,4H),2.86–2.66(m,4H),2.58(s,3H).13C NMR(101MHz,DMSO-d6)δ161.2,155.5,143.8,139.0,135.3,129.6,129.2,128.8,126.8,126.6,125.2,121.8,113.5,49.8,35.2,9.6.HRMS(ESI)[M-H]-理论值C26H24NO5S:462.1375；实测值：462.1377.
实施例181
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S63)
Figure BDA0003601498440001401
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-63，其余条件均一致。得白色固体81mg，收率78％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.74–7.58(m,2H),7.43(d,J＝8.4Hz,1H),7.26(t,J＝7.1Hz,2H),7.16(dd,J＝24.8,7.0Hz,3H),6.85(q,J＝8.8Hz,4H),3.73(d,J＝9.7Hz,6H),3.11(s,4H),2.63(t,J＝6.9Hz,2H),2.44(s,3H).13C NMR(101MHz,DMSO-d6)δ163.1,154.7,150.7,138.8,132.3,130.8,129.9,129.7,129.2,128.7,126.7,124.4,120.7,116.3,115.1,112.3,66.5,51.7,48.4,34.6,9.4.HRMS(ESI)[M-H]-理论值C28H27N2O6S:519.1590；实测值：519.1584.
实施例182
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S64)
Figure BDA0003601498440001402
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-64，其余条件均一致。得白色固体40mg，收率94％。M.p.152-153℃.1H NMR(400MHz,DMSO-d6)δ11.66(s,1H),7.96(d,J＝1.7Hz,1H),7.79(d,J＝8.8Hz,1H),7.52(dd,J＝8.8,1.9Hz,1H),7.24(t,J＝7.2Hz,2H),7.17(td,J＝7.3,6.2,3.0Hz,1H),7.14–7.08(m,2H),6.94(d,J＝9.1Hz,2H),6.87(d,J＝9.0Hz,2H),3.90–3.71(m,4H),3.45(d,J＝10.8Hz,2H),3.15(dq,J＝21.9,11.6,10.7Hz,4H),2.78(d,J＝4.0Hz,3H),2.62(t,J＝7.2Hz,2H),2.51(s,3H).13C NMR(101MHz,DMSO-d6)δ161.0,155.6,149.4,143.7,138.7,133.6,130.3,129.9,129.4,129.2,128.7,127.1,126.7,125.2,122.2,116.1,113.2,52.4,51.7,45.3,42.2,34.5,9.5.HRMS(ESI)[M-H]-理论值C29H30N3O5S:532.1906；实测值：532.1904.
实施例183
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S65)
Figure BDA0003601498440001411
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-65，其余条件均一致。得白色固体205mg，收率83％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.68(s,1H),7.63(d,J＝8.6Hz,1H),7.42(d,J＝8.6Hz,1H),7.26(t,J＝7.2Hz,2H),7.19(t,J＝7.2Hz,1H),7.13(d,J＝7.0Hz,2H),6.94–6.79(m,4H),3.74(t,J＝7.2Hz,2H),3.44(s,4H),3.22–3.03(m,4H),2.62(t,J＝7.2Hz,2H),2.43(s,3H),1.42(s,9H).13C NMR(101MHz,DMSO-d6)δ163.0,154.6,154.4,152.3,150.5,138.8,132.2,130.8,129.9,129.8,129.2,128.7,126.7,124.5,120.7,116.3,115.9,112.3,79.5,51.7,48.1,34.6,28.5,9.4.HRMS(ESI)[M-H]-理论值C33H36N3O7S:618.2274；实测值：618.2267.
实施例184
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S66)
Figure BDA0003601498440001421
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-66，其余条件均一致。得白色固体108mg，收率87％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.82–7.56(m,2H),7.44(d,J＝8.6Hz,1H),7.31–7.10(m,5H),6.87(q,J＝8.6Hz,4H),3.75(t,J＝7.3Hz,2H),3.63(p,J＝4.8Hz,4H),3.14(dt,J＝10.7,4.9Hz,4H),2.63(t,J＝7.3Hz,2H),2.45(s,3H),2.28(s,2H),1.00(s,9H).13C NMR(101MHz,DMSO)δ169.9,162.8,154.7,150.4,138.8,132.3,130.7,129.8,129.8,129.2,128.7,126.7,124.7,120.9,115.7,112.4,51.7,48.6,48.3,46.0,44.1,41.1,34.6,31.5,30.2,9.4.HRMS(ESI)[M-H]-理论值C34H38N3O6S:616.2481；实测值：616.2490.
实施例185
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S67)
Figure BDA0003601498440001422
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-67，其余条件均一致。得淡黄色固体130mg，收率99％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.70(d,J＝1.9Hz,1H),7.65(d,J＝8.7Hz,1H),7.43(dd,J＝8.6,1.9Hz,1H),7.26(dd,J＝7.9,6.5Hz,2H),7.22–7.11(m,3H),6.91–6.80(m,4H),3.98(t,J＝6.6Hz,2H),3.74(t,J＝7.2Hz,2H),3.49(t,J＝5.2Hz,4H),3.15(t,J＝5.2Hz,4H),2.62(t,J＝7.2Hz,2H),2.44(s,3H),1.59(h,J＝7.1Hz,2H),0.90(t,J＝7.4Hz,3H).13C NMR(101MHz,DMSO-d6)δ162.9,155.1,154.7,151.6,150.4,138.8,132.3,130.7,129.9,129.8,129.2,128.7,126.7,124.7,120.8,117.1,115.9,112.4,66.8,51.7,48.1,43.6,34.6,22.4,10.8,9.4.HRMS(ESI)[M-H]-理论值C32H34N3O7S:604.2117；实测值：604.2109.
实施例186
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S68)
Figure BDA0003601498440001431
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-68，其余条件均一致。得白色固体72mg，收率64％。M.p.183-184℃.1H NMR(400MHz,DMSO-d6)δ7.83(d,J＝8.2Hz,1H),7.70(d,J＝8.6Hz,1H),7.54–7.39(m,1H),7.26–7.04(m,5H),6.94–6.76(m,4H),3.72(t,J＝7.1Hz,2H),3.59–3.30(m,4H),3.14(tt,J＝25.5,5.2Hz,4H),2.59(t,J＝7.3Hz,2H),2.46(s,3H),1.99(s,3H).13C NMR(101MHz,DMSO-d6)δ168.8,161.8,155.4,150.4,149.8,138.7,133.4,130.4,129.8,129.6,129.2,128.7,126.7,121.9,116.1,115.8,112.9,51.7,48.4,48.0,45.8,41.0,34.6,21.6,9.5.HRMS(ESI)[M-H]-理论值C30H30N3O6S:560.1855；实测值：560.1852.
实施例187
3-甲基-5-(N-(4-(4-苯甲酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S69)
Figure BDA0003601498440001441
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-69，其余条件均一致。得白色固体90mg，收率72％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.78–7.61(m,2H),7.45(q,J＝9.0,6.4Hz,6H),7.31–7.10(m,5H),6.95–6.79(m,4H),3.75(t,J＝7.4Hz,4H),3.47(s,2H),3.19(s,4H),2.63(t,J＝7.3Hz,2H),2.45(s,3H).13C NMR(101MHz,DMSO-d6)δ169.5,163.0,154.7,151.8,150.3,138.8,136.3,132.3,130.7,130.1,129.9,129.8,129.2,128.9,128.7,127.4,126.7,124.6,120.8,116.9,115.9,112.3,51.7,48.3,34.6,9.5.HRMS(ESI)[M-H]-理论值C35H32N3O6S:622.2012；实测值：622.2010.
实施例188
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S70)
Figure BDA0003601498440001442
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-70，其余条件均一致。得白色固体62mg，收率51％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.77(s,1H),7.69(d,J＝8.6Hz,1H),7.48(d,J＝8.2Hz,1H),7.33(d,J＝4.1Hz,4H),7.25(t,J＝6.6Hz,3H),7.16(dd,J＝24.4,7.1Hz,3H),6.83(q,J＝9.0Hz,4H),3.74(t,J＝7.4Hz,2H),3.53(s,2H),3.15(s,4H),2.62(t,J＝7.4Hz,2H),2.50(s,4H),2.47(s,3H).13CNMR(101MHz,DMSO-d6)δ162.5,155.0,150.6,149.2,138.8,138.3,132.9,130.3,129.7,129.4,129.2,128.7,128.7,127.5,126.7,125.4,121.3,119.5,115.4,112.6,62.4,52.9,51.8,48.1,34.6,9.4.HRMS(ESI)[M-H]-理论值C35H34N3O5S:608.2219；实测值：608.2211.
实施例189
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S71)
Figure BDA0003601498440001451
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-71，其余条件均一致。得白色固体69mg，收率58％。M.p.192-193℃.1H NMR(400MHz,DMSO-d6)δ13.75(s,1H),7.96(s,1H),7.78(d,J＝8.8Hz,1H),7.55(d,J＝8.7Hz,1H),7.32–7.06(m,5H),6.87(q,J＝9.0Hz,4H),3.76(t,J＝7.3Hz,2H),3.36–3.00(m,8H),2.76(s,6H),2.62(t,J＝7.3Hz,2H),2.51(s,3H).13C NMR(101MHz,DMSO-d6)δ164.1,161.1,155.6,150.6,143.6,138.7,133.7,129.8,129.5,129.3,129.2,128.7,127.1,126.7,125.2,122.2,115.7,113.2,51.8,48.0,46.7,38.5,34.6,9.5.HRMS(ESI)[M-H]-理论值C31H33N4O6S:589.2121；实测值：589.2115.
实施例190
3-甲基-5-(N-(4-(4-(甲磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S72)
Figure BDA0003601498440001461
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-72，其余条件均一致。得白色固体126mg，收率99％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.75(d,J＝1.9Hz,1H),7.67(d,J＝8.7Hz,1H),7.46(dd,J＝8.7,1.9Hz,1H),7.26(dd,J＝8.0,6.5Hz,2H),7.22–7.10(m,3H),6.96–6.82(m,4H),3.75(t,J＝7.3Hz,2H),3.25(q,J＝5.7Hz,8H),2.93(s,3H),2.63(t,J＝7.3Hz,2H),2.46(s,3H).13C NMR(101MHz,DMSO-d6)δ162.7,154.9,150.1,138.8,132.5,130.5,130.2,129.8,129.2,128.7,126.7,125.0,121.1,118.3,116.1,112.5,51.7,48.0,45.7,34.6,34.4,9.5.HRMS(ESI)[M-H]-理论值C29H30N3O7S2:596.1525；实测值：596.1525.
实施例191
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S73)
Figure BDA0003601498440001462
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-73，其余条件均一致。得白色固体96mg，收率38％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.71–7.55(m,2H),7.44(d,J＝8.5Hz,1H),7.21(tt,J＝14.6,7.2Hz,5H),7.12(d,J＝7.3Hz,2H),6.95(d,J＝8.2Hz,2H),4.06(d,J＝12.4Hz,2H),3.77(t,J＝7.3Hz,2H),3.02–2.66(m,3H),2.63(t,J＝7.4Hz,2H),2.41(s,3H),1.75(d,J＝12.2Hz,2H),1.54–1.44(m,2H),1.41(s,9H).13C NMR(101MHz,DMSO-d6)δ163.1,154.7,154.4,152.2,145.9,138.7,137.2,132.0,130.8,129.2,129.0,128.7,127.7,126.7,124.4,120.8,116.5,112.4,79.0,51.5,41.6,34.7,33.1,28.6,9.4.HRMS(ESI)[M-H]-理论值C34H37N2O7S:617.2321；实测值：617.2318.
实施例192
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S74)
Figure BDA0003601498440001471
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-74，其余条件均一致。得淡黄色固体114mg，收率83％。M.p.215-216℃.1H NMR(400MHz,DMSO-d6)δ7.86–7.70(m,2H),7.60–7.43(m,2H),7.31–7.05(m,7H),3.85(t,J＝7.1Hz,2H),3.43(t,J＝4.8Hz,4H),2.81(t,J＝4.8Hz,4H),2.68(t,J＝7.1Hz,2H),2.48(s,3H),1.42(s,9H).13CNMR(101MHz,DMSO-d6)δ162.2,155.4,154.3,151.6,138.5,136.0,133.9,132.3,130.1,129.2,128.6,126.7,126.2,125.8,125.7,125.2,122.5,121.7,113.0,79.5,53.2,51.4,34.8,28.5,9.3.19F NMR(376MHz,DMSO-d6)δ-59.16.HRMS(ESI)[M-H]-理论值C34H35N3O7SF3:686.2148；实测值：686.2136.
实施例193
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S75)
Figure BDA0003601498440001472
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-75，其余条件均一致。得白色固体207mg，收率83％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ7.71(d,J＝31.0Hz,3H),7.44(d,J＝8.7Hz,1H),7.35–6.96(m,6H),6.86–6.63(m,1H),3.76(s,2H),3.49(s,4H),3.41(s,4H),2.65(s,2H),2.45(s,3H),1.42(s,9H).13C NMR(101MHz,DMSO-d6)δ162.9,158.0,154.8,154.4,152.3,148.7,138.6,137.8,132.2,131.0,129.2,128.7,126.7,125.5,124.4,120.7,116.4,112.5,107.1,79.5,51.6,44.7,34.7,28.5,9.4.HRMS(ESI)[M-H]-理论值C32H35N4O7S:619.2226；实测值：619.2230.
实施例194
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S76)
Figure BDA0003601498440001481
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-76，其余条件均一致。得白色固体185mg，收率97％。M.p.234-235℃.1H NMR(400MHz,DMSO-d6)δ7.77(d,J＝1.9Hz,1H),7.73(d,J＝8.7Hz,1H),7.51(dd,J＝8.7,1.9Hz,1H),7.24(dd,J＝13.8,7.7Hz,4H),7.18(d,J＝7.1Hz,1H),7.11(d,J＝7.1Hz,2H),6.99(d,J＝8.2Hz,2H),3.81(t,J＝7.3Hz,2H),3.49(s,2H),3.32(t,J＝5.1Hz,4H),2.64(t,J＝7.3Hz,2H),2.46(s,3H),2.30(t,J＝4.9Hz,4H),1.38(s,9H).13C NMR(101MHz,DMSO-d6)δ162.0,155.3,154.3,147.5,138.7,138.0,137.9,132.7,130.0,129.8,129.2,128.8,128.7,126.7,125.8,121.6,121.1,112.8,79.2,61.7,52.7,51.5,34.7,28.5,9.3.HRMS(ESI)[M-H]-理论值C34H38N3O7S:632.2430；实测值：632.2432.
实施例195
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S77)
Figure BDA0003601498440001491
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-77，其余条件均一致。得白色固体63mg，收率67％。M.p.168-169℃.1H NMR(400MHz,DMSO-d6)δ8.25(d,J＝1.8Hz,1H),7.97–7.77(m,2H),7.38–7.29(m,1H),7.22(d,J＝8.0Hz,1H),7.18–7.03(m,5H),6.95(d,J＝7.0Hz,2H),3.96(d,J＝74.5Hz,2H),3.28(d,J＝24.7Hz,4H),2.94(s,2H),2.58(s,7H),1.39(s,9H).13C NMR(101MHz,DMSO-d6)δ161.3,155.6,154.4,151.0,144.3,138.6,135.9,133.6,131.3,129.7,129.6,128.9,128.7,127.0,126.6,124.7,123.1,122.2,113.5,79.4,52.1,50.6,34.4,28.5,9.5.HRMS(ESI)[M-H]-理论值C33H36N3O7S:618.2274；实测值：618.2280.
实施例196
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S78)
Figure BDA0003601498440001492
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-78，其余条件均一致。得白色固体112mg，收率99％。M.p.232-233℃.1H NMR(400MHz,DMSO-d6)δ7.90(s,1H),7.71(d,J＝8.7Hz,1H),7.50(d,J＝8.7Hz,1H),7.25–7.03(m,6H),6.95–6.86(m,1H),6.57(s,1H),6.44(d,J＝7.9Hz,1H),3.76(t,J＝7.2Hz,2H),3.27(d,J＝6.3Hz,4H),3.08(t,J＝5.0Hz,4H),2.63(d,J＝21.3Hz,5H),2.47(s,3H).13C NMR(101MHz,DMSO-d6)δ162.1,155.4,150.8,145.9,140.1,138.7,133.2,129.9,129.8,129.2,128.7,126.7,126.5,122.9,122.0,120.0,116.7,115.6,112.9,52.7,51.6,46.1,43.0,34.7,9.5.HRMS(ESI)[M-H]-理论值C29H30N3O5S:532.1906；实测值：532.1906.
实施例197
3-甲基-5-(N-(4-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S79)
Figure BDA0003601498440001501
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-79，其余条件均一致。得白色固体73mg，收率68％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.27–8.13(m,1H),7.91(dd,J＝8.8,1.6Hz,1H),7.82(d,J＝8.8Hz,1H),7.16(dq,J＝15.5,7.1Hz,5H),7.00(d,J＝7.0Hz,2H),6.87(d,J＝8.5Hz,2H),4.32(s,2H),3.76–3.67(m,4H),3.34–3.24(m,2H),3.12–3.00(m,4H),2.55(d,J＝10.5Hz,5H).13C NMR(101MHz,DMSO)δ161.4,155.4,151.0,138.8,135.6,129.8,129.6,129.0,128.8,127.1,126.7,126.4,121.8,115.3,113.4,66.5,51.2,49.4,48.7,34.9,9.6.HRMS(ESI)[M-H]-理论值C29H29N2O6S:533.1746；实测值：533.1737.
实施例198
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S80)
Figure BDA0003601498440001502
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-80，其余条件均一致。得白色固体77mg，收率94％。M.p.>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.22(s,1H),7.90(d,J＝8.8Hz,1H),7.82(d,J＝8.8Hz,1H),7.23–7.14(m,4H),7.11(t,J＝7.2Hz,1H),7.05–6.88(m,4H),4.32(s,2H),3.45(s,4H),3.25(d,J＝7.8Hz,6H),2.75(s,3H),2.61–2.51(m,5H).13C NMR(101MHz,DMSO-d6)δ155.4,149.6,138.8,135.4,129.9,129.7,129.0,128.8,128.0,126.7,126.4,121.7,116.2,113.4,52.4,51.1,49.3,45.8,42.4,34.8,9.6.HRMS(ESI)[M-H]-理论值C30H32N3O5S:546.2063；实测值：546.2056.
实施例198
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S81)
Figure BDA0003601498440001511
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-81，其余条件均一致。得白色固体160mg，收率84％。M.p.166-167℃.1H NMR(400MHz,DMSO-d6)δ8.21(s,1H),7.91(d,J＝8.6Hz,1H),7.82(d,J＝8.7Hz,1H),7.17(p,J＝9.8,8.4Hz,5H),6.99(d,J＝7.0Hz,2H),6.89(d,J＝8.3Hz,2H),4.31(s,2H),3.43(s,4H),3.34–3.22(m,2H),3.07(s,4H),2.55(d,J＝12.9Hz,5H),1.41(s,9H).13C NMR(101MHz,DMSO-d6)δ161.4,155.4,154.3,150.8,138.8,135.6,129.8,129.7,129.0,128.8,127.3,126.7,126.4,121.8,116.1,113.4,79.4,51.2,49.3,48.6,34.8,28.5,9.5.HRMS(ESI)[M-H]-理论值C34H38N3O7S:632.2430；实测值：632.2438.
实施例199
3-甲基-5-(N-(4-(4-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S86)
Figure BDA0003601498440001512
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-86，其余条件均一致。得白色固体30mg，收率55％。M.p.302-303℃.1H NMR(400MHz,DMSO-d6)δ8.06(d,J＝1.9Hz,1H),7.89–7.59(m,2H),7.45–7.30(m,4H),7.26–7.09(m,4H),7.06–6.91(m,6H),4.38(s,2H),3.35–3.26(m,2H),2.54(d,J＝19.3Hz,5H).13C NMR(101MHz,DMSO-d6)δ162.9,157.1,156.5,154.6,152.1,138.8,134.0,132.4,131.1,130.6,130.5,129.0,128.8,126.7,124.1,123.9,120.5,119.1,119.0,116.8,112.7,51.2,49.8,34.9,9.5.HRMS(ESI)[M-H]-理论值C31H26NO6S:540.1481；实测值：540.1477.
实施例200
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S87)
Figure BDA0003601498440001521
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-87，其余条件均一致。得白色固体144mg，收率75％。M.p.158-159℃.1H NMR(400MHz,DMSO-d6)δ8.29(d,J＝1.9Hz,1H),7.97(dd,J＝8.8,1.9Hz,1H),7.87(d,J＝8.8Hz,1H),7.42(d,J＝7.0Hz,1H),7.30(t,J＝7.6Hz,1H),7.23–7.09(m,5H),6.95(d,J＝7.0Hz,2H),4.53(s,2H),3.41(s,4H),3.33–3.23(m,2H),2.78(t,J＝4.8Hz,4H),2.61(s,3H),2.56–2.52(m,2H),1.43(s,9H).13C NMR(101MHz,DMSO-d6)δ161.6,155.4,154.4,151.7,138.8,135.0,131.6,129.9,128.8,128.8,126.7,126.3,124.4,121.7,120.6,113.3,79.4,52.8,49.9,46.8,34.5,28.5,9.5.HRMS(ESI)[M-H]-理论值C34H38N3O7S:632.2430；实测值：632.2423.
实施例201
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S88)
Figure BDA0003601498440001522
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M8-88，其余条件均一致。得白色固体53mg，收率42％。M.p.104-105℃.1H NMR(400MHz,DMSO-d6)δ8.26(d,J＝1.6Hz,1H),7.94(dd,J＝8.8,1.8Hz,1H),7.83(d,J＝8.8Hz,1H),7.25–7.09(m,4H),7.01(d,J＝7.0Hz,2H),6.89–6.81(m,1H),6.77(d,J＝7.5Hz,1H),6.72(s,1H),4.36(s,2H),3.47–3.36(m,4H),3.35–3.28(m,2H),2.94(s,4H),2.59(d,J＝10.7Hz,5H),1.41(s,9H).13C NMR(101MHz,DMSO-d6)δ161.2,155.5,154.3,151.4,144.0,138.9,137.8,135.6,129.6,129.6,129.0,128.8,126.7,126.6,125.0,121.9,119.9,116.1,115.6,113.5,79.4,51.9,49.5,48.6,34.8,28.5,9.5.HRMS(ESI)[M-H]-理论值C34H38N3O7S:632.2430；实测值：632.2421.
实施例202
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-1)
Figure BDA0003601498440001531
将4-(2-(((2-(乙氧基羰基)-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)哌嗪-1-羧酸叔丁酯(96mg,0.15mmol)，三氟乙酸(85.5mg,0.75mmol)加入二氯甲烷(5mL)中，室温搅拌2h，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(20mL)溶解，加入适量碳酸氢钠调pH至7～8，二氯甲烷(20mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(DCM/CH3OH＝15/1～10/1))得淡黄色固体85mg，收率99％。1H NMR(400MHz,氯仿-d)δ8.17(d,J＝1.5Hz,1H),7.91(dd,J＝8.8,1.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.34(dt,J＝8.5,4.5Hz,1H),7.23–7.13(m,4H),7.04(d,J＝4.1Hz,2H),6.97(d,J＝6.6Hz,2H),4.49(q,J＝7.1Hz,2H),4.17(s,1H),3.88(s,1H),3.26–2.75(m,8H),2.61(s,5H),1.47(t,J＝7.1Hz,3H),1.27(s,1H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,151.5,143.0,138.4,136.3,133.6,130.7,129.3,129.3,128.6,128.4,126.8,126.4,125.6,124.0,122.6,122.0,112.9,61.6,51.1,34.7,29.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C30H34N3O5S:548.2219；实测值：548.2230.
实施例203
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-2)
Figure BDA0003601498440001541
将5-(N-(2-(4-(叔丁氧羰基)哌嗪)苄基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(1.981g,3.0mmol)溶于二氯甲烷(20mL)，加入三氟乙酸(1.337mL,18.0mmol)搅拌1h，TLC检测反应完全后，减压蒸馏除去溶剂，真空泵抽干，得到白色固体1.65g，产率98％。1H NMR(400MHz,氯仿-d)δ8.17(d,J＝2.0Hz,1H),7.90(dd,J＝8.7,2.0Hz,1H),7.67(d,J＝8.7Hz,1H),7.47–7.08(m,7H),6.98–6.86(m,2H),4.61–4.42(m,4H),3.83(d,J＝41.7Hz,2H),3.31(t,J＝8.1Hz,2H),2.61(d,J＝23.8Hz,5H),1.48(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ159.9,155.8,143.0,138.3,135.3,131.0,130.2,129.5,129.0,128.5,128.5,126.5,126.2,125.5,121.5,120.8,113.1,61.6,49.4,47.1,47.1,45.2,35.0,14.4,9.4.
实施例204
4-(2-((2-(乙氧基羰基)-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-90)
Figure BDA0003601498440001542
将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(200mg,0.36mmol)，碘甲烷(102mg,0.72mmol)，碳酸钾(100mg,0.72mmol)加入乙腈(2mL)中，室温反应过夜，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，二氯甲烷(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(DCM/CH3OH＝20/1～10/1)得白色固体163mg，收率79％。1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.91(d,J＝8.8Hz,2H),7.53(d,J＝7.2Hz,1H),7.42(t,J＝8.2Hz,1H),7.14(dt,J＝13.9,7.5Hz,4H),6.98(t,J＝6.3Hz,3H),4.39(q,J＝7.1Hz,2H),4.00(s,1H),3.85(s,1H),3.48(s,4H),3.36(s,4H),3.24(s,6H),3.15(s,2H),2.60(s,3H),1.36(t,J＝7.1Hz,3H).13CNMR(101MHz,DMSO-d6)δ159.6,155.7,149.9,142.8,138.6,135.7,134.1,131.0,129.8,129.4,129.0,128.7,127.5,126.7,126.1,125.8,124.3,122.6,113.8,61.7,51.4,45.9,34.3,14.6,9.6.HRMS(ESI)[M]+理论值C32H38N3O5S+:576.2532；实测值：576.2535.
实施例205
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)
Figure BDA0003601498440001551
将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(150mg,0.27mmol)，N,N-二异丙基乙胺(70mg,0.54mmol)，4-二甲氨基吡啶(4mg,0.03mmol)加入二氯甲烷(1mL)中,0℃下搅拌30mins后，滴加乙酸酐(37mg,0.32mmol)的二氯甲烷(1mL)溶液，室温搅拌5h后，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，二氯甲烷(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝1/2)得白色固体129mg，收率81％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.8Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.63(d,J＝8.7Hz,1H),7.35(td,J＝7.7,1.6Hz,1H),7.21–7.12(m,4H),7.07(td,J＝7.6,1.4Hz,1H),6.94(ddd,J＝7.6,3.6,1.5Hz,3H),4.48(q,J＝7.1Hz,2H),4.17–3.93(m,2H),3.81(s,1H),3.59(s,2H),3.44(d,J＝18.9Hz,2H),3.10(s,1H),2.84(s,2H),2.68(s,1H),2.60(s,4H),2.12(s,3H),1.46(t,J＝7.1Hz,3H).13CNMR(101MHz,氯仿-d)δ169.2,159.8,155.8,151.1,143.1,138.1,136.0,134.1,130.3,129.5,129.4,128.5,126.8,126.5,125.5,124.6,122.9,122.1,112.9,61.6,53.0,51.8,51.5,46.9,42.0,34.6,21.4,14.4,9.4.HRMS(ESI)[M+H]+理论值C32H36N3O6S:590.2325；实测值：590.2331.
实施例206
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)
Figure BDA0003601498440001561
将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(168mg,0.3mmol)，三乙胺(50μL,0.36mmol)加入二氯甲烷(1mL)中,0℃下搅拌30mins后，滴加N,N-二甲基氨基甲酰氯(53μL,0.36mmol)的二氯甲烷(1mL)溶液，室温搅拌5h后，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，二氯甲烷(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(DCM/MeOH＝50/1)得白色固体141mg，产率76％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.6Hz,1H),7.89(dd,J＝8.8,1.8Hz,1H),7.62(d,J＝8.8Hz,1H),7.32(t,J＝7.0Hz,1H),7.22–7.09(m,4H),7.06–6.96(m,2H),6.93(d,J＝6.6Hz,2H),4.47(q,J＝7.1Hz,2H),3.97(d,J＝113.4Hz,2H),3.34(d,J＝46.4Hz,6H),δ2.90–2.78(m,8H),2.70–2.50(m,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ164.7,159.8,155.8,151.0,143.0,138.2,136.2,133.8,130.5,129.3,129.3,128.5,128.4,126.8,126.4,125.5,124.2,122.6,122.0,112.9,61.5,52.2,51.2,47.2,38.5,34.7,14.3,9.3.
实施例207
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)
Figure BDA0003601498440001571
按照3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)所用方法，将N,N-二甲基氨基甲酰氯替换为甲基磺酰氯，其余条件均一致。得淡黄色液体158mg，收率94％。1H NMR(400MHz,氯仿-d)δ8.12(d,J＝1.9Hz,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.37(td,J＝7.7,1.6Hz,1H),7.29–7.23(m,1H),7.22–7.05(m,4H),7.00–6.93(m,2H),6.90(dd,J＝7.9,1.4Hz,1H),4.48(q,J＝7.1Hz,2H),4.01(s,1H),3.78(s,1H),3.36(d,J＝12.9Hz,6H),2.97(s,2H),2.83(s,3H),2.69(s,1H),2.60(s,3H),2.54(s,1H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.9,151.3,143.1,138.0,135.7,134.5,130.0,129.6,129.4,128.5,126.8,126.6,125.5,125.1,123.4,122.1,113.0,61.6,52.0,51.7,46.4,34.6,34.5,31.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C31H36N3O7S2:626.1995；实测值：626.1990.
实施例208
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)
Figure BDA0003601498440001572
将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(200mg,0.36mmol)，3,3-二甲基-1-丁酸(92mg,0.79mmol)，1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(152mg,0.79mmol)，1-羟基苯并三唑(107mg,0.79mmol)，N,N-二异丙基乙胺(150mg,1.08mmol)，4-二甲氨基吡啶(5mg,0.04mmol)加入二氯甲烷(2mL)中，室温搅拌过夜后，TLC检测反应完毕后，减压蒸馏除去溶剂，加水(10mL)溶解，二氯甲烷(10mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝8/1～6/1)得白色固体120mg，收率52％。1H NMR(400MHz,氯仿-d)δ8.15(d,J＝1.8Hz,1H),7.89(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.38–7.31(m,1H),7.23–7.12(m,4H),7.10–7.04(m,1H),6.99–6.92(m,3H),4.49(q,J＝7.1Hz,2H),4.25–3.94(m,2H),3.88–3.76(m,1H),3.75–3.30(m,4H),3.10(s,1H),2.84(s,2H),2.74–2.65(m,1H),2.61(s,4H),2.30(s,2H),1.47(t,J＝7.1Hz,3H),1.08(s,9H).13C NMR(101MHz,氯仿-d)δ170.6,159.8,155.8,150.9,143.1,138.1,136.0,134.0,130.4,129.5,129.4,128.5,128.5,126.8,126.5,125.5,124.6,122.8,122.1,112.9,61.6,51.4,44.7,34.6,31.5,30.1,29.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H44N3O6S:646.2951；实测值：646.2958.
实施例209
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-95)
Figure BDA0003601498440001581
将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(164mg,0.3mmol)和碳酸钾(83mg,0.6mmol)溶于乙腈(2mL)中，加入苄溴(54μL,0.45mmol)，60℃下反应过夜，TLC检测反应完全后，减压蒸馏除去溶剂，加水(20mL)溶解，乙酸乙酯(20mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(DCM/MeOH＝50/1)得白色固体129mg，产率67％。1H NMR(400MHz,氯仿-d)δ8.19(d,J＝1.6Hz,1H),7.93(dd,J＝8.8,1.9Hz,1H),7.63(d,J＝8.8Hz,1H),7.42–7.30(m,6H),7.24–7.14(m,4H),7.06(qd,J＝7.9,1.7Hz,2H),7.02–6.96(m,2H),4.51(q,J＝7.1Hz,2H),4.29–4.09(m,1H),3.92(s,1H),3.55(s,2H),3.23(s,2H),3.00–2.79(m,2H),2.74–2.63(m,2H),2.56(dd,J＝16.2,5.9Hz,4H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,151.2,143.0,138.4,137.9,136.4,133.5,130.8,129.3,129.2,128.6,128.5,128.4,128.3,127.5,127.2,126.9,126.9,126.4,125.6,123.8,122.4,122.0,112.8,63.2,61.6,53.6,52.2,51.1,34.8,14.4,9.4.
实施例210
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)
Figure BDA0003601498440001591
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为苯甲酸，其余条件均一致。得白色固体148mg，收率63％。1H NMR(400MHz,氯仿-d)δ8.14(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.43(dt,J＝4.9,3.4Hz,5H),7.35(td,J＝7.7,1.6Hz,1H),7.25–7.05(m,5H),6.96(ddd,J＝9.5,7.8,1.5Hz,3H),4.48(q,J＝7.1Hz,2H),4.29–3.94(m,2H),3.90–3.45(m,4H),3.27(s,2H),3.04–2.63(m,3H),2.59(s,4H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ170.5,159.8,155.8,151.0,143.1,138.1,135.9,135.8,134.1,130.3,129.7,129.5,129.4,128.5,127.1,126.8,126.5,125.5,124.7,122.9,122.1,112.9,61.6,51.5,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C37H38N3O6S:652.2481；实测值：652.2487.
实施例211
3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-98)
Figure BDA0003601498440001592
按照3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，碘甲烷(102mg,0.36mmol)，其余条件均一致。得白色固体113mg，产率66％。1H NMR(400MHz,氯仿-d)δ8.15(s,1H),7.89(d,J＝8.6Hz,1H),7.65(d,J＝8.7Hz,1H),7.38–7.25(m,3H),7.24–7.04(m,5H),6.87(d,J＝6.8Hz,2H),4.61–4.36(m,4H),3.26(t,J＝8.1Hz,2H),3.00(d,J＝69.2Hz,8H),2.61(s,3H),2.53(s,5H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,151.3,143.0,138.2,135.1,130.9,130.4,129.5,129.2,128.5,128.4,126.4,126.2,125.5,124.9,121.4,121.2,113.1,61.6,54.9,51.6,49.3,47.5,45.1,34.9,14.4,9.4.
实施例212
4-(2-((2-(乙氧基羰基)-3-甲基-N-苄基乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-99)
Figure BDA0003601498440001601
按照3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-90)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得黄色固体81mg，产率76％。1H NMR(400MHz,氯仿-d)δ8.16(s,1H),7.93(d,J＝8.8Hz,1H),7.68(d,J＝8.8Hz,1H),7.49(d,J＝7.8Hz,1H),7.37(t,J＝7.2Hz,1H),7.26–7.04(m,5H),6.80(d,J＝6.7Hz,2H),4.44(d,J＝7.6Hz,4H),3.94(s,4H),3.63(s,6H),3.30(s,4H),3.22–3.11(m,2H),2.61(s,3H),2.44–2.27(m,2H),1.42(t,J＝7.0Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,150.1,143.0,138.0,134.2,131.7,131.2,130.0,129.6,128.5,128.5,126.5,126.4,126.1,125.6,123.3,121.6,113.4,62.6,61.6,52.7,49.9,49.5,46.8,35.5,14.3,9.6.
实施例213
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-100)
Figure BDA0003601498440001611
按照3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得白色固体154mg，产率86％。1H NMR(400MHz,氯仿-d)δ8.16(s,1H),7.88(d,J＝10.4Hz,1H),7.63(d,J＝8.7Hz,1H),7.38(d,J＝7.0Hz,1H),7.29(t,J＝7.6Hz,1H),7.18–7.06(m,5H),6.89(s,2H),4.58(s,2H),4.47(q,J＝7.1Hz,2H),3.65(d,J＝56.1Hz,4H),3.37–3.28(m,2H),2.84(d,J＝20.5Hz,4H),2.65–2.53(m,5H),2.12(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ169.1,159.8,155.7,151.0,143.0,138.3,135.3,130.9,130.1,129.4,128.9,128.5,126.5,126.2,125.5,124.9,121.5,120.4,113.0,61.6,53.2,52.8,49.4,46.8,46.6,41.8,35.0,21.4,14.4,9.4.
实施例214
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-101)
Figure BDA0003601498440001612
按照3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得白色固体162mg，产率85％。1H NMR(400MHz,氯仿-d)δ8.16(d,J＝1.8Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.7Hz,1H),7.43(d,J＝7.7Hz,1H),7.28(t,J＝8.3Hz,1H),7.20–7.05(m,5H),6.90(d,J＝6.6Hz,2H),4.59(s,2H),4.48(q,J＝7.1Hz,2H),3.35(d,J＝3.9Hz,6H),2.91–2.79(m,10H),2.65–2.56(m,5H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ164.7,159.9,155.7,151.2,142.9,138.3,135.4,130.9,130.0,129.4,128.7,128.5,128.5,126.4,126.2,125.5,124.7,121.5,120.2,113.0,61.6,52.9,49.4,47.1,46.4,38.5,34.8,14.4,9.4.
实施例215
3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-102)
Figure BDA0003601498440001621
按照3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得到白色固体86mg，产率83％。1HNMR(400MHz,氯仿-d)δ8.17(s,1H),7.91(d,J＝8.8Hz,1H),7.67(d,J＝8.7Hz,1H),7.38–7.27(m,2H),7.16(dd,J＝18.9,7.8Hz,5H),6.91(d,J＝7.2Hz,2H),4.56(s,2H),4.49(q,J＝7.1Hz,2H),3.40(s,4H),3.30(t,J＝8.1Hz,2H),2.99(s,4H),2.84(s,3H),2.67–2.52(m,5H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.8,155.8,151.2,143.0,138.3,135.2,131.0,130.4,129.4,129.2,128.5,126.5,126.2,125.5,125.1,121.5,121.1,113.1,61.6,52.5,49.4,47.5,46.2,35.2,34.5,14.4,9.4.
实施例216
3-甲基-5-(N-(2-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-103)
Figure BDA0003601498440001622
按照3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得到白色固体197mg，产率99％。1HNMR(400MHz,氯仿-d)δ8.16(d,J＝1.8Hz,1H),7.88(dd,J＝8.8,1.8Hz,1H),7.63(d,J＝8.8Hz,1H),7.38(d,J＝7.7Hz,1H),7.28(t,J＝7.6Hz,1H),7.19–7.05(m,5H),6.89(d,J＝6.6Hz,2H),4.57(s,2H),4.47(q,J＝7.1Hz,2H),3.70(d,J＝49.1Hz,4H),3.36–3.28(m,2H),2.84(dt,J＝16.4,4.4Hz,4H),2.61(d,J＝3.8Hz,5H),2.32(s,2H),1.45(t,J＝7.1Hz,3H),1.07(s,9H).13C NMR(101MHz,氯仿-d)δ170.8,159.8,155.7,151.0,143.0,138.3,135.3,130.9,130.1,129.4,128.8,128.5,128.5,126.4,126.2,125.5,124.8,121.5,120.4,113.0,61.6,53.3,52.9,49.4,47.8,46.8,44.6,41.9,35.0,31.6,30.1,14.4,9.4.
实施例217
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-104)
Figure BDA0003601498440001631
按照3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-95)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得到白色固体138mg，产率71％。1H NMR(400MHz,氯仿-d)δ8.18(d,J＝1.5Hz,1H),7.91(dd,J＝8.8,1.9Hz,1H),7.66(d,J＝8.8Hz,1H),7.44(dd,J＝7.7,1.6Hz,1H),7.40–7.34(m,4H),7.33–7.25(m,2H),7.22–7.05(m,5H),6.95(d,J＝6.6Hz,2H),4.61(s,2H),4.52(q,J＝7.1Hz,2H),3.58(s,2H),3.42–3.26(m,2H),2.92(s,4H),2.65(s,9H),1.50(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ159.9,155.8,151.7,142.9,138.5,137.8,135.7,130.7,129.9,129.4,129.2,128.6,128.4,128.3,127.2,127.0,126.4,126.3,125.6,124.3,121.5,120.1,113.0,63.1,61.6,53.5,53.0,49.3,46.0,34.7,14.4,9.5.
实施例218
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-105)
Figure BDA0003601498440001641
按照3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)所用方法，将3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-1)替换为3-甲基-5-N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M9-2)，其余条件均一致。得白色固体181mg，产率95％。1HNMR(400MHz,氯仿-d)δ8.18(d,J＝1.8Hz,1H),8.12(dd,J＝8.3,1.2Hz,1H),7.94–7.86(m,1H),7.66(d,J＝8.7Hz,1H),7.45(s,6H),7.22–7.10(m,5H),6.92(dd,J＝7.7,1.4Hz,2H),4.60(s,2H),4.50(q,J＝7.1Hz,2H),δ3.59(s,4H),3.38–3.29(m,2H),2.91(s,4H)2.63(s,5H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,氯仿-d)δ170.6,159.9,155.8,150.9,143.0,138.3,135.6,135.3,133.5,130.9,130.2,130.1,129.8,129.4,129.0,128.6,128.5,128.4,127.1,126.5,126.2,125.5,125.0,121.5,120.5,113.1,61.6,49.5,46.9,35.0,14.4,9.4.
实施例219
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S89)
Figure BDA0003601498440001642
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-89，其余条件均一致。得白色固体49mg，收率55％。Mp 172-173℃.1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.92–7.81(m,2H),7.39(t,J＝7.3Hz,1H),7.28(d,J＝7.7Hz,1H),7.17–7.04(m,4H),7.01(d,J＝7.7Hz,1H),6.95(d,J＝7.1Hz,2H),3.96(s,2H),3.79(s,2H),3.28(s,2H),3.11(s,4H),3.03(s,2H),2.58(s,3H),2.43(s,1H).13C NMR(101MHz,DMSO-d6)δ161.1,155.7,150.6,143.8,138.5,135.5,134.1,131.0,129.9,129.6,128.9,128.7,127.1,126.6,125.4,125.3,123.3,122.5,113.6,51.0,49.2,43.7,34.2,9.5.HRMS(ESI)[M-H]-理论值C28H28N3O5S:518.1750；实测值：518.1755.
实施例220
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S90)
Figure BDA0003601498440001651
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-90，其余条件均一致。得白色固体97mg，收率74％。Mp 246-247℃.1H NMR(400MHz,DMSO-d6)δ8.19(s,1H),7.85(s,2H),7.53(d,J＝8.0Hz,1H),7.40(t,J＝7.6Hz,1H),7.12(dt,J＝13.9,7.4Hz,4H),6.98(d,J＝7.5Hz,3H),4.09–3.92(m,1H),3.89–3.71(m,1H),3.49(t,J＝5.3Hz,4H),3.38(d,J＝13.5Hz,2H),3.26(s,6H),3.12(d,J＝13.9Hz,2H),2.57(s,4H),2.44(s,1H).13C NMR(101MHz,DMSO-d6)δ161.3,155.6,149.9,145.0,138.6,135.4,134.2,131.0,129.8,129.0,128.7,126.8,126.6,125.7,124.2,124.0,122.2,113.5,61.6,51.3,45.9,34.3,9.5.HRMS(ESI)[M]+理论值C30H34N3O5S+:548.2219；实测值：548.2222.
实施例221
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S91)
Figure BDA0003601498440001661
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-91，其余条件均一致。得白色固体59mg，收率75％。Mp 196-197℃.1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.89(q,J＝8.8Hz,2H),7.36(t,J＝7.7Hz,1H),7.24(d,J＝8.0Hz,1H),7.12(dt,J＝12.6,7.1Hz,4H),7.02(d,J＝7.8Hz,1H),6.95(d,J＝7.2Hz,2H),4.06(s,1H),3.84(s,1H),3.43(d,J＝37.5Hz,6H),3.13(s,1H),2.95(s,1H),2.73(s,2H),2.59(s,3H),2.02(s,3H).13C NMR(101MHz,DMSO-d6)δ168.8,161.3,155.6,151.1,138.6,135.9,133.8,131.0,129.7,129.7,128.9,128.7,126.9,126.6,124.7,123.1,122.3,113.5,52.6,52.0,50.8,46.6,41.7,34.3,21.7,9.5.HRMS(ESI)[M-H]-理论值C30H30N3O6S:560.1855；实测值：560.1865.
实施例222
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S92)
Figure BDA0003601498440001662
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-92，其余条件均一致。得白色固体97mg，收率83％。Mp>380℃(分解).1H NMR(400MHz,DMSO-d6)δ8.19(s,1H),7.93–7.77(m,2H),7.34(t,J＝7.4Hz,1H),7.22(d,J＝7.9Hz,1H),7.18–7.02(m,5H),6.95(d,J＝7.1Hz,2H),3.86(s,2H),3.17(s,2H),3.13–2.91(m,4H),2.74(s,8H),2.58(s,3H),2.51(s,2H).13C NMR(101MHz,DMSO-d6)δ164.1,155.3,151.0,138.6,135.5,133.6,131.1,130.3,129.5,128.8,128.7,126.6,126.0,124.4,122.8,121.7,113.2,52.0,50.6,47.3,38.5,34.4,9.5.HRMS(ESI)[M-H]-理论值C31H33N4O6S:589.2126；实测值：589.2122.
实施例223
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S93)
Figure BDA0003601498440001671
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-93，其余条件均一致。得白色固体60mg，收率72％。Mp 144-145℃.1H NMR(400MHz,DMSO-d6)δ8.22(s,1H),7.94–7.81(m,2H),7.41–7.27(m,2H),7.11(dd,J＝13.5,6.9Hz,4H),6.99(dd,J＝19.9,7.3Hz,3H),3.93(d,J＝62.2Hz,4H),3.13(s,6H),2.87(d,J＝23.0Hz,5H),2.58(s,3H).13C NMR(101MHz,DMSO-d6)δ161.3,155.6,151.0,144.4,138.6,135.8,134.0,131.1,129.7,129.7,128.9,128.7,127.0,126.6,125.1,124.7,123.6,122.3,113.5,51.9,51.0,46.3,34.6,34.3,9.5.HRMS(ESI)[M-H]-理论值C29H30N3O7S2:596.1525；实测值：596.1534.
实施例224
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S94)
Figure BDA0003601498440001672
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-94，其余条件均一致。得白色固体66mg，收率89％。Mp 191-192℃.1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.88(q,J＝8.1Hz,2H),7.35(t,J＝6.5Hz,1H),7.23(d,J＝7.6Hz,1H),7.19–7.02(m,5H),6.96(d,J＝6.4Hz,2H),4.06(s,1H),3.87(s,1H),3.71–3.27(m,6H),2.98(d,J＝37.3Hz,2H),2.70(s,2H),2.59(s,3H),2.22(s,2H),0.98(s,9H).13C NMR(101MHz,DMSO-d6)δ170.0,161.3,155.6,151.0,138.6,135.9,133.7,131.2,129.7,129.6,128.9,128.7,126.9,126.6,124.7,123.1,122.3,113.5,52.9,52.0,50.8,46.9,44.1,41.7,34.4,31.5,30.2,9.5.HRMS(ESI)[M-H]-理论值C34H38N3O6S:616.2481；实测值：616.2470.
实施例225
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S95)
Figure BDA0003601498440001681
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-95，其余条件均一致。得白色固体90mg，收率74％。Mp 161-162℃.1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.95–7.79(m,2H),7.66–7.52(m,2H),7.48–7.33(m,4H),7.26(d,J＝7.9Hz,1H),7.15(dt,J＝13.8,6.2Hz,4H),7.05–6.92(m,3H),4.16(d,J＝8.5Hz,2H),4.00(s,1H),3.88–3.72(m,1H),3.27(s,2H),3.00(d,J＝37.0Hz,6H),2.59(s,3H),2.51(s,2H).13C NMR(101MHz,DMSO-d6)δ161.2,155.6,150.3,144.0,138.6,135.5,133.8,131.3,131.1,129.8,129.6,129.3,129.0,128.9,128.7,127.1,126.7,125.1,125.0,123.0,122.4,113.5,59.8,51.9,51.0,49.6,34.3,9.6.HRMS(ESI)[M-H]-理论值C35H34N3O5S:608.2225；实测值:608.2216.
实施例226
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S96)
Figure BDA0003601498440001691
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-96，其余条件均一致。得白色固体68mg，收率73％。Mp 128-129℃.1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),7.87(q,J＝9.0Hz,2H),7.52–7.21(m,7H),7.09(dt,J＝22.3,7.0Hz,5H),6.97(d,J＝6.3Hz,2H),4.06(s,1H),3.86(s,1H),3.44(d,J＝120.0Hz,6H),2.99(d,J＝26.6Hz,2H),2.76(d,J＝26.4Hz,2H),2.56(s,3H).13C NMR(101MHz,DMSO-d6)δ169.5,161.3,155.6,150.9,138.6,136.3,135.8,133.7,131.3,130.0,129.7,129.6,128.9,128.8,128.7,127.3,127.0,126.6,124.8,124.6,123.2,122.2,113.5,50.8,34.4,9.5.HRMS(ESI)[M-H]-理论值C35H32N3O6S:622.2012；实测值：622.2005.
实施例227
3-甲基-5-(N-(2-(哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S97)
Figure BDA0003601498440001692
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-97，其余条件均一致。得白色固体80mg，收率75％。Mp 223-224℃.1H NMR(400MHz,DMSO-d6)δ9.83(s,1H),8.25(s,1H),7.95(d,J＝8.8Hz,1H),7.85(d,J＝8.8Hz,1H),7.41(d,J＝7.6Hz,1H),7.30(d,J＝7.8Hz,1H),7.14(dt,J＝15.6,7.0Hz,5H),6.91(d,J＝7.2Hz,2H),4.51(s,2H),3.23(d,J＝21.6Hz,6H),3.07(s,4H),2.58(s,3H),2.46(s,2H).13C NMR(101MHz,DMSO-d6)δ161.2,155.5,151.0,138.7,136.3,135.0,131.9,130.2,129.7,129.1,128.9,128.8,126.7,125.0,122.0,120.7,113.5,110.0,49.9,49.7,47.4,43.6,34.7,9.6.HRMS(ESI)[M-H]-理论值C29H30N3O5S:532.1912；实测值:532.1896.
实施例228
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S98)
Figure BDA0003601498440001701
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-98，其余条件均一致。得白色固体77mg，收率71％。Mp 190-191℃.1H NMR(400MHz,DMSO-d6)δ8.34(s,1H),8.01(d,J＝8.7Hz,1H),7.89(d,J＝8.7Hz,1H),7.41(d,J＝7.4Hz,1H),7.32(t,J＝7.6Hz,1H),7.16(dt,J＝15.7,6.6Hz,5H),6.93(d,J＝7.0Hz,2H),4.53(s,2H),3.42(s,4H),3.13(s,6H),2.78(s,3H),2.60(s,3H),2.49–2.40(m,2H).13C NMR(101MHz,DMSO)δ161.1,155.6,150.4,138.7,135.1,131.9,130.0,129.7,129.0,128.9,128.8,126.8,126.7,125.3,125.0,122.1,120.6,113.6,110.0,53.3,50.1,49.7,47.1,42.5,34.7,9.6.HRMS(ESI)[M-H]-理论值C30H32N3O5S:546.2068；实测值：546.2057.
实施例229
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺胺基)甲基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S99)
Figure BDA0003601498440001702
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-99，其余条件均一致。得白色固体81mg，收率76％。Mp 143-144℃.1H NMR(400MHz,DMSO-d6)δ8.36(s,1H),8.03(d,J＝8.7Hz,1H),7.90(d,J＝8.7Hz,1H),7.46–7.31(m,3H),7.16(dt,J＝15.7,7.1Hz,4H),6.93(d,J＝7.1Hz,2H),4.56(s,2H),3.61–3.53(m,4H),3.25(d,J＝7.5Hz,8H),3.21(d,J＝5.5Hz,4H),2.60(s,3H),2.45(t,J＝8.1Hz,2H).13C NMR(101MHz,DMSO-d6)δ161.1,155.6,150.1,143.7,138.7,135.1,132.3,129.9,129.7,128.9,128.9,128.8,126.9,126.7,125.3,125.3,122.1,121.6,113.6,61.6,56.5,50.3,47.4,46.4,34.8,9.6.HRMS(ESI)[M]+理论值C31H36N3O5S:562.2370；实测值：562.2383.
实施例230
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S100)
Figure BDA0003601498440001711
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-100，其余条件均一致。得白色固体92mg，收率61％。Mp 236-237℃.1H NMR(400MHz,DMSO-d6)δ13.74(s,1H),δ8.30(s,1H),8.03–7.82(m,2H),7.39(d,J＝7.3Hz,1H),7.29(t,J＝7.6Hz,1H),7.14(dq,J＝15.0,8.0,7.3Hz,5H),6.94(d,J＝7.2Hz,2H),4.54(s,3H),3.51(s,4H),3.37–3.23(m,4H),2.78(dt,J＝28.9,4.9Hz,4H),2.59(s,3H),2.54–2.49(m,2H),2.02(s,3H).13CNMR(101MHz,DMSO-d6)δ168.8,161.1,155.5,151.6,143.7,138.7,135.2,131.7,129.9,129.6,128.9,128.8,128.8,126.8,126.7,125.3,124.5,122.0,120.7,113.5,56.5,53.1,52.9,49.8,46.7,46.5,41.7,34.5,21.7,19.0,9.6.HRMS(ESI)[M-H]-理论值C31H32N3O6S:574.2017；实测值：574.2017.
实施例231
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S101)
Figure BDA0003601498440001721
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-101，其余条件均一致。得白色固体45mg，收率28％。Mp 118-119℃.1H NMR(400MHz,DMSO-d6)δ8.29(s,1H),7.90(dd,J＝53.2,8.7Hz,2H),7.41(d,J＝7.5Hz,1H),7.24(dd,J＝26.0,7.5Hz,3H),7.10(dd,J＝17.5,7.1Hz,4H),6.92(d,J＝7.3Hz,2H),4.60(s,2H),3.33–3.15(m,6H),2.87(s,4H),2.73(s,6H),2.49(s,2H).13C NMR(101MHz,DMSO-d6)δ164.0,161.0,155.5,143.7,138.7,135.2,131.5,130.0,129.6,129.0,128.8,128.7,126.7,126.6,125.2,125.0,122.0,120.7,113.5,53.0,49.9,46.9,46.8,38.5,34.5,9.5.HRMS(ESI)[M-H]-理论值C32H35N4O6S:603.2283；实测值：603.2270.
实施例232
3-甲基-5-(N-(2-(4-(甲磺酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S102)
Figure BDA0003601498440001722
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-102，其余条件均一致。得白色固体52mg，收率57％。Mp 150-151℃.1H NMR(400MHz,DMSO-d6)δ8.29(s,1H),7.92(dd,J＝41.7,9.3Hz,2H),7.38(d,J＝7.4Hz,1H),7.29(t,J＝7.4Hz,1H),7.15(ddd,J＝29.1,12.9,7.2Hz,5H),6.94(d,J＝7.1Hz,2H),4.54(s,2H),3.29(t,J＝7.9Hz,2H),3.21(s,4H),2.97–2.84(m,7H),2.59(s,3H),2.54(t,2H).13C NMR(101MHz,DMSO-d6)δ161.3,155.5,151.3,144.1,138.7,135.2,131.7,129.8,129.7,128.9,128.8,126.7,126.6,124.8,124.7,122.0,120.8,113.5,52.4,49.9,46.8,46.3,34.6,34.5,9.6.HRMS(ESI)[M-H]-理论值C30H32N3O7S2:610.1687；实测值：610.1687.
实施例233
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S103)
Figure BDA0003601498440001731
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-94，其余条件均一致。得白色固体75mg，收率39％。Mp 190-191℃.1H NMR(400MHz,DMSO-d6)δ8.29(s,1H),7.98(d,J＝10.5Hz,1H),7.87(d,J＝8.8Hz,1H),7.40(d,J＝7.3Hz,1H),7.28(t,J＝7.5Hz,1H),7.14(dq,J＝15.0,7.4Hz,5H),6.94(d,J＝7.0Hz,2H),4.54(s,2H),3.56(s,4H),3.32–3.24(m,2H),2.76(dt,J＝17.5,4.9Hz,4H),2.59(s,3H),2.52(d,J＝10.3Hz,2H),2.25(s,2H),0.99(s,9H).13C NMR(101MHz,DMSO-d6)δ170.0,161.1,155.5,151.5,143.7,138.7,135.2,131.6,129.9,129.6,128.9,128.8,128.8,126.8,126.7,125.3,124.5,122.0,120.6,113.5,53.3,53.0,49.8,46.8,44.1,41.6,34.5,31.5,30.2,9.6.HRMS(ESI)[M-H]-理论值C35H42N3O6S:632.2789；实测值:632.2802.
实施例234
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S104)
Figure BDA0003601498440001732
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-104，其余条件均一致。得白色固体107mg，收率82％。Mp 154-155℃.1H NMR(400MHz,DMSO-d6)δ8.30(s,1H),7.98(d,J＝10.4Hz,1H),7.87(d,J＝8.8Hz,1H),7.59(d,J＝5.7Hz,2H),7.46–7.25(m,5H),7.20–7.05(m,5H),6.91(d,J＝7.1Hz,2H),4.50(s,2H),4.14(s,2H),3.25(s,2H),3.07(d,J＝23.3Hz,8H),2.59(s,3H),2.51–2.43(m,2H).13C NMR(101MHz,DMSO-d6)δ161.2,155.5,150.7,144.2,138.7,135.1,132.0,131.6,131.4,129.8,129.7,129.3,129.0,128.9,128.8,128.8,126.7,126.6,124.8,124.8,121.9,120.5,113.5,59.8,51.8,50.2,50.0,46.9,34.6,9.6.HRMS(ESI)[M-H]-理论值C36H36N3O5S:622.2381；实测值：622.2374.
实施例235
基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S105)
Figure BDA0003601498440001741
按照5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27)所用方法，将5-(N-苄基-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S8)替换为M10-105，其余条件均一致。得白色固体133mg，收率78％。Mp 163-164℃.1H NMR(400MHz,DMSO-d6)δ8.18(d,J＝1.8Hz,1H),7.93–7.76(m,2H),7.51–7.36(m,6H),7.28(t,J＝8.1Hz,1H),7.14(dt,J＝25.5,7.5Hz,5H),6.92(d,J＝7.0Hz,2H),4.53(s,2H),3.56(d,J＝124.8Hz,4H),3.30–3.20(m,2H),2.82(s,4H),2.59–2.47(m,5H).13C NMR(101MHz,DMSO-d6)δ169.5,162.8,155.0,151.5,149.0,138.8,136.3,134.3,131.7,130.5,130.0,129.9,129.7,128.9,128.8,128.8,127.4,126.7,125.2,124.5,121.1,120.7,119.9,113.0,52.8,49.9,46.9,34.5,9.5.HRMS(ESI)[M-H]-理论值C36H34N3O6S:636.2174；实测值：636.2177.
实施例236
3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-106)
Figure BDA0003601498440001751
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-甲基苯甲酸，其余条件均一致。得白色固体170mg，收率100％。1H NMR(400MHz,Chloroform-d)δ8.15(d,J＝1.5Hz,1H),7.89(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.36(d,J＝8.0Hz,3H),7.29–7.13(m,6H),7.11–7.04(m,1H),7.00–6.93(m,3H),4.50(q,J＝7.1Hz,2H),4.24–2.51(m,15H),2.40(s,3H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ170.8,159.9,155.8,151.1,143.0,139.9,138.1,135.9,134.1,132.7,130.3,130.1,129.5,129.4,129.1,128.5,127.3,126.8,126.5,125.5,124.6,122.9,122.1,112.9,61.6,51.5,34.7,21.4,14.4,9.4.
实施例237
3-甲基-5-(N-(2-(4-(2-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-107)
Figure BDA0003601498440001752
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为邻甲基苯甲酸，其余条件均一致。得到白色固体122.2mg，产率92％。1H NMR(400MHz,Chloroform-d)δ8.14(d,J＝1.5Hz,1H),7.88(dd,J＝8.8,1.8Hz,1H),7.64(d,J＝8.8Hz,1H),7.37(t,J＝7.0Hz,1H),7.32–7.13(m,8H),7.08(t,J＝7.6Hz,1H),6.95(d,J＝7.9Hz,3H),4.50(q,J＝7.1Hz,2H),4.31–4.02(m,2H),3.88–3.61(m,2H),3.45–3.16(m,4H),3.00(s,1H),2.81–2.48(m,6H),2.36(s,3H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ170.2,159.8,155.8,151.0,143.1,138.1,136.0,135.8,134.1,132.4,131.3,130.4,130.3,129.5,129.4,128.9,128.5,126.8,126.5,126.0,125.9,125.5,124.7,122.8,122.1,113.0,61.6,53.4,51.7(d,J＝38.5Hz),42.0,34.6,19.1,14.4,9.4.
实施例238
3-甲基-5-(N-(2-(4-(3-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-108)
Figure BDA0003601498440001761
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为间甲基苯甲酸，其余条件均一致。得到白色固体119.3mg，产率90％。1H NMR(400MHz,Chloroform-d)δ8.15(d,J＝1.6Hz,1H),7.95–7.86(m,1H),7.64(d,J＝8.8Hz,1H),7.41–7.11(m,9H),7.08(t,J＝8.3Hz,1H),6.96(d,J＝9.5Hz,3H),4.50(q,J＝7.1Hz,2H),4.26–4.04(m,2H),3.92–3.52(m,4H),3.38–3.19(m,2H),3.07–2.55(m,7H),2.40(s,3H),1.48(t,J＝7.1Hz,3H).13CNMR(101MHz,Chloroform-d)δ170.8,159.9,155.8,151.1,143.1,138.4,138.1,135.9,135.7,134.1,130.5,130.3,129.5,129.4,128.5,128.3,127.7,127.2,126.8,126.5,125.5,124.6,124.0,122.8,122.1,113.0,61.6,51.5,34.7,21.4,14.4,9.4.
实施例239
5-(N-(2-(4-(4-乙酰氨基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-109)
Figure BDA0003601498440001771
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为对氨乙酰基苯甲酸，其余条件均一致。得到白色固体72.8mg，产率51％。1H NMR(400MHz,Chloroform-d)δ8.46(s,1H),8.14(s,1H),7.88(d,J＝8.8Hz,1H),7.64(d,J＝8.8Hz,1H),7.52(d,J＝8.3Hz,2H),7.41–7.30(m,3H),7.25–7.11(m,4H),7.08(t,J＝7.5Hz,1H),6.99–6.90(m,3H),4.50(q,J＝7.1Hz,2H),4.16–3.96(m,2H),3.88–3.52(m,4H),3.35–3.19(m,2H),3.07–2.66(m,3H),2.64–2.50(m,1H),2.15(s,3H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ170.4,169.0,159.9,155.8,151.1,143.1,139.9,138.0,135.8,134.1,130.6,130.2,129.6,129.4,128.5,128.1,126.8,126.5,125.5,124.7,122.9,122.1,119.6,113.0,61.6,51.5,34.6,29.7,24.4,14.4,9.4.
实施例240
5-(N-(2-(4-(4-乙酰氨基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-110)
Figure BDA0003601498440001772
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为对三氟甲基苯甲酸，其余条件均一致。得到白色固体113.1mg，产率79％。1H NMR(400MHz,Chloroform-d)δ8.14(d,J＝1.4Hz,1H),7.93–7.84(m,1H),7.72(d,J＝8.1Hz,2H),7.65(d,J＝8.8Hz,1H),7.57(d,J＝8.1Hz,2H),7.38(t,J＝7.7Hz,1H),7.25–7.06(m,5H),6.94(dd,J＝12.0,7.3Hz,3H),4.50(q,J＝7.1Hz,2H),4.24–4.03(m,2H),3.88–3.65(m,2H),3.62–3.49(m,2H),3.40–3.21(m,2H),3.08–2.68(m,3H),2.64–2.48(m,4H),1.48(t,J＝7.1Hz,3H).HRMS(ESI)[M+H]+理论值C38H37F3N3O6S:720.2350；实测值：720.2343.
实施例241
5-(N-(2-(4-(4-氰基苯基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-111)
Figure BDA0003601498440001781
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为对氰基苯甲酸，其余条件均一致。得到白色固体101.0mg，产率75％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.6Hz,1H),7.87(dd,J＝8.8,1.8Hz,1H),7.75(d,J＝8.3Hz,2H),7.65(d,J＝8.8Hz,1H),7.56(d,J＝8.3Hz,2H),7.37(d,J＝8.0Hz,1H),7.25–7.13(m,4H),7.09(t,J＝7.6Hz,1H),6.99–6.87(m,3H),4.50(q,J＝7.1Hz,2H),4.25–4.00(m,2H),3.83–3.65(m,2H),3.60–3.44(m,2H),3.39–3.24(m,2H),3.10–2.94(m,1H),2.87–2.64(m,2H),2.64–2.50(m,4H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ168.4,159.8,155.9,151.0,143.1,140.1,138.0,135.7,134.3,132.5,130.1,129.6,129.4,128.5,128.5,127.8,126.8,126.6,125.5,124.9,123.0,122.1,118.1,113.6,113.0,61.6,51.7,34.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C38H37N4O6S:677.2428；实测值：677.2439.
实施例242
5-(N-(2-(4-(4-氟苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-112)
Figure BDA0003601498440001791
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为对氟苯甲酸，其余条件均一致。得到白色固体107.5mg，产率80％。1H NMR(400MHz,Chloroform-d)δ8.14(d,J＝1.6Hz,1H),7.89(dd,J＝8.8,1.9Hz,1H),7.65(d,J＝8.8Hz,1H),7.46(dd,J＝8.7,5.3Hz,2H),7.41–7.33(m,1H),7.24–7.04(m,7H),6.99–6.91(m,3H),4.51(q,J＝7.1Hz,2H),4.19–2.48(m,15H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ169.6,162.2,159.9,155.8,151.0,143.1,138.0,135.8,134.2,130.2,129.5,129.5,129.4,129.4,128.5(d,J＝1.7Hz),126.8,126.6,125.5,124.7,122.9,122.1,115.7,115.5,113.0,61.6,51.6,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C37H37FN3O6S:670.2382；实测值：670.2396.
实施例243
5-(N-(2-(4-(4-((叔丁氧基羰基)氨基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-113)
Figure BDA0003601498440001792
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-(N-叔丁氧基羰基)氨基苯甲酸，其余条件均一致。得到白色固体121.6mg，产率79％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.6Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.49–7.32(m,5H),7.23–7.00(m,6H),6.98–6.92(m,3H),4.48(q,J＝7.1Hz,2H),4.16–2.44(m,15H),1.51(s,9H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ170.3,159.9,155.8,152.6,151.1,143.0,140.2,138.1,135.9,134.1,130.3,129.7,129.5,129.3,128.5,128.4,126.8,126.5,125.5,124.6,122.9,122.1,118.0,112.9,80.8,61.6,60.4,51.5,34.7,28.3,14.4,14.2,9.4.
实施例244
3-甲基-5-(N-(2-(4-(4-硝基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-114)
Figure BDA0003601498440001801
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-(N-叔丁氧基羰基)氨基苯甲酸，其余条件均一致。得到白色固体56.6mg，产率41％。1H NMR(400MHz,Chloroform-d)δ8.30(d,J＝8.8Hz,2H),8.13(d,J＝1.6Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.63(t,J＝8.8Hz,3H),7.38(t,J＝8.4Hz,1H),7.27–7.04(m,5H),6.99–6.84(m,3H),4.49(q,J＝7.1Hz,2H),4.27–3.97(m,2H),3.86–3.66(m,2H),3.60–3.47(m,2H),3.41–3.25(m,2H),3.08–2.66(m,3H),2.63–2.47(m,4H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ168.1,159.8,155.8,151.0,148.4,143.1,142.0,138.0,135.7,134.3,130.1,129.6,129.4,128.5,128.5,128.2,126.8,126.6,125.5,124.9,123.9,123.0,122.1,113.0,61.6,51.7,34.6,14.4,9.4.
实施例245
5-(N-(2-(4-(4-乙酰苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-115)
Figure BDA0003601498440001811
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为对乙酰基苯甲酸，其余条件均一致。得到白色固体84.2mg，产率61％。1H NMR(400MHz,Chloroform-d)δ8.12(d,J＝1.5Hz,1H),8.01(d,J＝8.3Hz,2H),7.86(dd,J＝8.8,1.8Hz,1H),7.62(d,J＝8.8Hz,1H),7.52(d,J＝8.3Hz,2H),7.36(t,J＝8.2Hz,1H),7.24–7.03(m,5H),6.97–6.90(m,3H),4.47(q,J＝7.1Hz,2H),4.24–3.97(m,2H),3.90–3.63(m,2H),3.59–3.45(m,2H),3.41–3.18(m,2H),3.05–2.64(m,3H),2.63(s,3H),2.61–2.50(m,4H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ197.3,169.3,159.8,155.8,151.0,143.0,140.2,138.0,137.8,135.8,134.2,130.2,129.6,129.3,1286,128.5,128.5,127.3,126.8,126.5,125.5,124.8,122.9,122.1,113.0,61.6,60.4,51.6,34.6,26.7,14.4,14.2,9.4.
实施例246
3-甲基-5-(N-(2-(4-烟酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-116)
Figure BDA0003601498440001812
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为烟酸，其余条件均一致。得到白色固体71.1mg，产率55％。1H NMR(400MHz,Chloroform-d)δ8.76–8.62(m,2H),8.12(s,1H),7.82(dd,J＝36.0,8.3Hz,2H),7.63(d,J＝8.8Hz,1H),7.43–7.32(m,2H),7.14(ddd,J＝36.9,18.4,7.5Hz,5H),6.98–6.88(m,3H),4.48(q,J＝7.1Hz,2H),4.23–3.97(m,2H),3.86–3.49(m,4H),3.40–3.20(m,2H),3.07–2.65(m,3H),2.64–2.50(m,4H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ167.9,159.8,155.8,151.0,150.8,148.1,143.1,138.0,135.7,135.0,134.2,131.6,130.1,129.6,129.4,128.5,128.5,126.8,126.5,125.5,124.8,123.4,123.0,122.1,113.0,61.6,51.6,34.6,14.4,9.4.
实施例247
3-甲基-5-(N-苯乙基-N-(2-(4-吡啶甲酰基哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-117)
Figure BDA0003601498440001821
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-吡啶甲酸，其余条件均一致。得到白色固体69.5mg，产率53％。1H NMR(400MHz,Chloroform-d)δ8.61(d,J＝4.6Hz,1H),8.15(s,1H),7.89(d,J＝10.5Hz,1H),7.82(t,J＝8.5Hz,1H),7.70–7.59(m,2H),7.36(t,J＝6.8Hz,2H),7.27–7.11(m,4H),7.07(t,J＝7.1Hz,1H),6.97(t,J＝8.7Hz,3H),4.49(q,J＝7.1Hz,2H),4.22–4.04(m,2H),3.92–3.61(m,4H),3.40–3.21(m,2H),3.07–2.66(m,3H),2.64–2.50(m,4H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ167.7,159.9,155.8,154.1,151.0,148.4,143.0,138.1,137.1,136.0,134.0,130.4,129.5,129.3,128.5,126.8,126.5,125.6,124.6,124.5,123.8,122.8,122.1,112.9,61.6,53.1,51.5,47.8,34.7,14.4,9.4.
实施例248
3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-118)
Figure BDA0003601498440001831
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-噻吩甲酸，其余条件均一致。得到白色固体28.4mg，产率21％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(dd,J＝8.8,1.8Hz,1H),7.65(d,J＝8.8Hz,1H),7.47(dd,J＝5.0,1.2Hz,1H),7.37(t,J＝8.3Hz,1H),7.32(d,J＝3.5Hz,1H),7.25–7.13(m,4H),7.13–7.04(m,2H),6.97(d,J＝5.9Hz,3H),4.50(q,J＝7.1Hz,2H),4.21–3.68(m,6H),3.41–3.18(m,2H),3.01–2.67(m,3H),2.67–2.49(m,4H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ163.7,159.9,155.8,151.0,138.1,137.0,135.9,134.1,130.3,129.5,129.4,128.9,128.6,128.5,126.8,126.7,126.5,125.5,124.7,122.9,122.1,113.0,61.6,51.5,34.7,14.4,9.4.
实施例249
3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-3-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-119)
Figure BDA0003601498440001832
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为3-噻吩甲酸，其余条件均一致。得到白色固体69.7mg，产率53％。13C NMR(101MHz,Chloroform-d)δ165.8,159.8,155.8,151.0,143.1,138.1,136.3,135.9,134.1,130.3,129.5,129.4,128.5,127.1,126.8,126.5,126.0,125.5,124.6,122.9,122.1,113.0,61.6,51.5,34.7,14.4,9.4.
实施例250
(E)-5-(N-(2-(4-(但-2-烯酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-120)
Figure BDA0003601498440001841
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为反式-2-丁烯酸，其余条件均一致。得到白色固体67.3mg，产率55％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(dd,J＝8.8,1.7Hz,1H),7.65(d,J＝8.8Hz,1H),7.36(t,J＝8.3Hz,1H),7.22–7.12(m,4H),7.08(t,J＝7.6Hz,1H),7.00–6.93(m,3H),6.93–6.86(m,1H),6.33–6.25(m,1H),4.50(q,J＝7.1Hz,2H),4.22–4.00(m,2H),3.89–3.29(m,5H),3.20–3.08(m,1H),2.96–2.66(m,3H),2.66–2.49(m,4H),1.91(d,J＝8.0Hz,3H),1.48(t,J＝7.1Hz,3H).13CNMR(101MHz,Chloroform-d)δ165.8,159.9,155.8,151.1,143.1,141.7,138.1,136.0,134.1,130.3,129.5,129.4,128.5,126.8,126.5,125.6,124.6,122.8,122.1,121.5,113.0,61.6,51.5,34.7,18.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C34H38N3O6S:616.2476；实测值：616.2479.
实施例251
5-(N-(2-(4-(呋喃-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-121)
Figure BDA0003601498440001842
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-呋喃甲酸，其余条件均一致。得到白色固体106.2mg，产率83％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(d,J＝8.0Hz,1H),7.65(d,J＝8.2Hz,1H),7.51(s,1H),7.43–7.31(m,1H),7.24–6.88(m,9H),6.50(s,1H),4.50(q,J＝7.3Hz,2H),4.22–3.67(m,6H),3.41–3.22(m,2H),3.08–2.84(m,2H),2.78–2.42(m,5H),1.47(t,J＝7.2Hz,3H).13C NMR(101MHz,Chloroform-d)δ159.8,159.3,155.8,151.0,147.9,143.7,143.1,138.1,136.0,134.0,130.4,129.5,129.4,128.5,126.8,126.5,125.5,124.6,122.8,122.1,116.4,113.0,111.3,61.6,51.5,34.7,14.4,9.4.
实施例252
5-(N-(2-(4-(环戊烷羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-122)
Figure BDA0003601498440001851
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为环戊基甲酸，其余条件均一致。得到黄色液体104.5mg，产率81％。1H NMR(400MHz,Chloroform-d)δ8.14(d,J＝1.6Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.33(td,J＝7.7,1.6Hz,1H),7.22–7.09(m,4H),7.06(td,J＝7.6,1.5Hz,1H),6.94(ddd,J＝8.8,5.5,1.5Hz,2H),4.47(q,J＝7.1Hz,2H),4.16–3.95(m,2H),3.62–3.52(m,2H),3.46–3.33(m,2H),3.15–3.02(m,1H),2.95–2.64(m,4H),2.62–2.48(m,4H),1.95–1.65(m,8H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ174.8,159.9,155.8,151.0,143.0,138.1,136.0,134.0,130.3,129.4,129.3,128.4,128.4,126.8,126.4,125.5,124.5,122.7,122.1,112.9,61.6,58.2,51.4,41.1,34.6,30.0,26.0,18.3,14.4,9.4.
实施例253
5-(N-(2-(4-(5-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-123)
Figure BDA0003601498440001861
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为5-溴-2-噻吩甲酸，其余条件均一致。得到白色固体104.7mg，产率71％。1H NMR(400MHz,Chloroform-d)δ8.16(d,J＝1.5Hz,1H),7.90(d,J＝10.5Hz,1H),7.66(d,J＝8.8Hz,1H),7.38(t,J＝7.7Hz,1H),7.20(dd,J＝10.4,7.8Hz,4H),7.09(d,J＝4.0Hz,2H),7.04(d,J＝3.9Hz,1H),6.96(t,J＝8.8Hz,3H),4.51(q,J＝7.1Hz,2H),4.20–3.69(m,6H),3.39–3.23(m,2H),3.03–2.83(m,2H),2.83–2.46(m,5H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.4,159.9,155.9,151.0,143.1,138.8,138.0,135.8,134.2,130.2,129.7,129.6,129.4,128.5,128.5,126.8,126.6,125.5,124.8,122.9,122.1,116.7,113.0,61.6,51.6,34.7,14.4,9.4.
实施例254
5-(N-(2-(4-(1H-吡咯-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-124)
Figure BDA0003601498440001862
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-吡咯甲酸，其余条件均一致。得到白色固体125.2mg，产率98％。1H NMR(400MHz,Chloroform-d)δ9.62(s,1H),8.18(s,1H),7.92(d,J＝10.3Hz,1H),7.66(d,J＝8.8Hz,1H),7.37(t,J＝8.0Hz,2H),7.25–7.14(m,4H),7.09(t,J＝7.3Hz,1H),7.02–6.93(m,4H),6.54(s,1H),6.32–6.23(m,1H),4.51(q,J＝7.1Hz,2H),4.25–3.76(m,6H),3.38–3.20(m,2H),2.99–2.87(m,2H),2.80–2.52(m,5H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ161.8,159.9,155.8,151.1,143.1,138.14,136.0,134.1,130.4,129.5,129.4,128.5,128.5,126.8,126.5,125.6,124.6,122.8,122.1,121.0,113.0,112.2,110.0,109.6,61.6,52.5,51.5,34.7,14.4,9.4.
实施例255
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-125)
Figure BDA0003601498440001871
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为3-溴-2-噻吩甲酸，其余条件均一致。得到白色固体97.5mg，产率66％。1H NMR(400MHz,Chloroform-d)δ8.15(d,J＝1.5Hz,1H),7.89(dd,J＝8.8,1.8Hz,1H),7.65(d,J＝8.8Hz,1H),7.38(q,J＝5.4,4.4Hz,2H),7.25–7.14(m,4H),7.10(t,J＝7.6Hz,1H),7.02–6.92(m,4H),4.51(q,J＝7.1Hz,2H),4.21–3.99(m,2H),3.89–3.22(m,6H),3.01–2.85(m,2H),2.81–2.51(m,5H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.2,159.9,155.8,151.0,143.1,138.1,135.9,134.1,132.0,130.3,130.2,129.5,129.4,128.5,127.3,126.8,126.6,125.5,124.7,122.9,122.1,113.0,109.7,61.6,51.5,34.7,14.4,9.4.
实施例256
5-(N-(2-(4-(3-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-126)
Figure BDA0003601498440001872
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为3-氯-2-噻吩甲酸，其余条件均一致。得到白色固体97.5mg，产率71％。1H NMR(400MHz,Chloroform-d)δ8.16(d,J＝1.6Hz,1H),7.89(dd,J＝8.8,1.9Hz,1H),7.65(d,J＝8.8Hz,1H),7.43–7.33(m,2H),7.26–7.13(m,4H),7.09(d,J＝7.7Hz,1H),7.01–6.91(m,4H),4.51(q,J＝7.1Hz,2H),4.21–4.03(m,2H),3.91–3.51(m,4H),3.41–3.23(m,2H),2.99–2.83(m,2H),2.78–2.52(m,5H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ161.7,159.9,155.8,151.0,143.1,138.1,135.9,134.1,130.3,130.1,129.5,129.4,128.5,127.7,126.8,126.6,125.5,124.7,124.0,122.9,122.1,113.0,61.6,51.5,34.7,14.4,9.4.
实施例257
5-(N-(2-(4-(4-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-127)
Figure BDA0003601498440001881
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-溴-2-噻吩甲酸，其余条件均一致。得到白色固体96.6mg，产率66％。1H NMR(400MHz,Chloroform-d)δ8.16(d,J＝1.5Hz,1H),7.90(dd,J＝8.8,1.8Hz,1H),7.66(d,J＝8.8Hz,1H),7.42–7.34(m,1H),7.26–7.14(m,5H),7.12(s,1H),6.96(d,J＝23.0Hz,3H),4.51(q,J＝7.1Hz,2H),4.18–3.68(m,6H),3.40–3.26(m,2H),3.00–2.70(m,3H),2.65–2.53(m,4H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.2,159.9,155.9,151.1,143.1,138.4,138.0,135.8,134.2,131.0,130.1,129.6,129.4,128.5,128.5,126.8,126.6,126.1,125.5,124.7,122.9,122.2,113.0,109.4,61.6,51.6,34.6,14.4,9.4.
实施例258
5-(N-(2-(4-(5-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-128)
Figure BDA0003601498440001891
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为5-氯-2-噻吩甲酸，其余条件均一致。得到白色固体101.5mg，产率74％。1H NMR(400MHz,Chloroform-d)δ8.16(d,J＝1.6Hz,1H),7.90(dd,J＝8.8,1.8Hz,1H),7.66(d,J＝8.8Hz,1H),7.38(t,J＝8.3Hz,1H),7.26–7.14(m,2H),7.15–7.05(m,4H),6.96(t,J＝8.7Hz,3H),6.90(d,J＝3.9Hz,1H),4.51(q,J＝7.1Hz,2H),4.20–3.68(m,6H),3.41–3.23(m,2H),3.00–2.85(m,2H),2.77–2.54(m,5H),1.49(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.4,159.9,155.9,151.0,143.1,138.0,135.9,135.8,134.2,134.1,130.2,129.6,129.4,128.6,128.5,128.5,126.8,126.6,126.0,125.5,124.8,122.9,122.1,113.0,61.6,51.6,34.7,14.4,9.4.
实施例259
3-甲基-5-(N-苯乙基-N-(2-(4-(噻唑-5-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-129)
Figure BDA0003601498440001892
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为噻唑-5-甲酸，其余条件均一致。得到白色固体115.4mg，产率84％。1H NMR(400MHz,Chloroform-d)δ8.91(s,1H),8.15(d,J＝1.6Hz,1H),8.10(s,1H),7.89(dd,J＝8.8,1.9Hz,1H),7.66(d,J＝8.8Hz,1H),7.38(t,J＝8.4Hz,1H),7.27–7.14(m,4H),7.10(t,J＝7.6Hz,1H),7.02–6.89(m,3H),4.51(q,J＝7.1Hz,2H),4.16–3.69(m,6H),3.42–3.27(m,2H),3.05–2.68(m,3H),2.66–2.52(m,4H),1.48(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ161.4,159.9,155.9,155.1,151.0,143.8,143.1,138.0,135.7,134.3,130.1,129.6,129.4,128.5,128.5,126.8,126.6,125.5,124.9,123.0,122.1,113.0,61.6,51.7,34.6,14.4,9.4.
实施例260
5-(N-(2-(4-(1H-吡唑-3-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(M10-130)
Figure BDA0003601498440001901
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为吡唑-3-甲酸，其余条件均一致。得到白色固体84.3mg，产率66％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(d,J＝8.7Hz,1H),7.67–7.57(m,2H),7.35(t,J＝7.4Hz,1H),7.24–6.92(m,8H),6.69(s,1H),4.50(q,J＝7.1Hz,2H),4.24–3.55(m,6H),3.39–3.15(m,2H),3.04–2.52(m,7H),1.47(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,160.0,155.8,150.9,143.0,138.1,136.0,133.9,130.5,129.5,129.4,128.5,128.5,126.8,126.5,125.6,124.5,122.7,122.1,113.0,107.5,61.7,51.4,34.7,14.4,9.4.
实施例261
3-甲基-5-(N-(2-(4-(恶唑-5-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-131)
Figure BDA0003601498440001902
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为噁唑-5-羧酸，其余条件均一致。得到白色固体68.6mg，产率54％。1H NMR(400MHz,Chloroform-d)δ8.15(s,1H),7.97(s,1H),7.89(dd,J＝8.8,1.6Hz,1H),7.68–7.57(m,2H),7.36(t,J＝7.6Hz,1H),7.25–7.03(m,5H),6.95(t,J＝7.4Hz,3H),4.49(q,J＝7.1Hz,3H),4.16–3.67(m,6H),3.52–3.16(m,2H),3.01–2.84(m,2H),2.78–2.52(m,5H),1.47(t,J＝7.1Hz,3H).13CNMR(101MHz,Chloroform-d)δ159.8,157.4,155.8,151.5,151.0,145.2,143.1,138.02,135.8,134.2,131.6,130.2,129.6,129.4,128.5,1285,126.8,126.6,125.5,124.8,122.9,122.1,113.0,61.6,51.6,34.6,14.4,9.4.
实施例262
5-(N-(2-(4-(3,4-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-132)
Figure BDA0003601498440001911
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为3,5-二甲基苯甲酸，其余条件均一致。得到白色固体82.4mg，产率30％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.34(td,J＝7.6,1.6Hz,1H),7.23–7.02(m,8H),6.98–6.85(m,3H),4.47(q,J＝7.1Hz,2H),4.23–3.11(m,8H),3.07–2.59(m,1H),2.58(s,3H),2.28(d,J＝1.9Hz,6H),1.45(t,J＝7.1Hz,3H).13CNMR(101MHz,CDCl3)δ170.8,159.8,155.8,151.1,143.1,138.5,138.1,136.9,136.0,134.1,133.2,130.3,129.5,129.5,129.4,128.5,128.4,126.8,126.5,125.5,124.6,122.8,122.1,113.0,61.6,51.5,34.7,19.8,19.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C39H42N3O6S:680.2794；实测值：680.2798.
实施例263
5-(N-(2-(4-(2,6-二甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-133)
Figure BDA0003601498440001921
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2,6-二甲氧基苯甲酸，其余条件均一致。得到白色固体58.7mg，产率22％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.43–6.86(m,10H),6.56(d,J＝8.4Hz,2H),4.48(q,J＝7.1Hz,2H),4.34–4.01(m,2H),3.82(s,8H),3.44–3.11(m,4H),2.58(s,7H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ165.5,159.9,156.7,155.9,151.1,143.1,138.2,136.1,133.8,130.5,130.4,129.5,129.4,128.6,128.5,126.9,126.6,125.6,124.4,122.6,122.1,114.3,113.0,104.0,61.6,55.9,53.4,51.6,51.3,47.2,41.9,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C39H42N3O8S:712.2693；实测值：712.2689.
实施例264
5-(N-(2-(4-(2-苄基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-134)
Figure BDA0003601498440001922
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-苄基苯甲酸，其余条件均一致。得到白色固体57.5mg，产率19％。1H NMR(400MHz,Chloroform-d)δ8.12(s,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.43–6.82(m,18H),4.48(q,J＝7.1Hz,2H),4.28–3.89(m,4H),3.84–3.41(m,2H),3.26–2.31(m,10H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ169.9,159.9,155.9,143.1,140.4,138.4,138.2,136.1,136.1,131.0,130.4,129.4,129.2,128.6,128.5,126.8,126.6,126.5,126.4,126.3,125.6,122.1,113.0,61.7,52.4,51.5,47.3,41.8,39.2,34.8,14.5,9.5.HRMS(ESI)[M+H]+理论值C44H44N3O6S:742.2951；实测值：742.2938.
实施例265
5-(N-(2-(4-(2,4,6-三甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-135)
Figure BDA0003601498440001931
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2,4,6-三甲基苯甲酸，其余条件均一致。得到白色固体21.2mg，产率25％。1H NMR(400MHz,Chloroform-d)δ8.12(d,J＝1.9Hz,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.35(td,J＝7.7,1.6Hz,1H),7.23–7.02(m,5H),6.96–6.90(m,3H),6.85(s,2H),4.48(q,J＝7.1Hz,2H),4.34–3.53(m,4H),3.39–3.09(m,4H),2.58(s,7H),2.26(d,J＝9.8Hz,9H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ170.0,159.9,155.9,151.2,143.1,138.2,138.1,135.9,134.1,133.6,133.2,130.3,129.6,129.4,128.6,128.4,126.9,126.6,125.6,124.7,122.8,122.2,113.0,61.7,53.6,52.0,51.6,46.7,41.7,34.7,21.1,19.2,14.4,9.4.HRMS(ESI)[M+H]+理论值C40H44N3O6S:694.2951；实测值：694.2955.
实施例266
5-(N-(2-(4-(2-甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-136)
Figure BDA0003601498440001932
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-甲氧基苯甲酸，其余条件均一致。得到白色固体76.5mg，产率56％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.35(td,J＝8.0,1.7Hz,2H),7.29–7.22(m,1H),7.22–7.10(m,4H),7.06(td,J＝7.6,1.4Hz,1H),7.01–6.88(m,5H),4.48(q,J＝7.1Hz,2H),4.25–4.00(m,2H),3.94–3.51(m,5H),3.44–3.10(m,4H),3.07–2.46(m,7H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ167.9,159.8,155.8,155.3,151.1,143.1,138.1,136.0,133.9,130.5,130.4,129.5,129.4,128.5,128.5,128.0,126.8,126.5,125.7,125.5,124.5,122.7,122.1,120.9,112.9,111.0,61.6,55.6,53.2,51.7,51.4,47.5,42.1,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C38H40N3O7S:682.2587；实测值：682.2577.
实施例267
5-(N-(2-(4-(2,5-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-137)
Figure BDA0003601498440001941
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2,5-二甲基苯甲酸，其余条件均一致。得到白色固体28.2mg，产率21％。1H NMR(400MHz,Chloroform-d)δ8.12(d,J＝1.9Hz,1H),7.86(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.35(td,J＝7.7,1.6Hz,1H),7.23–7.02(m,7H),6.99(s,1H),6.93(dd,J＝7.8,1.7Hz,3H),4.48(q,J＝7.1Hz,2H),4.34–3.51(m,4H),3.48–3.07(m,4H),3.05–2.41(m,7H),2.30(d,J＝14.5Hz,6H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ170.5,160.0,156.0,151.2,143.2,138.2,136.1,136.0,135.7,134.2,130.9,130.4,130.4,129.8,129.6,129.5,128.6,126.9,126.7,126.5,125.6,124.7,122.9,122.2,113.1,61.7,53.5,52.0,51.6,42.1,34.7,21.0,18.7,14.5,9.5.HRMS(ESI)[M+H]+理论值C39H42N3O6S:680.2794；实测值：680.2795.
实施例268
5-(N-(2-(4-(4-(苯乙炔基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-138)
Figure BDA0003601498440001951
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-(苯乙炔基)苯甲酸，其余条件均一致。得到黄色固体128.3mg，产率85％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.64–7.51(m,5H),7.43(d,J＝8.1Hz,2H),7.38–7.28(m,4H),7.23–7.03(m,5H),7.00–6.85(m,3H),4.47(q,J＝7.1Hz,2H),4.26–3.94(m,2H),3.87–3.46(m,4H),3.27(s,2H),2.59(s,7H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ169.8,159.8,155.8,151.1,143.1,138.1,135.8,135.3,134.2,131.7,131.7,130.2,129.6,129.4,128.6,128.5,128.4,127.3,126.8,126.6,125.5,124.9,124.8,123.0,122.9,122.1,113.0,90.9,88.7,61.6,51.6,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C45H42N3O6S:752.2794；实测值：752.2789.
实施例269
5-(N-(2-(4-(5-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-139)
Figure BDA0003601498440001952
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为5-甲基-2-噻吩甲酸，其余条件均一致。得到黄色固体93.9mg，产率23％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.34(td,J＝7.6,1.6Hz,1H),7.22–7.02(m,6H),6.95(ddd,J＝7.6,5.7,1.6Hz,3H),6.69(dd,J＝3.7,1.3Hz,1H),4.47(q,J＝7.1Hz,2H),4.20–3.60(m,6H),3.21(d,J＝45.4Hz,2H),2.99–2.51(m,7H),2.49(s,3H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ163.7,159.8,155.8,151.0,143.9,143.1,138.1,136.0,134.6,134.1,130.3,129.5,129.5,129.4,128.5,126.8,126.5,125.5,125.2,125.1,124.6,122.9,122.1,113.0,61.6,52.5,51.5,34.7,15.3,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H38N3O6S2:672.2202；实测值：672.2194.
实施例270
5-(N-(2-(4-(4-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-140)
Figure BDA0003601498440001961
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为4-甲基-2-噻吩甲酸，其余条件均一致。得到黄色固体80.4mg，产率20％。1H NMR(400MHz,Chloroform-d)δ8.14(d,J＝1.9Hz,1H),7.88(dd,J＝8.7,1.9Hz,1H),7.63(d,J＝8.8Hz,1H),7.35(td,J＝7.7,1.6Hz,1H),7.22–7.00(m,7H),6.94(dd,J＝7.7,1.6Hz,3H),4.47(q,J＝7.1Hz,2H),4.27–3.57(m,6H),3.29(s,2H),3.03–2.44(m,7H),2.27(s,3H),1.45(t,J＝7.1Hz,3H).13CNMR(101MHz,CDCl3)δ163.9,159.9,155.9,151.1,143.1,138.1,137.4,136.7,136.0,134.1,131.2,130.3,129.6,129.4,128.6,126.9,126.6,125.6,124.7,124.2,122.9,122.2,113.0,61.6,52.5,51.6,34.7,15.6,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H38N3O6S2:672.2202；实测值：672.2191.
实施例271
5-(N-(2-(4-(3-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-141)
Figure BDA0003601498440001962
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为3-甲基-2-噻吩甲酸，其余条件均一致。得到黄色固体119.5mg，产率30％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.8Hz,1H),7.87(dd,J＝8.7,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.35(td,J＝7.7,1.6Hz,1H),7.27(d,J＝4.9Hz,1H),7.22–7.10(m,4H),7.07(td,J＝7.6,1.5Hz,1H),6.95(ddd,J＝7.8,4.6,1.6Hz,3H),6.84(d,J＝5.0Hz,1H),4.48(q,J＝7.1Hz,2H),4.21–3.51(m,6H),3.26(s,2H),2.59(s,7H),2.28(s,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ164.8,159.9,155.9,151.0,143.1,138.1,137.3,135.9,134.1,130.3,130.3,129.8,129.5,129.4,128.5,126.8,126.6,126.0,125.5,124.7,122.9,122.1,113.0,61.6,52.6,51.5,34.7,14.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C36H38N3O6S2:672.2202；实测值：672.2195.
实施例272
5-(N-(2-(4-(1H-咪唑-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-142)
Figure BDA0003601498440001971
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为1H-咪唑-2-羧酸，其余条件均一致。得到白色固体50.5mg，产率13％。1H NMR(400MHz,Chloroform-d)δ11.8(s,1H),8.2(d,J＝1.9Hz,1H),7.9(dd,J＝8.8,1.9Hz,1H),7.6(d,J＝8.8Hz,1H),7.3(td,J＝7.6,1.7Hz,1H),7.2–7.1(m,6H),7.1(td,J＝7.6,1.7Hz,1H),7.0–6.9(m,3H),4.8(d,J＝141.8Hz,2H),4.5(q,J＝7.1Hz,2H),4.2–3.7(m,4H),3.5–2.6(m,9H),1.5(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ160.0,158.1,155.9,151.1,143.1,141.4,138.3,136.1,134.2,130.5,129.8,129.6,129.5,128.6,128.6,127.0,126.6,125.7,124.6,122.9,122.2,118.5,113.0,61.7,52.9,52.5,51.6,47.2,43.5,34.9,14.5,9.5.HRMS(ESI)[M+H]+理论值C34H36N5O6S:642.2386；实测值：642.2388.
实施例273
5-(N-(2-(4-(四氢噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-143)
Figure BDA0003601498440001981
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为四氢噻吩-2-甲酸，其余条件均一致。得到白色固体113.5mg，产率28％。1H NMR(400MHz,Chloroform-d)δ8.15(d,J＝1.9Hz,1H),7.88(dd,J＝8.8,1.9Hz,1H),7.63(d,J＝8.8Hz,1H),7.34(td,J＝7.6,1.7Hz,1H),7.23–7.03(m,5H),6.97(dd,J＝17.6,7.4Hz,3H),4.48(q,J＝7.1Hz,2H),4.16–3.73(m,4H),3.71–3.24(m,4H),3.12(s,1H),3.05–2.75(m,4H),2.74–2.42(m,6H),2.30–2.21(m,1H),2.10–1.87(m,2H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ170.8,159.8,155.7,150.9,142.9,138.0,135.8,133.9,130.3,129.4,129.3,128.4,128.4,126.7,126.4,125.5,124.6,122.8,122.0,112.9,61.5,52.7,51.6,51.3,46.3,45.1,42.5,34.6,33.4,33.0,31.3,14.3,9.4.HRMS(ESI)[M+H]+理论值C35H40N3O6S2:662.2359；实测值：662.2357.
实施例274
5-(N-(2-(4-(1H-咪唑-4-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-144)
Figure BDA0003601498440001982
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为1H-咪唑-4-甲酸，其余条件均一致。得到白色固体118.5mg，产率31％。1H NMR(400MHz,Chloroform-d)δ11.55(s,1H),8.13(d,J＝1.9Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.65–7.57(m,2H),7.46(s,1H),7.32(t,J＝7.7Hz,1H),7.21–6.82(m,8H),4.45(q,J＝7.1Hz,2H),4.35–3.59(m,6H),3.30(s,2H),2.91(d,J＝10.6Hz,2H),2.76–2.42(m,5H),1.43(t,J＝7.1Hz,3H).13CNMR(101MHz,CDCl3)δ163.4,159.9,155.8,151.0,143.0,138.1,135.9,135.5,133.9,130.3,129.5,129.3,128.5,128.5,126.8,126.5,125.6,124.5,122.8,122.1,112.9,61.6,51.4,34.6,29.6,14.3,9.4.HRMS(ESI)[M+H]+理论值C34H36N5O6S:642.2386；实测值：642.2394.
实施例275
5-(N-(2-(4-(2-乙基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-145)
Figure BDA0003601498440001991
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为2-乙基丁酸，其余条件均一致。得到白色固体138.2mg，产率31％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.89(d,J＝8.8Hz,1H),7.64(d,J＝8.8Hz,1H),7.35(t,J＝7.7Hz,1H),7.23–7.03(m,5H),6.95(t,J＝8.2Hz,3H),4.48(q,J＝7.1Hz,2H),4.11(dd,J＝13.4,7.0Hz,2H),3.92–3.33(m,5H),3.22–2.48(m,9H),1.86–1.39(m,7H),0.89(t,J＝7.4Hz,6H).13C NMR(101MHz,CDCl3)δ174.5,159.8,155.8,151.0,143.1,138.1,136.0,134.0,130.4,129.5,129.4,128.5,128.5,126.8,126.5,125.5,124.6,122.7,122.1,113.0,61.6,53.5,52.1,51.4,46.3,44.0,42.2,34.6,25.6,14.4,12.1,9.4.HRMS(ESI)[M+H]+理论值C36H44N3O6S:646.2951；实测值：646.2940.
实施例276
5-(N-(2-(4-(异恶唑-5-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-146)
Figure BDA0003601498440001992
按照3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)所用方法，将3,3-二甲基-1-丁酸替换为异恶唑-5-甲酸，其余条件均一致。得到白色固体42.1mg，产率21％。
实施例277
5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-147)
Figure BDA0003601498440002001
将对3-溴噻吩-2-甲酸(223mg,1.078mmol)，EDCI(207mg,1.078mmol)，HOBt(146mg,1.078mmol),DIPEA(1.47mmol,242μL)溶于4毫升DCM中，室温下搅拌。待TLC监测原料羧酸没有剩余，向体系中加入5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(275mg,0.49mmol)。室温反应过夜。TLC检测反应完全后，加水20mL，用20mL乙酸乙酯萃取三次，合并有机相，减压浓缩后柱层析分离(PE:EtOAc＝3:1)，得到白色固体366.5mg，产率99％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(dd,J＝8.8,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.45(d,J＝5.3Hz,2H),7.34(ddd,J＝8.8,7.0,1.9Hz,1H),7.28–7.10(m,5H),7.08–6.92(m,6H),4.48(q,J＝7.1Hz,2H),4.19–2.95(m,6H),2.80–2.48(m,6H),2.28–1.57(m,4H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ159.9,159.7,155.8,151.7,143.0,138.3,136.2,135.1,133.8,132.0,130.6,130.1,129.3,128.6,128.5,126.8,126.5,125.6,124.2,122.9,122.1,112.9,110.0,108.4,61.6,51.3,47.0,34.8,14.4,9.4.
实施例278
5-(N-(2-(3-溴噻吩-2-羰基)-2,8-重氮螺环[4.5]癸-8-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-148)
Figure BDA0003601498440002011
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2,8-二氮螺环[4.5]癸-8-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体98.0mg，产率57％。1H NMR(400MHz,Chloroform-d)δ8.17(s,1H),7.91(t,J＝8.1Hz,1H),7.63(d,J＝8.6Hz,1H),7.35(s,2H),7.25–7.10(m,4H),7.08–6.86(m,4H),4.49(q,J＝6.9Hz,2H),3.87(s,1H),3.74(s,1H),3.64–3.45(m,2H),3.32(s,1H),3.28–3.00(m,2H),2.96–2.48(m,8H),1.97–1.80(m,2H),1.80–1.57(m,4H),1.47(t,J＝7.0Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.0,159.9,155.8,151.8,143.0,138.3,136.2,133.7,133.3,130.5,130.3,129.3,128.5,128.4,126.9,126.8,126.4,125.6,124.0,122.6,122.5,122.1,112.9,109.4,61.6,58.2,55.3,51.1,50.0,46.5,44.5,39.4,34.9,34.7,21.1,14.4,9.4.
实施例279
5-(N-(2-(7-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-2-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-149)
Figure BDA0003601498440002012
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2,7-二氮螺环[3.5]壬-2-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体220.2mg，产率59％。1H NMR(400MHz,Chloroform-d)δ8.04(s,1H),7.83(d,J＝8.6Hz,1H),7.64(d,J＝8.6Hz,1H),7.44–7.04(m,7H),6.99(s,1H),6.51(s,2H),6.34(d,J＝7.6Hz,1H),4.49(q,J＝6.7Hz,2H),4.09–3.26(m,10H),2.93–2.76(m,1H),2.76–2.62(m,1H),2.00–1.81(m,4H),1.47(t,J＝6.9Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.1,159.9,156.0,148.7,143.0,138.0,134.0,132.3,130.2,129.3,129.3,128.7,128.6,128.5,127.4,127.0,126.7,125.6,123.8,122.7,116.9,113.9,112.7,109.6,62.4,61.6,52.9,34.7,34.2,14.4,9.4.
实施例280
5-(N-(2-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-7-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-150)
Figure BDA0003601498440002021
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2,7-重氮螺环[3.5]壬-7-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体539.7mg，产率68％。1H NMR(400MHz,Chloroform-d)δ8.15(d,J＝1.9Hz,1H),7.89(dd,J＝8.7,1.9Hz,1H),7.62(d,J＝8.8Hz,1H),7.38(d,J＝5.2Hz,1H),7.36–7.28(m,1H),7.21–7.09(m,4H),7.09–6.96(m,3H),6.97–6.90(m,2H),4.49(q,J＝7.1Hz,2H),4.15–3.74(m,7H),3.12(s,2H),2.84–2.47(m,6H),1.89(d,J＝21.8Hz,4H),1.47(t,J＝7.1Hz,3H).13CNMR(101MHz,Chloroform-d)δ163.2,159.9,155.8,151.6,143.0,138.3,136.2,133.8,131.4,130.5,130.1,129.3,129.3,128.5,128.5,128.1,126.8,126.5,125.6,124.2,122.7,122.1,112.9,111.8,61.6,51.2,49.8,36.0,34.7,33.9,14.4,14.2,9.4.
实施例281
5-(N-(2-(6-(3-溴噻吩-2-羰基)-3,6-二氮杂双环[3.1.1]庚烷-3-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-151)
Figure BDA0003601498440002031
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(3,6-二氮杂双环[3.1.1]庚烷-3-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体291mg，产率30％。1H NMR(400MHz,Chloroform-d)δ7.94(s,1H),7.73(d,J＝8.8Hz,1H),7.59(d,J＝8.8Hz,1H),7.42–7.10(m,6H),7.02(d,J＝19.6Hz,3H),6.78(s,1H),6.55(s,1H),4.65(s,2H),4.47(q,J＝7.1Hz,2H),4.12–3.90(m,2H),3.74–3.30(m,3H),2.91–2.48(m,6H),1.53–1.34(m,5H).13C NMR(101MHz,Chloroform-d)δ162.8,159.8,155.9,149.2,143.0,137.9,131.5,131.1,129.5,129.2,129.0,128.6,128.6,128.1,127.3,126.6,125.6,122.6,121.7,120.9,112.6,111.5,61.6,52.4,49.9,34.3,26.9,14.4,9.3.
实施例282
(S)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-152)
Figure BDA0003601498440002032
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为(S)-3-甲基-5-(N-(2-(2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体398mg，产率73％。
实施例283
(R)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-153)
Figure BDA0003601498440002041
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为(R)-3-甲基-5-(N-(2-(2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体354mg，产率73％。
实施例284
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-1,4-二氮杂草-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-154)
Figure BDA0003601498440002042
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(1,4-二氮杂环丙烷-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体727.1mg，产率53％。1H NMR(400MHz,DMSO-d6)δ8.23(d,J＝26.6Hz,1H),7.88(d,J＝22.2Hz,2H),7.72(d,J＝16.7Hz,1H),7.41–7.05(m,6H),7.03–6.81(m,4H),4.39(q,J＝7.1Hz,2H),4.17–2.93(m,12H),2.58(s,3H),2.09–1.63(m,2H),1.36(t,J＝7.1Hz,3H).13CNMR(101MHz,DMSO)δ162.3,159.1,155.2,151.4,142.3,138.0,135.3,132.5,132.0,130.0,129.7,129.1,128.9,128.5,128.3,127.0,126.2,125.7,122.8,122.1,113.2,108.4,61.2,54.8,50.5,49.9,46.7,44.3,33.7,27.3,14.1,9.1.HRMS(ESI)[M+H]+理论值C36H37N3O6S2Br:750.1307；实测值：750.1295.
实施例285
5-(N-(2-(3-(3-溴噻吩-2-甲酰基)-3，8-二氮杂草[3.2.1]环辛烷-8-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-155)
Figure BDA0003601498440002051
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(3,8-二氮杂双环[3.2.1]辛烷-8-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体149.0mg，产率43.4％。1H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.90(t,J＝8.9Hz,1H),7.65(d,J＝8.8Hz,1H),7.35(d,J＝5.2Hz,1H),7.21(ddd,J＝21.5,14.9,6.7Hz,4H),7.06–6.66(m,6H),4.73–3.98(m,6H),3.89–3.58(m,2H),3.55–3.08(m,2H),2.86–2.46(m,5H),2.14(s,1H),2.02–1.74(m,3H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ163.9,159.9,156.0,143.2,138.1,132.1,130.4,129.5,129.0,128.6,127.2,127.0,126.7,125.6,125.3,122.4,120.4,119.2,113.1,109.7,109.4,61.7,34.4,26.8,14.4,9.4,1.1.HRMS(ESI)[M+H]+理论值C37H37N3O6S2Br:762.1307；实测值：762.1312.
实施例286
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-3-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-156)
Figure BDA0003601498440002052
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(3-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体1.751g，产率54.5％。1H NMR(400MHz,Chloroform-d)δ8.13(d,J＝1.8Hz,1H),7.87(dd,J＝8.8,1.9Hz,1H),7.64(t,J＝8.4Hz,1H),7.42–7.29(m,2H),7.28–7.12(m,4H),7.10–6.69(m,5H),4.49(qd,J＝7.1,1.9Hz,2H),4.07(dtd,J＝13.3,10.6,5.8Hz,1H),3.83(tdd,J＝13.3,10.6,5.8Hz,1H),3.71–3.31(m,2H),3.29–2.40(m,9H),1.61(d,J＝7.2Hz,2H),1.46(td,J＝7.1,2.9Hz,5H).13C NMR(101MHz,CDCl3)δ162.2,160.0,156.0,151.9,151.4,143.2,134.5,134.2,130.3,129.7,128.7,128.7,128.6,128.6,127.1,126.9,126.8,126.7,124.8,124.5,122.4,122.2,113.1,109.6,61.7,52.6,51.5,34.7,34.4,14.5,9.5.HRMS(ESI)[M+H]+理论值C36H37N3O6S2Br:750.1307；实测值：750.1309.
实施例287
5-(N-(2-(5-(3-溴噻吩-2-甲酰基)-2,5-二氮杂二环[2.2.1]庚-2-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-157)
Figure BDA0003601498440002061
按照5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M10-132)所用方法，将5-(N-(2-(4-氨基哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯替换为5-(N-(2,5-二氮杂双环[2.2.1]庚烷-2-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体782mg，产率40％。1H NMR(400MHz,Chloroform-d)δ8.19–7.52(m,3H),7.41–7.15(m,5H),7.10–6.69(m,4H),6.65–6.27(m,2H),5.37–4.34(m,4H),4.27–3.31(m,6H),3.06–2.40(m,5H),2.21–1.89(m,2H),1.45(td,J＝8.4,7.2,2.5Hz,3H).13C NMR(101MHz,CDCl3)δ159.9,156.1,146.1,143.0,138.0,130.7,130.5,129.9,129.5,128.8,128.7,128.7,127.5,127.2,126.8,126.7,126.1,125.7,123.0,122.8,116.6,113.0,112.7,110.0,61.7,58.6,53.4,33.9,14.5,9.5,9.4.HRMS(ESI)[M+H]+理论值C36H35N3O6S2Br:748.1151；实测值：748.1147.
实施例288
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)
Figure BDA0003601498440002071
将对3-溴噻吩-2-甲酸(167mg,0.814mmol)，EDCI(156mg,0.814mmol)，HOBt(110mg,0.814mmol),DIPEA(1.14mmol,183μL)溶于4毫升DCM中，室温下搅拌。待TLC监测原料羧酸没有剩余，向体系中加入3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯(206.7mg,0.37mmol)。室温反应过夜。TLC检测反应完全后，加水20mL，用20mL乙酸乙酯萃取三次，合并有机相，减压浓缩后柱层析分离(PE:EtOAc＝3:1)，得到白色固体203.3mg，产率73％。1H NMR(400MHz,Chloroform-d)δ8.28(s,1H),7.99–7.79(m,2H),7.44–7.33(m,2H),7.25–7.05(m,5H),7.03–6.89(m,4H),4.44(q,J＝7.0Hz,2H),4.16–2.83(m,10H),2.77(s,3H),2.73–2.52(m,2H),1.45(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,162.2,150.9,144.1,140.8,139.9,138.1,137.0,134.1,132.0,130.4,130.2,129.8,129.5,128.5,127.3,126.5,124.9,124.7,123.7,123.5,122.8,109.7,61.6,51.5,34.7,14.4,13.2.HRMS(ESI)[M+H]+理论值C35H35BrN3O5S3:752.0917；实测值：752.0921.
实施例289
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸乙酯(M10-159)
Figure BDA0003601498440002072
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体79.4mg，产率57％。1H NMR(400MHz,Chloroform-d)δ8.34(s,1H),8.12(s,1H),7.97(d,J＝8.5Hz,1H),7.84(d,J＝8.5Hz,1H),7.49–6.89(m,11H),4.47(q,J＝7.0Hz,2H),4.16–2.48(m,12H),1.46(t,J＝7.0Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.2,162.0,150.9,145.6,138.3,138.0,137.7,136.8,134.1,132.0,130.4,130.2,129.5,129.2,128.6,128.5,127.3,126.6,125.4,124.8,124.8,123.6,122.9,109.7,62.1,51.6,34.7,14.3.HRMS(ESI)[M+H]+理论值C34H33BrN3O5S3:738.0760；实测值：738.0760.
实施例290
6-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸乙酯(M10-160)
Figure BDA0003601498440002081
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为6-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体45.7mg，产率62％。1H NMR(400MHz,Chloroform-d)δ8.34(s,1H),8.12(s,1H),7.98(d,J＝8.5Hz,1H),7.81(d,J＝8.5Hz,1H),7.37(d,J＝5.3Hz,2H),7.19(d,J＝7.8Hz,4H),7.10(t,J＝7.7Hz,1H),6.99(d,J＝5.1Hz,4H),4.47(q,J＝7.2Hz,2H),4.11(dd,J＝21.1,11.4Hz,2H),3.88(s,1H),3.56(s,3H),3.26(s,2H),3.02–2.49(m,4H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.2,162.0,150.9,150.7,141.7,141.3,138.8,138.4,138.0,134.0,132.0,130.6,130.2,129.6,129.4,128.5,127.2,126.6,126.0,124.9,123.5,123.0,122.9,109.7,62.1,60.4,51.6,34.8,14.3,14.2.HRMS(ESI)[M+H]+理论值C34H33BrN3O5S3:738.0760；实测值：738.0770.
实施例291
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-氯-1H-吲哚-2-羧酸乙酯(M10-161)
Figure BDA0003601498440002091
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为3-氯-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)-1H-吲哚-2-羧酸乙酯，其余条件均一致。得到白色固体179.5mg，产率70％。1H NMR(400MHz,Chloroform-d)δ10.15(s,1H),8.50–8.09(m,1H),7.87–7.65(m,1H),7.56–6.75(m,11H),4.50(q,J＝8.2,7.7Hz,2H),4.09–2.46(m,12H),1.48(t,J＝8.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.4,160.5,150.7,138.1,136.3,134.2,133.4,131.9,130.5,130.2,129.4,128.5,127.4,126.5,125.6,124.9,124.8,124.7,122.5,121.6,113.3,113.2,109.7,61.9,51.5,34.6,14.4.HRMS(ESI)[M+H]+理论值C34H33BrClN4O5S2:755.0759；实测值：755.0770.
实施例292
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-162)
Figure BDA0003601498440002092
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体183.0mg，产率47％。1H NMR(400MHz,Chloroform-d)δ8.17(d,J＝1.9Hz,1H),7.85(dd,J＝8.8,1.9Hz,1H),7.64(d,J＝8.8Hz,1H),7.56(s,1H),7.32(t,J＝6.7Hz,2H),7.20–7.01(m,5H),6.93(dd,J＝6.5,4.2Hz,4H),4.44(q,J＝7.1Hz,2H),4.28–3.43(m,6H),3.25(d,J＝11.6Hz,2H),2.97–2.44(m,4H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ162.1,158.7,156.9,150.8,147.8,138.0,136.5,134.0,131.9,130.3,130.1,129.4,128.4,128.4,127.3,127.1,126.6,126.5,124.7,123.5,122.8,113.6,113.0,109.5,61.9,51.4,34.5,14.2.HRMS(ESI)[M+H]+理论值C34H33N3O6S2Br:722.0994；实测值：722.0997.
实施例293
6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯(M10-163)
Figure BDA0003601498440002101
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为3-甲基-6-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体92.2mg，产率22％。1HNMR(400MHz,Chloroform-d)δ8.07–8.00(m,1H),7.76(dq,J＝12.8,8.1,6.2Hz,2H),7.35(h,J＝4.9Hz,2H),7.24–7.04(m,5H),7.02–6.80(m,4H),4.51–4.43(m,2H),4.34–3.11(m,9H),2.89(s,2H),2.71–2.40(m,5H),1.50–1.42(m,3H).13C NMR(101MHz,CDCl3)δ162.2,159.9,153.2,150.9,144.0,139.9,138.1,134.2,132.7,132.1,130.3,130.2,129.6,128.6,128.6,127.3,126.6,124.9,122.9,122.3,121.9,112.4,109.7,61.7,51.7,34.7,14.4,9.4.HRMS(ESI)[M+H]+理论值C35H35N3O6S2Br:736.1151；实测值：736.1158.
实施例294
6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-164)
Figure BDA0003601498440002111
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为6-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体386.9mg，产率30％。1H NMR(400MHz,Chloroform-d)δ8.06(d,J＝1.4Hz,1H),7.83–7.72(m,2H),7.57(d,J＝1.4Hz,1H),7.39–7.30(m,2H),7.23–7.03(m,5H),7.00–6.91(m,4H),4.47(q,J＝7.1Hz,2H),4.21–3.10(m,8H),3.04–2.45(m,4H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ162.2,158.9,154.4,150.9,148.9,139.7,138.0,134.1,132.0,130.7,130.3,130.2,129.6,128.6,128.5,127.3,126.5,125.0,123.5,122.9,122.9,113.1,112.6,109.7,62.1,51.7,34.7,14.3.HRMS(ESI)[M+H]+理论值C34H33N3O6S2Br:722.0994；实测值：722.0992.
实施例295
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)
Figure BDA0003601498440002112
将对(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮(119.4mg,0.24mmol)，5-(氯磺酰基)-3-甲基苯并[b]噻吩-2-羧酸乙酯(90mg,0.29mmol),DIPEA(0.6mmol,99μL)溶于4毫升DCM中，40℃下搅拌反应直到TLC监测原料没有剩余。TLC检测反应完全后，加水20mL，用20mL乙酸乙酯萃取三次，合并有机相，减压浓缩后柱层析分离(PE:EtOAc＝5:1)，得到白色固体33.0mg，产率18％。1H NMR(400MHz,Chloroform-d)δ8.24(s,1H),7.96–7.76(m,2H),7.36(d,J＝5.1Hz,2H),7.21(d,J＝7.3Hz,1H),7.08(d,J＝8.3Hz,3H),7.02–6.93(m,2H),6.84(d,J＝8.3Hz,2H),4.44(q,J＝7.1Hz,2H),4.14–2.80(m,10H),2.76(s,3H),2.71–2.46(m,2H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.9,162.4,151.0,144.3,140.9,140.0,137.0,136.6,134.1,132.5,132.10,130.7,130.3,130.1,129.9,129.7,128.7,127.4,124.9,123.8,123.6,123.0,109.8,61.8,51.3,34.1,14.5,13.3.
实施例296
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-甲基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-166)
Figure BDA0003601498440002121
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((4-甲基苯基乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体76.6mg，产率29％。1H NMR(400MHz,Chloroform-d)δ8.26(s,1H),7.95–7.76(m,2H),7.35(d,J＝5.0Hz,2H),7.20(d,J＝7.9Hz,1H),7.08(t,J＝7.4Hz,1H),7.03–6.91(m,4H),6.82(d,J＝7.7Hz,2H),4.43(q,J＝7.1Hz,2H),4.13–2.85(m,10H),2.76(s,3H),2.69–2.45(m,2H),2.24(s,3H),1.44(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,150.9,144.1,140.9,139.9,137.0,136.1,134.9,134.1,132.0,130.4,130.2,129.8,129.5,129.2,128.4,127.3,125.0,124.7,123.7,123.4,122.8,109.7,61.6,51.6,34.2,21.0,14.4,13.2.
实施例297
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(甲氧基羰基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-167)
Figure BDA0003601498440002131
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为4-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨基)乙基)苯甲酸甲酯，其余条件均一致。得到白色固体79.8mg，产率25％。1H NMR(400MHz,Chloroform-d)δ8.23(d,J＝1.7Hz,1H),7.92(d,J＝8.5Hz,1H),7.84(dd,J＝8.6,1.8Hz,1H),7.80–7.75(m,2H),7.40–7.34(m,2H),7.23(dd,J＝8.1,1.5Hz,1H),7.12(d,J＝1.5Hz,1H),7.06–6.95(m,4H),4.45(q,J＝7.1Hz,2H),4.22–4.08(m,2H),3.96–3.83(m,4H),3.69–3.07(m,5H),2.97–2.84(m,2H),2.78–2.73(m,4H),2.63(q,J＝7.8Hz,1H).13CNMR(101MHz,Chloroform-d)δ166.6,162.7,162.2,150.9,144.1,143.5,140.7,139.9,136.9,133.9,132.0,130.7,130.2,130.0,129.7,128.5,128.4,127.3,124.9,124.8,123.6,123.4,122.9,109.7,61.6,52.0,50.9,34.6,14.3,13.2.
实施例298
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氰基苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-168)
Figure BDA0003601498440002132
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为4-(2-((2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨基)乙基)苯甲腈，其余条件均一致。得到白色固体43.0mg，产率14％。1H NMR(400MHz,Chloroform-d)δ8.24(d,J＝1.6Hz,1H),7.94(d,J＝8.5Hz,1H),7.83(dd,J＝8.6,1.7Hz,1H),7.47–7.34(m,4H),7.22(d,J＝7.6Hz,1H),7.14–6.96(m,5H),4.45(q,J＝7.2Hz,2H),4.12–3.00(m,8H),2.91–2.57(m,7H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,162.2,150.8,144.2,143.7,140.6,139.9,136.7,133.8,132.2,131.9,130.6,130.2,129.8,129.3,127.3,124.9,124.7,123.7,123.5,123.0,118.5,110.5,109.7,61.7,50.69,34.9,14.3,13.2.
实施例299
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(三氟甲基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-169)
Figure BDA0003601498440002141
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((4-(三氟甲基)苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体51mg，产率18％。1H NMR(400MHz,Chloroform-d)δ8.29(d,J＝1.7Hz,1H),7.98–7.76(m,2H),7.40(dd,J＝16.5,6.8Hz,4H),7.23(dd,J＝8.1,1.5Hz,1H),7.13–6.93(m,5H),4.46(q,J＝7.1Hz,2H),4.17–3.11(m,7H),2.98–2.54(m,8H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,162.2,150.8,144.2,142.2,140.7,139.9,136.8,133.9,132.0,130.5,130.2,130.1,129.7,128.8,127.3,125.4,125.4,124.9,124.7,123.7,123.5,122.9,109.7,61.7,51.0,34.6,14.3,13.2.
实施例300
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-甲氧基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-170)
Figure BDA0003601498440002151
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((3-甲氧基苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体81mg，产率36％。
实施例301
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-171)
Figure BDA0003601498440002152
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((3-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体38.8mg，产率24％。1H NMR(400MHz,Chloroform-d)δ8.38–8.19(m,1H),8.02–7.78(m,2H),7.38(d,J＝4.7Hz,2H),7.22(d,J＝7.9Hz,1H),7.10(q,J＝7.1,6.5Hz,3H),7.01(t,J＝6.7Hz,2H),6.91(s,1H),6.84(d,J＝6.9Hz,1H),4.46(q,J＝7.1Hz,2H),4.18–3.14(m,8H),2.98–2.47(m,7H),1.47(t,J＝7.0Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,150.8,144.2,140.8,140.1,139.9,136.9,134.2,134.0,132.0,130.5,130.2,129.7,129.6,128.7,127.3,126.6,124.8,123.7,123.5,122.8,109.7,61.7,51.1,34.3,29.7,14.3,13.2.
实施例302
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-172)
Figure BDA0003601498440002161
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((2-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体15mg，产率13％。1H NMR(400MHz,Chloroform-d)δ8.36(d,J＝1.6Hz,1H),8.03–7.86(m,2H),7.37(d,J＝5.2Hz,2H),7.25–7.15(m,2H),7.14–7.06(m,4H),6.99(d,J＝5.0Hz,2H),4.46(q,J＝7.1Hz,2H),4.17–3.18(m,8H),2.96–2.60(m,7H),1.47(t,J＝7.2Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,150.7,144.1,140.9,139.9,137.2,135.7,134.0,133.9,132.0,130.8,130.6,130.2,129.5,128.1,127.2,126.9,124.8,124.7,123.8,123.5,122.7,109.7,61.6,49.2,32.9,14.3,13.2.
实施例303
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-甲氧基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-173)
Figure BDA0003601498440002171
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((2-甲氧基苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体70.7mg，产率28％。1H NMR(400MHz,Chloroform-d)δ8.32(s,1H),7.98–7.83(m,2H),7.37(d,J＝4.9Hz,2H),7.22(d,J＝7.9Hz,1H),7.16–7.05(m,2H),7.05–6.96(m,2H),6.87(dd,J＝7.4,1.7Hz,1H),6.78(t,J＝7.3Hz,1H),6.69(d,J＝8.2Hz,1H),4.45(q,J＝7.1Hz,2H),4.16–3.77(m,2H),3.72–3.43(m,6H),3.37–2.75(m,8H),2.69–2.53(m,2H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,157.4,150.9,144.0,141.0,139.8,137.4,134.2,132.1,130.6,130.2,130.2,129.7,129.3,127.9,127.2,126.3,125.0,124.6,123.8,123.3,122.7,120.4,110.2,109.7,61.6,55.0,49.5,29.9,14.3,13.2.
实施例304
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-硝基苯乙基)氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-174)
Figure BDA0003601498440002172
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((2-硝基苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体27.6mg，产率15％。1H NMR(400MHz,Chloroform-d)δ8.37(d,J＝1.6Hz,1H),8.04–7.90(m,2H),7.83(d,J＝8.2Hz,1H),7.53–7.43(m,1H),7.39–7.30(m,3H),7.23–7.15(m,2H),7.10(d,J＝4.4Hz,2H),6.98(d,J＝5.2Hz,1H),4.46(q,J＝7.1Hz,2H),4.30–3.11(m,7H),3.05–2.68(m,8H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,162.2,150.4,144.2,140.9,140.0,137.2,133.7,133.3,132.5,132.0,130.6,130.2,130.0,129.6,127.9,127.2,124.9,124.8,124.7,123.7,123.6,122.7,109.7,61.7,50.0,32.9,14.3,13.2.
实施例305
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-苯基丙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-175)
Figure BDA0003601498440002181
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为((3-溴噻吩-2-基)(4-(2-((3-苯基丙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体62.5mg，产率30％。1H NMR(400MHz,Chloroform-d)δ8.28(s,1H),8.01–7.80(m,2H),7.42–7.31(m,2H),7.23–6.90(m,9H),4.45(q,J＝7.1Hz,2H),3.90–3.02(m,8H),2.89–2.61(m,5H),2.62–2.38(m,2H),1.46(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.8,162.1,150.8,144.0,140.7,139.9,137.3,134.2,132.0,130.4,130.2,129.9,129.4,128.4,128.1,127.2,126.1,124.9,124.8,123.7,123.5,122.8,109.6,61.6,49.4,32.8,29.4,14.4,13.2.
实施例306
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-176)
Figure BDA0003601498440002191
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(4-(2-氨基苯基)哌嗪-1-基)(3-溴噻吩-2-基)甲酮，其余条件均一致。得到白色固体180.0mg，产率93％。1H NMR(400MHz,Chloroform-d)δ8.31(d,J＝1.4Hz,1H),8.03(s,1H),7.91–7.81(m,2H),7.66(d,J＝8.1Hz,1H),7.38(d,J＝5.2Hz,1H),7.21–6.92(m,4H),4.42(p,J＝7.1Hz,2H),3.92–3.24(m,4H),2.80–2.68(m,3H),2.53(t,J＝5.1Hz,4H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.6,162.2,144.4,141.4,140.6,139.8,136.0,132.9,131.7,130.3,130.1,127.6,126.7,125.0,123.9,123.5,123.0,122.1,119.4,109.,61.7,52.6,14.3,13.1.
实施例307
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-(4-甲氧基苯乙基)氨磺酰基)3-甲基苯并噻吩-2-羧酸乙酯(M10-177)
Figure BDA0003601498440002192
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((4-甲氧基苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体112.3mg，产率31％。1H NMR(400MHz,Chloroform-d)δ8.25(d,J＝1.7Hz,1H),7.90(d,J＝8.6Hz,1H),7.83(dd,J＝8.5,1.7Hz,1H),7.39–7.30(m,2H),7.20(dd,J＝8.2,1.5Hz,1H),7.08(td,J＝7.6,1.5Hz,1H),7.03–6.93(m,2H),6.87–6.81(m,2H),6.70–6.64(m,2H),4.42(q,J＝7.1Hz,2H),4.20–3.75(m,3H),3.71(s,3H),3.42(d,J＝122.1Hz,5H),2.90(s,2H),2.75(s,3H),2.69–2.40(m,2H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ162.8,162.2,158.2,150.9,144.0,140.8,139.9,137.1,134.1,132.1,130.5,130.2,130.0,129.9,129.5,129.4,127.3,125.0,124.7,123.7,123.4,122.8,113.9,109.7,61.6,55.2,51.7,33.7,29.7,14.4,13.2,1.1.HRMS(ESI)[M+H]+理论值C36H37N3O6S3 Br:782.1028；实测值：782.1033.
实施例308
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-(3-甲氧基苯乙基)氨磺酰基)3-甲基苯并噻吩-2-羧酸乙酯(M10-178)
Figure BDA0003601498440002201
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((3-甲氧基苯乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体81.0mg，产率36％。1H NMR(400MHz,Chloroform-d)δ8.26(d,J＝1.8Hz,1H),7.91(d,J＝8.5Hz,1H),7.83(dd,J＝8.5,1.8Hz,1H),7.40–7.31(m,2H),7.20(dd,J＝8.1,1.4Hz,1H),7.12–6.91(m,4H),6.64(dd,J＝8.5,2.9Hz,1H),6.58–6.46(m,2H),4.43(q,J＝7.1Hz,2H),4.18–3.74(m,3H),3.70(s,3H),3.66–2.81(m,7H),2.76(s,3H),2.60(dt,J＝35.8,8.0Hz,2H),1.43(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ162.8,162.3,159.7,151.0,144.2,141.0,139.9,139.7,137.1,134.2,132.1,130.5,130.3,129.9,129.6,129.6,127.3,125.0,124.8,123.8,123.5,122.9,120.8,114.6,111.5,109.7,61.7,55.2,51.5,34.7,14.4,13.3.HRMS(ESI)[M+H]+理论值C36H37N3O6S3 Br:782.1028；实测值：782.1046.
实施例309
3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)
Figure BDA0003601498440002211
将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(170mg，0.26mmol)溶于乙醇(3mL)与水(1mL)的混合溶剂中，加入NaOH(31mg，0.78mmol)，回流搅拌至TLC检测原料消失。减压浓缩除去体系中的乙醇，向体系中加5mL水，滴加1M稀盐酸至pH为酸性并快速搅拌10min，期间有固体析出。用抽滤漏斗抽滤并用水洗涤，得到白色固体168.6mg，产率100％。1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.96–7.79(m,2H),7.43–7.20(m,6H),7.18–7.05(m,5H),6.98(d,J＝7.1Hz,2H),4.17–2.54(m,15H),2.35(s,3H).13C NMR(101MHz,DMSO-d6)δ169.1,160.7,155.1,150.4,143.6,139.2,138.2,135.4,133.2,132.8,130.8,129.3,129.2,129.1,128.8,128.5,128.2,127.0,126.6,126.2,124.3,122.8,121.8,113.0,50.3,34.0,20.9,9.0.HRMS(ESI)[M+H]+理论值C36H34N3O6S:636.2174；实测值：636.2170.
实施例310
3-甲基-5-(N-(2-(4-(2-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S107)
Figure BDA0003601498440002212
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(4-(2-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体99.5mg，产率87％。1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),7.96–7.74(m,2H),7.43–7.21(m,5H),7.17–7.04(m,6H),6.97(d,J＝7.1Hz,2H),4.14–2.53(m,15H),2.21(s,3H).13C NMR(101MHz,DMSO-d6)δ169.0,161.3,155.5,150.8,138.6,136.7,135.7,134.0,133.7,131.3,130.6,129.7,129.6,129.1,128.9,128.7,126.9,126.6,126.2,126.1,124.8,124.4,123.2,122.2,113.4,52.7,51.4(d,J＝122.5Hz),41.7,34.4,19.0,9.5.HRMS(ESI)[M+H]+理论值C36H34N3O6S:636.2174；实测值：636.2155.
实施例311
3-甲基-5-(N-(2-(4-(3-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S108)
Figure BDA0003601498440002221
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(4-(3-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体50.3mg，产率44％。1H NMR(400MHz,DMSO-d6)δ13.73(s,1H),8.25(s,1H),7.94–7.81(m,2H),7.40–7.23(m,4H),7.21–7.04(m,7H),6.97(s,2H),4.14–2.53(m,15H),2.34(s,3H).13C NMR(101MHz,DMSO-d6)δ169.6,161.1,155.6,150.9,143.8,138.6,138.3,136.3,135.9,133.7,131.2,130.5,129.6,128.9,128.7,127.8,127.1,126.6,125.2,124.8,124.3,123.2,122.3,113.5,50.8,34.4,21.4,9.5.HRMS(ESI)[M+H]+理论值C36H34N3O6S:636.2174；实测值：636.2163.
实施例312
5-(N-(2-(4-(4-乙酰氨基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S109)
Figure BDA0003601498440002231
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-乙酰氨基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体127.6mg，产率100％。1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),7.88(q,J＝8.7Hz,2H),7.65(d,J＝8.0Hz,2H),7.44–7.25(m,4H),7.19–6.90(m,7H),4.16–2.51(m,15H),2.07(s,3H).13C NMR(101MHz,DMSO-d6)δ169.4,169.1,161.2,155.6,151.0,141.0,138.6,135.7,133.7,131.0,130.4,129.7,128.9,128.7,128.5,127.0,126.6,124.8,123.3,122.3,118.9,113.5,110.0,52.3,50.8,34.3,24.5,9.5.
实施例313
3-甲基-5-(N-苯乙基-N-(2-(4-(4-(三氟甲基)苯甲酰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S110)
Figure BDA0003601498440002232
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-苯乙基-N-(2-(4-(4-(三氟甲基)苯甲酰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体127.6mg，产率100％。1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.87(dd,J＝24.6,9.0Hz,4H),7.66(d,J＝7.9Hz,2H),7.38(t,J＝7.4Hz,1H),7.29(d,J＝7.7Hz,1H),7.21–7.02(m,5H),6.98(d,J＝7.1Hz,2H),4.21–2.69(m,10H),2.59(s,4H).13CNMR(101MHz,DMSO-d6)δ168.1,161.3,155.6,150.9,144.37,140.43,138.59,135.70,133.83,131.02,129.68,129.65,128.89,128.66,128.22,127.0,126.6,125.9,125.9,124.8,124.7,123.2,122.3,113.5,50.9,34.3,9.5.HRMS(ESI)[M+H]+理论值C36H31F3N3O6S:690.1891；实测值：690.1889.
实施例314
5-(N-(2-(4-(4-氰基苯基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S111)
Figure BDA0003601498440002241
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-氰基苯基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体54.4mg，产率56％。1H NMR(400MHz,DMSO-d6)δ8.19(s,1H),7.95(d,J＝8.2Hz,2H),7.84(d,J＝5.3Hz,2H),7.48(d,J＝8.0Hz,2H),7.31(dd,J＝30.1,7.1Hz,2H),7.18–7.00(m,5H),6.97(d,J＝7.1Hz,2H),4.14–2.66(m,13H),2.58(s,4H).13C NMR(101MHz,DMSO-d6)δ168.8,167.8,162.1,155.3,150.9,138.9,138.6,137.9,135.6,135.3,133.8,133.0,131.1,130.1,129.6,128.9,128.7,128.1,127.3,126.6,126.3,124.8,123.3,121.9,113.3,50.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C36H33N4O7S:665.2075；实测值：665.2065.
实施例315
5-(N-(2-(4-(4-氟苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S112)
Figure BDA0003601498440002251
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-氟苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体67.1mg，产率65％。1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.88(q,J＝8.6Hz,2H),7.57–7.43(m,2H),7.42–7.21(m,4H),7.20–7.03(m,5H),6.98(d,J＝6.9Hz,2H),4.13–2.69(m,11H),2.58(s,4H).13C NMR(101MHz,DMSO-d6)δ168.6,163.0(d,J＝246.6Hz),161.4,155.5,150.9,144.7,138.6,135.7,133.8,132.7,131.2,130.0(d,J＝8.4Hz),129.7(d,J＝12.0Hz),128.9,128.7,126.9,126.6,124.8,124.3,123.2,122.2,115.9,115.7,113.5,50.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C35H31FN3O6S:640.1923；实测值：640.1909.
实施例316
5-(N-(2-(4-(4-((叔丁氧基羰基)氨基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯(F27-S113)
Figure BDA0003601498440002252
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-((叔丁氧基羰基)氨基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体83.7mg，产率72％。1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),8.23(d,J＝1.8Hz,1H),8.00–7.77(m,2H),7.55(d,J＝8.2Hz,2H),7.40–7.31(m,3H),7.28(d,J＝8.0Hz,1H),7.12(ddd,J＝12.7,8.2,4.3Hz,4H),7.03(dd,J＝7.9,1.5Hz,1H),6.99–6.94(m,2H),4.15–2.70(m,12H),2.59(s,3H),1.49(s,9H).13C NMR(101MHz,DMSO-d6)δ169.4,161.5,155.5,153.1,151.0,141.3,138.6,135.6,133.8,130.9,129.8,129.6,129.4,128.9,128.7,128.6,126.7,126.6,124.7,123.2,122.2,117.9,113.4,110.0,79.8,52.3,50.8,34.3,28.5,9.5.HRMS(ESI)[M+H]+理论值C40H41N4O8S:737.2651；实测值：737.2644.
实施例317
3-甲基-5-(N-(2-(4-(4-硝基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S114)
Figure BDA0003601498440002261
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(4-(4-硝基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体29.3mg，产率53％。1H NMR(400MHz,DMSO-d6)δ9.38(s,1H),8.31(t,J＝9.0Hz,1H),8.23(s,1H),8.21–8.14(m,1H),7.92–7.84(m,2H),7.71(d,J＝8.6Hz,1H),7.45–7.32(m,1H),7.33–7.23(m,1H),7.19–6.92(m,7H),4.20–2.70(m,11H),2.63–2.54(m,4H).13CNMR(101MHz,DMSO-d6)δ167.6,161.4,155.6,150.9,150.6,148.3,142.7,138.5,135.3,134.1,133.8,131.1,129.9,129.8,128.9,128.7,126.9,126.6,125.3,124.2,124.1,123.2,122.4,113.5,51.1,49.2,43.8,34.2,9.5.HRMS(ESI)[M+H]+理论值C35H31N4O8S:667.1868；实测值：667.1864.
实施例318
5-(N-(2-(4-(4-乙酰苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S115)
Figure BDA0003601498440002271
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-乙酰苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体66.4mg，产率82％。1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.23(s,1H),8.11–7.98(m,2H),7.86(t,J＝7.7Hz,2H),7.56(d,J＝8.2Hz,1H),7.44–7.34(m,1H),7.29(t,J＝6.6Hz,1H),7.19–6.92(m,7H),4.17–2.69(m,11H),2.66–2.58(m,4H).13C NMR(101MHz,DMSO-d6)δ197.9,168.6,161.8,155.4,150.9,140.6,138.6,138.5,137.7,135.5,135.4,134.1,133.8,131.1,129.9,129.6,128.9,128.8,128.7,127.6,126.6,124.8,123.2,122.1,113.4,50.8,49.3,43.7,34.4,27.3,9.5.HRMS(ESI)[M+H]+理论值C37H34N3O7S:664.2123；实测值：664.2110.
实施例319
3-甲基-5-(N-(2-(4-烟酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S116)
Figure BDA0003601498440002281
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(4-烟酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体37.2mg，产率54％。1H NMR(400MHz,DMSO-d6)δ8.74–8.60(m,1H),8.20(s,1H),7.94–7.78(m,3H),7.54–7.45(m,1H),7.42–7.25(m,2H),7.21–6.80(m,8H),4.19–2.69(m,11H),2.65–2.51(m,4H).13C NMR(101MHz,DMSO-d6)δ167.3,161.,155.4,150.9,148.1,145.9,138.6,135.5,135.2,133.8,132.1,131.1,131.0,129.9,129.6,128.9,128.7,126.6,126.5,124.8,123.9,123.2,122.0,113.3,52.2,50.8,49.4,34.4,9.5.HRMS(ESI)[M+H]+理论值C34H31N4O6S:623.1970；实测值：623.1971.
实施例320
3-甲基-5-(N-苯乙基-N-(2-(4-吡啶甲酰基哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S117)
Figure BDA0003601498440002282
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-苯乙基-N-(2-(4-吡啶甲酰基哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体47.1mg，产率71％。1H NMR(400MHz,DMSO-d6)δ8.60(d,J＝4.6Hz,1H),8.26(s,1H),8.04–7.80(m,3H),7.59(d,J＝7.8Hz,1H),7.49(dd,J＝7.5,4.9Hz,1H),7.36(t,J＝6.8Hz,1H),7.27(d,J＝7.2Hz,1H),7.21–7.03(m,5H),6.98(d,J＝6.9Hz,2H),4.21–2.65(m,11H),2.64–2.55(m,4H).13C NMR(101MHz,DMSO-d6)δ167.2,161.2,155.6,154.3,150.8,148.8,144.2,139.1,138.6,137.8,135.8,133.7,131.3,129.6(d,J＝3.8Hz),128.9,128.7,127.0,126.6,125.3,125.0,124.8,123.6,123.2,122.3,113.5,52.3(d,J＝81.1Hz),50.7,44.9(d,J＝511.4Hz),34.4,9.5.HRMS(ESI)[M+H]+理论值C34H31N4O6S:623.1970；实测值：623.1961.
实施例321
3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S118)
Figure BDA0003601498440002291
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体10.6mg，产率40％。1H NMR(400MHz,DMSO-d6)δ8.20(d,J＝14.9Hz,1H),7.86(td,J＝8.8,5.7Hz,2H),7.76(d,J＝5.0Hz,1H),7.37(dd,J＝14.1,5.8Hz,2H),7.27(d,J＝7.8Hz,1H),7.21–6.94(m,8H),4.22–3.50(m,7H),3.09–2.69(m,4H),2.57(s,4H).13C NMR(101MHz,DMSO-d6)δ168.1,162.8,155.5,150.8,145.5,138.6,137.5,135.6,133.8,132.0,131.2,129.9,129.6,129.6,128.9,128.7,127.5,126.6,124.8,123.2,122.1,113.4,110.0,52.3,50.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H30N3O6S2:628.1582；实测值：628.1580.
实施例322
3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-3-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S119)
Figure BDA0003601498440002301
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-苯乙基-N-(2-(4-(噻吩-3-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体28.0mg，产率42％。1H NMR(400MHz,DMSO-d6)δ8.22(d,J＝1.8Hz,1H),7.94–7.82(m,2H),7.79(d,J＝2.8Hz,1H),7.62(dd,J＝5.0,2.9Hz,1H),7.42–7.32(m,1H),7.27(d,J＝8.0Hz,1H),7.21(d,J＝5.0Hz,1H),7.19–7.02(m,5H),7.02–6.94(m,2H),4.15–2.70(m,11H),2.58(d,J＝3.5Hz,4H).13C NMR(101MHz,DMSO-d6)δ165.0,161.6,155.5,150.9,138.6,136.7,135.6,133.8,131.1,129.9,128.9,128.7,127.8,127.3,127.0,126.6,124.8,123.6,123.2,122.1,113.4,103.5,52.5,50.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H30N3O6S2:628.1582；实测值：628.1579.
实施例323
(E)-5-(N-(2-(4-(但-2-烯酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S120)
Figure BDA0003601498440002302
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为(E)-5-(N-(2-(4-(但-2-烯酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体41.5mg，产率46％。1H NMR(400MHz,DMSO-d6)δ8.25(s,1H),7.89(q,J＝8.8Hz,2H),7.36(t,J＝7.7Hz,1H),7.25(d,J＝8.0Hz,1H),7.12(dd,J＝13.0,7.0Hz,4H),7.03(d,J＝7.9Hz,1H),6.97(d,J＝7.3Hz,2H),6.70(dd,J＝14.6,7.0Hz,1H),6.52(d,J＝15.0Hz,1H),4.16–3.54(m,6H),3.20–2.67(m,5H),2.59(s,4H),1.85(d,J＝6.5Hz,3H).13C NMR(101MHz,DMSO-d6)δ164.8,161.4,155.5,151.0,141.2,138.6,135.8,133.8,131.1,129.7,129.6,128.9,128.7,126.8,126.6,124.8,124.7,124.3,123.2,122.4,122.3,113.5,52.9,50.8,34.3,18.2,9.5.HRMS(ESI)[M+H]+理论值C32H32N3O6S:586.2017；实测值：586.2007.
实施例324
5-(N-(2-(4-(呋喃-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S121)
Figure BDA0003601498440002311
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(呋喃-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体87.2mg，产率85％。1H NMR(400MHz,DMSO-d6)δ8.20(d,J＝12.6Hz,1H),7.89–7.80(m,2H),7.44–7.32(m,1H),7.30–7.24(m,1H),7.19–6.95(m,8H),6.63(dd,J＝3.4,1.7Hz,1H),4.15–3.52(m,6H),3.19–2.72(m,5H),2.64–2.54(m,4H).13C NMR(101MHz,DMSO-d6)δ167.3,158.8,155.4,150.8,147.4,145.2,138.6,138.6,134.1,133.7,131.2,130.0,129.6,128.9,128.7,126.7,126.6,124.8,123.2,122.0,122.0,116.1,113.3,111.7,50.8,49.3,43.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H30N3O7S:612.1810；实测值：612.1808.
实施例325
5-(N-(2-(4-(环戊烷羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S122)
Figure BDA0003601498440002321
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(环戊烷羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体80.7mg，产率82％。1H NMR(400MHz,DMSO-d6)δ13.75(s,1H),δ8.28(s,1H),7.99–7.83(m,2H),7.36(t,J＝7.6Hz,1H),7.25(d,J＝9.0Hz,1H),7.19–7.02(m,5H),6.97(d,J＝6.7Hz,2H),4.20–3.24(m,6H),3.10–2.65(m,6H),2.60(s,4H),1.79–1.43(m,8H).13C NMR(101MHz,DMSO-d6)δ173.9,161.1,155.6,151.0,143.9,138.6,136.0,133.7,131.2,129.6,128.9,128.7,127.1,126.6,125.2,124.7,123.1,122.4,113.5,52.5(d,J＝87.1Hz),50.7,45.8,42.1,34.4,30.0,26.1,9.5.HRMS(ESI)[M+H]+理论值C34H36N3O6S:614.2330；实测值：614.2326.
实施例326
5-(N-(2-(4-(5-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S123)
Figure BDA0003601498440002322
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(5-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体83.3mg，产率74％。1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),7.88(q,J＝9.3,8.7Hz,2H),7.36(t,J＝7.4Hz,1H),7.30–7.23(m,3H),7.19–6.93(m,9H),4.15–3.52(m,7H),3.16–2.73(m,4H),2.67–2.54(m,4H).13C NMR(101MHz,DMSO-d6)δ161.5,161.4,155.5,150.9,139.7,138.6,135.7,133.8,131.1,131.0,130.6,129.8,129.7,128.9,128.7,126.8,126.6,124.8,124.1,123.3,122.2,116.1,113.5,52.2,50.9,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H29BrN3O6S2:706.0687；实测值：706.0677.
实施例327
5-(N-(2-(4-(1H-吡咯-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S124)
Figure BDA0003601498440002331
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(1H-吡咯-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体58.6mg，产率48％。1H NMR(400MHz,DMSO-d6)δ11.47(s,1H),8.19(s,1H),7.85(q,J＝8.8Hz,2H),7.35(t,J＝6.9Hz,1H),7.25(d,J＝7.9Hz,1H),7.20–6.93(m,7H),6.89(s,1H),6.42(s,1H),6.12(s,1H),4.17–3.50(m,7H),3.10–2.69(m,4H),2.64–2.52(m,4H).13C NMR(101MHz,DMSO-d6)δ162.1,161.9,155.3,150.9,138.7,135.4,133.7,131.2,130.2,129.6,128.9,128.7,126.6,126.1,124.6,124.6,123.1,121.8,121.6,113.2,112.3,108.8,52.4,50.7,45.2,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H31N4O6S:611.1970；实测值：611.1971.
实施例328
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S125)
Figure BDA0003601498440002341
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体74.1mg，产率80％。1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.86(q,J＝9.5,8.8Hz,2H),7.79(d,J＝5.2Hz,1H),7.36(t,J＝7.6Hz,1H),7.26(d,J＝7.7Hz,1H),7.11(ddt,J＝18.4,12.7,6.4Hz,6H),6.98(d,J＝7.0Hz,2H),4.10–3.77(m,4H),3.62–2.68(m,9H),2.62–2.52(m,4H).13C NMR(101MHz,DMSO-d6)δ161.6,161.4,155.5,150.7,138.6,135.7,133.7,132.4,131.3,130.3,129.7,129.7,129.3,128.9,128.7,126.9,126.6,124.8,123.2,122.2,113.4,110.0,109.2,50.8,34.4,9.5.HRMS(ESI)[M+H]+理论值C33H29BrN3O6S2:706.0687；实测值：706.0686.
实施例329
5-(N-(2-(4-(3-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S126)
Figure BDA0003601498440002342
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体69.6mg，产率75％。1H NMR(400MHz,DMSO-d6)δ8.19(d,J＝5.2Hz,1H),7.89–7.77(m,3H),7.44–7.32(m,1H),7.27(t,J＝8.1Hz,1H),7.18–6.91(m,8H),4.13–2.71(m,11H),2.66–2.53(m,4H).13C NMR(101MHz,DMSO-d6)δ161.9,161.0,155.4,150.7,150.6,138.6,138.6,135.4,135.0,134.1,133.8,131.2,130.4,130.1,130.0,129.8,129.6,128.9,128.7,127.9,126.6,126.4,125.3,124.8,123.2,121.9,50.9(d,J＝26.3Hz),49.4,43.7,34.3(d,J＝11.4Hz),9.5.HRMS(ESI)[M+H]+理论值C33H29ClN3O6S2:662.1192；实测值：662.1185.
实施例330
5-(N-(2-(4-(4-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S127)
Figure BDA0003601498440002351
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体65.3mg，产率71％。1H NMR(400MHz,DMSO-d6)δ8.20(d,J＝7.7Hz,1H),7.87(dd,J＝17.3,6.4Hz,3H),7.49(s,1H),7.42–7.32(m,1H),7.28(d,J＝7.7Hz,1H),7.12(dt,J＝12.6,7.1Hz,4H),7.04(d,J＝7.1Hz,1H),6.98(d,J＝6.9Hz,2H),4.22–2.75(m,11H),2.66–2.53(m,4H).13C NMR(101MHz,DMSO-d6)δ161.8,161.4,155.4,151.0,150.6,139.1,138.6,138.6,135.4,135.1,134.1,133.9,131.3,130.9,129.9,129.6,128.9,128.7,128.7,127.7,126.6,126.6,126.4,124.8,123.2,122.1,113.4,108.8,52.2,50.9,49.4,43.8,34.3,34.24,9.5.HRMS(ESI)[M+H]+理论值C33H29BrN3O6S2:706.0687；实测值：706.0675.
实施例331
5-(N-(2-(4-(5-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S128)
Figure BDA0003601498440002361
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(5-氯噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体65.2mg，产率67％。1H NMR(400MHz,DMSO-d6)δ8.18(d,J＝7.1Hz,1H),7.84(d,J＝9.1Hz,2H),7.50–7.22(m,3H),7.13(dq,J＝12.2,7.1,5.1Hz,5H),7.08–7.00(m,1H),6.98(t,J＝5.7Hz,2H),4.16–3.49(m,4H),3.33–2.95(m,6H),2.87–2.73(m,1H),2.67–2.53(m,4H).13C NMR(101MHz,DMSO-d6)δ162.2,161.3,155.3,150.7(d,J＝23.0Hz),138.6(d,J＝6.8Hz),137.0,135.3,134.9,134.1,133.8,132.4,131.0,130.2,129.8,129.6,128.9,128.7,127.6,126.6,126.2,125.3,123.1,121.9,113.2,51.0(d,J＝18.5Hz),49.4,43.7,34.3(d,J＝15.0Hz),9.5.HRMS(ESI)[M+H]+理论值C33H29ClN3O6S2:662.1192；实测值：662.1184.
实施例332
3-甲基-5-(N-苯乙基-N-(2-(4-(噻唑-5-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S129)
Figure BDA0003601498440002362
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-苯乙基-N-(2-(4-(噻唑-5-羰基)哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体63.8mg，产率58％。1H NMR(400MHz,DMSO-d6)δ9.25(s,1H),8.21(d,J＝4.0Hz,1H),7.92–7.81(m,2H),7.43–7.33(m,1H),7.28(d,J＝8.0Hz,1H),7.18–7.07(m,4H),7.03(t,J＝7.3Hz,1H),6.97(d,J＝6.6Hz,2H),4.13–3.58(m,4H),3.35–2.97(m,6H),2.84(s,1H),2.65–2.54(m,4H).13C NMR(101MHz,DMSO-d6)δ161.7(d,J＝6.3Hz),161.0,157.1,155.5,150.6,144.2,138.6,135.5,135.2,134.1,133.8,132.8,130.9,130.0,129.9,129.7,128.9,128.7,128.7,126.6,125.3,123.2,122.2,113.4,51.0,49.3,43.7,34.2,9.5.HRMS(ESI)[M+H]+理论值C32H29N4O6S2:629.1534；实测值：629.1536.
实施例333
5-(N-(2-(4-(1H-吡唑-3-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S130)
Figure BDA0003601498440002371
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(1H-吡唑-3-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体49.8mg，产率61％。1H NMR(400MHz,DMSO-d6)δ8.28–8.22(m,1H),7.96–7.82(m,2H),7.78(d,J＝1.9Hz,1H),7.35(t,J＝7.6Hz,1H),7.27(d,J＝7.9Hz,1H),7.18–7.01(m,5H),6.97(d,J＝6.8Hz,2H),6.58(d,J＝2.3Hz,1H),4.17–3.49(m,7H),3.18–3.00(m,2H),2.88–2.72(m,2H),2.64–2.53(m,4H).13C NMR(101MHz,DMSO-d6)δ162.5,161.3,155.6,151.0,144.4,138.6,135.8,133.7,131.1,129.7,129.6,128.9,128.7,126.9,126.6,124.7,124.6,123.2,122.3,113.5,107.5,50.7,34.3,9.5.HRMS(ESI)[M+H]+理论值C32H30N5O6S:612.1922；实测值：612.1919.
实施例334
3-甲基-5-(N-(2-(4-(恶唑-5-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S131)
Figure BDA0003601498440002381
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为3-甲基-5-(N-(2-(4-(恶唑-5-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体60.0mg，产率91％。1H NMR(400MHz,DMSO-d6)δ8.57(s,1H),8.20(d,J＝7.3Hz,1H),7.86(q,J＝9.7,9.1Hz,2H),7.73(s,1H),7.45–7.32(m,1H),7.30–7.23(m,1H),7.17–6.88(m,7H),4.16–2.92(m,10H),2.87–2.69(m,1H),2.65–2.53(m,4H).13C NMR(101MHz,DMSO-d6)δ161.8,160.3,157.3,155.4,153.6,150.9,150.6,138.6,138.6,135.4,135.1,134.1,133.9,133.9,130.9,128.9,128.7,126.6,126.4,122.0,113.3,49.4,43.8,34.3,9.5.HRMS(ESI)[M+H]+理论值C32H29N4O7S:613.1762；实测值：613.1752.
实施例335
5-(N-(2-(4-(3,4-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S132)
Figure BDA0003601498440002382
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3,4-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体58.1mg，产率59％。1H NMR(400MHz,DMSO-d6)δ8.22(d,J＝1.8Hz,1H),7.92–7.81(m,2H),7.41–7.30(m,1H),7.26(dd,J＝8.1,1.5Hz,1H),7.22–7.02(m,8H),7.00–6.94(m,2H),4.26–3.40(m,6H),3.26–2.57(m,6H),2.56(s,3H),2.25(s,6H).13C NMR(101MHz,DMSO-d6)δ169.2,161.0,155.1,150.4,138.2,137.9,136.4,135.2,133.2,130.8,129.3,129.2,129.1,128.5,128.2,128.1,126.4,126.2,124.4,124.3,122.8,121.7,113.0,50.3,33.9,19.3,9.0.HRMS(ESI)[M+H]+理论值C37H36N3O6S:650.2325；实测值：650.2327.
实施例336
5-(N-(2-(4-(2,6-二甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S133)
Figure BDA0003601498440002391
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2,6-二甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体36.4mg，产率69％。1H NMR(400MHz,DMSO-d6)δ8.24(d,J＝1.8Hz,1H),7.92–7.80(m,2H),7.41–7.26(m,2H),7.22(d,J＝8.0Hz,1H),7.17–6.99(m,5H),6.96(d,J＝7.2Hz,2H),6.67(d,J＝8.4Hz,2H),4.23–3.60(m,10H),3.17–2.67(m,6H),2.64–2.51(m,5H).13C NMR(101MHz,DMSO)δ163.9,160.7,156.0,155.1,150.3,138.2,135.3,133.0,130.9,130.3,129.1,128.4,128.2,126.6,126.1,124.6,124.1,122.5,121.8,113.9,113.0,104.1,55.7,52.4,51.4,50.1,46.2,41.1,33.9,9.0.HRMS(ESI)[M+H]+理论值C37H36N3O8S:682.2223；实测值：682.2219.
实施例337
5-(N-(2-(4-(2-苄基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S134)
Figure BDA0003601498440002392
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2-苄基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体38.3mg，产率80％。1H NMR(400MHz,DMSO-d6)δ8.05(d,J＝22.4Hz,1H),7.85–7.67(m,2H),7.42–7.24(m,4H),7.20–7.03(m,11H),6.93(d,J＝29.9Hz,3H),4.07–3.25(m,11H),3.15–2.50(m,6H).13C NMR(101MHz,DMSO)δ168.5,154.4,140.2,138.2,138.0,135.9,130.6,130.5,129.0,128.9,128.4,128.3,128.2,126.2,126.0,124.5,120.5,112.3,46.5,41.0,34.0,9.0.HRMS(ESI)[M+H]+理论值C42H38N3O6S:712.2481；实测值：712.2490.
实施例338
5-(N-(2-(4-(2,4,6-三甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S135)
Figure BDA0003601498440002401
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2-苄基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体39.1mg，产率74％。1H NMR(400MHz,DMSO-d6)δ8.20(d,J＝1.8Hz,1H),7.88–7.77(m,2H),7.34(td,J＝7.6,7.1,1.7Hz,1H),7.25(dd,J＝8.1,1.6Hz,1H),7.18–7.02(m,5H),6.99–6.93(m,2H),6.87(s,2H),4.10–3.49(m,5H),3.18–2.51(m,10H),2.24(s,3H),2.10(s,6H).13C NMR(101MHz,DMSO)δ168.3,154.9,150.4,138.2,137.3,135.1,133.3,133.3,132.9,130.9,129.5,129.2,128.4,128.2,127.9,126.1,124.4,122.7,121.5,112.8,52.5,51.6,50.4,45.7,40.8,33.9,20.6,18.6,9.0.HRMS(ESI)[M+H]+理论值C38H38N3O6S:664.2481；实测值：664.2471.
实施例339
5-(N-(2-(4-(2-甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S136)
Figure BDA0003601498440002411
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2-甲氧基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体46.2mg，产率73％。1H NMR(400MHz,DMSO-d6)δ8.23(d,J＝1.9Hz,1H),7.92–7.80(m,2H),7.43–7.30(m,2H),7.24(d,J＝8.0Hz,1H),7.20–7.03(m,7H),6.98(q,J＝7.2Hz,3H),4.13–3.83(m,2H),3.81–3.33(m,7H),2.93–2.51(m,8H).13C NMR(101MHz,DMSO)δ166.5,160.8,155.1,154.8,150.4,138.2,135.3,133.1,130.9,130.4,129.2,128.4,128.2,127.6,126.5,126.1,125.5,124.2,121.8,120.6,113.0,111.3,55.4,51.4,50.2,41.4,33.9,9.0.HRMS(ESI)[M+H]+理论值C36H34N3O7S:652.2117；实测值：652.2118.
实施例340
5-(N-(2-(4-(2,5-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S137)
Figure BDA0003601498440002412
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2,5-二甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体18.3mg，产率79％。1H NMR(400MHz,DMSO-d6)δ8.03(d,J＝1.9Hz,1H),7.81–7.69(m,2H),7.38–7.30(m,1H),7.28–7.21(m,1H),7.12(dq,J＝13.8,7.6,7.0Hz,6H),7.05–6.88(m,4H),4.24–3.49(m,4H),3.36–2.53(m,11H),2.28(s,3H),2.16(s,3H).13CNMR(101MHz,DMSO)δ168.7,154.3,150.4,138.2,136.2,134.9,134.0,130.4,130.0,129.2,129.0,128.4,128.2,126.2,126.1,124.1,120.5,112.2,52.0,51.6,50.0,46.6,41.2,33.8,20.4,18.1,9.0.HRMS(ESI)[M+H]+理论值C37H36N3O6S:650.2325；实测值：650.2325.
实施例341
5-(N-(2-(4-(4-(苯乙炔基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S138)
Figure BDA0003601498440002421
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-(苯乙炔基)苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体82.3mg，产率70％。1H NMR(400MHz,DMSO-d6)δ8.20(d,J＝1.9Hz,1H),7.91–7.79(m,2H),7.69–7.54(m,4H),7.50–7.40(m,5H),7.35(td,J＝7.7,1.6Hz,1H),7.27(dd,J＝8.2,1.5Hz,1H),7.17–6.93(m,7H),4.29–3.72(m,3H),3.69–3.27(m,4H),3.25–2.53(m,8H).13C NMR(101MHz,DMSO)δ168.3,154.9,150.5,138.1,135.8,135.0,133.4,131.5,131.4,130.5,129.6,129.2,129.0,128.8,128.4,128.2,127.5,126.2,125.9,124.3,123.4,122.8,122.0,121.5,112.8,90.5,88.7,50.4,33.9,9.0.HRMS(ESI)[M+H]+理论值C43H36N3O6S:722.2325；实测值：722.2310.
实施例342
5-(N-(2-(4-(5-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S139)
Figure BDA0003601498440002431
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(5-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体76.0mg，产率83％。1H NMR(400MHz,DMSO-d6)δ8.24(d,J＝1.9Hz,1H),7.93–7.82(m,2H),7.51–6.89(m,10H),6.81(d,J＝3.6Hz,1H),3.97(d,J＝74.9Hz,2H),3.62(d,J＝30.4Hz,4H),3.37–2.52(m,9H),2.46(s,3H).13C NMR(101MHz,DMSO)δ162.2,160.9,155.1,150.4,143.4,138.2,135.3,134.6,133.3,130.8,129.5,129.3,129.1,128.4,128.2,126.4,126.2,125.5,124.3,122.8,121.7,113.0,51.9,50.3,34.0,14.9,9.0.HRMS(ESI)[M+H]+理论值C34H32N3O6S2:642.1733；实测值：642.1740.
实施例343
5-(N-(2-(4-(4-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S140)
Figure BDA0003601498440002432
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(4-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体57.3mg，产率77％。1H NMR(400MHz,DMSO-d6)δ8.21(d,J＝1.9Hz,1H),7.92–7.81(m,2H),7.50–7.01(m,10H),6.98(d,J＝7.3Hz,2H),4.15–3.49(m,7H),3.06(s,2H),2.79(s,2H),2.57(s,4H),2.24(s,3H).13C NMR(101MHz,DMSO)δ162.3,155.0,150.4,138.2,137.1,136.7,135.1,133.3,131.1,130.6,129.4,129.2,128.4,128.2,126.2,124.6,124.3,122.8,121.6,112.9,51.9,50.4,33.9,15.3,9.0.HRMS(ESI)[M+H]+理论值C34H32N3O6S2:642.1733；实测值：642.1736.
实施例344
5-(N-(2-(4-(3-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S141)
Figure BDA0003601498440002441
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-甲基噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体78.4mg，产率68％。1H NMR(400MHz,DMSO-d6)δ8.23(d,J＝1.8Hz,1H),7.91–7.80(m,2H),7.56(d,J＝5.0Hz,1H),7.39–7.31(m,1H),7.26(dd,J＝8.1,1.5Hz,1H),7.19–7.02(m,5H),7.01–6.95(m,2H),6.92(d,J＝5.0Hz,1H),4.27–3.20(m,7H),3.06–2.54(s,8H),2.17(s,3H).13C NMR(101MHz,DMSO)δ163.4,160.9,155.1,150.3,138.2,136.5,135.2,133.2,130.8,130.2,129.7,129.3,129.1,128.4,128.2,126.5,126.4,126.1,124.3,122.8,121.7,112.9,51.9,50.3,33.9,14.3,9.0.HRMS(ESI)[M+H]+理论值C34H32N3O6S2:642.1733；实测值：642.1741.
实施例345
5-(N-(2-(4-(1H-咪唑-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S142)
Figure BDA0003601498440002442
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(1H-咪唑-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体30.3mg，产率63％。1H NMR(400MHz,DMSO-d6)δ12.90(s,1H),8.22(d,J＝16.8Hz,1H),7.96–7.79(m,2H),7.74–7.45(m,1H),7.42–6.89(m,10H),4.48(s,1H),4.17–3.58(m,3H),3.54–2.57(m,11H).13C NMR(101MHz,DMSO)δ161.0,157.4,155.1,150.4,150.1,140.8,138.2,138.1,133.6,133.2,129.4,129.4,129.1,128.4,128.2,126.3,126.2,126.2,124.9,124.2,121.8,121.7,113.0,50.2,48.8,43.3,33.9,33.8,9.1.HRMS(ESI)[M+H]+理论值C32H30N5O6S:612.1917；实测值：612.1924.
实施例346
5-(N-(2-(4-(四氢噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S143)
Figure BDA0003601498440002451
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(四氢噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体81.7mg，产率75％。1H NMR(400MHz,DMSO-d6)δ13.71(s,1H),8.26(s,1H),7.94–7.82(m,2H),7.39–7.31(m,1H),7.26–7.19(m,1H),7.17–7.01(m,5H),7.01–6.93(m,2H),4.19(t,J＝6.1Hz,1H),3.96(d,J＝69.3Hz,2H),3.41(d,J＝61.7Hz,5H),3.13–2.65(m,6H),2.59(s,4H),2.32–1.74(m,4H).13C NMR(101MHz,DMSO)δ170.1,160.7,155.2,150.4,143.4,138.2,135.5,133.3,129.2,129.2,128.4,128.2,126.6,126.1,124.7,124.3,122.7,121.9,113.1,51.4,50.3,45.7,44.4,41.9,33.9,32.6,30.8,9.1.HRMS(ESI)[M+H]+理论值C33H34N3O6S2:632.1889；实测值：632.1891.
实施例347
5-(N-(2-(4-(1H-咪唑-4-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S144)
Figure BDA0003601498440002461
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(1H-咪唑-4-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体73.5mg，产率64％。1H NMR(400MHz,DMSO-d6)δ13.09(s,1H),8.27(d,J＝1.9Hz,1H),7.96–7.75(m,3H),7.64(s,1H),7.38–7.30(m,1H),7.25(d,J＝8.0Hz,1H),7.17–7.02(m,5H),7.00–6.90(m,2H),4.67–3.31(m,7H),3.06(s,2H),2.76(d,J＝12.8Hz,2H),2.58(s,4H).13C NMR(101MHz,DMSO)δ161.7,160.7,155.2,150.5,143.3,138.2,138.1,135.5,133.2,130.7,129.1,128.4,128.2,126.6,126.1,124.8,124.2,122.6,121.9,113.1,52.2,50.2,33.9,9.1.HRMS(ESI)[M+H]+理论值C32H30N5O6S:612.1917；实测值：612.1909.
实施例348
5-(N-(2-(4-(2-乙基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S145)
Figure BDA0003601498440002462
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(2-乙基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体88.6mg，产率81％。1H NMR(400MHz,DMSO-d6)δ8.25(d,J＝1.9Hz,1H),7.93–7.81(m,2H),7.38–7.30(m,1H),7.23(d,J＝8.0Hz,1H),7.17–7.02(m,5H),7.00–6.93(m,2H),4.25–3.28(m,7H),2.98(d,J＝42.7Hz,2H),2.70(s,2H),2.63–2.55(m,5H),1.57–1.42(m,2H),1.41–1.28(m,2H),0.78(t,J＝7.4Hz,6H).13C NMR(101MHz,DMSO)δ173.2,160.9,155.1,150.5,138.2,135.4,133.3,130.7,129.3,129.2,128.4,128.2,126.4,126.1,124.3,122.6,121.8,113.0,52.7,51.8,50.3,45.5,42.5,41.5,33.9,25.1,11.7,9.1.HRMS(ESI)[M+H]+理论值C34H38N3O6S:616.2481；实测值：616.2484.
实施例349
5-(N-(2-(4-(异恶唑-5-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S146)
Figure BDA0003601498440002471
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(异恶唑-5-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体26.0mg，产率16％。1H NMR(400MHz,DMSO-d6)δ13.72(s,1H),8.66(s,1H),8.25(t,J＝5.7Hz,1H),7.86(td,J＝14.4,12.4,8.0Hz,2H),7.49–6.78(m,10H),4.18–3.64(m,3H),3.61–3.36(m,3H),3.04(d,J＝32.6Hz,2H),2.76(d,J＝44.1Hz,2H),2.57(d,J＝6.5Hz,4H),2.48–2.30(m,1H).13C NMR(101MHz,DMSO)δ167.2,160.6,155.2,155.2,155.2,150.0,143.3,138.1,138.1,135.4,135.0,133.6,133.4,128.4,128.4,128.2,128.2,128.1,126.1,124.8,113.1,50.6,50.3,48.8,43.5,33.8,9.0.HRMS(ESI)[M+H]+理论值C32H29N4O7S:613.1757；实测值：613.1747.
实施例350
5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S147)
Figure BDA0003601498440002481
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-甲酰胺基)哌啶-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体102.6mg，产率60％。1H NMR(400MHz,DMSO-d6)δ8.24–8.09(m,2H),7.87(d,J＝8.7Hz,1H),7.82–7.76(m,2H),7.39–7.30(m,1H),7.26(d,J＝7.9Hz,1H),7.21–7.01(m,5H),6.95(d,J＝7.0Hz,2H),4.21–2.86(m,8H),2.67–2.52(m,4H),2.02–1.51(m,4H).13CNMR(101MHz,DMSO-d6)δ162.7,160.2,155.0,151.5,138.7,135.2,134.1,133.6,131.7,130.9,130.7,129.8,129.4,128.8,128.8,126.7,125.3,124.1,122.8,121.2,119.1,113.0,110.2,50.5,47.2,34.5,32.3,9.5.HRMS(ESI)[M+H]+理论值C34H31BrN3O6S2:720.0843；实测值：720.0836.
实施例351
5-(N-(2-(3-溴噻吩-2-羰基)-2,8-重氮螺环[4.5]癸-8-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S148)
Figure BDA0003601498440002482
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(3-溴噻吩-2-羰基)-2,8-重氮螺环[4.5]癸-8-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体51.1mg，产率54％。1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.97–7.81(m,2H),7.77(d,J＝5.0Hz,1H),7.38–7.25(m,2H),7.18–7.00(m,6H),6.94(s,2H),3.99(d,J＝68.4Hz,2H),3.53(s,1H),3.38(s,3H),3.26–2.64(m,5H),2.58(s,4H),1.80(s,2H),1.52(s,4H).13C NMR(101MHz,DMSO-d6)δ161.3,155.5,151.8,151.6,144.3,138.7,136.2,133.8,133.5,131.3,130.4,129.7,129.5,128.8,128.7,126.9,126.6,124.7,124.3,123.1,122.2,113.4,108.7,50.5,49.9,46.4,44.5,35.2,34.6,34.4,9.5.HRMS(ESI)[M+H]+理论值C37H35BrN3O6S2:760.1156；实测值：760.1144.
实施例352
5-(N-(2-(7-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-2-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S149)
Figure BDA0003601498440002491
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(7-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-2-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体88.7mg，产率42％。1H NMR(400MHz,DMSO-d6)δ8.09(d,J＝8.6Hz,1H),7.85(d,J＝8.8Hz,1H),7.80–7.69(m,2H),7.30–7.01(m,7H),6.57–6.41(m,3H),3.91–3.76(m,3H),3.73–3.63(m,2H),3.60–3.48(m,1H),2.80–2.68(m,1H),2.66–2.58(m,1H),2.54(s,3H).13C NMR(101MHz,DMSO-d6)δ161.4,161.3,155.6,148.9,148.8,144.5,138.6,134.1,133.9,133.3,132.8,130.3,129.6,129.4,129.1,128.9,127.3,126.8,123.9,122.7,117.1,114.1,113.2,109.0,62.3,52.4,34.5,34.0,33.1,31.8,9.5.HRMS(ESI)[M+H]+理论值C36H33BrN3O6S2:746.1000；实测值：746.0996.
实施例353
5-(N-(2-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-7-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S150)
Figure BDA0003601498440002501
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(3-溴噻吩-2-羰基)-2,7-二氮螺环[3.5]壬-7-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体87.5mg，产率29％。1H NMR(400MHz,DMSO-d6)δ8.26(s,1H),7.99–7.77(m,3H),7.36–7.28(m,1H),7.26–7.00(m,7H),6.92(d,J＝6.3Hz,2H),4.21–3.52(m,9H),3.15–2.83(m,2H),2.71–2.53(m,4H),1.88–1.63(m,4H).13C NMR(101MHz,DMSO-d6)δ162.5,161.1,155.6,151.7,143.8,138.6,136.2,133.4,131.5,131.1,130.5,130.2,129.6,129.5,128.8,128.7,127.0,126.6,125.2,124.4,123.2,122.3,113.5,111.1,50.6,49.7,35.8,34.4,33.8,9.5.HRMS(ESI)[M+H]+理论值C36H33BrN3O6S2:746.1000；实测值：746.0992.
实施例354
5-(N-(2-(6-(3-溴噻吩-2-羰基)-3,6-二氮杂双环[3.1.1]庚烷-3-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S151)
Figure BDA0003601498440002502
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(6-(3-溴噻吩-2-羰基)-3,6-二氮杂双环[3.1.1]庚烷-3-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体186.2mg，产率64％。1H NMR(400MHz,DMSO-d6)δ8.05(s,1H),7.90–7.66(m,3H),7.37–6.96(m,8H),6.88–6.65(m,2H),4.61–4.40(m,2H),4.03–3.71(m,3H),3.68–3.47(m,2H),2.82–2.44(m,6H),1.90(d,J＝8.4Hz,1H),1.25(d,J＝11.6Hz,1H).13C NMR(101MHz,DMSO-d6)δ162.9,161.4,155.6,149.0,144.7,138.5,133.9,131.8,131.2,130.4,129.8,129.6,129.0,128.8,127.2,126.8,124.3,122.6,121.1,113.2,111.3,110.0,63.6,59.9,51.7,33.9,28.5,9.5.HRMS(ESI)[M+H]+理论值C34H29BrN3O6S2:718.0687；实测值：718.0674.
实施例355
(S)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S152)
Figure BDA0003601498440002511
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为(S)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体250.7mg，产率63％。1H NMR(400MHz,DMSO-d6)δ8.23(s,1H),8.00–7.71(m,3H),7.52–6.73(m,10H),4.24–2.74(m,10H),2.65–2.53(m,4H),0.99–0.62(m,3H).13C NMR(101MHz,DMSO-d6)δ162.3,161.8,155.4,148.7,145.6,138.5,138.4,135.9,133.1,132.6,132.3,130.3,129.9,129.7,129.3,128.8(d,J＝6.3Hz),128.6(d,J＝6.6Hz),126.6,125.2,123.4,122.1,115.1,113.4,109.3,53.0,49.0,43.6,34.3,34.1,16.2,9.6.HRMS(ESI)[M+H]+理论值C34H31BrN3O6S2:720.0843；实测值：720.0840.
实施例356
(R)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸(F27-S153)
Figure BDA0003601498440002521
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为(R)-5-(N-(2-(4-(3-溴噻吩-2-羰基)-2-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体237.2mg，产率67％。1H NMR(400MHz,DMSO-d6)δ8.21(s,1H),7.95–7.69(m,3H),7.48–6.76(m,10H),4.29–2.70(m,10H),2.66–2.52(m,4H),0.96–0.67(m,3H).13C NMR(101MHz,DMSO-d6)δ162.0,161.6,155.3,148.7,146.3,138.4,138.3,134.5,133.0,132.1,130.2,130.0,129.3,128.7,128.6,126.5,126.2,125.1,122.6,121.8(d,J＝18.6Hz),113.3,109.2,53.0,50.2,43.6,34.3,34.1,16.1,14.9,9.5.HRMS(ESI)[M+H]+理论值C34H31BrN3O6S2:720.0843；实测值：720.0829.
实施例357
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-1,4-二氮杂草-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S154)
Figure BDA0003601498440002522
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-1,4-二氮杂草-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体577.6mg，产率85％。1H NMR(400MHz,DMSO-d6)δ8.19(d,J＝25.8Hz,1H),7.97–7.63(m,3H),7.37–6.80(m,10H),4.23–2.94(m,11H),2.57(s,4H),2.08–1.70(m,2H).13C NMR(101MHz,DMSO)δ162.3,160.9,155.1,138.1,132.5,129.7,129.2,129.1,128.5,128.3,126.5,126.2,123.9,122.8,121.9,113.0,107.8,54.6,50.5,33.7,9.1.HRMS(ESI)[M+H]+理论值C34H31N3O6S2Br:720.0838；实测值：720.0832.
实施例358
5-(N-(2-(3-(3-溴噻吩-2-甲酰基)-3，8-二氮杂草[3.2.1]环辛烷-8-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S155)
Figure BDA0003601498440002531
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(3-(3-溴噻吩-2-甲酰基)-3，8-二氮杂草[3.2.1]环辛烷-8-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体99.6mg，产率69％。1H NMR(400MHz,DMSO-d6)δ8.24(s,1H),7.93–7.81(m,2H),7.78(d,J＝5.2Hz,1H),7.30–7.20(m,1H),7.20–7.06(m,4H),7.06–6.97(m,3H),6.91–6.86(m,2H),4.55–3.52(m,6H),3.06(t,J＝59.2Hz,3H),2.55(s,4H),2.03(s,1H),1.85–1.51(m,3H).13C NMR(101MHz,DMSO)δ162.8,161.0,155.1,138.1,134.3,131.6,129.9,129.4,129.1,128.7,128.5,128.3,126.4,126.2,123.5,122.2,119.2,113.0,108.6,56.7,33.5,26.3,9.0.HRMS(ESI)[M+H]+理论值C35H31N3O6S2Br:732.0838；实测值：732.0830.
实施例359
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-3-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S156)
Figure BDA0003601498440002532
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-甲酰基)-3-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体240.8mg，产率62％。1H NMR(400MHz,DMSO-d6)δ8.25–8.19(m,1H),7.89–7.74(m,3H),7.50–7.24(m,2H),7.22–6.76(m,8H),4.93–3.57(m,4H),3.55–3.32(m,1H),3.22–2.71(m,4H),2.56(d,J＝8.8Hz,4H),2.50–2.36(m,1H),1.36(dd,J＝62.4,6.8Hz,3H).13C NMR(101MHz,DMSO)δ161.1,155.1,151.1,150.5,138.1,138.0,135.0,133.3,131.9,129.9,129.3,129.2,128.5,128.4,128.3,128.2,126.3,126.2,124.4,121.7,112.9,108.6,51.3,50.3,33.9,33.4,9.0.HRMS(ESI)[M+H]+理论值C34H31 N3O6S2Br:720.0838；实测值：720.0833.
实施例360
5-(N-(2-(5-(3-溴噻吩-2-甲酰基)-2,5-二氮杂二环[2.2.1]庚-2-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S157)
Figure BDA0003601498440002541
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(5-(3-溴噻吩-2-甲酰基)-2,5-二氮杂二环[2.2.1]庚-2-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体467.0mg，产率68％。1H NMR(400MHz,DMSO-d6)δ13.62(s,1H),8.18(s,1H),7.98–7.57(m,3H),7.31–6.73(m,8H),6.51(dd,J＝34.7,19.5Hz,2H),4.96–4.10(m,2H),4.04–3.06(m,7H),2.76(s,1H),2.45(s,3H),1.81(d,J＝56.1Hz,2H).13C NMR(101MHz,DMSO)δ160.7,155.3,145.7,143.8,137.9,130.1,129.9,129.2,129.0,128.7,128.6,128.4,128.3,127.0,126.4,126.3,125.6,122.5,122.3,117.8,116.6,116.2,113.0,112.7,61.4,58.6,57.0,52.8,37.1,34.1,32.8,9.0,9.0.HRMS(ESI)[M+H]+理论值C34H29N3O6S2Br:718.0681；实测值：718.0675.
实施例361
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸(F27-S158)
Figure BDA0003601498440002551
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体127.4mg，产率65％。1H NMR(400MHz,DMSO-d6)δ8.31–8.13(m,2H),7.86(dd,J＝8.5,1.7Hz,1H),7.80(d,J＝5.2Hz,1H),7.44–7.31(m,1H),7.26(d,J＝8.1Hz,1H),7.18–7.03(m,6H),7.01–6.93(m,2H),4.14–2.91(m,9H),2.85–2.69(m,5H),2.65–2.56(m,1H).13CNMR(101MHz,DMSO-d6)δ164.6,161.6,150.8,143.7,140.3,138.6,136.9,133.7,132.4,131.2,130.3,129.7,129.3,128.9,128.7,126.6,124.9,124.9,124.6,123.4,123.2,110.0,109.2,52.2,50.8,34.4,13.1.HRMS(ESI)[M+H]+理论值C33H29BrN3O5S3:722.0458；实测值：722.0453.
实施例362
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸(F27-S159)
Figure BDA0003601498440002552
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体24.9mg，产率32％。1H NMR(400MHz,DMSO-d6)δ8.54(s,1H),8.25(d,J＝16.5Hz,2H),7.90–7.70(m,2H),7.46–6.87(m,10H),4.11–2.71(m,11H),2.67–2.40(m,4H).13C NMR(101MHz,DMSO-d6)δ163.8,161.6,150.8,145.4,139.3,138.6,137.2,133.8,132.4,131.3,130.3,130.0,129.7,129.3,128.9,128.7,126.7,125.6,125.0,124.7,124.5,123.3,109.3,52.5,51.0,34.4.HRMS(ESI)[M+H]+理论值C32H27BrN3O5S3:708.0302；实测值：708.0295.
实施例363
6-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸(F27-S160)
Figure BDA0003601498440002561
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为6-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并[b]噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体23.2mg，产率51％。1H NMR(400MHz,DMSO-d6)δ8.64(s,1H),8.21–8.06(m,2H),7.86–7.69(m,2H),7.42–6.84(m,10H),4.18–2.68(m,10H),2.64–2.43(m,5H).13C NMR(101MHz,DMSO-d6)δ163.8,161.6,154.4,150.7,142.4,141.6,138.6,133.7,132.3,131.5,130.3,129.7,129.3,129.0,128.7,128.6,128.6,126.7,123.6,123.5,123.3,116.4,109.2,53.2,50.9,34.5.HRMS(ESI)[M+H]+理论值C32H27BrN3O5S3:708.0302；实测值：708.0299.
实施例364
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-氯-1H-吲哚-2-羧酸(F27-S161)
Figure BDA0003601498440002571
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-氯-1H-吲哚-2-羧酸乙酯，其余条件均一致。得到白色固体98.4mg，产率57％。1H NMR(400MHz,DMSO-d6)δ12.48(s,1H),8.01(s,1H),7.86–6.57(m,13H),4.18–2.57(m,12H).13C NMR(101MHz,DMSO-d6)δ162.1,161.6,150.7,138.6,136.5,134.0,132.4,131.0,130.3,129.5,129.3,128.9,128.7,126.7,125.1,124.7,123.8,123.0,120.0,114.5,113.7,109.2,52.2,51.0,34.4.HRMS(ESI)[M+H]+理论值C32H27BrClN4O5S2：725.0300；实测值：725.0303.
实施例365
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S162)
Figure BDA0003601498440002572
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体336.2mg，产率24％。1H NMR(400MHz,DMSO-d6)δ8.31(d,J＝1.9Hz,1H),7.93–7.83(m,2H),7.79(d,J＝5.2Hz,1H),7.72(s,1H),7.39–7.31(m,1H),7.26(d,J＝8.0Hz,1H),7.20–7.06(m,5H),7.05–6.96(m,3H),4.22–3.35(m,6H),3.18–2.53(m,6H).13C NMR(101MHz,DMSO)δ161.2,159.9,156.4,150.3,138.1,135.6,133.3,131.9,130.7,129.8,129.2,128.9,128.5,128.3,127.6,126.2,126.0,124.5,123.5,122.8,113.1,108.8,50.5,33.9.HRMS(ESI)[M+H]+理论值C32H27N3O6S2Br:692.0525；实测值：692.0532.
实施例366
6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸(F27-S163)
Figure BDA0003601498440002581
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体71.0mg，产率80％。1H NMR(400MHz,DMSO-d6)δ13.77(s,1H),8.12(d,J＝1.5Hz,1H),7.99(d,J＝8.3Hz,1H),7.82–7.67(m,2H),7.39–7.32(m,1H),7.29–7.21(m,1H),7.13(h,J＝6.9Hz,5H),7.05–6.94(m,3H),3.96(d,J＝64.6Hz,2H),3.34(s,3H),2.84(dd,J＝80.9,39.5Hz,5H),2.56(s,4H).13C NMR(101MHz,DMSO)δ161.1,160.6,152.5,150.3,144.4,138.9,138.1,133.3,132.5,131.9,130.7,129.8,129.2,128.9,128.5,128.2,126.1,124.5,123.9,122.8,122.6,122.0,111.6,108.8,50.4,33.9,9.1.HRMS(ESI)[M+H]+理论值C33H29N3O6S2Br:706.0681；实测值：706.0682.
实施例367
6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S164)
Figure BDA0003601498440002591
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为6-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯，其余条件均一致。得到白色固体69.3mg，产率60％。1H NMR(400MHz,DMSO-d6)δ8.17(s,1H),7.98(d,J＝8.3Hz,1H),7.79(d,J＝5.1Hz,1H),7.74(dd,J＝8.4,1.4Hz,2H),7.35(td,J＝7.6,1.6Hz,1H),7.26(dd,J＝8.4,1.6Hz,1H),7.18–7.06(m,5H),7.05–6.95(m,3H),3.96(d,J＝64.4Hz,2H),3.42(s,4H),3.10–2.56(m,6H).13C NMR(101MHz,DMSO)δ161.1,159.8,153.8,150.3,138.4,138.1,133.3,131.9,131.0,130.7,129.8,129.2,128.8,128.5,128.2,126.1,124.5,124.0,122.8,122.4,112.4,111.8,108.8,50.4,33.9.HRMS(ESI)[M+H]+理论值C32H27N3O6S2Br:692.0525；实测值：692.0527.
实施例368
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-(4-甲氧基苯乙基)氨磺酰基)3-甲基苯并噻吩-2-羧酸(F27-S165)
Figure BDA0003601498440002592
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-(4-甲氧基苯乙基)氨磺酰基)3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体81.9mg，产率73％。1H NMR(400MHz,DMSO-d6)δ8.25–8.18(m,2H),7.85(dd,J＝8.5,1.8Hz,1H),7.79(d,J＝5.1Hz,1H),7.40–7.32(m,1H),7.26(dd,J＝8.5,1.8Hz,1H),7.19–7.02(m,3H),6.90–6.83(m,2H),6.72–6.62(m,2H),3.91(d,J＝66.8Hz,3H),3.64(s,3H),3.57–3.15(m,4H),2.91(d,J＝84.3Hz,4H),2.72(s,3H),2.42(s,1H).13C NMR(101MHz,DMSO)δ161.1,157.6,150.3,143.1,139.8,136.6,133.2,131.9,130.8,129.9,129.8,129.4,129.2,128.8,124.5,124.4,124.1,122.9,113.6,108.8,54.9,50.5,32.9,12.6.HRMS(ESI)[M+H]+理论值C34H31N3O6S3Br:752.0558；实测值：752.0567.
实施例369
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S166)
Figure BDA0003601498440002601
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体21.0mg，产率65％。1H NMR(400MHz,DMSO-d6)δ8.28–8.12(m,2H),7.87–7.73(m,2H),7.36(t,J＝7.4Hz,1H),7.27(d,J＝8.0Hz,1H),7.18–7.02(m,5H),6.98(d,J＝8.1Hz,2H),4.15–2.90(m,9H),2.85–2.68(m,5H),2.65–2.55(m,1H).13C NMR(101MHz,DMSO-d6)δ164.5,161.6,150.7,143.7,140.3,137.7,136.8,133.6,132.4,131.4,131.3,130.8,130.3,129.7,129.3,128.4,124.9,124.8,124.5,123.3,118.1,110.0,109.2,50.4,33.6,13.1.HRMS(ESI)[M+H]+理论值C33H28BrClN3O5S:756.0068；实测值：756.0070.
实施例370
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-甲基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S167)
Figure BDA0003601498440002611
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-甲基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体27.1mg，产率37％。1H NMR(400MHz,DMSO-d6)δ8.21(t,J＝4.2Hz,2H),7.94–7.68(m,2H),7.36(t,J＝7.6Hz,1H),7.27(d,J＝8.0Hz,1H),7.20–7.00(m,3H),6.90–6.73(m,4H),4.13–2.92(m,8H),2.87–2.64(m,6H),2.47–2.35(m,1H),2.14(s,3H).13C NMR(101MHz,DMSO-d6)δ164.4,161.6,150.8,143.7,140.2,140.0,137.1,135.6,135.4,133.7,132.4,131.3,130.3,129.7,129.3,129.2,128.7,125.1,124.9,124.6,123.5,123.3,109.2,52.3,50.8,33.8,21.0,13.1.HRMS(ESI)[M+H]+理论值C34H31BrN3O5S3:736.0615；实测值：736.0603.
实施例371
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-羧基苯乙基)氨磺酰)-3-甲苯并噻吩-2-羧酸(F27-S168)
Figure BDA0003601498440002612
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(甲氧基羰基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体58.2mg，产率76％。1H NMR(400MHz,DMSO-d6)δ8.30–8.15(m,2H),7.86(dd,J＝8.6,1.9Hz,1H),7.78(d,J＝5.1Hz,1H),7.67(d,J＝8.1Hz,2H),7.41–7.32(m,1H),7.30–7.22(m,1H),7.17–6.98(m,5H),4.23–2.90(m,8H),2.86–2.65(m,6H),2.61–2.54(m,1H).13C NMR(101MHz,DMSO-d6)δ167.5,164.2,161.6,150.7,143.9,143.7,140.3,140.1,137.0,133.6,132.4,131.4,131.3,130.3,129.8,129.6,129.3,129.1,129.1,125.2,125.0,124.7,123.6,123.3,109.2,52.4,50.3,34.3,13.2.HRMS(ESI)[M+H]+理论值C35H31BrN3O7S3:766.0356；实测值：766.0355.
实施例372
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氰基苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S169)
Figure BDA0003601498440002621
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氰基苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体33mg，产率77％。1H NMR(400MHz,DMSO-d6)δ13.68(s,1H),8.32(s,1H),8.24–8.12(m,1H),7.79(d,J＝9.1Hz,2H),7.68(d,J＝7.8Hz,1H),7.48(d,J＝7.8Hz,1H),7.42–7.32(m,2H),7.26(d,J＝7.3Hz,1H),7.17–7.06(m,4H),4.21–2.89(m,6H),2.80–2.71(m,9H).13C NMR(101MHz,DMSO-d6)δ164.2,161.4,150.7,144.9,143.5,140.0,137.6,132.4,132.2,131.2,130.3,130.0,129.2,128.8,127.9,126.3,125.7,124.5,123.5,122.9,122.6,109.2,109.1,52.0,31.7,25.8,13.2(d,J＝6.7Hz).HRMS(ESI)[M+H]+理论值C34H28BrN4O5S3:747.0411；实测值：747.0413.
实施例373
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(三氟甲基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S170)
Figure BDA0003601498440002631
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(三氟甲基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体36mg，产率72％。1H NMR(400MHz,DMSO-d6)δ8.17–7.95(m,2H),7.72(dd,J＝8.5,1.8Hz,1H),7.45(d,J＝7.9Hz,3H),7.34(t,J＝7.6Hz,1H),7.25–6.84(m,6H),4.02(d,J＝73.5Hz,2H),3.20–2.76(m,9H),2.74–2.62(m,4H).13C NMR(101MHz,DMSO-d6)δ165.8,162.0,150.9,144.1,143.6,143.3,141.6,135.8,133.6,131.9,131.0,129.7,129.6,127.6,127.2,126.1,125.4(q),124.5,123.9,122.92,122.7,122.3,51.2,49.9,44.8,34.2,12.5.HRMS(ESI)[M+H]+理论值C34H28BrF3N3O5S3:790.0332；实测值：790.0336.
实施例374
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-(三氟甲基)苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S171)
Figure BDA0003601498440002641
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-甲氧基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体20.4mg，产率26％。1H NMR(400MHz,DMSO-d6)δ8.30–8.12(m,2H),7.84(dd,J＝8.6,1.7Hz,1H),7.79(d,J＝5.2Hz,1H),7.46–7.31(m,1H),7.28–7.18(m,1H),7.18–6.94(m,4H),6.69–6.45(m,3H),4.20–3.79(m,2H),3.71–3.56(m,4H),3.52–2.90(m,6H),2.84–2.54(m,6H).13C NMR(101MHz,DMSO-d6)δ164.8,161.6,159.6,150.8,143.7,140.4,140.2,139.0,136.9,133.7,132.4,131.2,130.3,129.6,129.3,124.8,124.6,123.4,123.2,122.6,121.1,114.5,112.1,109.2,55.2,50.7,34.7,13.1.HRMS(ESI)[M+H]+理论值C34H31BrN3O6S3:752.0564；实测值：752.0564.
实施例375
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S172)
Figure BDA0003601498440002642
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体21.5mg，产率57％。1H NMR(400MHz,DMSO-d6)δ8.23–8.08(m,2H),7.84–7.71(m,2H),7.43–7.29(m,1H),7.28–7.19(m,1H),7.17–7.07(m,4H),7.04–6.84(m,3H),4.19–2.93(m,8H),2.82–2.59(m,7H).13C NMR(101MHz,DMSO-d6)δ165.8,161.6,150.7,143.5,141.3,141.0,136.2,133.8,133.3,132.4,131.1,130.3,129.6,129.3,128.8,127.6,126.5,124.7,124.3,123.9,123.1,122.8,118.6,109.2,50.3,33.9,12.7.HRMS(ESI)[M+H]+理论值C33H28BrClN3O5S3:756.0068；实测值：756.0067.
实施例376
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S173)
Figure BDA0003601498440002651
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-氯苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体13.5mg，产率91％。1H NMR(400MHz,DMSO-d6)δ8.28–8.16(m,2H),7.87(dd,J＝8.6,1.7Hz,1H),7.79(d,J＝5.2Hz,1H),7.41–7.34(m,1H),7.26(d,J＝8.3Hz,2H),7.19–7.09(m,6H),4.18–3.76(m,2H),3.14–2.61(m,13H).HRMS(ESI)[M+H]+理论值C33H28BrClN3O5S3:756.0068；实测值：756.0070.
实施例377
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-甲氧基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S174)
Figure BDA0003601498440002661
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-甲氧基苯乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体59.0mg，产率88％。1H NMR(400MHz,DMSO-d6)δ8.22–8.09(m,2H),7.86–7.75(m,2H),7.36(ddd,J＝8.5,6.8,2.0Hz,1H),7.26(dd,J＝8.1,1.5Hz,1H),7.18–7.01(m,4H),6.88(dd,J＝7.4,1.8Hz,1H),6.81–6.67(m,2H),4.16–3.72(m,2H),3.59–3.24(m,7H),3.16–2.64(m,9H).13C NMR(101MHz,DMSO-d6)δ161.6,159.1,157.5,150.7,143.5,140.8,136.7,133.8,132.4,131.1,130.3,129.6,129.3,128.2,126.3,124.7,124.3,124.1,123.0,122.8,120.7,111.0,109.3,55.5,49.0,29.6,12.8.HRMS(ESI)[M+H]+理论值C34H31BrN3O6S3:752.0564；实测值：752.0566.
实施例378
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-硝基苯乙基)氨磺酰)-3-甲苯并噻吩-2-羧酸(F27-S175)
Figure BDA0003601498440002662
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-硝基苯乙基)氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体17.0mg，产率64％。1H NMR(400MHz,DMSO-d6)δ8.31(d,J＝1.7Hz,1H),8.26(d,J＝8.6Hz,1H),7.91(dd,J＝8.6,1.8Hz,1H),7.85–7.74(m,2H),7.59–7.51(m,1H),7.47–7.32(m,2H),7.28(dd,J＝12.6,7.8Hz,2H),7.18–7.07(m,3H),4.29–3.86(m,2H),3.67–2.59(m,13H).13C NMR(101MHz,DMSO-d6)δ164.3,161.6,150.4,149.4,143.8,143.1,140.2,137.1,133.8,132.9,132.8,132.4,131.2,130.3,129.7,129.3,128.4,124.9,123.5,123.2,111.5,110.0,109.2,49.6,31.9,13.2.HRMS(ESI)[M+H]+理论值C33H28BrN4O7S3:767.0309；实测值：767.0310.
实施例379
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-苯基丙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S176)
Figure BDA0003601498440002671
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(3-苯基丙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体17.0mg，产率28％。1H NMR(400MHz,DMSO-d6)δ8.16–7.95(m,2H),7.87–7.58(m,2H),7.40–7.03(m,8H),6.99–6.85(m,2H),3.94–3.49(m,3H),3.18–2.58(m,10H),2.46–2.35(m,2H),1.57–1.38(m,2H).13C NMR(101MHz,DMSO-d6)δ165.7,165.5,151.0,149.8,143.2,141.7,141.5,140.4,136.8,136.3,136.0,133.9,131.5,131.0,130.1,129.5,128.6,128.5,126.2,123.9,122.9,122.7,122.1,51.5,45.1,32.4,29.7,12.4.HRMS(ESI)[M+H]+理论值C34H31BrN3O5S3:736.0615；实测值：736.0600.
实施例380
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲苯并噻吩-2-羧酸(F27-S177)
Figure BDA0003601498440002681
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体108.0mg，产率63％。1H NMR(400MHz,DMSO-d6)δ9.27(s,1H),8.32(d,J＝1.7Hz,1H),8.17(d,J＝8.6Hz,1H),7.84–7.65(m,2H),7.50–7.32(m,1H),7.22–6.98(m,4H),3.89–3.00(m,4H),2.69(s,3H),2.49–2.26(m,4H).13C NMR(101MHz,DMSO-d6)δ164.2,161.4,144.9,143.5,140.0,137.6,132.5,132.4,131.2,130.3,129.2,126.3,125.7,124.5,123.5,122.9,122.6,109.1,52.5,13.1.HRMS(ESI)[M+H]+理论值C25H21BrN3O5S3:617.9832；实测值：617.9821.
实施例381
5-(N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)3-甲基苯并呋喃-2-甲酰胺(F27-S178)
Figure BDA0003601498440002682
将5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)-3-甲基苯并呋喃-2-羧酸(F27-S125)(0.042mmol,30.0mg),CDI(0.042mmol,7.0mg)溶于1mLDCM,室温搅拌20分钟，加入0.5mL氨水，室温搅拌3小时，TLC监测反应后，用0.5mL 1M盐酸水溶液淬灭，加入20mL水，用20mL乙酸乙酯萃取三次，合并有机相后浓缩，柱层析分离(DCM:MeOH＝20:1)，得到白色固体25.8mg，产率87％。1H NMR(400MHz,Chloroform-d)δ8.11(s,1H),7.88(d,J＝8.8Hz,1H),7.55(d,J＝8.8Hz,1H),7.35(t,J＝5.4Hz,2H),7.21–6.87(m,7H),6.57(s,1H),6.11(s,1H),4.30–3.75(m,3H),3.44(d,J＝119.4Hz,4H),2.79(d,J＝86.6Hz,3H),2.62(s,2H),1.26(s,3H).13C NMR(101MHz,CDCl3)δ162.3,161.3,155.0,151.0,144.4,138.2,136.0,134.2,132.1,130.4,130.3,130.1,129.6,128.6,127.4,126.7,126.6,124.8,123.7,122.9,122.0,112.5,109.8,51.6,34.8,29.8,29.4,9.1.HRMS(ESI)[M+H]+理论值C33H32N4O5S2Br:707.0997；实测值：707.1000.
实施例382
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-1,3-二甲基-1H-吲哚-2-羧酸乙酯(M10-179)
Figure BDA0003601498440002691
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲苯并噻吩-2-羧酸乙酯(M10-158)所用方法，将3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并[b]噻吩-2-羧酸乙酯替换为5-(氯磺酰基)-1,3-二甲基-1H-吲哚-2-羧酸乙酯，其余条件均一致。得到白色固体316.1mg，产率99％。1H NMR(400MHz,Chloroform-d)δ8.23(d,J＝1.8Hz,1H),7.79(dd,J＝8.9,1.8Hz,1H),7.44(d,J＝8.8Hz,1H),7.36(dd,J＝12.2,4.6Hz,2H),7.23–7.12(m,4H),7.07(d,J＝4.3Hz,2H),7.01–6.95(m,3H),4.47(q,J＝7.1Hz,2H),4.20–3.95(m,5H),3.91–2.76(m,8H),2.74–2.47(m,5H).13C NMR(101MHz,Chloroform-d)δ162.5,162.2,150.7,139.9,138.3,134.4,132.1,131.5,130.5,130.2,129.2,128.5,128.5,127.2,126.5,126.4,124.4,123.6,122.3,122.3,121.8,110.6,109.6,60.9,51.4,34.7,32.6,14.4,10.9.
实施例383
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-1,3-二甲基-1H-吲哚-2-羧酸(F27-S179)
Figure BDA0003601498440002701
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-1,3-二甲基-1H-吲哚-2-羧酸乙酯，其余条件均一致。得到白色固体280.5mg，产率92％。1H NMR(400MHz,DMSO-d6)δ8.13(s,1H),7.79–7.60(m,3H),7.39–7.27(m,1H),7.23–7.04(m,8H),6.96(d,J＝7.2Hz,2H),4.00(s,3H),3.34–2.65(m,10H),2.61–2.43(m,5H).13C NMR(101MHz,DMSO-d6)δ163.9,161.6,150.5,139.8,138.7,133.9,132.3,1312,131.1,130.3,129.4,129.3,128.8,128.7,126.6,126.3,124.5,123.3,122.7,121.6,120.2,112.0,109.2,52.1,50.6,34.4,32.8,10.8.HRMS(ESI)[M-H]-理论值C34H32BrN4O5S2:719.1003；实测值:719.0997.
实施例384
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-环己基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-180)
Figure BDA0003601498440002702
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-((2-环己基乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体102mg，产率47％。1H NMR(400MHz,Chloroform-d)δ8.32(d,J＝1.7Hz,1H),8.04–7.84(m,2H),7.38(d,J＝5.3Hz,1H),7.34(ddd,J＝8.7,7.4,1.6Hz,1H),7.18(dd,J＝8.1,1.5Hz,1H),7.06(td,J＝7.6,1.5Hz,1H),7.01–6.93(m,2H),4.45(q,J＝7.1Hz,2H),4.26–3.39(m,6H),3.01–2.71(m,6H),1.64–1.53(m,4H),1.50–1.40(m,4H),1.16–0.99(m,5H),0.75(q,J＝10.6,9.8Hz,2H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,150.94,144.0,140.9,139.9,137.3,134.3,132.0,130.2,130.2,129.8,129.3,127.3,125.0,124.6,123.7,123.4,122.7,109.7,61.6,48.2,35.5,35.2,33.1,26.3,26.1,14.4,13.2.
实施例385
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-环己基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S180)
Figure BDA0003601498440002711
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-环己基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体73.0mg，产率72％。1H NMR(400MHz,DMSO-d6)δ8.27(t,J＝4.2Hz,2H),7.91(d,J＝8.6Hz,1H),7.80(d,J＝5.2Hz,1H),7.29(dd,J＝33.0,8.3Hz,2H),7.18–7.00(m,3H),3.94–2.91(m,8H),2.87–2.63(m,5H),1.57–1.28(m,4H),1.15–0.77(m,7H),0.74–0.52(m,2H).13C NMR(101MHz,DMSO-d6)δ164.7,161.6,150.8,143.6,140.4,138.9,137.1,133.9,132.4,131.1,130.3,129.6,129.3,124.9,124.6,123.3,123.2,109.2,52.4,47.4,35.4,34.6,32.9,26.4,26.1,13.0.HRMS(ESI)[M+H]+理论值C33H35BrN3O5S3:728.0928；实测值：728.0918.
实施例386
5-(N-苄基-N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-181)
Figure BDA0003601498440002721
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为4-(2-(苄基氨基)苯基)哌嗪-1-基)(3-溴噻吩-2-基)甲酮，其余条件均一致。得到白色固体74.0mg，产率46％。1H NMR(400MHz,Chloroform-d)δ8.24(d,J＝1.6Hz,1H),8.00–7.80(m,2H),7.38(d,J＝5.2Hz,1H),7.28(s,1H),7.16(qd,J＝8.0,7.2,2.8Hz,4H),7.09–6.97(m,4H),6.87(dd,J＝7.9,1.5Hz,1H),4.81(d,J＝122.3Hz,2H),4.45(q,J＝7.1Hz,2H),4.00–3.34(m,4H),3.30–2.93(m,2H),2.76(s,3H),2.68–2.24(m,2H).13C NMR(101MHz,Chloroform-d)δ162.8,162.1,151.4,144.1,141.0,139.9,137.1,135.7,135.1,132.1,130.2,129.8,129.8,129.4,129.4,128.3,128.0,127.2,125.2,124.9,123.9,123.3,123.3,109.7,61.6,55.0,14.,13.2.
实施例387
5-(N-苄基-N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S181)
Figure BDA0003601498440002722
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-苄基-N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体56.0mg，产率80％。1H NMR(400MHz,DMSO-d6)δ8.35–8.18(m,2H),7.90(d,J＝8.6Hz,1H),7.79(d,J＝5.2Hz,1H),7.40–6.83(m,10H),5.18–4.68(m,2H),4.14–3.07(m,6H),2.95–2.58(m,7H).13C NMR(101MHz,DMSO-d6)δ164.4,161.6,150.9,143.7,140.2,137.2,136.5,134.3,132.4,131.3,130.3,129.6,129.4,129.3,128.5,128.0,125.3,125.0,124.6,123.7,123.5,110.0,109.2,53.8,52.2,13.2.HRMS(ESI)[M-H]-理论值C32H27BrN3O5S3:708.0302；实测值：708.0294.
实施例388
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-甲基氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-182)
Figure BDA0003601498440002731
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为(3-溴噻吩-2-基)(4-(2-(甲氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体137.7mg，产率76％。1H NMR(400MHz,Chloroform-d)δ8.24(s,1H),8.07–7.69(m,2H),7.50–7.17(m,2H),7.14–6.66(m,4H),4.43(q,J＝7.2Hz,2H),4.18–3.41(m,5H),3.31–3.15(m,3H),2.77(s,3H),1.44(t,J＝7.2Hz,3H).13C NMR(101MHz,Chloroform-d)δ162.7,162.2,150.3,144.1,140.9,139.9,135.8,135.4,132.1,130.2,129.8,129.3,128.1,127.3,125.1,123.9,123.7,123.4,121.6,109.7,61.6,51.7,38.5,14.4,13.2.
实施例389
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-甲基氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S182)
Figure BDA0003601498440002741
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-甲基氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体78.0mg，产率58％。1H NMR(400MHz,DMSO-d6)δ8.26(d,J＝8.5Hz,1H),8.19(s,1H),7.82(dd,J＝15.7,7.0Hz,2H),7.29(t,J＝7.9Hz,1H),7.15(q,J＝8.7,5.5Hz,2H),6.97(dd,J＝26.4,7.9Hz,2H),3.98–3.10(m,8H),2.98(s,3H),2.74(s,3H).13C NMR(101MHz,DMSO-d6)δ164.7,161.6,150.3,143.7,140.3,139.1,135.8,132.4,130.3,129.5,129.3,129.0,125.1,124.5,124.0,123.5,122.2,109.2,51.7,38.6,13.1.HRMS(ESI)[M-H]-理论值C26H23BrN3O5S3:631.9989；实测值：631.9986.
实施例390
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-(噻吩-2-基)乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-183)
Figure BDA0003601498440002742
按照5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(4-氯苯基乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯(M10-165)所用方法，将(3-溴噻吩-2-基)(4-(2-((4-氯苯基乙基)氨基)苯基)哌嗪-1-基)甲酮替换为3-溴噻吩-2-基)(4-(2-(噻吩-2-基)乙基)氨基)苯基)哌嗪-1-基)甲酮，其余条件均一致。得到白色固体10.0mg，产率7％。1H NMR(400MHz,Chloroform-d)δ8.31(s,1H),8.04–7.82(m,2H),7.45–7.33(m,2H),7.26–7.15(m,2H),7.13–6.95(m,3H),6.87–6.78(m,1H),6.65(s,1H),4.46(q,J＝6.6Hz,2H),4.22–3.12(m,9H),3.02–2.69(m,6H),1.45(t,3H).13C NMR(101MHz,Chloroform-d)δ162.8,162.2,150.8,140.3,139.9,137.1,134.0,132.0,130.5,130.2,129.9,129.6,127.2,126.9,125.2,124.8,123.8,123.7,123.5,123.2,122.9,109.7,61.6,51.6,29.7,22.7,14.3.
实施例391
5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-(噻吩-2-基)乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸(F27-S183)
Figure BDA0003601498440002751
照3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S106)所用方法，将3-甲基-5-(N-(2-(4-(4-甲基苯甲酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯替换为5-(N-(2-(4-(3-溴噻吩-2-羰基)哌嗪-1-基)苯基)-N-(2-(噻吩-2-基)乙基)氨磺酰)-3-甲基苯并噻吩-2-羧酸乙酯，其余条件均一致。得到白色固体14.0mg，产率100％。1H NMR(400MHz,DMSO-d6)δ8.26(s,2H),7.92–7.73(m,2H),7.36(s,1H),7.30–7.07(m,4H),6.97(s,1H),6.82(s,1H),6.74(s,1H),4.22–3.37(m,5H),3.09–2.67(m,10H).HRMS(ESI)[M-H]-理论值C31H27BrN3O5S4:728.0022；实测值：728.0023.
实施例392
N-(2-(4-(3-溴噻吩-2-甲酰基)哌嗪-1-基)苯基)-2-羟甲基-3-甲基-N-苯乙基苯并呋喃-5-磺酰胺(F27-S184)
Figure BDA0003601498440002752
将3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)(248mg，0.34mmol)溶于无水四氢呋喃(0.5mL)中，在0度下缓慢滴加到搅拌的氢化锂铝-四氢呋喃溶液中(14mg氢化锂铝，溶于1mL无水四氢呋喃)，室温下反应2小时，至薄层色谱监测到原料消失。向反应体系中滴加1.5mL饱和碳酸钾溶液，并搅拌15min。再将反应体系倒入5mL的乙酸乙酯中，搅拌15min。加入20mL水，萃取3次，无水硫酸钠干燥有机层。柱层析(PE：EA＝3：1～1：1)得到目标产物105mg，收率45％。1H NMR(400MHz,CDCl3)δ8.05(d,J＝2.0Hz,1H),7.81(dd,J＝8.7,2.0Hz,1H),7.61–7.53(m,2H),7.37(dd,J＝9.7,6.2Hz,2H),7.24–7.14(m,5H),7.03–6.93(m,3H),5.49(s,2H),4.32–2.48(m,14H),2.39(s,3H).13C NMR(101MHz,CDCl3)δ162.2,151.0,149.4,138.2,135.0,134.3,133.6,133.2,132.1,131.9,130.2,129.8,129.4,128.5,127.2,126.5,124.8,124.6,122.7,120.8,116.8,112.0,111.9,109.7,63.5,56.9,51.5,34.6,8.0.HRMS(ESI)[M-H]-理论值C33H31BrN3O5S2:692.0894；实测值：692.0898.
制备例1
5-(2,5-二甲基苯氧基)-N-(2-(4-羟基苯基)-2-氧代乙基)-2,2-二甲基戊酰胺(SIPI-7623)
Figure BDA0003601498440002761
将2-氨基-4'-羟基苯乙酮盐酸盐(0.38g,2mmol)，2,2-二甲基-5-(2,5-二甲基苯氧基)戊酸(0.5g,2mmol)，三乙胺(0.6g,4mmol)，1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.77g,4mmol)，1-羟基苯并三唑(0.54g,4mmol)加入无水二氯甲烷(10mL)中，室温反应13h，TLC检测反应完毕后，经饱和碳酸钠溶液(10mL)洗涤，加乙酸乙酯(30mL)萃取三次，有机相用饱和氯化钠水溶液洗，加无水硫酸钠干燥，粗品经柱层析分离(PE/EA＝1/1)得白色固体0.39g，收率51％。经核磁和质谱数据核对，本制备例得到化合物与文献报道的化合物一致！
制备例2
1-((3S,8R,9S,10R,13S,14S)-3-羟基-10,13-二甲基-2,3,4,7,8,9,10,11,12,13,14,15-十二氢-1H-环戊基[a]菲-17-基)乙烷-1-酮(Centatin)
Figure BDA0003601498440002771
将(3S,8R,9S,10R,13S,14S)-17-乙酰基-10,13-二甲基-2,3,4,7,8,9,10,11,12,13,14,15-十二氢-1H-环戊基[a]菲-3-乙酸酯(5.34g,15mmol)溶于叔丁醇(125mL)，再加入氢氧化钾(4.2g,75mmol)的水溶液(5mL)，30℃搅拌过夜，TLC检测反应完毕后，减压蒸馏除去溶剂，冰水(25mL)洗涤5次，用DCM/CH3OH(9:1)重结晶得白色固体4.58g，收率97％。经核磁和质谱数据核对，本制备例得到化合物与文献报道的化合物一致！
生物活性部分
一、生物活性评价实验方法
1.1FXR活性评价
FXR活性通过时间分辨荧光共振能量转移(time-resolved fluorescenceresonance energy transfer,TR-FRET)实验评价，使用LanthaScreenTMTR-FRET FXR共激活实验试剂盒(ThermoFisher,Cat.PV4833)。激动剂筛选，取384孔黑板(Coring)，每孔依次加入10μL含相应浓度待测化合物的Complete Coregulator buffer G，5μL 20nM FXR-LBDComplete Coregulator buffer G，5μL 2.0μM Fluorescein-SRC2-2/20nM Tb-anti-GSTantibody Complete Coregulator buffer G，室温孵育1h后，酶标仪检测520nm和495nm处的荧光值，所测数值用520nm/495nm表示。每个化合物三个复孔，以CDCA作为阳性化合物，DMSO作为溶剂对照。拮抗剂筛选，取384孔黑板(Coring)，每孔依次加入5μL含相应浓度待测化合物的Complete Coregulator buffer G，5μL 20nM FXR-LBD Complete Coregulatorbuffer G，5μL 200μM CDCA FXR-LBD Complete Coregulator buffer G，5μL 2.0μMFluorescein-SRC2-2/20nM Tb-anti-GST antibody Complete Coregulator buffer G，室温孵育10h，余同激动剂筛选。
1.2细胞培养与传代
人胚胎肾细胞系HEK293A传代培养，培养条件为含有青霉素(终浓度为100U/mL)、链霉素(终浓度为100μg/mL)以及10％FBS的MEM培养基，置于95％空气和5％二氧化碳的湿润气氛下37℃恒温培养。当细胞融合至90％时，弃去旧培养基，用2mL PBS洗涤细胞2次，弃去PBS后加入2mL 0.25％胰蛋白酶-0.25％EDTA混合消化液，置显微镜下观察，当细胞变圆后迅速加入2mL完全培养基终止消化，轻轻吹打，收集细胞。800rpm，4℃，离心5min，弃去上清，用完全培养基重悬细胞，分瓶培养，隔天换液。
人肝癌细胞系HepG2传代培养，培养条件为含有青霉素(终浓度为100U/mL)、链霉素(终浓度为100μg/mL)以及10％FBS的DMEM培养基，余同HEK293A传代培养相同。
1.3细胞增殖抑制实验
通过MTT法检测化合物的细胞增殖抑制能力。HepG2和HEK293细胞以30％的密度接种于96孔板，孵育18h使细胞贴壁后，移除原有培养基，每孔加入给定浓度的待测化合物，对照组加入等量的DMSO。每个化合物设置三个复孔。给药48h后，MTT法检测细胞活力，空白组为不加入细胞的孔，随后用酶标仪在490nm处读取其OD值。细胞活力的计算公式为：细胞活力(％)＝(OD待测-OD空白)/(OD对照-OD空白)×100。
1.4细胞TC/TG检测
细胞TC/TG用南京建成TG测试盒、TC测试盒检测。HepG2细胞用0.5mmol/L FFA(油酸与棕榈酸酯按照2:1混合)和溶剂或不同浓度(20μM、40μM、80μM)的化合物孵育24h。吸弃培养液，用0.01M,pH 7.4PBS清洗一遍细胞。用细胞刮板刮下细胞，加入2-5mL,0.01M,pH7.4PBS，收集细胞悬液后，1000×g，4℃，离心10min收集细胞，按照106个细胞加入300-500μL匀浆介质的比例加入异丙醇，进行机械匀浆，充分破碎至无明显的细胞沉淀。10000×g，4℃，离心10min，取上清置于冰上待测。取2.5μL蒸馏水、标准品或样品分别与250μL蒸馏水混匀，37℃孵育10分钟，酶标仪510nm测定各孔吸光度值。TC/TG浓度计算公式：样品浓度(mmol/g protein)＝(OD样品-OD空白)/(OD标准-OD空白)×标准品浓度(mmol/L)/蛋白浓度(gprotein/L)。
BCA法蛋白定量
蛋白标准品的准备：a.取1.2mL蛋白标准配制液加入到一管蛋白标准(30mg BSA))中，充分溶解后配制成25mg/mL的蛋白标准溶液。b.取适量25mg/mL蛋白标准，稀释至终浓度为0.5mg/mL。BCA工作液配制：根据样品数量，按50体积BCA试剂A加1体积BCA试剂B(50:1)配制适量BCA工作液，充分混匀。蛋白浓度测定：a.将标准品按0、1、2、4、8、12、16、20μL加到96孔板的标准品孔中，加标准品稀释液补足到20μL，相当于标准品浓度分别为0、0.025、0.05、0.1、0.2、0.3、0.4、0.5mg/mL。b.加适当体积样品到96孔板的样品孔中。如果样品不足20μL，需加标准品稀释液补足到20μL。c.各孔加入200μL BCA工作液，37℃放置20-30分钟。d.用酶标仪测定A562 nm波长处的吸光度。e.根据标准曲线和使用的样品体积计算出样品的蛋白浓度。
结果与讨论
FXR拮抗活性结果与讨论
A:0.1μM<IC50<10μM
B:10μM<IC50<50μM
C:50μM<IC50<100μM
表1.1化合物的FXR拮抗活性
Figure BDA0003601498440002791
Figure BDA0003601498440002801
Figure BDA0003601498440002811
Figure BDA0003601498440002821
Figure BDA0003601498440002831
Figure BDA0003601498440002841
表1.2化合物的FXR拮抗活性
Figure BDA0003601498440002842
Figure BDA0003601498440002851
Figure BDA0003601498440002861
Figure BDA0003601498440002871
Figure BDA0003601498440002881
a数据以至少两个独立运行的几何平均值来表示.b Z-GS,SIPI-7623和Centatin为阳性对照。SIPI-7623处于I期临床研究，Centatin处于III期临床研究.
降脂活性结果与讨论
化合物人胚胎肾细胞HEK293A和人肝癌细胞HepG2细胞毒性评价。如表1.3所示，所有测试的苯并呋喃类FXR拮抗剂均没有明显的细胞毒性(CC50>160μM)。
表1.3苯并呋喃类FXR拮抗剂的细胞毒评价结果
Figure BDA0003601498440002882
表中数据为三次独立重复试验的平均值。
本发明人选取了三期临床研究的Centatin、一期临床研究的SIPI-7623和Z-GS作为阳性参照。分析TG和TC结果表明(图1)，20μM的Z-GS、SIPI-7623、Centatin和F27-S96，均能显著降低油酸与棕榈酸酯诱导的HepG2细胞TG和TC水平升高，阳性药中Centatin的效果最好，SIPI-7623次之，Z-GS最差。化合物F27-S96降TG和TC效果与SIPI-7623相近，并且对TG、TC抑制效果具有一定的剂量依赖性。

Claims (18)

1.一种苯并呋喃衍生物，所述苯并呋喃衍生物如式(I)所示：
Figure FDA0003601498430000011
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(I)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基和取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
并规定，
当R1为-(CH2)n-R4，n为1，R4为苯基，R3为甲基时，R2不为羟基；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
2.根据权利要求1所述的苯并呋喃衍生物，其中，式(I)中R3为甲基，和/或R2为羟基。
3.根据权利要求1所述的苯并呋喃衍生物，其中，式(I)中R2为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、仲丁氧基、叔丁氧基或苄基；优选地，R2为乙氧基。
4.根据权利要求1所述的苯并呋喃衍生物，其中，式(I)中R2为-NR5R6；这里，R5和R6各自独立地选自氢、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、新戊基、苄基和苯乙基；优选地，R2为苯乙胺基。
5.根据权利要求1至4中任一项所述的苯并呋喃衍生物，其中，式(I)中n为0；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6烷基、卤代C1-C6烷基、卤代C1-C6烷氧基、氨甲酰基、卤代C1-C6烷硫基、C1-C6烷酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：未取代的C1-C6烷基、苯基取代的C1-C6烷基、未取代的C1-C6烷氧羰酰基、未取代的C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰，或者C1-C6烷基与吗啉基、哌嗪基、哌嗪甲基和哌啶基中的N形成季铵。
6.根据权利要求1至4中任一项所述的苯并呋喃衍生物，其中，式(I)中n为1或2；R4为苯基、萘基、吡啶基、或喹啉，或者被一个或多个如下基团取代的苯基、萘基、吡啶基、或喹啉：苄基、苯氧基、卤素、硝基、氰基、羧基、未取代的C1-C6、卤代C1-C4烷基、卤代C1-C4烷氧基、C1-C6烷酰基、羧基取代的C1-C6烷基、C1-C6烷氧羰酰基、氨甲酰基、卤代C1-C4烷硫基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、氨甲酰基、吗啉基、哌嗪基、哌嗪甲基和哌啶基；这里，所述哌嗪基、哌嗪甲基和哌啶基任选地被一个或多个如下基团所取代：C1-C6烷基、苯基取代的C1-C6烷基、C1-C6烷氧羰酰基、C1-C6烷酰基、苯基取代的C1-C6烷酰基、C1-C4烷烃磺酰基、单或双C1-C4取代胺甲酰。
7.根据权利要求1所述的苯并呋喃衍生物，选自下列化合物：
3-甲基-5-(N-苄基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(F27-S8)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-26)；
3-甲基-5-(N-3-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-31)；
3-甲基-5-(N-(4-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-32)；
3-甲基-5-(N-(4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-36)；
3-甲基-5-(N-(4-(叔丁基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-38)；
3-甲基-5-(N-(4-(甲氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-40)；
3-甲基-5-(N-(4-(2-甲氧基-2-氧乙基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-41)；
(E)-3-甲基-5-(N-(4-(3-甲氧基-3-氧代丙-1-烯-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-42)；
3-甲基-5-(N-(萘-1-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-53)；
3-甲基-5-(N-(2-氟-4-氰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-54)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-58)；
3-甲基-5-(N-(2-三氟甲基-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-82)；
3-甲基-5-(N-((2’-氰基-[1,1’-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M4-84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M4-85)；
3-甲基-5-(N-(2-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S14)；
3-甲基-5-(N-(2-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S15)；
3-甲基-5-(N-(2-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S16)；
3-甲基-5-(N-(2-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S17)；
3-甲基-5-(N-(2-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S18)；
3-甲基-5-(N-(2-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S19)；
3-甲基-5-(N-(3-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S20)；
3-甲基-5-(N-(3-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S21)；
3-甲基-5-(N-(3-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S22)；
3-甲基-5-(N-(3-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S23)；
3-甲基-5-(N-(3-三氟甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S24)；
3-甲基-5-(N-(3-硝基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S25)；
3-甲基-5-(N-([1,1'-联苯]-3-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S26)；
3-甲基-5-(N-(3-苯氧基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S27)；
3-甲基-5-(N-(4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S28)；
3-甲基-5-(N-(4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S29)；
3-甲基-5-(N-(4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S30)；
3-甲基-5-(N-(4-甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S31)；
3-甲基-5-(N-(4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S32)；
3-甲基-5-(N-(4-氨甲酰苄基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S33)；
3-甲基-5-(N-(4-(三氟甲氧基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S34)；
3-甲基-5-(N-(4-(三氟甲硫基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S35)；
3-甲基-5-(N-(4-异丙基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S36)；
3-甲基-5-(N-(4-叔丁基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S37)；
3-甲基-5-(N-(4-乙酰基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S38)；
3-甲基-5-(N-(4-羧苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S39)；
3-甲基-5-(N-(4-(叔丁氧羰基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S40)；
3-甲基-5-(N-(4-(羧甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S41)；
(E)-3-甲基-5-(N-(4-(2-羧基乙烯基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S42)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S43)；
3-甲基-5-(N-(喹啉-8-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S44)；
3-甲基-5-(N-(萘-2-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S45)；
3-甲基-5-(N-(2,6-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S46)；
3-甲基-5-(N-(2-氟-6-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S47)；
3-甲基-5-(N-(2-氟-6-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S48)；
3-甲基-5-(N-(2,6-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S49)；
3-甲基-5-(N-(2,6-二甲基苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S50)；
3-甲基-5-(N-(2,4-二氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S51)；
3-甲基-5-(N-(2-氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S52)；
3-甲基-5-(N-(2-氟-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S53)；
3-甲基-5-(N-(2-氟-4-(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S55)；
3-甲基-5-(N-(2-氯-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S56)；
3-甲基-5-(N-(2-(三氟甲基)-4-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S57)；
3-甲基-5-(N-(2,4-二(三氟甲基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S58)；
3-甲基-5-(N-(2-(三氟甲基)-4-溴苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S59)；
3-甲基-5-(N-(2,4-二氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S60)；
3-甲基-5-(N-(2-甲基-5-氟苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S61)；
3-甲基-5-(N-(2,6-二氟-4-氯苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S62)；
3-甲基-5-(N-([1,1'-联苯]-4-基甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S82)；
3-甲基-5-(N-(2'-氰基-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S83)；
3-甲基-5-(N-((2'-(叔丁氧羰基)-[1,1'-联苯]-4-基)甲基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S84)；
3-甲基-5-(N-(4-苯甲酰基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S85)；
3-甲基-5-(N-苯基-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-12)；
3-甲基-5-(N,N-二苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-68)；
3-甲基-5-(N-(4-(4-苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)-3-甲基苯并呋喃-2-羧酸乙酯(M8-69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-71)；
3-甲基-5-(N-(4-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M8-75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-78)；
3-甲基-5-(N-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-81)；
3-甲基-5-(N-苯乙基-N-(4-苯氧基苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M8-86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸乙酯(M8-88)；
3-甲基-5-(N-苯乙基-N-苯基氨磺酰)苯并呋喃-2-羧酸(F27-S10)；
3-甲基-5-(N-(4-苄基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S11)；
3-甲基-5-(N-(4-苯氧基苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S12)；
3-甲基-5-(N,N-二苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S13)；
3-甲基-5-(N-(4-吗啉苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S63)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S64)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S65)；
3-甲基-5-(N-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S66)；
3-甲基-5-(N-(4-(4-(丙氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S67)；
3-甲基-5-(N-(4-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S68)；
3-甲基-5-(N-(4-(4-苯甲酰哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S69)；
3-甲基-5-(N-(4-(4-苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S70)；
3-甲基-5-(N-(4-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S71)；
3-甲基-5-(N-(4-(4-(甲磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S72)；
3-甲基-5-(N-(4-(1-(叔丁氧羰基)哌啶-4-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S73)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)-3-(三氟甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S74)；
3-甲基-5-(N-(6-(4-(叔丁氧羰基)哌嗪-1-基)吡啶-3-基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S75)；
3-甲基-5-(N-(4-((4-(叔丁氧羰基)哌嗪-1-基)甲基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S76)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S77)；
3-甲基-5-(N-(3-(4-甲基哌嗪-1-基)苯基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S78)；
3-甲基-5-(N-(4-(4-吗啉苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S79)；
3-甲基-5-(N-(4-(4-甲基哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S80)；
3-甲基-5-(N-(4-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S81)；
3-甲基-5-(N-(4-(4-苯氧基苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S86)；
3-甲基-5-(N-(2-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S87)；
3-甲基-5-(N-(3-(4-(叔丁氧羰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰)苯并呋喃-2-羧酸(F27-S88)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-1)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苄基)氨磺酰)苯并呋喃-2-羧酸乙酯(M9-2)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-91)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸乙酯(M10-96)；
3-甲基-5-(N-(2-(4-甲基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-98)；
4-(2-((2-(乙氧基羰基)-3-甲基-N-苄基乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(M10-99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-100)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-101)；
3-甲基-5-(N-(2-(4-甲磺酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-102)；
3-甲基-5-(N-(2-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-104)；
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸乙酯(M10-105)；
3-甲基-5-(N-苯乙基-N-(2-(哌嗪-1-基)苯基)氨磺酰基)苯并呋喃-2-羧酸(F27-S89)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺酰胺基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S90)；
3-甲基-5-(N-(2-(4-乙酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S91)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S92)；
3-甲基-5-(N-(2-(4-(甲基磺酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S93)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S94)；
3-甲基-5-(N-(2-(4-(4-(苄基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S95)；
3-甲基-5-(N-(2-(4-(苯甲酰基哌嗪-1-基)苯基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S96)；
3-甲基-5-(N-(2-(哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S97)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S98)；
4-(2-((2-羧基-3-甲基-N-苯乙基苯并呋喃)-5-磺胺基)甲基)苯基)-1,1-二甲基哌嗪-1-鎓(F27-S99)；
3-甲基-5-(N-(2-(4-乙酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S100)；
3-甲基-5-(N-(2-(4-(二甲基氨甲酰)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S101)；
3-甲基-5-(N-(2-(4-(甲磺酰基)哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S102)；
3-甲基-5-(N-(2-(4-(4-(3,3-二甲基丁酰基)哌嗪-1-基)苄基)-N-苯乙基氨磺酰基)苯并呋喃-2-羧酸(F27-S103)；
3-甲基-5-(N-(2-(4-苄基哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S104)；和
3-甲基-5-(N-(2-(4-苯甲酰哌嗪-1-基)苄基)-N-苯乙氨磺酰)苯并呋喃-2-羧酸(F27-S105)；
或者，其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
8.包含权利要求1至7中任一项所述苯并呋喃衍生物的药物组合物。
9.一种苯并呋喃衍生物作为FXR调节剂的用途，所述苯并呋喃衍生物如式(II)所示：
Figure FDA0003601498430000151
其中，R1为-(CH2)n-R4，这里，n为0至6的整数，R4为未取代的芳烃基、取代的芳烃基、未取代的杂芳基、取代的杂芳基；所述取代的芳烃基或所述取代的杂芳基是指芳烃基或杂芳基被一个或多个选自A组基团所取代；
式(II)中R2为羟基、未取代的C1-C6烷氧基、取代的C1-C6烷氧基、或-NR5R6；这里，R5和R6各自独立地选自氢、未取代的C1-C6烷基和取代的C1-C6烷基；所述取代的C1-C6烷氧基是指该C1-C6烷氧基上的一个或多个氢被选自苯基、卤素、硝基、羟基和C1-C6烷基的基团所取代；所述取代的C1-C6烷基是指该C1-C6烷基上的一个或多个氢被选自苯基、卤素、羟基和C1-C6烷基的基团所取代；
R3为未取代的C1-C6烷基和取代的C1-C6烷基；
所述A组基团为下列基团中一种或多种：卤素、硝基、氰基、取代的或未取代的芳烃基、取代的或未取代的芳烃氧基、未取代的C1-C6烷基、未取代的C2-C6烯烃基、羧基取代的C2-C6烯烃基、未取代的C2-C6炔烃基、羧基取代的C2-C6炔烃基、氨甲酰基、卤代C1-C6烷基、芳烃取代的C1-C6烷基、羧基取代的C1-C6烷基、C1-C6烷氧基羰酰基、未取代的C1-C6烷氧基、卤代C1-C6烷氧基、未取代的C1-C6烷硫基、卤代C1-C6烷硫基、C1-C6烷酰胺基、取代的或未取代的杂环烷基；这里，所述取代的芳烃基、取代的芳烃氧基或取代的杂环烷基是指芳烃基、芳烃氧基或杂环烷基被一个或多个B组基团所取代、或者C1-C6烷基与杂环烷基中的N形成季铵；
所述B组基团选自：氰基、芳烃基取代的C1-6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C6烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基和C1-C6烷氧基羰酰；
或者，所述苯并呋喃衍生物的药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
10.根据权利要求9所述用途，其中，所述苯并呋喃衍生物作为FXR调节剂的用途，优选地，是作为FXR拮抗剂或抑制剂的用途，包括但不限于降脂活性、抗高脂血症活性、抗血脂异常活性、抗动脉粥样硬化活性、抗肥胖症活性、和/或抗糖尿病活性。
11.式(1)所示的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物；
Figure FDA0003601498430000161
其中，Q选自氢、6至10元芳基、5至14元杂芳基、3至6元环烷基、3至6元杂环基；任选地，所述6至10元芳基、5至14元杂芳基、3至6元环烷基、3至6元杂环基被一个或多个M取代，M选自以下基团：卤素、硝基、羟基、氰基、C1-C6烷基、C2-C6烯基、C2-C6炔基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6烷酰基、C1-C6酰胺基；
L1不存在或选自-(CH2)n-，n为选自1至6的整数；任选地，-(CH2)n-被一个或多个选自以下的基团取代：苯基、卤素、硝基、氰基、羟基、C1-C6烷基、氘、氚；
R1为-(CH2)n-R4，这里，n为0至6的整数，R4和A组基团如权利要求1-6或9任一项所定义；
B组基团选自：氰基、芳烃基取代的C1-C6烷酰基、芳烃基取代的C1-C6烷基、未取代的C1-C6烷基、未取代的C1-C7烷酰基、未取代的C1-C6烷烃磺酰基、芳烃基取代的C1-C6烷烃磺酰基、单或双C1-C6取代胺甲酰、氨甲酰基、C1-C6烷氧基羰酰基、未取代的3-6元环烷基羰酰基、取代的3-6元环烷基羰酰基、取代的5-14元杂芳基羰酰基、未取代的5-14元杂芳基羰酰基、未取代的C2-C6烯基羰酰基、未取代的5-10元杂环基羰酰基、取代的5-10元杂环基羰酰基；
W为5-6元杂芳基；
R8选自氢、卤素、未取代的C1-C6烷基或取代的C1-C6烷基；m选自1、2、3、4；当有多个R8时，各个R8可以相同或不同；
R9选自-CH2OH或-(C＝O)R2，R2如权利要求1-6任一项所定义。
12.权利要求11的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，
其中，Q选自6至10元芳基、5至8元单环杂芳基、8至14元稠杂芳基、5至6元环烷基、5至6元杂环基；任选地，所述6至10元芳基、5至8元单环杂芳基、8至14元稠杂芳基、5至6元环烷基、5至6元杂环基被一个或多个M取代；
优选地，Q选自6至10元芳基、5至8元单环杂芳基、5至6元环烷基；
优选地，Q选自苯基、噻吩基、环己烷基；
优选地，Q为苯基。
13.权利要求11或12的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，
其中，L1不存在或选自-(CH2)n-，n为1、2或3；
优选地，L1为-(CH2)2-。
14.权利要求11-13任一项的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，
其中，R1为被一个或多个选自A组基团所取代的苯基；
优选地，A为未取代的或被一个或多个B组基团所取代的杂环烷基；
优选地，所述杂环基为5-7元单杂环基、9-10元螺杂环基或6-8元桥杂环基；
优选地，所述杂环基为5-7元含氮单杂环基、9-10元含氮螺杂环基或6-8元含氮桥杂环基；
优选地，所述杂环基为哌嗪基；
优选地，B选自：-(C＝O)-苯基、-(C＝O)-5～6元杂芳基、-(C＝O)-丙烯基、-(C＝O)-5～6元环烷基、-(C＝O)-5～6元杂环基、-(C＝O)-C1-C6烷基；
任选地，所述苯基、5～6元杂芳基、5～6元环烷基、5～6元杂环基被1、2或3个选自以下的取代基所取代：C1-C6烷基(例如甲基)、甲酰胺基、乙酰胺基、C1-C6卤代烷基(例如三氟甲基)、氰基、卤素(例如氟、氯、溴)、氨基、硝基、C1-C6烷酰基(例如乙酰基)、C1-C6烷氧基(例如甲氧基)、苄基、乙炔苯基；
优选地，所述5～6元杂芳基选自吡啶基、噻吩基、呋喃基、吡咯基、咪唑基、恶唑基、噻唑基、吡唑基；任选地，所述5～6元杂芳基被一个或多个C1-C6烷基(例如甲基)或卤素(例如溴)取代；
优选地，所述5～6元杂环基为四氢噻吩基；
优选地，B选自-(C＝O)-苯基、-(C＝O)-噻吩基。
15.权利要求11-14任一项的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，所述化合物如式(2)、(3)、(4)或(5)所示，
Figure FDA0003601498430000181
Figure FDA0003601498430000191
其中，X为O、S、N-R8，R8为氢或未取代的C1-C6烷基
优选地，式(2)、(3)、(4)或(5)中，R8为甲基；
优选地，式(2)、(3)、(4)或(5)中，R2为羟基或未取代的C1-C6烷氧基。
16.权利要求11-15任一项的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物，所述化合物选自：
Figure FDA0003601498430000201
Figure FDA0003601498430000211
Figure FDA0003601498430000221
Figure FDA0003601498430000231
Figure FDA0003601498430000241
17.药物组合物，包含权利要求11-16任一项的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物。
18.权利要求1-7或11-16任一项的化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物用于制备药物的用途，所述药物用于治疗与FXR相关的疾病；
优选地，所述化合物、其药学上可接受的盐或酯、立体异构体、互变异构体、几何异构体、前药、水合物、溶剂合物、晶型、它们的代谢物形式、或它们的任意组合或混合物作为FXR激动剂或FXR拮抗剂被使用；
优选地，所述与FXR有关的疾病选自代谢相关疾病、心血管疾病、肝脏疾病、癌症、肾病、肠病、炎症或其任意组合；
优选地，所述代谢相关疾病选自糖脂代谢疾病、胆固醇代谢疾病、脂质代谢疾病、胆汁酸代谢疾病或其任意组合；
优选地，所述糖脂代谢疾病选自肥胖症、糖尿病(如2型糖尿病)、血脂异常、高脂血症、高胆固醇、胆汁淤积症、非酒精性脂肪肝、非酒精性脂肪性肝炎或其任意组合；
优选地，所述心血管疾病选自动脉粥样硬化、心肌缺血再灌注损伤或其组合；
优选地，所述肝脏疾病选自肝切除、肝损伤或其组合；
优选地，所述癌症选自乳腺癌、黑色素瘤、脑膜瘤、软组织肉瘤、唾液腺肿瘤、原发性肝癌、椎管内肿瘤、纵隔肿瘤、脑癌、骨癌、阴茎癌、骨肉瘤、颅内肿瘤、舌癌、上颌窦癌、甲状腺癌、恶性淋巴瘤、多发性骨髓瘤、脑垂体腺瘤、睾丸肿瘤、非何杰金氏淋巴癌、膀胱癌、白血病、胃癌、鼻咽癌、喉癌、口腔癌、食管癌、肺癌、肾癌、宫颈癌、绒毛膜癌、外阴癌、皮肤癌、子宫内膜癌、卵巢癌、前列腺癌、胰腺癌、结肠癌、直肠癌、大肠癌、卡波西肉瘤、非黑色素瘤皮肤癌(包括鳞状细胞癌和基底细胞癌)、血管瘤、神经胶质瘤及这些疾病的继发性并发症；
优选地，所述肾病选自肾炎、肾病综合征、动脉粥样栓塞性肾脏疾病或其任意组合。
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