CN114641477A - 对葡萄糖神经酰胺合酶具有抑制活性的新化合物或其药学上可接受的盐、制备其的方法和包含其的药物组合物 - Google Patents
对葡萄糖神经酰胺合酶具有抑制活性的新化合物或其药学上可接受的盐、制备其的方法和包含其的药物组合物 Download PDFInfo
- Publication number
- CN114641477A CN114641477A CN202080075799.4A CN202080075799A CN114641477A CN 114641477 A CN114641477 A CN 114641477A CN 202080075799 A CN202080075799 A CN 202080075799A CN 114641477 A CN114641477 A CN 114641477A
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- China
- Prior art keywords
- quinuclidin
- carbamate
- dimethylchroman
- chroman
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- 238000002360 preparation method Methods 0.000 abstract description 54
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
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Abstract
本发明提供一种具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的新化合物或其药学上可接受的盐、该新化合物或其药学上可接受的盐的制备方法、包含该新化合物或其药学上可接受的盐的药物组合物及它们的用途。具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的化合物或其药学上可接受的盐具有对葡萄糖神经酰胺合酶(GCS)的抑制活性,因此可以用于预防或治疗与GCS相关的各种疾病例如戈谢病、法布里病、泰‑萨克斯病、帕金森病等。
Description
技术领域
本发明涉及一种对葡萄糖神经酰胺合酶(glucosylceramide synthase,GCS)具有抑制活性的新化合物,即具有苯并二氢吡喃、异苯并二氢吡喃(isochromane)、硫代苯并二氢吡喃(thiochromane)或四氢喹啉部分的衍生物,或该新化合物的药学上可接受的盐、用于制备它们的方法和包含它们的药物组合物,以及它们的用途。
背景技术
溶酶体贮积症(Lysosomal storage disorders,LSDs)是由溶酶体中某些酶的遗传性缺乏或缺陷引起的代谢紊乱。随着不代谢(non-metabolized)或不降解(non-degraded)底物(substrate)的积累,LSDs在全身表现出各种病理性症状。目前,已知的LSDs约有50种类型,根据所积累的物质,这些LSDs主要分为例如粘多糖贮积症(mucopolysaccaridose)、寡糖贮积症(oligosaccharidosis)和神经鞘脂贮积症(sphingolipidoses)等疾病。
在这些疾病中,神经鞘脂贮积症为与鞘脂代谢相关的一类糖脂贮积障碍,表现出由于各种膜鞘糖脂(membrane glycosphingolipids,GSLs)如葡萄糖神经酰胺(glucosylceramide)、三己环神经酰胺(trihexocylceramide)等的积累而引起的病症。例如,当与鞘脂代谢相关的酶,如β-葡萄糖苷酶、α-半乳糖苷酶等,不具有正常的活性时,其底物(如葡萄糖神经酰胺、三己环神经酰胺等)积累,从而表现出各种病症,例如戈谢病(Gaucher disease)、法布里病(Fabry disease)等。
已知有两种类型的用于LSDs的疗法。第一种方法是替代或补充不足或有缺陷的代谢酶。虽然这种酶替代疗法(enzyme replacement therapy,ERT)是安全有效的,但需要定期静脉内给药相关酶,并根据酶反应调节剂量,成本较高。特别是,由于难以将酶分配到神经系统,因此ERT在治疗与神经系统相关的症状方面没有显示令人满意的功效。此外,还存在经常产生针对所施用的酶(administered enzyme)的自身抗体的问题。
第二种方法是底物减少疗法(substrate reduction therapy,SRT),用于抑制累积的底物的合成。葡萄糖神经酰胺合酶(GCS)(也称为“UDP-葡萄糖:神经酰胺糖基转移酶”、“UDP-葡萄糖:N-酰基鞘氨醇D-葡糖基转移酶”或“EC 2.4.1.80”)是一种涉及鞘脂代谢的酶,参与神经酰胺与葡萄糖反应生成葡萄糖神经酰胺。所得到的葡萄糖神经酰胺被转化为各种GSL。葡萄糖神经酰胺合酶(GCS)抑制剂抑制GCS的活性,从而减少体内葡萄糖神经酰胺的产生,并防止糖脂例如三己环神经酰胺、GM1和GM2在细胞或器官内的异常积累。
因此,GCS抑制剂抑制GCS的活性以防止糖脂的积累,因此可用于治疗溶酶体贮积症,尤其是糖脂贮积障碍,例如GM1神经节苷脂贮积症(gangliosidosis)、泰-萨克斯病(Tay-Sachs disease)、桑德霍夫病(Sandhoff disease)、戈谢病、法布里病、尼曼-皮克病(Niemann-Pick disease)(A型和B型)、异染性脑白质营养不良(metachromaticleukodystrophy)、克拉伯病(Krabbe disease)等。GCS抑制剂也可以用于治疗与糖脂贮积相关的继发性疾病(secondary diseases),例如尼曼-皮克病(C型)、粘多糖贮积症(mucopolysaccharidosis)和粘脂贮积症Ⅳ型(mucolipidosis typeⅣ)(参见Chen CS,etal.,Abnormal transport along the lysosomal pathway in mucolipidosis,typeⅣdisease Proc Natl Acad Sci U S A.1998 May 26;95(11):6373-8;和Goodman LA,etal.,Ectopic dendrites occur only on cortical pyramidal cells containingelevated GM2 ganglioside in α-mannosidosis,Proc Natl Acad Sci U S A.1991Dec15;88(24):11330-4)。此外,据报道,GCS抑制剂可用于治疗与糖脂积累相关的疾病,例如肾肥大(例如糖尿病肾病);高血糖症或高胰岛素血症;糖脂合成异常的癌症;由使用细胞表面糖脂作为受体的生物体(organism)引起的传染病;葡萄糖神经酰胺的合成是必需的或重要的传染病;出现糖脂合成过多的疾病(例如,动脉粥样硬化、多囊肾病和肾肥大);与巨噬细胞的补充和活性相关的神经障碍和/或神经损伤(例如,阿尔茨海默病(Alzheimer'sdisease)、癫痫、中风、脊髓疾病、帕金森病(Parkinson's disease)等);炎症性疾病或障碍(例如,类风湿性关节炎、克罗恩病(Crohn's disease)、哮喘、败血症);以及糖尿病和肥胖症(参见WO 2006/053043)。并且,GCS的过表达干扰神经酰胺诱导的细胞凋亡(参见Liu YY,et al.,Uncoupling ceramide glycosylation by transfection of glucosylceramidesynthase antisense reverses adriamycin resistance,J Biol Chem.2000Mar 10;275(10):7138-43)。因此,GCS抑制剂可用于通过诱导患病细胞凋亡来治疗增殖性疾病,例如癌症。
已经进行了各种研究以开发GCS抑制剂。例如,在WO 2005/068426、WO 2006/053043、WO 2008/150486、WO 2009/117150、WO 2010/014554、WO 2014/043068等中公开了对GCS具有抑制活性的各种化合物。
发明内容
技术问题
本发明人发现具有6,6-稠合双环部分(6,6-fused bicyclic moiety),即苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐对葡萄糖神经酰胺合酶(GCS)具有优异的抑制活性。因此,具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受盐可以用于预防或治疗与GCS相关的各种疾病例如戈谢病、法布里病、泰-萨克斯病、帕金森病等。
因此,本发明提供了上述具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或该衍生物的药学上可接受的盐、它们的制备方法、包含它们的药物组合物及它们的用途。
技术方案
根据本发明的一个方面,提供一种具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐。
根据本发明的另一个方面,提供了用于制备所述具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐的方法。
根据本发明的又另一个方面,提供了一种包含所述具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐作为活性成分的药物组合物。
根据本发明的又另一个方面,提供了一种治疗方法,其包括施用所述具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐。
根据本发明的又另一个方面,提供了所述具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐在制备用于抑制葡萄糖神经酰胺合酶的药物中的用途。
发明的有益效果
本发明发现具有6,6-稠合双环部分,即苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐对葡萄糖神经酰胺合酶(GCS)具有优异的抑制活性。因此,根据本发明的化合物或其药学上可接受的盐可以用于预防或治疗与GCS相关的各种疾病例如戈谢病、法布里病、泰-萨克斯病、帕金森病等。
具体实施方式
如本文所用,术语“烷基”是指直链或支链脂族烃基(aliphatic hydrocarbonradical)。例如,C1~C6烷基是指具有1至6个碳原子的直链或支链脂肪烃,例如甲基、乙基、丙基、正丁基、正戊基、正己基、异丙基、异丁基、仲丁基、叔丁基、新戊基和异戊基。
术语“羟基”是指“-OH”基团。术语“烷氧基”是指通过用烷基取代羟基中的氢原子而形成的基团。例如,C1~C6烷氧基包括甲氧基、乙氧基、丙氧基、正丁氧基、正戊氧基、异丙氧基、仲丁氧基、叔丁氧基、新戊氧基(neopentyloxy)和异戊氧基(isopentyloxy)。
术语“卤素”是指氟、溴、氯或碘基团。
除非另有定义,否则术语“环烷基”是指饱和脂肪族3-元环至10-元环,优选3-元环至7-元环。典型的环烷基包括环丙基、环丁基、环戊基、环己基等,但不限于此。
术语“芳基”是指通过从芳烃中除去一个氢原子而衍生的有机基团,该芳烃包括单稠环体系或多稠环体系(mono or poly-fused ring system),例如5-元至14-元取代或未取代的环,并且包括其中多个芳基通过单键连接的形式(form)。“芳基”包括例如苯基、萘基、联苯基、三联苯基、蒽基、茚基(indenyl)、芴基(fluorenyl)、菲基(phenanthryl)、三亚苯基、芘基(pyrenyl)、苝基(perylenyl)、基(chrysenyl)、并四苯基(naphthacenyl)、荧蒽基(fluoranthenyl)等,但不限于此。
术语“杂芳基(heteroaryl)”是指具有1至3个选自氮(N)原子、氧(O)原子和硫(S)原子的杂原子的5-元至12-元芳族基团,包括5-元或6-元单环杂芳基和通过5-元或6-元单环杂芳基与苯或吡啶环稠合形成的双环杂芳基。并且,术语“杂环(heterocycle)”是指具有一个或多个,优选1个至4个选自氧(O)原子、氮(N)原子和硫(S)原子的相同或不同杂原子的3-元至12-元单环或多环,但不含芳环。杂芳基或杂环的非限制性实例包括氧杂环丁烷(oxetane)、吡咯烷、吡咯、四氢呋喃、呋喃、四氢噻吩、噻吩、咪唑烷(imidazolidine)、咪唑、吡唑烷(pyrazolidine)、吡唑、吡咯嗪(pyrrolizine)、噁唑烷(oxazolidine)、噁唑、异噁唑烷、异噁唑、噻唑烷(thiazolidine)、噻唑、异噻唑烷、异噻唑、二氧戊环(dioxolane)、二硫戊环(dithiolane)、噁二唑、噻二唑、二噻唑、四唑(tetrazole)、噁四唑(oxatetrazole)、噻四唑(thiatetrazole)、哌啶、吡啶、嘧啶、四氢吡喃、吡喃、噻烷(thiane)、噻喃、哌嗪(piperazine)、二嗪(diazine)、吗啉、噁嗪、二噁烷(dioxane)、吲哚、二氢吲哚、苯并二氧杂环戊烯、苯并噻吩、苯并呋喃、苯并咪唑、苯并噁唑、苯并异噁唑、苯并噻唑、苯并噻二唑、苯并三唑、喹啉、异喹啉、嘌呤、呋喃并吡啶(furopyridine)、单或双氮杂双环类(例如奎宁环、二氮杂双环庚烷、单氮杂双环辛烷、二氮杂螺十一烷(diazaspiroundecane)等)、六氢吡咯并吡咯(hexahydropyrrolopyrrole)、吡咯并吡咯、吡咯并吡啶、咪唑并哒嗪(imidazopyridazine)、二氢苯并二噁英、二氢苯并呋喃等,但不限于此。
术语“氨基”是指“-NH2”基团。术语“烷基氨基”是指被单烷基或二烷基取代的氨基。例如,C1~C6烷基氨基包括被单个或两个C1~C6烷基取代的氨基。
术语“烷硫基”是指“-SR”基团,其中R是烷基。术语“氰基(cyano)”是指“-CN”。
本发明提供了具有6,6-稠合双环部分即苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的衍生物或其药学上可接受的盐,即式1的化合物或其药学上可接受的盐:
<式1>
其中,
L是-O-、-CO-、-CR1R2-或-NR3-,
X是氢;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C1~C6烷氧基;或被1至3个卤素原子取代的C1~C6烷氧基,
Y是-CR4R5-;-NR3-;-O-;或-S-,
P是-CR4R5-,
Q是-O-或-CR4R5-,
Z是-CR6-,
R1和R2彼此独立地是氢;卤素;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基;或R1和R2与它们所连接的碳原子一起形成C3~C10环烷基,
R3是氢;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基,
R4和R5彼此独立地是氢;卤素;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基;或R4和R5与它们所连接的P或Q的碳原子一起形成C3~C10环烷基,
R6是氢;C1~C6烷基;或具有氮原子、氧原子或硫原子的C1~C6烷基,
W是一个键、-CH2-、-O-、-NH-、-CH2CH2-、-CH=CH-或-C≡C-,
A环是6-元至12-元芳基;5-元至12-元杂芳基;C3~C10环烷基;或3-元至12-元杂环,并且
X1、X2、X3和X4彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;3-元至12-元杂环;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;C1~C6烷硫基;氨基;单或双C1~C6烷基氨基;吗啉基;吡咯烷基-磺酰基;苄基;羟基;或硝基。
在根据本发明的式1的化合物或其药学上可接受的盐中,L可以是-O-。
在根据本发明的式1的化合物或其药学上可接受的盐中,X可以是氢;卤素;或C1~C6烷氧基。
在根据本发明的式1的化合物或其药学上可接受的盐中,R3可以是C1~C6烷基;R4、R5和R6可以彼此独立地是氢或C1~C6烷基。在一个实施方案中,Y可以是-O-,其中式1的化合物可以具有苯并二氢吡喃部分。在另一个实施方案中,Q可以是-O-,其中式1的化合物可以具有异苯并二氢吡喃部分。在又一个实施方案中,Y可以是-S-,其中式1的化合物可以具有硫代苯并二氢吡喃部分。在又一个实施方案中,Y可以是-NR3-,其中式1的化合物可以具有四氢喹啉部分。
在根据本发明的式1的化合物或其药学上可接受的盐中,W可以是键(即,A环直接与苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分连接)、-CH2-或-CH=CH-。
在根据本发明的式1的化合物或其药学上可接受的盐中,A环可以是苯基、联苯基、噻吩基、吡唑基、噻唑基、萘基、苯并噻二唑基(benzothiadiazolyl)、苯并二氧杂环戊烯基(benzodioxolyl)、2,3-二氢苯并二噁英基(2,3-dihydrobenzodioxinyl)、苯并呋喃基、2,3-二氢苯并呋喃基、1,3-二氢异苯并呋喃基、3,4-二氢-1,4-苯并噁嗪基、3-氧代-3,4-二氢-1,4-苯并噁嗪基、苯并噻吩基、吲哚基、吲唑基、异喹啉基、喹啉基、3,4-二氢-苯并二氧杂环庚三烯基(3,4-dihydro-benzodioxepinyl)、苯并[c][1,2-5]噁二唑基(benzo[c][1,2-5]oxadiazolyl)、吡啶基、6-氧代-1,6-二氢吡啶基、苯并二氢吡喃基(chromanyl)、二苯并呋喃基、或嘧啶基。
在根据本发明的式1的化合物或其药学上可接受的盐中,X1、X2、X3和X4可以彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;吗啉基;单或双C1~C6烷基氨基;吡咯烷基-磺酰基;苄基;四氢吡喃基;C1~C6烷硫基;或异噁唑基(isoxazolyl)。
在本发明优选的实施方案中,
L是-O-,
X是氢;卤素;或C1~C6烷氧基,
Y是-CR4R5-;-NR3-;-O-;或-S-,
P是-CR4R5-,
Q是-O-或-CR4R5-,
Z是-CR6-,
R3是C1~C6烷基,
R4、R5和R6彼此独立地是氢或C1~C6烷基,
W是一个键、-CH2-或-CH=CH-,
A环是苯基、联苯基、噻吩基、吡唑基、噻唑基、萘基、苯并噻二唑基、苯并二氧杂环戊烯、2,3-二氢苯并二噁英基、苯并呋喃基、2.3-二氢苯并呋喃基、1,3-二氢异苯并呋喃基、3,4-二氢-1,4-苯并噁嗪基、3-氧代-3,4-二氢-1,4-苯并噁嗪基、苯并噻吩基、吲哚基、吲唑基、异喹啉基、喹啉基、3,4-二氢-苯并二氧杂环庚三烯基、苯并[c][1,2-5]噁二唑基、吡啶基、6-氧代-1,6-二氢吡啶基、苯并二氢吡喃基、二苯并呋喃基或嘧啶基,并且
X1、X2、X3和X4彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;吗啉基;单或双C1~C6烷基氨基;吡咯烷基-磺酰基;苄基;四氢吡喃基;C1~C6烷硫基;或异噁唑基。
在式1的化合物或药学上可接受的盐中,优选的化合物包括选自以下的化合物,包括其药学上可接受的盐:
(S)-奎宁环-3-基(7-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-环丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲哚-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(喹啉-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1,3-二氢异苯并呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基[6,7'-二苯并二氢吡喃]-4'-基氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基-5-(三氟甲基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(8-甲基喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(萘-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(萘-1-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氯-5-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二甲基-4-丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁氧基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-丁氧基-6-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(6-(2,2,2-tri氟乙氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-8-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-环丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3',3'-二甲基-[6,7'-二苯并二氢吡喃]-4'-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并呋喃-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噁二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(5-甲基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(噻唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基吡啶-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-6-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-环丙基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(二甲氨基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-乙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基-5-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(异噁唑-3-基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-苯基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-苄基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(间甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(邻甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-((E)-2-(噻吩-3-基)乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-烯丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-2-([1,1'-二苯基]-4-基)乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-环丙基嘧啶-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-((E)-4-(三氟甲基)苯乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-2,4-二氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-4-乙基苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-乙氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-3-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(二苯并[b,d]呋喃-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氰基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-6-氧代-1,6-二氢吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-4-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(4-甲基噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)异苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)异苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲硫基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-6-(4-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(2-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;和
(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯。
式1的化合物或其药学上可接受的盐可以是顺式几何异构体(geometricalisomer)或反式几何异构体的形式。除非另有说明,式1的化合物或其药学上可接受的盐包括顺式几何异构体和反式几何异构体。式1的化合物或其药学上可接受的盐也可以具有含有不对称原子的取代基,因此呈外消旋混合物(RS)形式或光学异构体形式,例如(R)异构体或(S)异构体。除非另有说明,式1的化合物或其药学上可接受的盐包括外消旋混合物(RS)和各光学异构体例如(R)异构体或(S)异构体。此外,式1的化合物或其药学上可接受的盐可以具有两个或多个手性中心,因此为一种或多种非对映异构体的形式或其混合物的形式。除非另有说明,式1的化合物或其药学上可接受的盐包含各非对映异构体及其混合物。
本发明的式1的化合物可以是药学上可接受的盐形式。该盐可以是常规的酸加成盐(acid addition salt)形式,其包括例如衍生自如盐酸、硫酸、硝酸、磷酸、高氯酸或氢溴酸的无机酸的盐;以及衍生自例如甲酸、乙酸、丙酸、草酸、琥珀酸、苯甲酸、柠檬酸、马来酸、丙二酸、苹果酸、酒石酸、葡萄糖酸、乳酸、龙胆酸(gentisic acid)、富马酸、乳糖酸、水杨酸、邻苯二甲酸、扑酸(embonic acid)、天冬氨酸、谷氨酸、或乙酰水杨酸的有机酸的盐。并且,该盐还包括例如衍生自氨基酸如甘氨酸、丙氨酸、缬氨酸、异亮氨酸、丝氨酸、半胱氨酸、胱氨酸、天冬氨酸、谷氨酰胺、赖氨酸、精氨酸、酪氨酸或脯氨酸的盐。此外,该盐包括例如衍生自磺酸如甲磺酸、乙磺酸、苯磺酸或甲苯磺酸的盐。
根据本发明的式1的化合物或其药学上可接受的盐可以根据各种方法制备。
例如,根据本发明的式1a的化合物或其药学上可接受的盐可以通过包括以下的方法制备:使式2的化合物或其盐与氯甲酸乙酯反应得到式3的化合物;将式3的化合物与式4的化合物偶联,得到式5的化合物;使式5的化合物与被X1、X2、X3或X4取代的A-W-硼酸反应,得到式1a的化合物;并且任选地将式1a的化合物转化为其药学上可接受的盐,如以下反应方案1所示。
<反应方案1>
在反应方案1中,X、Y、P、Q、Z、W、A环、X1、X2、X3和X4与上文限定的相同。
式2的化合物是市售的或已知的化合物,可以根据文献合成。式2的化合物或其盐与氯甲酸乙酯之间的反应可以在有机碱例如三乙胺、N,N-二异丙基乙胺等或无机碱例如碳酸钾等的存在下进行。基于1当量的式2的化合物,可以以1当量至1.5当量范围内的量使用碱或基于1当量式2的化合物的盐(例如盐酸盐),可以以3当量至5当量范围内的量使用碱。该反应可以在溶剂如二氯甲烷或四氢呋喃中进行,优选在0℃至室温下进行。
式3的化合物和式4的化合物(即,奎宁环醇)之间的偶联可以通过包括除去乙醇的缩合反应来进行。该反应可以优选在碱例如氢化钠的存在下进行。此外,可以在120℃至140℃下,在例如甲苯的非极性有机溶剂中进行反应。
式5的化合物与被X1、X2、X3和X4取代的A-W-硼酸之间的反应可以根据铃木反应(Suzuki reaction)进行。所述铃木反应可以使用钯催化剂,例如四(三苯基膦)钯(tetrakis(triphenylphosphine)palladium)(0)(Pd(PPh3)4)、乙酸钯(Ⅱ)(Pd(OAc)2)、[1,1'-双(二苯基膦基)二茂铁]二氯钯(Ⅱ)(Pd(dppf)Cl2)等进行。此外,所述铃木反应可以在无机碱如碳酸铯(Cs2CO3)、碳酸钠(Na2CO3)、碳酸钾(K2CO3)、磷酸钾(K3PO4)等的存在下进行。所述铃木反应可以在例如甲苯的非极性有机溶剂或例如1,4-二氧六环、四氢呋喃、乙腈、1,2-二甲氧基乙烷或N,N-二甲基甲酰胺的极性有机溶剂中,在50℃至150℃,优选80℃至120℃下进行。包括反应时间在内的其他反应条件可以根据已知的铃木反应方法确定。
式1a的化合物向其药学上可接受的盐的转化可以按照常规方法进行。例如,式1a的化合物的药学上可接受的盐可以通过将式1a的化合物溶解在水混溶性溶剂(water-miscible solvent)如甲醇、乙醇、丙酮或1,4-二氧六环中,然后加入游离酸(free acid)或游离碱(free base)用于其结晶来制备。
此外,根据本发明的式1a的化合物或其药学上可接受的盐可以通过包括以下的方法制备:使式4的化合物与双(4-硝基苯基)碳酸酯反应得到式7的化合物;使式7的化合物与式2的化合物反应得到式5的化合物;使式5的化合物与被X1、X2、X3或X4取代的A-W-硼酸反应,得到式1a的化合物;并且任选地将式1a的化合物转化为其药学上可接受的盐,如以下反应方案2所示。
<反应方案2>
在反应方案2中,X、Y、P、Q、Z、W、A环、X1、X2、X3和X4与上文限定的相同。
式4的化合物(即奎宁环醇)与双(4-硝基苯基)碳酸酯之间的反应可以在极性溶剂如N,N-二甲基甲酰胺中优选在0℃至25℃下进行。也可以通过使式4的化合物与氯甲酸-4-硝基苯酯(4-nitrophenyl chloroformate)在碱例如三乙胺的存在下,在溶剂例如二氯甲烷、乙腈等中反应来制备式7的化合物。
式7的化合物和式2的化合物之间的反应可以在0℃至25℃下,在溶剂例如N,N-二甲基甲酰胺、四氢呋喃或乙腈中,在碱例如N,N-二异丙基乙胺或三乙胺的存在下进行。
式5的化合物与被X1、X2、X3或X4取代的A-W-硼酸之间的反应可以根据如上所述的铃木反应进行。此外,式1a的化合物向其药学上可接受的盐的转化可以按照上述常规方法进行。
根据本发明的具有苯并二氢吡喃、异苯并二氢吡喃、硫代苯并二氢吡喃或四氢喹啉部分的化合物,即式1的化合物或其药学上可接受的盐对葡萄糖神经酰胺合酶(GCS)具有优异的抑制活性,因此可以用于预防或治疗与GCS相关的各种疾病。
因此,本发明在其范围内包括一种用于抑制葡萄糖神经酰胺合酶(GCS)的药物组合物,该药物组合物包含治疗有效量的式1的化合物或其药学上可接受的盐作为活性成分。在一个实施方案中,本发明提供了一种用于预防或治疗与GCS相关的疾病,例如戈谢病、法布里病、泰-萨克斯病、帕金森病等的药物组合物,该药物组合物包含治疗有效量的式1的化合物或其药学上可接受的盐作为活性成分。
本发明的药物组合物可以包含药学上可接受的载体,例如稀释剂、崩解剂、甜味剂、润滑剂或调味剂。药物组合物可配制成口服剂型,例如片剂、胶囊剂、散剂、颗粒剂、混悬剂(suspension)、乳剂(emulsion)或糖浆剂;或肠胃外剂型(parenteral dosage form),例如外用溶液剂、外用混悬剂、外用乳剂、凝胶剂(例如软膏)、吸入剂、雾化剂、注射剂。剂型(dosage form)可以是各种形式,例如单次给药或多次给药的剂型。
本发明的药物组合物可以包含例如稀释剂(例如乳糖、玉米淀粉等);润滑剂(例如硬脂酸镁);乳化剂(emulsifying agent);悬浮剂(suspending agent);稳定剂(stabilizer);和/或等渗剂(isotonic agent)。如果需要,该组合物进一步包含甜味剂和/或调味剂。
本发明的组合物可以口服或肠胃外给药,包括吸入的、静脉内的、腹膜内的、皮下的、直肠的和局部的给药途径。因此,本发明的组合物可以配制成各种剂型,例如片剂、胶囊剂、水溶液或混悬剂。在用于口服给药的片剂的情况下,通常使用载体例如乳糖、玉米淀粉和例如硬脂酸镁的润滑剂。在用于口服给药的胶囊剂的情况下,乳糖和/或干玉米淀粉可以用作稀释剂。当口服给药需要水混悬剂时,活性成分可以与乳化剂和/或悬浮剂组合。如果需要,可以使用某些甜味剂和/或调味剂。对于肌肉内的、腹膜内的、皮下的和静脉内的给药,通常制备活性成分的无菌溶液,并适当调节和缓冲(buffered)溶液的pH。对于静脉内的给药,应控制溶质的总浓度以使制剂等渗(isotonic)。本发明的组合物可以是含有药学上可接受的载体的水溶液形式,例如pH值为7.4的盐水。溶液可以通过局部团注(bolusinjection)引入患者的肌肉内血流中。
式1的化合物或其药学上可接受的盐可以以每天约0.0001mg/kg至约100mg/kg的治疗有效量施用于受试患者。当然,剂量可以根据患者的年龄、体重、敏感性、症状或化合物的活性而改变。
本发明在其范围内包括在哺乳动物中抑制葡萄糖神经酰胺合酶(GCS)的方法,该方法包括向有需要的哺乳动物施用治疗有效量的式1的化合物或其药学上可接受的盐。在一个实施方案中,本发明提供了一种用于治疗与GCS相关的疾病,例如戈谢病、法布里病、泰-萨克斯病、帕金森病等的方法,该方法包括向有需要的哺乳动物施用治疗有效量的式1的化合物或其药学上可接受的盐。
本发明还提供了式1的化合物或其药学上可接受的盐在制备用于抑制哺乳动物中的葡萄糖神经酰胺合酶(GCS)的药物中的用途。在一个实施方案中,本发明提供了式1的化合物或其药学上可接受的盐在制备用于预防或治疗与GCS相关的疾病例如戈谢病、法布里病、泰-萨克斯病、帕金森病等的药物中的用途。
提供以下实施例和实验例仅用于说明目的,并不旨在限制本发明的范围。
在以下实施例中,盐水是指饱和氯化钠水溶液。除非另有说明,否则所有温度均以摄氏度(℃)为单位。除非另有说明,否则所有反应均在室温下进行。
以下制备例(Preparation)和实施例中制得的化合物的分析如下进行:核磁共振(NMR)光谱分析使用Bruker 400MHz光谱仪进行,其化学位移以ppm为单位进行分析。在硅胶(Merck,70-230目)上进行柱层析。每种起始材料是根据文献合成或商业购买的已知化合物。在250nm硅胶板上通过薄层色谱(TLC)分析所有反应和色谱馏分(chromatographicfraction),并用紫外线或碘(I2)染色进行可视化。
制备例1.(S)-奎宁环-3-基(7-溴代苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 7-溴-3,4-二氢-2H-苯并二氢吡喃-4-胺
在室温下,将7-溴代苯并二氢吡喃-4-酮(10.0g,44.04mmol)溶解在甲醇(100ml)和异丙醇(125ml)的混合溶剂中,然后将醋酸铵(67.9g,880.9mmol)和氰基硼氢化钠(13.84g,220.2mmol)加入其中。将反应混合物在室温搅拌4小时,然后在80℃搅拌回流12小时。将反应混合物冷却至室温,减压浓缩,用1N氢氧化钠溶液碱化(basified)至pH8~9,然后用乙酸乙酯萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩。所得残余物通过柱色谱法(二氯甲烷/甲醇=5/1,v/v)纯化,得到标题化合物,为淡黄色油状物。(7.8g,产率:77%)
步骤2.(S)-奎宁环-3-基(7-溴代苯并二氢吡喃-4-基)氨基甲酸酯
在室温下将(S)-(+)-3-奎宁环醇(558mg,4.38mmol)溶解在N,N-二甲基甲酰胺(9ml)中,然后将双(4-硝基苯基)碳酸酯(1.47g,4.82mmol)加入到其中。将反应混合物搅拌过夜。将步骤1中制备的7-溴-3,4-二氢-2H-苯并二氢吡喃-4-胺(1.0g,4.38mmol)缓慢加入反应混合物中,然后在室温下搅拌过夜。将反应混合物用水稀释,然后用乙酸乙酯萃取。有机层用10%氨水、饱和碳酸氢钠溶液和盐水洗涤,用无水硫酸镁干燥,然后减压过滤并浓缩。所得残余物通过柱色谱法(乙酸乙酯/(甲醇/氨水=1/1)=9/1,v/v)纯化,得到标题化合物,为白色固体。(1.23g,产率:73%)
1H-NMR(400MHz,CDCl3)δ7.14(t,1H),7.05~7.03(m,1H),7.00(s,1H),5.20~5.18(m,1H),4.84~4.83(m,1H),4.76~4.74(m,1H),4.27~4.26(m,1H),4.18~4.17(m,1H),3.25~3.21(m,1H),2.84~2.70(m,5H),2.19~2.17(m,1H),2.08~2.03(m,2H),1.79~1.78(m,1H),1.70~1.69(m,1H),1.57~1.56(m,1H),1.39~1.37(m,1H)
制备例2.(S)-奎宁环-3-基-(6-溴代苯并二氢吡喃-4-基)氨基甲酸酯
步骤1.乙基-(6-溴代苯并二氢吡喃-4-基)氨基甲酸酯
将6-溴代苯并二氢吡喃-4-胺(3g,13.27mmol)溶解在二氯甲烷(100mL)中,然后向其中缓慢加入三乙胺(1.9ml,13.27mmol)和氯甲酸乙酯(1.4ml,1.46mmol)。将反应混合物在室温搅拌4小时。向反应混合物中加入水,然后用二氯甲烷萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩。所得残余物通过柱色谱法(正己烷/乙酸乙酯=1/1,v/v)纯化,得到标题化合物,为白色固体。(3.6g,产率:90%)
步骤2.(S)-奎宁环-3-基(6-溴代苯并二氢吡喃-4-基)氨基甲酸酯
在0℃下,将(S)-(+)-3-奎宁环醇(2.54g,20.0mmol)溶解在甲苯(33ml)中,然后将氢化钠(239.9mg,1mmol)加入到其中。将反应混合物搅拌15分钟,然后向其中加入步骤1中制备的乙基(6-溴代苯并二氢吡喃-4-基)氨基甲酸酯(3g,1mmol)。将反应混合物在140℃搅拌回流20小时,然后冷却至室温。向反应混合物中加入盐水,然后用乙酸乙酯萃取。有机层用盐水洗涤两次,用无水硫酸镁干燥,然后减压浓缩。所得残余物通过柱色谱法(乙酸乙酯/(甲醇/氨水=1/1)=9/1,v/v)纯化,得到标题化合物,为白色固体。(1.1g,产率:29%)
1H-NMR(400MHz,CDCl3)δ7.37~7.24(m,2H),6.74~6.69(m,1H),4.80(s,1H),4.23(s,2H),3.27(q,1H),2.88~2.65(m,4H),2.17~1.90(m,4H),1.84~1.76(m,1H),1.71~1.60(m,1H),1.56~1.46(m,1H)
制备例3.(S)-奎宁环-3-基(7-溴-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 7-溴-3,3-二甲基苯并二氢吡喃-4-酮
将7-溴代苯并二氢吡喃-4-酮(20g,88.1mmol)溶解在四氢呋喃(400ml)中,然后在-78℃下向其中缓慢加入碘甲烷(37.5g,264.3mmol)。向反应混合物中加入叔丁醇钾(Potassium tert-butoxide)(49.4g,440.4mmol),将其温度缓慢升高至室温,然后搅拌16小时。向反应混合物中加入水,然后用乙醚萃取。有机层用无水硫酸镁干燥,然后减压浓缩。所得残余物通过柱色谱法(正己烷/乙酸乙酯=10/1,v/v)纯化,得到标题化合物,为白色固体。(11.8g,产率:52%)
1H-NMR(400MHz,CDCl3)δ7.76(d,1H),7.17~7.15(m,2H),4.15(s,2H),1.20(s,6H)
步骤2. 7-溴-3,3-二甲基苯并二氢吡喃-4-胺
使用步骤1中制备的7-溴-3,3-二甲基苯并二氢吡喃-4-酮,按照与制备例1的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.25(d,1H),7.04(d,1H),6.97(s,1H),3.97(d,1H),3.75(d,1H),3.55(s,1H),0.96(d,6H)
步骤3.(S)-奎宁环-3-基(7-溴-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用步骤2中制备的7-溴-3,3-二甲基苯并二氢吡喃-4-胺,按照与制备1的步骤2相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.09~7.03(m,2H),6.99(s,1H),4.87(t,1H),4.82~4.77(m,1H),4.63(d,1H),3.90~3.77(m,2H),3.31~3.21(m,1H),2.96~2.68(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.76~1.67(m,1H),1.64~1.54(m,1H),1.48~1.37(m,1H),1.03(d,3H),0.98(d,3H)
制备例4.(S)-奎宁环-3-基(6-溴-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
以6-溴代苯并二氢吡喃-4-酮为起始原料,按照与制备例3相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.31~7.23(m,2H),6.70(d,1H),4.93~4.84(m,1H),4.82~4.76(m,1H),4.69~4.66(m,1H),3.92~3.78(m,2H),3.32~3.21(m,1H),2.95~2.66(m,5H),2.16~2.09(m,1H),1.91~1.81(m,1H),1.75~1.68(m,1H),1.64~1.55(m,1H),1.49~1.39(m,1H),0.99(d,6H)
制备例5.(S)-奎宁环-3-基(7-溴-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 7-溴-2,2-二甲基苯并二氢吡喃-4-酮
将1-(4-溴-2-羟基苯基)乙-1-酮(1-(4-Bromo-2-hydroxyphenyl)ethan-1-one)(5.0g,23.25mmol)溶解在甲苯(77ml)中,然后缓慢加入丙酮(8.6ml,116.25mmol)和吡咯烷(1.91ml,23.25mmol)。将反应混合物在室温搅拌1小时,在搅拌下回流24小时,然后减压浓缩。将所得残余物用乙酸乙酯稀释,用6N盐酸溶液、2N氢氧化钠溶液和盐水洗涤,然后减压浓缩,得到标题化合物,为棕色固体。(3.6g,产率:60%)产物无需进一步纯化即用于后续反应。
1H-NMR(400MHz,CDCl3)δ7.71(d,1H),7.15~7.10(m,2H),2.72(s,2H),1.46(s,6H)
步骤2. 7-溴-2,2-二甲基-苯并二氢吡喃-4-胺盐酸盐
在室温下,将步骤1中制备的7-溴-2,2-二甲基苯并二氢吡喃-4-酮(3.57g,13.99mmol)溶解在异丙醇(46.65ml)中,然后将醋酸铵(21.57g,279.88mmol)和氰基硼氢化钠(4.4g,69.97mmol)加入其中。将反应混合物在室温搅拌4小时,然后在80℃搅拌回流22小时。将反应混合物冷却至室温,减压浓缩,用1N氢氧化钠溶液碱化至pH>12,然后用二氯甲烷萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩。向所得残余物中加入乙酸乙酯,然后向其中加入盐酸(4M)的1,4-二氧六环溶液。将混合物在室温搅拌1小时。减压过滤所得固体,用乙酸乙酯洗涤,然后干燥,得到标题化合物,为白色固体。(3.43g,产率:83.7%)
1H-NMR(400MHz,DMSO-d6)δ8.81(brs,3H),7.63(d,1H),7.16(d,1H),7.02(s,1H),4.47(dd,1H),2.31(dd,1H),1.80(t,1H),1.41(s,3H),1.21(s,3H)
步骤3.(S)-奎宁环-3-基(7-溴-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
在氮气氛下在25-30℃下,将(S)-(+)-3-奎宁环醇(1.91g,15.04mmol)溶解在N,N-二甲基甲酰胺(27.34ml)中,然后向其中加入氯甲酸硝基苯酯(3.03g,15.04mmol)。将反应混合物在相同温度下搅拌3小时以上。将步骤2中制备的7-溴-2,2-二甲基苯并二氢吡喃-4-胺盐酸盐(4g,13.67mmol)和N,N-二异丙胺(5.89ml,34.18mmol)加入到反应混合物中,然后将其在相同温度搅拌约4小时。向反应混合物中加入水(250ml),然后用乙酸乙酯萃取。萃取液(extract)用盐水洗涤,用无水硫酸镁干燥,然后减压过滤并浓缩。所得残余物通过柱色谱法(乙酸乙酯/(甲醇/氨水=1/1)=9/1,v/v),得到标题化合物,为白色固体。(620mg,产率:11%)
1H-NMR(400MHz,CDCl3)δ7.14(t,1H),7.00(t,1H),6.95(s,1H),5.11~5.01(m,1H),4.97~4.87(m,1H),4.83~4.74(m,1H),3.32~3.19(m,1H),2.91~2.66(m,5H),2.26~2.16(m,1H),2.13~2.01(m,1H),1.90~1.79(m,1H),1.76~1.66(m,2H),1.64~1.54(m,1H),1.48~1.37(m,4H),1.30(s,3H)
制备例6.(S)-奎宁环-3-基(6-溴-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
以6-溴-2,2-二甲基苯并二氢吡喃-4-胺为起始原料,根据与制备例5的步骤3相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.39(d,1H),7.24(d,1H),6.67(d,1H),5.15~5.06(m,1H),5.00~4.91(m,1H),4.85~4.73(m,1H),3.31~3.16(m,1H),3.00~2.65(m,5H),2.27~2.16(m,1H),2.13~2.00(m,1H),1.89~1.77(m,1H),1.74~1.64(m,2H),1.63~1.53(m,1H),1.49~1.37(m,4H),1.30(s,3H)
制备例7.(S)-奎宁环-3-基(7-溴-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 7-溴-4-甲基苯并二氢吡喃-4-醇
将7-溴代苯并二氢吡喃-4-酮(5.0g,22.02mmol)溶解在四氢呋喃(88ml)中,然后在-50℃下15分钟内缓慢加入甲基溴化镁(methylmagnesium bromide)(3M)的乙醚溶液(22.02ml,66.06mmol)。将反应混合物的温度升高至室温,然后搅拌20小时。通过向反应混合物中加入饱和氯化铵溶液淬灭(quenched)反应,然后用乙酸乙酯萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩。所得残余物通过柱色谱法(正己烷/乙酸乙酯=5/1,v/v)纯化,得到标题化合物,为淡黄色油状物。(4.87g,产率:90%)
步骤2. 4-叠氮基-7-溴-4-甲基苯并二氢吡喃
将步骤1中制备的7-溴-4-甲基苯并二氢吡喃-4-醇(2.0g,8.23mmol)溶解在二氯甲烷(30ml)中,然后向其中缓慢加入叠氮化钠(0.87ml,24.68mmol)。将反应混合物冷却至0℃后,在20分钟内将通过将三氟乙酸(1.89ml,24.68mmol)溶解在二氯甲烷(15ml)中得到的溶液缓慢加入其中。将反应混合物的温度升高至室温,然后搅拌3小时。通过向反应混合物中加入饱和碳酸氢钠溶液淬灭反应,然后用二氯甲烷萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩,得到标题化合物,为白色固体。(2.21g,产率:99.9%)
步骤3. 7-溴-4-甲基苯并二氢吡喃-4-胺
将步骤2中制备的4-叠氮基-7-溴-4-甲基苯并二氢吡喃(2.21g,8.23mmol)溶解在四氢呋喃(27.43ml)中,然后将水(0.3ml,16.46mmol)和三甲基膦的四氢呋喃溶液(9.05ml,9.05mmol)缓慢加入其中。将反应混合物加热至70℃,然后搅拌1小时。将水(1ml)另外加入到反应混合物中,然后将其在相同温度下搅拌过夜。将反应混合物冷却至室温,然后减压浓缩。将所得残余物通过柱色谱法(乙酸乙酯/甲醇=10/1,v/v)纯化,得到标题化合物,为淡黄色油状物。(1.71g,产率:85%)
1H-NMR(400MHz,CDCl3)δ7.30(d,1H),7.03(d,1H),6.97(s,1H),4.26~4.22(m,2H),2.03~1.90(m,2H),1.48(s,3H)
步骤4.(S)-奎宁环-3-基(7-溴-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用步骤3中制备的7-溴-4-甲基苯并二氢吡喃-4-胺,按照与制备例1的步骤2相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.22(d,1H),7.03(d,1H),6.99(s,1H),5.15~5.01(m,1H),4.68~4.58(m,1H),4.30~4.14(m,2H),3.24~3.09(m,1H),2.89~2.55(m,6H),2.00~1.86(m,2H),1.82~1.61(m,5H),1.56~1.46(m,1H),1.41~1.29(m,1H)
制备例8.(S)-奎宁环-3-基(7-溴代异苯并二氢吡喃-4-基)氨基甲酸酯
以-溴代异苯并二氢吡喃-4-酮为起始原料,按照与制备例1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.37(t,1H),7.30(t,1H),7.16(s,1H),5.45(t,1H),4.81~4.59(m,4H),4.10~4.00(m,1H),3.91~3.78(m,1H),3.31-3.15(m,1H),2.91~2.62(m,5H),2.06~1.97(m,1H),1.84~1.64(m,2H),1.61~1.51(m,1H),1.43~1.32(m,1H)
制备例9.(S)-奎宁环-3-基(7-溴-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯
步骤1. 7-溴-1-甲基-4-氧代-1,4-二氢喹啉-3-甲酸乙酯
将7-溴-4-氧代-1H-喹啉-3-甲酸乙酯(15.75g,53.19mmol)溶解在N,N-二甲基甲酰胺(118.2ml)中,然后向其中加入碳酸钾(18.36g,132.86mmol)和碘甲烷(16.55ml,265.87mmol)。将反应混合物加热至90℃,然后搅拌3小时。减压浓缩反应混合物,然后向其中加入水。将所得残余物减压过滤,用水洗涤,然后减压干燥,得到标题化合物,为淡黄色固体。产物无需进一步纯化即用于后续反应。
1H-NMR(400MHz,CDCl3)δ8.41(s,1H),8.35(d,1H),7.57(s,1H),7.54(dd,1H),4.38(q,2H),3.85(s,3H),1.40(t,3H)
步骤2. 7-溴-1-甲基-4-氧代-1,4-二氢喹啉-3-羧酸
将步骤1中制备的7-溴-1-甲基-4-氧代-1,4-二氢喹啉-3-甲酸乙酯(17.22g,55.52mmol)溶解在甲醇(100ml)中,然后向其中缓慢加入氢氧化钠的水(200ml)溶液(11.1g,277.62mmol)。将反应在90℃搅拌3小时,冷却至室温,然后减压浓缩。向所得残余物中加入水和10%柠檬酸溶液。减压过滤所得白色固体,然后减压干燥,得到标题化合物,为白色固体。(11.73g,产率:74%)
1H-NMR(400MHz,DMSO-d6)δ9.02(s,1H),8.25(d,1H),8.19(s,1H),7.82(d,1H),4.08(s,3H)
步骤3. 7-溴-1-甲基-2,3-二氢喹啉-4(1H)-酮
在室温下,将步骤2中制备的7-溴-1-甲基-4-氧代-1,4-二氢喹啉-3-羧酸(11.73g,41.58mmol)溶解在甲醇(415.82ml)中,然后将硼氢化钠(7.32ml,182.96mmol)缓慢加入其中。向反应混合物中加入4-甲基苯磺酸水合物(790.98mg,4.16mmol),然后在65℃搅拌1小时。将反应混合物冷却至室温,然后减压浓缩。向所得残余物中加入乙酸乙酯。有机层用饱和碳酸氢钠溶液和水洗涤,用无水硫酸镁干燥,然后减压过滤并浓缩,得到标题化合物,为白色固体。(5.74g,产率:57%)
1H-NMR(400MHz,CDCl3)δ7.74(d,1H),6.87~6.85(m,2H),3.49(t,2H),2.98(s,3H),2.72(t,2H)
步骤4. 7-溴-1-甲基-1,2,3,4-四氢喹啉-4-胺
使用步骤3中制备的7-溴-1-甲基-2,3-二氢喹啉-4(1H)-酮,按照与制备例1的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.03(d,1H),6.75(d,1H),6.69(s,1H),3.92(t,1H),3.39~3.32(m,1H),3.24~3.18(m,1H),2.90(s,3H),2.05~1.98(m,1H),1.84~1.79(m,1H)
步骤5.(S)-奎宁环-3-基(7-溴-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯
使用步骤4中制备的7-溴-1-甲基-1,2,3,4-四氢喹啉-4-胺,按照与制备例1的步骤2相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.00(d,1H),6.75(t,1H),6.71(s,1H),4.99~4.97(m,1H),4.80~4.77(m,2H),3.30~3.24(m,3H),2.96~2.72(m,8H),2.10~2.04(m,3H),1.88~1.84(m,1H),1.76~1.73(m,1H),1.67~1.64(m,1H),1.46~1.44(m,1H)
制备例10.(S)-奎宁环-3-基(6-溴代硫代苯并二氢吡喃-4-基)氨基甲酸酯
以6-溴代硫代苯并二氢吡喃-4-胺为起始原料,按照与制备例2相同的程序制备标题化合物。产物无需进一步纯化即用于后续反应。
制备例11.(S)-奎宁环-3-基(7-溴代硫代苯并二氢吡喃-4-基)氨基甲酸酯
以7-溴代硫代苯并二氢吡喃-4-胺为起始原料,按照与制备例2相同的程序制备标题化合物。产物无需进一步纯化即用于后续反应。
制备例12.(S)-奎宁环-3-基(6-溴-3,3-二甲硫基苯并二氢吡喃-4-基)氨基甲酸酯
以6-溴-硫代苯并二氢吡喃-4-酮为起始原料,按照与制备例3相同的程序制备标题化合物。产物无需进一步纯化即用于后续反应。
制备例13.(S)-奎宁环-3-基(7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 3-氯丙酸3-溴-4-氟苯基酯
将3-溴-4-氟苯酚(25.0g,130.89mmol)溶解于二氯甲烷(523.56ml)中,然后在-50℃下向其中缓慢加入氯化铝(Ⅲ)(26.18g,196.34mmol)。将3-氯丙酰氯(18.74ml,196.34mmol)缓慢加入反应混合物中,然后在室温下搅拌过夜。通过向反应混合物中加入盐水来使反应淬灭,然后用二氯甲烷萃取。有机层用无水硫酸镁干燥,然后减压浓缩。将所得残余物通过柱色谱法(正己烷/乙酸乙酯=1/1,v/v)进行纯化,得到标题化合物,为淡黄色油状物。(38g,产率:100%)
1H-NMR(400MHz,CDCl3)δ7.36(dd,1H),7.14(t,1H),7.08~7.04(m,1H),3.86(t,2H),3.05(t,2H)
步骤2. 7-溴-6-氟苯并二氢吡喃-4-酮
向步骤1中制备的3-氯丙酸3-溴-4-氟苯基酯(38.0g,134.99mmol)中缓慢加入三氟甲磺酸(75.08ml,850.41mmol)。将反应混合物在85℃搅拌1小时,然后冷却至0℃。将水(50ml)缓慢加入反应混合物中,然后用二氯甲烷萃取。有机层用无水硫酸镁干燥,然后减压浓缩,得到标题化合物,为棕色固体。(19.31g,产率:58%)
1H-NMR(400MHz,CDCl3)δ7.60(d,1H),7.25(d,1H),4.53(t,2H),2.81(t,2H)
步骤3. 7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-酮
使用步骤2中制备的7-溴-6-氟苯并二氢吡喃-4-酮,按照与制备例3的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.59(d,1H),7.24(d,1H),4.14(s,2H),1.20(s,6H)
步骤4. 7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-胺
使用步骤3中制备的7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-酮,按照与制备例1的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.21(d,1H),6.97(d,1H),3.93(d,1H),3.73(d,1H),3.53(s,1H),1.28(brs,2H),0.95(d,6H)
步骤5.(S)-奎宁环-3-基(7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用步骤4中制备的7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-胺,按照与制备例1的步骤2相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.04~6.91(m,2H),5.01(t,1H),4.82~4.73(m,1H),4.63(d,1H),3.89~3.73(m,2H),3.31~3.17(m,1H),2.94~2.63(m,5H),2.13~2.04(m,1H),1.85~1.76(m,1H),1.72~1.65(m,1H),1.61~1.52(m,1H),1.46~1.36(m,1H),1.02(d,3H),0.97(d,3H)
制备例14.(S)-奎宁环-3-基(7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
步骤1. 3-(3-溴-4-甲氧基苯氧基)丙腈
将3-溴-4-甲氧基苯酚(25.0g,123.13mmol)溶解在丙烯腈(80.66ml,1231.3mmol)中,并向其中缓慢加入碳酸钾(850.92mg,6.16mmol)和叔丁醇(1.17ml,12.31mmol)。将反应混合物在搅拌下回流8小时。向反应混合物中另外加入碳酸钾(850.92mg,6.16mmol),然后在搅拌下回流36小时。将反应混合物冷却至室温,然后减压浓缩。所得残余物用乙酸乙酯稀释,然后用1N氢氧化钠溶液洗涤。萃取有机层,然后再次用水萃取含水层(aqueous layer)。合并的有机层用无水硫酸镁干燥,然后减压浓缩。所得残余物通过柱色谱法(正己烷/乙酸乙酯=10/1,v/v)纯化,得到标题化合物。(25.44g,产率:80%)产物无需进一步纯化即用于后续反应。
步骤2. 7-溴-6-甲氧基苯并二氢吡喃-4-酮
在0℃下,将步骤1制备的3-(3-溴-4-甲氧基苯氧基)丙腈(25.44g,99.34mmol)溶解在三氟乙酸(38.01ml,496.68mmol)中,然后向其中缓慢加入三氟甲磺酸(13.15ml,149mmol)。将反应混合物在0℃搅拌5小时,在室温搅拌24小时,然后冷却至0℃。在0℃向反应混合物中缓慢加入水(3.58ml,198.67mmol),然后在室温下搅拌5小时。用乙酸乙酯和水稀释反应混合物,然后萃取有机层。将有机层用水洗涤,用无水硫酸镁干燥,然后减压浓缩。所得残余物通过柱色谱法(正己烷/乙酸乙酯=1/1,v/v)纯化,得到标题化合物。(17.2g,产率:67%)
1H-NMR(400MHz,CDCl3)δ7.33(s,1H),7.26(s,1H),4.50(t,2H),3.89(s,3H),2.79(t,2H)
步骤3. 7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-酮
使用步骤2制备的7-溴-6-甲氧基苯并二氢吡喃-4-酮,按照与制备例3的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.31(s,1H),7.23(s,1H),4.10(s,2H),3.87(s,3H),1.18(s,6H)
步骤4. 7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-胺
使用步骤3中制备的7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-酮,按照与制备例1的步骤1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.01(s,1H),6.98(s,1H),3.92-3.81(m,4H),3.70(d,1H),3.55(s,1H),2.01(brs,2H),0.95(d,6H)
步骤5.(S)-奎宁环-3-基(7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用步骤4中制备的7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-胺,按照与制备例1的步骤2相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.03(s,1H),6.71(d,1H),4.95(t,1H),4.80~4.74(m,1H),4.59(d,1H),3.87~3.70(m,5H),3.30~3.18(m,1H),2.91~2.66(m,5H),2.11~2.04(m,1H),1.85~1.76(m,1H),1.73~1.65(m,1H),1.61~1.51(m,1H),1.45~1.34(m,1H),1.02(d,3H),0.98(d,3H)
实施例1.(S)-奎宁环-3-基(7-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
向制备例1中制备的(S)-奎宁环-3-基(7-溴苯并二氢吡喃-4-基)氨基甲酸酯(50mg,0.13mmol)、3-氟苯基硼酸(28mg,0.2mmol)、磷酸钾(82.8mg,0.39mmol)和四(三苯基膦)钯(0)(15mg,10mol%)的混合物中,缓慢加入1,4-二氧六环(1ml)和水(0.5ml)。将反应混合物在搅拌下于120℃回流过夜,然后冷却至室温。向反应混合物中加入水,然后用乙酸乙酯萃取。有机层用无水硫酸镁干燥,然后减压过滤并浓缩。通过硅胶柱色谱法(乙酸乙酯/(甲醇/氨水=1/1)=9/1,v/v)纯化得到的黄色液体形式的残余物,得到标题化合物,为白色固体。(45mg,产率:85%)
1H-NMR(400MHz,CDCl3)δ7.39~7.32(m,3H),7.23(s,1H),7.15~7.11(m,1H),7.06~7.02(m,2H),5.08(m,1H),4.94~4.92(m,1H),4.79(m,1H),4.31~4.30(m,1H),4.24~4.22(m,1H),3.28~3.24(m,1H),2.88~2.69(m,5H),2.25~2.23(m,1H),2.13~2.03(m,2H),1.81(m,1H),1.71~1.68(m,1H),1.59~1.57(m,1H),1.40(m,1H)
实施例2至实施例84
分别使用制备例1中制备的(S)-奎宁环-3-基(7-溴苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸(substituted-boronic acid),按照与实施例1相同的程序制备实施例2至实施例84的标题化合物。
实施例2.(S)-奎宁环-3-基(7-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(s,1H),7.44~7.42(d,1H),7.37~7.31(m,3H),7.14~7.11(m,1H),7.03(d,1H),5.05(m,1H),4.94~4.92(m,1H),4.79(m,1H),4.31~4.30(m,1H),4.24~4.22(m,1H),3.29~3.25(m,1H),2.87~2.73(m,5H),2.26~2.23(m,1H),2.13~2.08(m,2H),1.82~1.79(m,1H),1.74~1.72(m,1H),1.70~1.68(m,1H),1.59~1.57(m,1H)
实施例3.(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.80(s,1H),7.74~7.25(d,1H),7.62~7.60(d,1H),7.57~7.53(t,1H),7.40~7.36(t,1H),7.17~7.14(t,1H),7.07(s,1H),5.02~5.00(m,1H),4.96~4.94(m,1H),4.80(m,1H),4.33~4.31(m,1H),4.26~4.22(m,1H),3.30~3.26(m,1H),2.89~2.71(m,5H),2.27~2.23(m,1H),2.14~2.04(m,2H),1.82~1.81(m,1H),1.71~1.63(m,2H),1.40(m,1H)
实施例4.(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.42(m,2H),7.39~7.34(m,2H),7.21~7.19(d,1H),7.15~7.11(t,1H),7.04(s,1H),5.09~5.07(m,1H),4.94~4.93(m,1H),4.79(m,1H),4.32~4.30(m,1H),4.25~4.22(m,1H),3.28~3.24(m,1H),2.88~2.69(m,5H),2.26~2.24(m,1H),2.13~2.08(m,2H),1.83~1.71(m,1H),1.71~1.68(m,1H),1.60~1.57(m,1H),1.40(m,1H)
实施例5.(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.27(m,2H),7.22~7.20(m,2H),7.18~7.05(m,2H),7.00(s,1H),5.23(m,1H),5.13(s,2H),4.92~4.91(m,1H),4.77(m,1H),4.28~4.19(m,2H),3.43(s,3H),3.25~3.22(m,1H),2.83~2.71(m,5H),2.25~2.21(m,1H),2.12~2.04(m,2H),1.81~1.80(m,1H),1.70~1.69(m,1H),1.59~1.57(m,1H),1.39(m,1H)
实施例6.(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35~7.29(m,2H),7.27~7.14(m,3H),7.05~7.01(m,2H),5.31~5.22(m,1H),5.21(s,2H),4.90(m,1H),4.76(m,1H),4.28~4.19(m,2H),3.49(s,3H),3.24~3.21(m,1H),2.83~2.70(m,5H),2.24~2.22(m,1H),2.21~2.07(m,2H),1.79~1.78(m,1H),1.69~1.68(m,1H),1.58~1.56(m,1H),1.39(m,1H)
实施例7.(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32~7.27(m,3H),7.18~7.16(m,1H),7.06(s,1H),7.05~6.99(m,2H),5.11~5.09(m,1H),4.92~4.91(m,1H),4.78(m,1H),4.29~4.27(m,1H),4.22~4.18(m,1H),4.13(t,2H),3.70(t,2H),3.39(s,3H),3.28~3.25(m,1H),2.87~2.73(m,5H),2.25~2.22(m,1H),2.12~2.04(m,2H),1.81(m,1H),1.70~1.69(m,1H),1.61~1.59(m,1H),1.45~1.36(m,1H)
实施例8.(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.27(m,2H),7.15~7.13(m,3H),7.04(s,1H),6.92~6.89(m,1H),5.30~5.29(m,1H),4.91~4.89(m,1H),4.77(m,1H),4.29~4.28(m,1H),4.22~4.19(m,1H),4.16(t,2H),3.77(t,2H),3.46(s,3H),3.24~3.21(m,1H),2.83~2.70(m,5H),2.28~2.21(m,1H),2.10~2.02(m,2H),1.80~1.79(m,1H),1.68~1.67(m,1H),1.58~1.56(m,1H),1.49~1.31(m,1H)
实施例9.(S)-奎宁环-3-基(7-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.40(m,1H),7.34~7.27(m,2H),7.21~7.11(m,3H),7.03(s,1H),5.18~5.04(m,1H),4.89~4.87(m,1H),4.77(m,1H),4.30~4.17(m,2H),3.26~3.23(m,1H),2.85~2.71(m,5H),2.22~2.21(m,1H),2.12~2.02(m,2H),1.84~1.78(m,1H),1.69~1.67(m,1H),1.58~1.57(m,1H),1.39(m,1H)
实施例10.(S)-奎宁环-3-基(7-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.46~7.44(m,1H),7.32~7.24(m,3H),7.18~7.16(m,1H),7.00(m,1H),6.91(s,1H),5.41~5.16(m,1H),4.88~4.86(m,1H),4.77(m,1H),4.29~4.16(m,2H),3.24~3.21(m,1H),2.83~2.69(m,5H),2.22~2.01(m,3H),1.80~1.77(m,1H),1.68~1.66(m,1H),1.57~1.56(m,1H),1.38(m,1H)
实施例11.(S)-奎宁环-3-基(7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.74~7.22(d,1H),7.56~7.52(t,1H),7.47~7.44(t,1H),7.30~7.26(m,2H),6.89~6.83(m,1H),6.80(s,1H),5.45~5.18(m,1H),4.93~4.76(m,2H),4.29~4.20(m,2H),3.24~3.21(m,1H),2.82~2.68(m,5H),2.25~2.24(m,1H),2.23~2.03(m,2H),1.81~1.79(m,1H),1.68~1.67(m,1H),1.58~1.55(m,1H),1.38(m,1H)
实施例12.(S)-奎宁环-3-基(7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.27(m,5H),7.03~7.00(m,1H),6.93(s,1H),5.47~5.45(d,1H),4.93~4.91(m,1H),4.78~4.76(m,1H),4.29~4.27(m,1H),4.22~4.20(m,1H),3.24~3.20(m,1H),2.85~2.68(m,5H),2.23(m,1H),2.12~2.03(m,2H),1.80~1.79(m,1H),1.69~1.65(m,1H),1.57~1.56(m,1H),1.38(m,1H)
实施例13.(S)-奎宁环-3-基(7-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.48(m,2H),7.31~7.25(m,2H),7.12~7.08(m,2H),7.00(s,1H),5.30(m,1H),4.95~4.80(m,1H),4.76(m,1H),4.29~4.18(m,2H),3.22~3.20(m,1H),2.82~2.69(m,5H),2.27~2.20(m,1H),2.10~2.02(m,2H),1.80~1.77(m,1H),1.68~1.66(m,1H),1.57~1.55(m,1H),1.38(m,1H)
实施例14.(S)-奎宁环-3-基(7-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.48~7.46(m,2H),7.39~7.37(m,2H),7.34~7.30(m,1H),7.12~7.10(m,1H),7.01(s,1H),5.25~5.23(m,1H),4.92~4.90(m,1H),4.77(m,1H),4.30~4.20(m,2H),3.25~3.21(m,1H),2.84~2.68(m,5H),2.24~2.02(m,3H),1.80~1.78(m,1H),1.68~1.67(m,1H),1.58~1.56(m,1H),1.48~1.25(m,1H)
实施例15.(S)-奎宁环-3-基(7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.69~7.64(m,4H),7.39~7.35(t,1H),7.17~7.07(m,1H),7.07(s,1H),5.12~5.10(m,1H),4.95~4.93(m,1H),4.79(m,1H),4.32~4.23(m,2H),3.28~3.24(m,1H),2.88~2.72(m,5H),2.26~2.24(m,1H),2.14~2.08(m,2H),1.87~1.79(m,1H),1.70~1.69(m,1H),1.59~1.58(m,1H),1.49~1.32(m,1H)
实施例16.(S)-奎宁环-3-基(7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.56~7.54(d,2H),7.33~7.31(m,1H),7.27~7.25(m,2H),7.17~7.10(m,1H),7.02(s,1H),5.29~5.27(m,1H),4.96~4.81(m,1H),4.76(m,1H),4.30~4.19(m,2H),3.23~3.21(m,1H),2.83~2.69(m,5H),2.21(m,1H),2.11~2.02(m,2H),1.79~1.77(m,1H),1.70~1.66(m,1H),1.59~1.55(m,1H),1.38(m,1H)
实施例17.(S)-奎宁环-3-基(7-(2-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34~7.27(m,3H),7.11~7.08(m,1H),7.04~6.84(m,3H),5.12(m,1H),4.92~4.89(m,1H),4.78~4.77(m,1H),4.30~4.18(m,2H),3.82(s,3H),3.27~3.24(m,1H),2.86~2.69(m,5H),2.25~2.22(m,1H),2.12~2.02(m,2H),1.86~1.79(m,1H),1.69~1.68(m,1H),1.59~1.57(m,1H),1.39(m,1H)
实施例18.(S)-奎宁环-3-基(7-(3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36~7.32(m,2H),7.31~7.27(m,1H),7.19~7.14(m,2H),7.09~7.06(m,2H),5.06(m,1H),4.95~4.82(m,1H),4.78(m,1H),4.30~4.20(m,2H),3.86(s,3H),3.27~3.26(m,1H),2.86~2.72(m,5H),2.23~2.22(m,1H),2.12~2.02(m,2H),1.80~1.69(m,2H),1.59~1.57(m,1H),1.39(m,1H)
实施例19.(S)-奎宁环-3-基(7-(4-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.49(m,2H),7.33~7.29(m,1H),7.13~7.10(t,1H),7.02(s,1H),6.98~6.95(d,2H),5.08~5.06(m,1H),4.92~4.91(m,1H),4.79~4.78(m,1H),4.30~4.29(m,1H),4.23~4.21(m,1H),3.85(s,3H),3.28~3.24(m,1H),2.86~2.69(m,5H),2.25~2.22(m,1H),2.12~2.05(m,2H),1.82~1.77(m,1H),1.71~1.67(m,1H),1.60~1.57(m,1H),1.39(m,1H)
实施例20.(S)-奎宁环-3-基(7-(2-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.27(m,4H),7.16~7.12(m,1H),7.05(s,1H),7.02~6.96(m,2H),5.12~5.10(m,1H),4.93~4.91(m,1H),4.79~4.77(m,1H),4.31~4.28(m,1H),4.22~4.20(m,1H),4.09~4.04(m,2H),3.28~3.24(m,1H),2.86~2.73(m,5H),2.25~2.23(m,1H),2.13~2.03(m,2H),1.82~1.77(m,1H),1.70~1.68(m,1H),1.59~1.58(m,1H),1.39~1.36(m,4H)
实施例21.(S)-奎宁环-3-基(7-(3-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35~7.31(m,2H),7.17~7.12(m,2H),7.08~7.06(m,2H),6.90~6.87(m,1H),5.06~5.02(m,1H),4.93~4.92(m,1H),4.78~4.77(m,1H),4.31~4.20(m,2H),4.10(q,2H),3.27~3.24(m,1H),2.86~2.72(m,5H),2.25~2.22(m,1H),2.13~2.02(m,2H),1.80~1.69(m,2H),1.59~1.57(m,1H),1.46~1.42(t,3H),1.40~1.36(m,1H)
实施例22.(S)-奎宁环-3-基(7-(4-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.47(d,2H),7.30~7.25(m,1H),7.19~7.17(m,1H),7.02(s,1H),6.96~6.94(m,2H),5.06~5.04(m,1H),4.89~4.87(m,1H),4.78~4.77(m,1H),4.30~4.26(m,1H),4.21~4.18(m,1H),4.10~4.05(m,2H),3.27~3.23(m,1H),2.86~2.69(m,5H),2.23~2.21(m,1H),2.11~2.02(m,2H),1.80~1.77(m,1H),1.69~1.67(m,1H),1.58~1.57(m,1H),1.46~1.39(m,4H)
实施例23.(S)-奎宁环-3-基(7-(3-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41(s,1H),7.37~7.31(m,3H),7.24~7.22(m,1H),7.18~7.16(m,1H),7.07(s,1H),5.09~5.07(m,1H),4.94~4.92(m,1H),4.79~4.78(m,1H),4.32~4.30(m,1H),4.24~4.21(m,1H),3.28~3.25(m,1H),2.99~2.95(m,1H),2.87~2.70(m,5H),2.26~2.24(m,1H),2.22~2.03(m,2H),1.80~1.77(m,1H),1.71~1.68(m,1H),1.60~1.57(m,1H),1.43~1.41(m,1H),1.30(d,6H)
实施例24.(S)-奎宁环-3-基(7-(4-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.48(d,2H),7.34~7.27(m,3H),7.15(t,1H),7.06(s,1H),5.15~5.12(m,1H),4.92~4.91(m,1H),4.79~4.78(m,1H),4.30~4.29(m,1H),4.23~4.20(m,1H),3.27~3.24(m,1H),2.97~2.92(m,1H),2.87~2.69(m,5H),2.25~2.22(m,1H),2.12~2.07(m,2H),1.88~1.85(m,1H),1.81~1.79(m,1H),1.70~1.68(m,1H),1.61~1.56(m,1H),1.29(d,6H)
实施例25.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.57(s,1H),7.40~7.32(m,4H),7.18~7.15(m,1H),7.07(s,1H),5.12~5.10(m,1H),4.94~4.92(m,1H),4.79~4.78(m,1H),4.34~4.30(m,1H),4.25~4.22(m,1H),3.28~3.24(m,1H),2.86~2.69(m,5H),2.26~2.23(m,1H),2.14~2.03(m,2H),1.84~1.80(m,1H),1.71~1.68(m,1H),1.60~1.57(m,1H),1.37~1.35(m,10H)
实施例26.(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.52~7.50(d,2H),7.47~7.45(d,2H),7.32(t,1H),7.16(t,1H),7.07(s,1H),5.12~5.10(m,1H),4.93~4.91(m,1H),4.79~4.78(m,1H),4.31~4.29(m,1H),4.24~4.21(m,1H),3.28~3.24(m,1H),2.88~2.69(m,5H),2.25~2.22(m,1H),2.13~2.03(m,2H),1.83~1.79(m,1H),1.71~1.67(m,1H),1.60~1.57(m,1H),1.36~1.34(m,10H)
实施例27.(S)-奎宁环-3-基(7-(2,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.24(m,4H),6.98~6.95(m,1H),6.89(s,1H),5.23~5.21(m,1H),4.94~4.93(m,1H),4.78~4.76(m,1H),4.33~4.29(m,1H),4.24~4.22(m,1H),3.27~3.23(m,1H),2.85~2.69(m,5H),2.26~2.22(m,1H),2.13~2.03(m,2H),1.80~1.79(m,1H),1.69~1.67(m,1H),1.59~1.56(m,1H),1.39~1.37(m,1H)
实施例28.(S)-奎宁环-3-基(7-(3,4-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.63(s,1H),7.57~7.48(m,1H),7.38~7.33(m,2H),7.11~7.01(m,1H),7.00(s,1H),5.06~5.04(m,1H),4.94~4.93(m,1H),4.79~4.76(m,1H),4.33~4.30(m,1H),4.24~4.22(m,1H),3.28~3.25(m,1H),2.87~2.73(m,5H),2.25~2.23(m,1H),2.13~2.03(m,2H),1.81~1.80(m,1H),1.79~1.68(m,1H),1.59~1.58(m,1H),1.40~1.37(m,1H)
实施例29.(S)-奎宁环-3-基(7-(3,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(s,1H),7.41~7.33(m,3H),7.09~7.06(m,1H),6.99(s,1H),5.17~5.15(m,1H),4.93~4.91(m,1H),4.79~4.76(m,1H),4.32~4.29(m,1H),4.24~4.21(m,1H),3.27~3.23(m,1H),2.86~2.72(m,5H),2.24~2.22(m,1H),2.13~2.03(m,2H),1.80~1.79(m,1H),1.70~1.69(m,1H),1.59~1.57(m,1H),1.48~1.35(m,1H)
实施例30.(S)-奎宁环-3-基(7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36(t,1H),7.12~7.06(m,1H),7.05~7.01(m,2H),6.96(s,1H),5.14~5.06(m,1H),4.99~4.89(m,1H),4.83~4.73(m,1H),4.37~4.28(m,1H),4.27~4.16(m,1H),3.33~3.19(m,1H),2.94~2.66(m,5H),2.30~2.21(m,1H),2.16~2.01(m,2H),1.85~1.75(m,1H),1.73~1.65(m,1H),1.62~1.52(m,1H),1.45~1.34(m,1H)
实施例31.(S)-奎宁环-3-基(7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(t,1H),7.25~7.18(m,1H),7.07~6.99(m,1H),6.95(s,1H),5.20~5.11(m,1H),4.98~4.89(m,1H),4.82~4.73(m,1H),4.36~4.27(m,1H),4.25~4.15(m,1H),3.31~3.18(m,1H),2.92~2.65(m,5H),2.31~2.19(m,1H),2.16~2.00(m,2H),1.85~1.75(m,1H),1.74~1.64(m,1H),1.62~1.50(m,1H),1.46~1.32(m,1H)
实施例32.(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(d,2H),7.33(t,1H),7.18(d,2H),7.11(t,1H),7.02(s,1H),6.54(t,1H),5.18~5.09(m,1H),4.96~4.88(m,1H),4.82~4.74(m,1H),4.36~4.27(m,1H),4.26~4.17(m,1H),3.31~3.19(m,1H),2.93~2.67(m,5H),2.30~2.19(m,1H),2.16~2.00(m,2H),1.86~1.76(m,1H),1.75~1.64(m,1H),1.61~1.52(m,1H),1.44~1.34(m,1H)
实施例33.(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.75(d,1H),7.73~7.67(m,1H),7.36(t,1H),7.28~7.23(m,1H),7.09(t,1H),7.00(s,1H),5.16~5.06(m,1H),5.00~4.89(m,1H),4.83~4.73(m,1H),4.37~4.29(m,1H),4.26~4.17(m,1H),3.32~3.20(m,1H),2.94~2.65(m,5H),2.32~2.20(m,1H),2.16~2.00(m,2H),1.85~1.77(m,1H),1.76~1.65(m,1H),1.63~1.53(m,1H),1.48~1.34(m,1H)
实施例34.(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.69(d,2H),7.58(s,1H),7.44~7.35(m,1H),7.15~7.09(m,1H),7.03(s,1H),5.15~5.06(m,1H),4.99~4.89(m,1H),4.84~4.75(m,1H),4.38~4.28(m,1H),4.26~4.17(m,1H),3.33~3.21(m,1H),2.95~2.67(m,5H),2.33~2.21(m,1H),2.18~2.00(m,2H),1.86~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.47~1.35(m,1H)
实施例35.(S)-奎宁环-3-基(7-(4-环丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45(d,2H),7.34~7.29(m,1H),7.14~7.12(m,3H),7.04(s,1H),5.09~5.02(m,1H),4.96~4.89(m,1H),4.83~4.74(m,1H),4.35~4.27(m,1H),4.25~4.14(m,1H),3.31~3.21(m,1H),2.93~2.67(m,5H),2.31~2.20(m,1H),2.17~2.00(m,2H),1.97~1.89(m,1H),1.86~1.76(m,1H),1.74~1.64(m,1H),1.63~1.52(m,1H),1.45~1.34(m,1H),1.04~0.95(m,2H),0.77~0.70(m,2H)
实施例36.(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(t,1H),7.28~7.21(m,2H),7.12~7.03(m,2H),6.98(s,1H),5.12~5.03(m,1H),4.97~4.89(m,1H),4.82~4.74(m,1H),4.36~4.28(m,1H),4.25~4.17(m,1H),3.31~3.20(m,1H),2.93~2.67(m,5H),2.30~2.20(m,1H),2.17~2.01(m,2H),1.87~1.76(m,1H),1.73~1.64(m,1H),1.63~1.51(m,1H),1.46~1.33(m,1H)
实施例37.(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.26(m,1H),7.12~7.02(m,3H),7.00(s,1H),6.91(d,1H),5.12~5.04(m,1H),4.95~4.87(m,1H),4.82~4.74(m,1H),4.34~4.26(m,5H),4.24~4.14(m,1H),3.31~3.20(m,1H),2.92~2.66(m,5H),2.29~2.19(m,1H),2.16~1.99(m,2H),1.85~1.75(m,1H),1.73~1.64(m,1H),1.62~1.52(m,1H),1.44~1.31(m,1H)
实施例38.(S)-奎宁环-3-基(7-(2,3-二氢呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39(s,1H),7.35~7.25(m,2H),7.13~7.06(m,1H),7.00(s,1H),6.83(d,1H),5.18~5.08(m,1H),4.96~4.86(m,1H),4.82~4.74(m,1H),4.61(t,2H),4.35~4.26(m,1H),4.24~4.14(m,1H),3.32~3.20(m,3H),2.94~2.66(m,5H),2.30~2.19(m,1H),2.16~2.01(m,2H),1.86~1.76(m,1H),1.75~1.64(m,1H),1.62~1.51(m,1H),1.45~1.32(m,1H)
实施例39.(S)-奎宁环-3-基(7-(3-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.81(s,1H),7.76(d,1H),7.62(d,1H),7.52(t,1H),7.37(t,1H),7.13~7.07(m,1H),7.01(s,1H),5.26~5.18(m,1H),4.96~4.89(m,1H),4.82~4.74(m,1H),4.36~4.28(m,1H),4.26~4.18(m,1H),3.30~3.18(m,1H),2.91~2.65(m,5H),2.31~2.20(m,1H),2.18~2.05(m,2H),1.86~1.75(m,1H),1.72~1.65(m,1H),1.62~1.51(m,1H),1.46~1.34(m,1H)
实施例40.(S)-奎宁环-3-基(7-(2-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.75(d,1H),7.63(t,1H),7.47(t,2H),7.39(t,1H),7.12(d,1H),6.99(s,1H),5.24~5.18(m,1H),4.98~4.91(m,1H),4.82~4.75(m,1H),4.36~4.28(m,1H),4.27~4.18(m,1H),3.31~3.20(m,1H),2.94~2.67(m,5H),2.32~2.20(m,1H),2.17~2.06(m,2H),1.87~1.76(m,1H),1.74~1.65(m,1H),1.63~1.52(m,1H),1.45~1.34(m,1H)
实施例41.(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36~7.28(m,2H),7.17(t,1H),7.08(s,1H),6.93~6.87(m,2H),6.75(d,1H),5.08~5.01(m,1H),4.96~4.89(m,1H),4.83~4.75(m,1H),4.35~4.28(m,1H),4.26~4.17(m,1H),3.30~3.20(m,1H),3.00(s,6H),2.91~2.68(m,5H),2.30~2.20(m,1H),2.16~1.99(m,2H),1.87~1.76(m,1H),1.74~1.65(m,1H),1.63~1.53(m,1H),1.44~1.34(m,1H)
实施例42.(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.82(d,1H),7.77(d,1H),7.52(s,1H),7.38~7.25(m,4H),7.19(s,1H),5.15~5.08(m,1H),4.95~4.87(m,1H),4.82~4.73(m,1H),4.36~4.28(m,1H),4.25~4.17(m,1H),3.32~3.20(m,1H),2.94~2.66(m,5H),2.31~2.20(m,1H),2.15~2.00(m,2H),1.89~1.77(m,1H),1.75~1.65(m,1H),1.63~1.53(m,1H),1.46~1.34(m,1H)
实施例43.(S)-奎宁环-3-基(7-(苯并呋喃-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.83(d,1H),7.78(s,1H),7.55(d,1H),7.40~7.29(m,3H),7.21(t,1H),7.14(s,1H),5.12~5.09(m,1H),4.98~4.91(m,1H),4.83~4.76(m,1H),4.37~4.30(m,1H),4.27~4.19(m,1H),3.32~3.21(m,1H),2.94~2.68(m,5H),2.32~2.21(m,1H),2.18~2.02(m,2H),1.90~1.77(m,1H),1.74~1.66(m,1H),1.63~1.53(m,1H),1.46~1.35(m,1H)
实施例44.(S)-奎宁环-3-基(7-(苯并呋喃-2-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(d,1H),7.51(d,1H),7.44~7.39(m,1H),7.36~7.20(m,4H),7.00(s,1H),5.20~5.12(m,1H),4.96~4.88(m,1H),4.82~4.75(m,1H),4.35~4.28(m,1H),4.26~4.18(m,1H),3.31~3.20(m,1H),2.93~2.67(m,5H),2.31~2.20(m,1H),2.15~2.01(m,2H),1.86~1.77(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.45~1.34(m,1H)
实施例45.(S)-奎宁环-3-基(7-(1H-吲哚-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.65(d,1H),7.68(d,1H),7.55(s,1H),7.37~7.30(m,2H),7.25~7.19(m,2H),7.13(s,1H),6.57(s,1H),5.24(d,1H),4.96~4.88(m,1H),4.83~4.76(m,1H),4.34~4.26(m,1H),4.24~4.16(m,1H),3.31~3.20(m,1H),2.93~2.66(m,5H),2.29~2.19(m,1H),2.14~2.03(m,2H),1.88~1.77(m,1H),1.73~1.66(m,1H),1.63~1.53(m,1H),1.46~1.35(m,1H)
实施例46.(S)-奎宁环-3-基(7-(1H-吲哚-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.67(d,1H),7.68(d,1H),7.55(s,1H),7.36~7.30(m,2H),7.25~7.19(m,2H),7.12(s,1H),6.56(s,1H),5.24(d,1H),4.96~4.88(m,1H),4.83~4.76(m,1H),4.33~4.26(m,1H),4.24~4.16(m,1H),3.32~3.19(m,1H),2.92~2.67(m,5H),2.28~2.19(m,1H),2.15~2.02(m,2H),1.88~1.77(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.35(m,1H)
实施例47.(S)-奎宁环-3-基(7-(1H-吲哚-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.70(d,1H),7.64(t,1H),7.40(t,1H),7.24~7.17(m,4H),7.13(s,1H),6.62(s,1H),5.32(d,1H),4.99~4.92(m,1H),4.83~4.73(m,1H),4.36~4.29(m,1H),4.27~4.18(m,1H),3.27~3.15(m,1H),2.90~2.61(m,5H),2.32~2.21(m,1H),2.18~2.02(m,2H),1.86~1.76(m,1H),1.74~1.65(m,1H),1.61~1.52(m,1H),1.46~1.35(m,1H)
实施例48.(S)-奎宁环-3-基(7-(1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.21(s,1H),7.50~7.37(m,3H),7.29~7.24(m,2H),7.21(d,1H),7.17(s,1H),5.38~5.29(m,1H),5.02~4.93(m,1H),4.85~4.76(m,1H),4.38~4.30(m,1H),4.28~4.20(m,1H),3.34~3.22(m,1H),2.93~2.70(m,5H),2.33~2.22(m,1H),2.19~2.02(m,2H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.63~1.55(m,1H),1.46~1.35(m,1H)
实施例49.(S)-奎宁环-3-基(7-(1H-吲唑-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.11(s,1H),7.74(d,1H),7.45~7.33(m,2H),7.25~7.18(m,3H),7.13(s,1H),5.71~5.56(m,1H),5.03~4.93(m,1H),4.80~4.72(m,1H),4.36~4.19(m,2H),3.20~3.07(m,1H),2.89~2.67(m,4H),2.55(dd,1H),2.31~2.19(m,1H),2.15~2.00(m,2H),1.84~1.74(m,1H),1.72~1.64(m,1H),1.61~1.50(m,1H),1.46~1.33(m,1H)
实施例50.(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.98(s,1H),7.76(d,1H),7.52(s,1H),7.36(d,2H),7.23(t,1H),7.14(s,1H),5.25~5.16(m,1H),4.98~4.90(m,1H),4.82~4.75(m,1H),4.37~4.29(m,1H),4.27~4.19(m,1H),4.10(s,3H),3.31~3.19(m,1H),2.93~2.67(m,5H),2.32~2.22(m,1H),2.17~2.00(m,2H),1.87~1.77(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.46~1.34(m,1H)
实施例51.(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.11(s,1H),7.48~7.36(m,3H),7.29~7.23(m,1H),7.22~7.14(m,1H),5.43~5.28(m,1H),5.02~4.92(m,1H),4.84~4.74(m,1H),4.38~4.30(m,1H),4.28~4.20(m,1H),4.10(s,3H),3.32~3.21(m,1H),2.90~2.67(m,5H),2.34~2.23(m,1H),2.19~2.01(m,2H),1.85~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.44~1.34(m,1H)
实施例52.(S)-奎宁环-3-基(7-(1-甲基-1H-吲哚-2-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.63(d,1H),7.40~7.33(m,2H),7.28~7.22(m,1H),7.14(t,1H),7.08(t,1H),6.99(s,1H),6.55(s,1H),5.18~5.12(m,1H),4.99~4.92(m,1H),4.83~4.75(m,1H),4.37~4.30(m,1H),4.27~4.21(m,1H),3.76(s,3H),3.32~3.21(m,1H),2.93~2.68(m,5H),2.33~2.23(m,1H),2.18~2.01(m,2H),1.86~1.77(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.45~1.36(m,1H)
实施例53.(S)-奎宁环-3-基(7-(异喹啉-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.22(s,1H),8.19(s,1H),8.01(d,1H),7.91(d,1H),7.69~7.58(m,2H),7.42(t,1H),7.04(t,1H),6.97(s,1H),6.15~6.03(m,1H),5.04~4.95(m,1H),4.85~4.77(m,1H),4.37~4.30(m,1H),4.28~4.21(m,1H),3.33~3.21(m,1H),2.92~2.68(m,5H),2.33~2.22(m,2H),2.20~2.12(m,1H),1.90~1.79(m,1H),1.75~1.66(m,1H),1.64~1.54(m,1H),1.47~1.35(m,1H)
实施例54.(S)-奎宁环-3-基(7-(异喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.29(s,1H),8.41(d,1H),7.98(d,1H),7.74(d,1H),7.68~7.61(m,2H),7.42(t,1H),7.03(t,1H),6.96(s,1H),5.43~5.34(m,1H),5.04~4.96(m,1H),4.85~4.77(m,1H),4.39~4.32(m,1H),4.30~4.22(m,1H),3.34~3.23(m,1H),2.94~2.69(m,5H),2.36~2.26(m,1H),2.22~2.13(m,1H),2.10~2.04(m,1H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.64~1.56(m,1H),1.46~1.36(m,1H)
实施例55.(S)-奎宁环-3-基(7-(喹啉-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.05(s,1H),8.26(s,1H),8.14(d,1H),7.87(d,1H),7.72(t,1H),7.58(t,1H),7.43(t,1H),7.29~7.23(m,1H),7.16(s,1H),5.46~5.37(m,1H),5.01~4.92(m,1H),4.85~4.76(m,1H),4.37~4.30(m,1H),4.27~4.19(m,1H),3.33~3.20(m,1H),2.94~2.68(m,5H),2.32~2.22(m,1H),2.18~2.03(m,2H),1.86~1.77(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.46~1.34(m,1H)
实施例56.(S)-奎宁环-3-基(7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.95(d,1H),8.20(d,1H),7.83(d,1H),7.70(d,1H),7.59(t,1H),7.44~7.35(m,2H),7.30~7.24(m,1H),7.16(s,1H),5.23~5.16(m,1H),5.00~4.91(m,1H),4.83~4.74(m,1H),4.37~4.29(m,1H),4.26~4.17(m,1H),3.32~3.20(m,1H),2.93~2.67(m,5H),2.32~2.22(m,1H),2.17~2.02(m,2H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.35(m,1H)
实施例57.(S)-奎宁环-3-基(7-(异喹啉-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.24(s,1H),8.52(d,1H),8.11(s,1H),7.95~7.87(m,2H),7.67(d,1H),7.40(t,1H),7.30~7.24(m,1H),7.18(d,1H),5.34~5.26(m,1H),5.01~4.92(m,1H),4.85~4.75(m,1H),4.38~4.30(m,1H),4.28~4.19(m,1H),3.33~3.20(m,1H),2.94~2.66(m,5H),2.34~2.22(m,1H),2.19~2.02(m,2H),1.87~1.77(m,1H),1.75~1.66(m,1H),1.64~1.54(m,1H),1.47~1.36(m,1H)
实施例58.(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.25(m,1H),7.18(s,1H),7.15~7.07(m,2H),7.03~6.98(m,2H),5.14~5.06(m,1H),4.94~4.87(m,1H),4.82~4.74(m,1H),4.34~4.15(m,6H),3.31~3.20(m,1H),2.92~2.66(m,5H),2.29~2.18(m,3H),2.15~1.98(m,2H),1.85~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.45~1.33(m,1H)
实施例59.(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.78(s,1H),7.64(d,2H),7.60~7.44(m,5H),7.39~7.34(m,2H),7.21(t,1H),7.13(s,1H),5.22~5.14(m,1H),4.97~4.90(m,1H),4.83~4.75(m,1H),4.36~4.29(m,1H),4.28~4.18(m,1H),3.32~3.21(m,1H),2.94~2.67(m,5H),2.31~2.21(m,1H),2.16~2.06(m,2H),1.86~1.78(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.45~1.30(m,1H)
实施例60.(S)-奎宁环-3-基(7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.00(s,1H),7.82~7.73(m,2H),7.58(t,1H),7.37(t,1H),7.19~7.13(m,1H),7.07(s,1H),5.20~5.09(m,1H),4.98~4.89(m,1H),4.82~4.73(m,1H),4.37~4.29(m,1H),4.27~4.17(m,1H),3.33~3.20(m,5H),2.92~2.66(m,5H),2.32~2.21(m,1H),2.17~2.01(m,2H),1.86~1.66(m,1H),1.62~1.53(m,1H),1.44~1.35(m,1H)
实施例61.(S)-奎宁环-3-基(7-(1,3-二氢异苯并呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.46(d,1H),7.41(s,1H),7.36~7.26(m,2H),7.13(t,1H),7.04(s,1H),5.20~5.09(m,5H),4.97~4.89(m,1H),4.82~4.75(m,1H),4.35~4.28(m,1H),4.25~4.17(m,1H),3.31~3.21(m,1H),2.92~2.67(m,5H),2.30~2.20(m,1H),2.16~2.01(m,2H),1.85~1.77(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.45~1.34(m,1H)
实施例62.(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.14(s,1H),8.05(d,1H),7.84(d,1H),7.41(t,1H),7.29~7.23(m,1H),7.17(s,1H),5.15~5.09(m,1H),5.00~4.93(m,1H),4.83~4.76(m,1H),4.38~4.31(m,1H),4.29~4.21(m,1H),3.33~3.22(m,1H),2.94~2.68(m,5H),2.33~2.23(m,1H),2.19~2.02(m,2H),1.86~1.76(m,1H),1.73~1.65(m,1H),1.64~1.53(m,1H),1.46~1.35(m,1H)
实施例63.(S)-奎宁环-3-基(7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.23(m,1H),7.14~7.05(m,2H),7.02~7.00(m,2H),6.71(d,1H),5.13~5.06(m,1H),4.92~4.86(m,1H),4.81~4.73(m,1H),4.35~4.25(m,3H),4.23~4.14(m,1H),3.34~3.19(m,3H),2.92(s,3H),2.89~2.67(m,5H),2.28~2.17(m,1H),2.14~2.00(m,2H),1.86~1.77(m,1H),1.73~1.65(m,1H),1.61~1.53(m,1H),1.43~1.34(m,1H)
实施例64.(S)-奎宁环-3-基(7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.43(s,1H),7.40~7.34(m,2H),7.32~7.25(m,1H),7.16(t,1H),7.07(s,1H),5.12~5.04(m,1H),4.94~4.87(m,1H),4.82~4.74(m,1H),4.34~4.27(m,1H),4.24~4.17(m,1H),3.31~3.21(m,1H),2.91~2.67(m,5H),2.29~2.19(m,1H),2.14~2.01(m,2H),1.90~1.77(m,1H),1.73~1.66(m,1H),1.63~1.53(m,1H),1.45~1.35(m,1H)
实施例65.(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36~7.30(m,2H),7.03~6.98(m,1H),6.91(s,1H),6.85~6.80(m,2H),5.32~5.25(m,1H),4.96~4.89(m,1H),4.81~4.73(m,1H),4.35~4.27(m,1H),4.25~4.16(m,1H),3.80(s,3H),3.30~3.19(m,1H),2.90~2.66(m,5H),2.30~2.20(m,1H),2.16~2.00(m,2H),1.85~1.77(m,1H),1.74~1.64(m,1H),1.62~1.52(m,1H),1.44~1.33(m,1H)
实施例66.(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41~7.38(m,1H),7.36~7.32(m,1H),7.16~7.06(m,3H),7.03(s,1H),5.19~5.10(m,1H),4.97~4.88(m,1H),4.81~4.74(m,1H),4.35~4.29(m,1H),4.26~4.18(m,1H),3.95(s,3H),3.31~3.20(m,1H),2.92~2.67(m,5H),2.29~2.20(m,1H),2.15~2.05(m,2H),1.86~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.44~1.34(m,1H)
实施例67.(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32(t,1H),7.28~7.23(m,1H),7.01~6.97(m,1H),6.96~6.89(m,3H),5.26~5.20(m,1H),4.97~4.89(m,1H),4.81~4.73(m,1H),4.35~4.27(m,1H),4.25~4.16(m,1H),3.94(s,3H),3.31~3.19(m,1H),2.91~2.66(m,5H),2.31~2.20(m,1H),2.16~1.99(m,2H),1.85~1.75(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.43~1.34(m,1H)
实施例68.(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.20(d,1H),7.37(t,1H),7.16(t,1H),7.08~7.05(m,2H),6.91(s,1H),5.10~5.04(m,1H),4.97~4.90(m,1H),4.82~4.74(m,1H),4.35~4.29(m,1H),4.26~4.18(m,1H),3.98(s,3H),3.33~3.20(m,1H),2.94~2.68(m,5H),2.31~2.21(m,1H),2.16~2.01(m,2H),1.86~1.76(m,1H),1.73~1.65(m,1H),1.62~1.52(m,1H),1.44~1.35(m,1H)
实施例69.(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32(t,1H),7.11(dd,1H),7.07~6.99(m,4H),5.11~5.05(m,1H),4.95~4.89(m,1H),4.82~4.74(m,1H),4.35~4.28(m,1H),4.25~4.17(m,1H),3.32~3.20(m,1H),2.89(s,6H),2.87~2.66(m,5H),2.30~2.20(m,1H),2.15~2.02(m,2H),1.85~1.76(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.44~1.35(m,1H)
实施例70.(S)-奎宁环-3-基[6,7'-二苯并二氢吡喃]-4'-基氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.23(m,3H),7.10(t,1H),7.00(s,1H),6.85(d,1H),5.10~5.03(m,1H),4.94~4.87(m,1H),4.82~4.73(m,1H),4.34~4.27(m,1H),4.25~4.15(m,3H),3.32~3.21(m,1H),2.93~2.67(m,7H),2.29~2.19(m,1H),2.15~2.00(m,4H),1.85~1.77(m,1H),1.73~1.66(m,1H),1.62~1.53(m,1H),1.44~1.35(m,1H)
实施例71.(S)-奎宁环-3-基(7-(6-甲氧基-5-(三氟甲基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.49(s,1H),8.01(s,1H),7.37(t,1H),7.11~7.05(m,1H),6.99(s,1H),5.12~5.05(m,1H),4.97~4.90(m,1H),4.83~4.73(m,1H),4.36~4.29(m,1H),4.27~4.19(m,1H),4.08(s,3H),3.31~3.20(m,1H),2.92~2.68(m,5H),2.30~2.21(m,1H),2.16~2.01(m,2H),1.85~1.77(m,1H),1.74~1.66(m,1H),1.62~1.53(m,1H),1.46~1.33(m,1H)
实施例72.(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.78(s,1H),7.58(s,1H),7.39~7.31(m,3H),7.29~7.19(m,1H),6.92(s,1H),5.32(s,3H),5.10~5.03(m,1H),4.90~4.83(m,1H),4.80~4.73(m,1H),4.30~4.23(m,1H),4.21~4.13(m,1H),3.30~3.20(m,1H),2.92~2.66(m,5H),2.26~2.16(m,1H),2.12~2.01(m,2H),1.82~1.75(m,1H),1.73~1.64(m,1H),1.61~1.53(m,1H),1.44~1.34(m,1H)
实施例73.(S)-奎宁环-3-基(7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55~7.49(m,2H),7.36~7.26(m,3H),7.18~7.12(m,1H),7.06(s,1H),5.13~5.07(m,1H),4.95~4.89(m,1H),4.81~4.76(m,1H),4.35~4.28(m,1H),4.14~4.07(m,2H),3.60~3.51(m,2H),3.31~3.21(m,1H),2.92~2.67(m,6H),2.31~2.19(m,1H),2.15~2.00(m,2H),1.91~1.78(m,5H),1.73~1.65(m,1H),1.62~1.52(m,1H),1.47~1.34(m,1H)
实施例74.(S)-奎宁环-3-基(7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(t,1H),7.19(d,1H),7.13~7.08(m,2H),7.05~6.99(m,2H),5.10~5.04(m,1H),4.97~4.90(m,1H),4.82~4.75(m,1H),4.65(s,2H),4.36~4.29(m,1H),4.27~4.18(m,1H),3.41(s,3H),3.32~3.21(m,1H),2.92~2.68(m,5H),2.31~2.20(m,1H),2.16~2.01(m,2H),1.86~1.75(m,1H),1.72~1.65(m,1H),1.63~1.53(m,1H),1.46~1.35(m,1H)
实施例75.(S)-奎宁环-3-基(7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41~7.35(m,2H),7.31(t,1H),7.16~7.10(m,1H),7.09~7.00(m,2H),5.15~5.07(m,1H),4.95~4.87(m,1H),4.82~4.74(m,1H),4.35~4.27(m,1H),4.25~4.15(m,1H),3.90~3.81(m,4H),3.33~3.20(m,1H),2.98~2.92(m,4H),2.90~2.68(m,5H),2.37(s,3H),2.31~2.19(m,1H),2.16~1.99(m,2H),1.86~1.77(m,1H),1.74~1.65(m,1H),1.63~1.52(m,1H),1.44~1.34(m,1H)
实施例76.(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.42(d,1H),7.32(t,1H),7.13~7.05(m,2H),7.00(s,1H),5.17~5.10(m,1H),4.95~4.88(m,1H),4.82~4.74(m,1H),4.34~4.27(m,1H),4.24~4.17(m,1H),3.94~3.83(m,4H),3.31~3.20(m,1H),3.14~3.04(m,4H),2.91~2.67(m,5H),2.29~2.19(m,1H),2.15~2.00(m,2H),1.85~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.44~1.34(m,1H)
实施例77.(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35~7.22(m,3H),7.10(t,1H),7.02~6.94(m,2H),5.10~5.07(m,1H),4.95~4.88(m,1H),4.81~4.74(m,1H),4.34~4.27(m,1H),4.24~4.16(m,1H),3.92~3.84(m,4H),3.32~3.21(m,1H),3.16~3.08(m,4H),2.91~2.66(m,5H),2.29~2.20(m,1H),2.14~2.00(m,2H),1.84~1.76(m,1H),1.73~1.65(m,1H),1.61~1.52(m,1H),1.44~1.34(m,1H)
实施例78.(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.76(s,1H),7.65(d,1H),7.38~7.34(m,2H),7.12~7.07(m,1H),7.00(s,1H),5.15~5.08(m,1H),4.97~4.89(m,1H),4.82~4.74(m,1H),4.36~4.29(m,1H),4.26~4.18(m,1H),3.30~3.21(m,1H),2.91~2.67(m,5H),2.58(s,3H),2.31~2.21(m,1H),2.16~2.01(m,2H),1.85~1.77(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.45~1.34(m,1H)
实施例79.(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.35(d,1H),8.28(s,1H),7.37(t,1H),7.31(s,1H),7.16~7.09(m,1H),7.03(s,1H),5.40~5.24(m,1H),4.98~4.89(m,1H),4.84~4.74(m,1H),4.38~4.29(m,1H),4.26~4.18(m,1H),3.91(s,3H),3.34~3.20(m,1H),2.94~2.67(m,5H),2.31~2.20(m,1H),2.17~2.02(m,2H),1.85~1.77(m,1H),1.73~1.66(m,1H),1.62~1.54(m,1H),1.45~1.35(m,1H)
实施例80.(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.24(s,1H),7.82(s,1H),7.36~7.33(m,1H),7.10~7.02(m,1H),6.97(s,1H),5.12~5.05(m,1H),4.97~4.88(m,1H),4.82~4.74(m,1H),4.35~4.28(m,1H),4.26~4.18(m,1H),4.06(s,3H),3.32~3.20(m,1H),2.93~2.68(m,5H),2.30~2.21(m,1H),2.15~2.01(m,2H),1.88~1.77(m,1H),1.73~1.66(m,1H),1.63~1.54(m,1H),1.46~1.34(m,1H)
实施例81.(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.32(s,1H),7.75(d,1H),7.33(t,1H),7.08(t,1H),6.98(s,1H),6.83(d,1H),5.15~5.06(m,1H),4.97~4.87(m,1H),4.81~4.74(m,1H),4.35~4.27(m,1H),4.25~4.19(m,1H),4.17(d,2H),3.31~3.20(m,1H),2.93~2.67(m,5H),2.30~2.20(m,1H),2.15~2.00(m,2H),1.83~1.75(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.45~1.36(m,1H),1.34~1.25(m,1H),0.68~0.59(m,2H),0.41~0.35(m,2H)
实施例82.(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.57(s,1H),7.38(d,1H),7.31(t,1H),7.09(t,1H),7.02~6.97(m,2H),5.10~5.03(m,1H),4.95~4.88(m,1H),4.82~4.75(m,1H),4.65~4.54(m,1H),4.35~4.27(m,1H),4.25~4.16(m,1H),3.32~3.21(m,1H),2.95~2.68(m,5H),2.31~2.19(m,1H),2.16~1.99(m,2H),1.87~1.76(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.47~1.34(m,7H)
实施例83.(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.75(s,1H),7.68(d,1H),7.33(t,1H),7.13~7.04(m,2H),7.01(s,1H),5.18~5.09(m,1H),4.97~4.88(m,1H),4.83~4.74(m,1H),4.35~4.28(m,1H),4.25~4.17(m,1H),3.94(s,3H),3.31~3.20(m,1H),2.91~2.66(m,5H),2.30~2.20(m,1H),2.15~2.01(m,2H),1.85~1.77(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.44~1.36(m,1H)
实施例84.(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32~7.25(m,2H),6.94~6.90(m,1H),6.85(s,1H),6.68~6.61(m,2H),5.28~5.20(m,1H),4.94~4.87(m,1H),4.81~4.73(m,1H),4.33~4.25(m,1H),4.21~4.14(m,1H),3.75(s,6H),3.31~3.19(m,1H),2.92~2.67(m,5H),2.29~2.20(m,1H),2.15~2.00(m,2H),1.85~1.77(m,1H),1.73~1.65(m,1H),1.61~1.53(m,1H),1.43~1.34(m,1H)
实施例85至实施例100
分别使用制备例2中制备的(S)-奎宁环-3-基(6-溴苯并二氢吡喃-4-基)氨基甲酸酯,和相应的取代硼酸,按照与实施例1相同的程序制备实施例85至实施例100的标题化合物。
实施例85.(S)-奎宁环-3-基(6-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.54~7.51(m,2H),7.44(d,1H),7.40~7.37(m,1H),7.15~7.10(m,1H),6.85(d,1H),4.77(s,1H),4.26(s,2H),3.31~3.21(m,2H),2.83~2.70(m,5H),2.23~2.12(m,1H),2.11~2.03(m,2H),1.97~1.85(m,1H),1.80~1.74(m,1H),1.69~1.59(m,1H),1.50~1.46(m,1H)
实施例86.(S)-奎宁环-3-基(6-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.51~7.36(m,4H),7.27(t,1H),7.01(t,1H),6.87(d,1H),4.78(s,1H),4.28(s,2H),3.33~3.21(m,2H),2.84~2.71(m,5H),2.23~2.14(m,1H),2.13~2.04(m,1H),1.98~1.87(m,1H),1.82~1.72(m,1H),1.70~1.61(m,1H),1.53~1.47(m,1H)
实施例87.(S)-奎宁环-3-基(6-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.44~7.41(m,2H),7.35~7.28(m,2H),7.21(t,1H),7.14(t,1H),6.86(d,1H),4.75(s,1H),4.27(s,2H),3.32~3.21(m,2H),2.83~2.72(m,5H),2.23~2.13(m,1H),2.10~2.02(m,2H),1.96~1.86(m,1H),1.80~1.70(m,1H),1.67~1.56(m,1H),1.51~1.37(m,1H)
实施例88.(S)-奎宁环-3-基(6-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.53~7.50(m,3H),7.40(t,3H),6.86(d,1H),4.77(s,1H),4.27(s,2H),3.32~3.21(m,2H),2.82~2.70(m,5H),2.22~2.12(m,1H),2.11~2.03(m,1H),1.97~1.86(m,1H),1.82~1.70(m,1H),1.68~1.60(m,1H),1.52~1.43(m,1H)
实施例89.(S)-奎宁环-3-基(6-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.54~7.36(m,5H),7.28(d,1H),6.87(d,1H),4.78(s,1H),4.27(s,2H),3.32~3.23(m,2H),2.84~2.73(m,5H),2.20~2.03(m,3H),1.98~1.87(m,1H),1.81~1.71(m,1H),1.69~1.58(m,1H),1.54~1.42(m,1H)
实施例90.(S)-奎宁环-3-基(6-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.46(d,1H),7.32~7.29(m,4H),7.22(d,1H),6.84(d,1H),4.74(s,1H),4.27(s,2H),3.32~3.21(m,2H),2.82~2.69(m,5H),2.47~2.14(m,1H),2.11~1.99(m,2H),1.96~1.84(m,1H),1.80~1.68(m,1H),1.67~1.57(m,1H),1.50~1.37(m,1H)
实施例91.(S)-奎宁环-3-基(6-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.73~7.70(m,4H),7.56(d,1H),6.90(d,1H),4.78(s,1H),4.28(s,2H),3.32~3.23(m,2H),2.83~2.70(m,5H),2.24~2.13(m,1H),2.11~2.03(m,2H),1.97~1.89(m,1H),1.82~1.71(m,1H),1.70~1.57(m,1H),1.54~1.40(m,1H)
实施例92.(S)-奎宁环-3-基(6-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.79(d,2H),7.58~7.46(m,4H),6.90(d,1H),4.78(s,1H),4.27(s,2H),3.32~3.23(m,2H),2.83~2.75(m,5H),2.25~2.14(m,1H),2.12~2.03(m,2H),1.97~1.85(m,1H),1.81~1.69(m,1H),1.68~1.55(m,1H),1.53~1.39(m,1H)
实施例93.(S)-奎宁环-3-基(6-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.75(d,1H),7.61(t,1H),7.51(t,1H),7.32(d,1H),7.18(d,1H),7.10(d,1H),6.82(d,1H),4.72(s,1H),4.28(s,2H),3.32~3.20(m,2H),2.82~2.69(m,5H),2.25~2.13(m,1H),2.12~2.01(m,2H),1.97~1.83(m,1H),1.80~1.68(m,1H),1.68~1.55(m,1H),1.50~1.43(m,1H)
实施例94.(S)-奎宁环-3-基(6-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.62(t,1H),7.49(d,1H),7.42(d,1H),7.30(d,2H),6.87(d,1H),4.77(s,1H),4.27(s,2H),3.32~3.22(m,2H),2.84~2.70(m,5H),2.24~2.13(m,1H),2.11~2.02(m,2H),1.97~1.84(m,1H),1.81~1.70(m,1H),1.69~1.55(m,1H),1.52~1.40(m,1H)
实施例95.(S)-奎宁环-3-基(6-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.55~7.41(m,5H),7.20(d,1H),6.88(d,1H),4.78(s,1H),4.27(s,2H),3.32~3.23(m,2H),2.84~2.73(m,5H),2.25~2.14(m,3H),2.13~2.03(m,2H),1.98~1.87(m,1H),1.81~1.70(m,1H),1.69~1.58(m,1H),1.52~1.41(m,1H)
实施例96.(S)-奎宁环-3-基(6-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.44~7.34(m,5H),7.27(d,1H),6.86(d,1H),4.75(s,1H),4.28(s,2H),3.32~3.23(m,2H),2.84~2.70(m,5H),2.25~2.13(m,1H),2.10~2.02(m,2H),1.97~1.85(m,1H),1.81~1.69(m,1H),1.68~1.56(m,1H),1.52~1.39(m,1H)
实施例97.(S)-奎宁环-3-基(6-(4-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.46(d,2H),7.40(d,2H),7.29(d,2H),6.84(d,1H),4.77(s,1H),4.26(s,2H),3.32~3.20(m,2H),2.83~2.73(m,5H),2.49(s,3H),2.22~2.13(m,1H),2.12~2.03(m,2H),1.97~1.87(m,1H),1.82~1.70(m,1H),1.70~1.57(m,1H),1.52~1.41(m,1H)
实施例98.(S)-奎宁环-3-基(6-(3-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.46(d,1H),7.40(d,2H),7.35~7.25(m,2H),7.19(d,1H),6.85(d,1H),4.78(s,1H),4.25(s,2H),3.32~3.20(m,2H),2.85~2.73(m,5H),2.51(s,3H),2.23-2.03(m,3H),1.97~1.83(m,1H),1.82~1.71(m,1H),1.68~1.58(m,1H),1.53~1.41(m,1H)
实施例99.(S)-奎宁环-3-基(6-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.46~7.38(m,4H),7.20(d,2H),6.86(d,1H),4.77(s,1H),4.25(s,2H),3.32~3.20(m,2H),2.83~2.70(m,5H),2.35(s,3H),2.23~2.13(m,1H),2.12~2.03(m,2H),1.98~1.86(m,1H),1.81~1.70(m,1H),1.69~1.56(m,1H),1.52~1.39(m,1H)
实施例100.(S)-奎宁环-3-基(6-(4-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.77~7.66(m,4H),7.57(d,1H),7.50(d,1H),6.90(d,1H),4.77(s,1H),4.25(s,2H),3.32~3.23(m,2H),2.85~2.74(m,5H),2.22~2.13(m,1H),2.11~2.03(m,2H),1.97~1.85(m,1H),1.82~1.69(m,1H),1.69~1.58(m,1H),1.52~1.41(m,1H)
实施例101.(S)-奎宁环-3-基(6-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用制备例4中制备的(S)-奎宁环-3-基(6-溴-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯和4-氟苯基硼酸,按照与实施例1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.41~7.30(m,3H),7.29~7.27(d,1H),7.20~7.18(d,1H),7.00~6.96(t,1H),6.90~6.87(d,1H),5.01~4.99(m,1H),4.80~4.72(m,2H),3.92~3.83(m,2H),3.27~3.21(m,1H),2.87~2.71(m,5H),2.26(m,1H),1.80(m,1H),1.71~1.67(m,1H),1.58~1.57(m,1H),1.40(m,1H),1.06(s,3H),1.02(s,3H)
实施例102至实施例293
分别使用制备例3中制备的(S)-奎宁环-3-基(7-溴-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯,和相应的取代硼酸,按照与实施例1相同的程序制备实施例102至实施例293的标题化合物。
实施例102.(S)-奎宁环-3-基(7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41~7.33(m,2H),7.30~7.25(m,2H),7.17~7.12(t,1H),7.06~7.04(m,2H),4.92~4.84(m,2H),4.74~4.71(m,1H),3.93~3.77(m,2H),3.30(m,1H),2.92~2.80(m,5H),2.15(m,1H),1.87(m,1H),1.75~1.74(m,1H),1.64(m,1H),1.49~1.45(m,1H),1.07(d,3H),1.01(d,3H)
实施例103.(S)-奎宁环-3-基(7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(s,1H),7.45~7.43(m,1H),7.38~7.25(m,3H),7.15~7.13(m,1H),7.03(s,1H),4.91(m,1H),4.81~4.79(m,1H),4.74~4.72(m,1H),3.91~3.86(m,2H),3.35~3.21(m,1H),2.91~2.72(m,5H),2.11~2.05(m,1H),1.90~1.81(m,1H),1.71~1.70(m,1H),1.70~1.54(m,1H),1.49~1.35(m,1H),1.07(d,3H),1.03(d,3H)
实施例104.(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.81(s,1H),7.75~7.73(d,1H),7.62~7.53(m,2H),7.34~7.27(m,1H),7.19~7.15(t,1H),7.06(s,1H),4.83~4.74(m,3H),3.96~3.85(m,2H),3.29~3.26(m,1H),2.90~2.73(m,5H),2.10(m,1H),1.84(m,1H),1.76~1.70(m,1H),1.63~1.60(m,1H),1.43~1.42(m,1H),1.27(d,3H),1.08(d,3H)
实施例105.(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.40(m,4H),7.32~7.28(m,1H),7.21~7.12(m,1H),7.04(s,1H),4.92~4.90(m,1H),4.81~4.80(m,1H),4.75~4.72(m,1H),3.94~3.84(m,2H),3.28~3.26(m,1H),2.89~2.75(m,5H),2.11~2.08(m,1H),1.83(m,1H),1.71~1.68(m,1H),1.59(m,1H),1.42(m,1H),1.08(d,3H),1.03(d,3H)
实施例106.(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32~7.21(m,4H),7.18~7.05(m,2H),7.00(s,1H),5.14(s,2H),4.83~4.79(m,2H),4.73~4.71(m,1H),3.90~3.82(m,2H),3.27(s,3H),3.28~3.27(m,1H),2.87~2.72(m,5H),2.10~2.02(m,1H),1.83~1.82(m,1H),1.71~1.69(m,1H),1.60(m,1H),1.43(m,1H),1.07~0.99(m,6H)
实施例107.(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.31(m,1H),7.27~7.15(m,5H),7.04~7.01(m,1H),5.21(s,2H),4.96~4.94(m,1H),4.79~4.78(m,1H),4.72~4.66(m,1H),3.89~3.81(m,2H),3.50(s,3H),3.30~3.19(m,1H),2.86~2.72(m,5H),2.10~2.08(m,1H),1.82~1.81(m,1H),1.70~1.68(m,1H),1.58~1.57(m,1H),1.55~1.35(m,1H),1.06~0.98(m,6H)
实施例108.(S)-奎宁环-3-基(7-(4-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.48(m,2H),7.21~7.14(s,1H),7.12~7.08(m,3H),7.01(s,1H),5.21(s,2H),4.85~4.81(m,2H),4.72~4.69(m,1H),3.92~3.82(m,2H),3.51(s,3H),3.28~3.26(m,1H),2.91~2.71(m,5H),2.10~2.08(m,1H),1.81(m,1H),1.71~1.69(m,1H),1.60~1.59(m,1H),1.42(m,1H),1.07~0.99(m,6H)
实施例109.(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.27(m,2H),7.22~7.15(m,3H),7.04~6.92(m,2H),5.10~4.95(m,1H),4.78~4.77(m,1H),4.70~4.65(t,1H),4.12~4.10(m,2H),3.87~3.80(m,2H),3.70~3.68(m,2H),3.37(s,3H),3.30~3.16(m,1H),2.87~2.71(m,5H),2.09~2.07(m,1H),1.82(m,1H),1.58(m,1H),1.39(m,1H),1.06~0.97(m,6H)
实施例110.(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35~7.23(m,2H),7.16~7.13(m,3H),7.04(s,1H),6.93~6.91(d,1H),4.85~4.79(m,2H),4.73~4.70(m,1H),4.19~4.16(m,2H),3.90~3.82(m,2H),3.79~3.77(m,2H),3.47(s,3H),3.27(m,1H),2.90~2.72(m,5H),2.10~2.08(m,1H),1.83(m,1H),1.71~1.69(m,1H),1.60~1.58(m,1H),1.50~1.35(m,1H),1.07~0.97(m,6H)
实施例111.(S)-奎宁环-3-基(7-(4-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.47(m,1H),7.27~7.17(m,3H),7.00~6.91(m,2H),6.82~6.80(d,1H),4.96~4.82(m,1H),4.79~4.77(m,1H),4.71~4.66(m,1H),4.17~4.14(m,2H),3.88~3.76(m,4H),3.46(s,3H),3.32~3.20(m,1H),2.88~2.70(m,5H),2.07~2.04(m,1H),1.82~1.81(m,1H),1.70~1.69(m,1H),1.58~1.57(m,1H),1.48~1.32(m,1H),1.06~0.97(m,6H)
实施例112.(S)-奎宁环-3-基(7-(3-(二氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.71~7.64(m,2H),7.55~7.46(m,2H),7.35~7.22(m,1H),7.20~7.13(m,1H),7.06(s,1H),6.70(t,1H),4.91~4.78(m,2H),4.76~4.69(m,1H),3.96~3.82(m,2H),3.35~3.23(m,1H),2.96~2.70(m,5H),2.14~2.07(m,1H),1.87~1.79(m,1H),1.76~1.68(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例113.(S)-奎宁环-3-基(3,3-二甲基-7-(8-甲基喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.95(d,1H),8.27(d,1H),7.60(d,1H),7.41~7.29(m,3H),7.01(t,1H),6.92(s,1H),4.98~4.89(m,1H),4.86~4.75(m,2H),3.99~3.83(m,2H),3.34~3.23(m,1H),2.96~2.68(m,8H),2.17~2.07(m,1H),1.90~1.81(m,1H),1.77~1.67(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.10(d,3H),1.07(d,3H)
实施例114.(S)-奎宁环-3-基(7-(3,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.21(m,1H),7.14(t,1H),7.04(s,1H),6.72~6.68(m,2H),6.46(s,1H),4.90~4.84(m,1H),4.82~4.77(m,1H),4.75~4.68(d,1H),3.95~3.78(m,8H),3.32~3.23(m,1H),2.94~2.69(m,5H),2.14~2.06(m,1H),1.85~1.78(m,1H),1.76~1.66(m,1H),1.63~1.54(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例115.(S)-奎宁环-3-基(7-(4-甲氧基-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.34(m,2H),7.28~7.19(m,1H),7.12(t,1H),7.01(s,1H),6.87(d,1H),5.00~4.91(m,1H),4.82~4.76(m,1H),4.68(d,1H),3.93~3.80(m,5H),3.32~3.21(m,1H),2.94~2.68(m,5H),2.27(s,3H),2.14~2.06(m,1H),1.87~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例116.(S)-奎宁环-3-基(7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.20(d,1H),7.13(d,1H),6.87(d,1H),6.83~6.75(m,3H),4.94~4.85(m,1H),4.83~4.77(m,1H),4.73(d,1H),3.95~3.80(m,5H),3.34~3.23(m,1H),2.96~2.69(m,5H),2.27(s,3H),2.14~2.06(m,1H),1.90~1.80(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例117.(S)-奎宁环-3-基(7-(3-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.42(d,1H),7.26~7.20(m,1H),7.09(t,1H),7.00~6.95(m,2H),4.94~4.86(m,1H),4.82~4.77(m,1H),4.69(d,1H),3.94(s,3H),3.92~3.80(m,2H),3.33~3.20(m,1H),2.95~2.67(m,5H),2.14~2.06(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.63~1.53(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例118.(S)-奎宁环-3-基(7-(3-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.20(m,3H),7.09(t,1H),7.04~6.96(m,2H),4.90(t,1H),4.83~4.76(m,1H),4.70(d,1H),3.92(s,3H),3.91~3.79(m,2H),3.31~3.22(m,1H),2.96~2.67(m,5H),2.13~2.06(m,1H),1.87~1.79(m,1H),1.74~1.66(m,1H),1.62~1.55(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例119.(S)-奎宁环-3-基(7-(2-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.28(m,2H),7.04~6.95(m,2H),6.91~6.82(m,2H),5.02(t,1H),4.82~4.76(m,1H),4.72(d,1H),3.95~3.78(m,5H),3.32~3.19(m,1H),2.93~2.67(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.47~1.35(m,1H),1.07(d,3H),1.03(d,3H)
实施例120.(S)-奎宁环-3-基(7-(4-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.28~7.19(m,2H),7.05(t,1H),6.95(s,1H),6.75~6.66(m,2H),4.87(t,1H),4.82~4.76(m,1H),4.70(d,1H),3.93~3.87(m,5H),3.85~3.76(m,4H),3.33~3.22(m,1H),2.93~2.68(m,5H),2.12~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例121.(S)-奎宁环-3-基(7-(2-氯-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.70~7.62(m,1H),7.49~7.42(m,1H),7.24~7.00(m,2H),6.96~6.89(m,1H),6.84~6.79(m,1H),4.93~4.84(m,1H),4.81~4.62(m,2H),3.95~3.73(m,5H),3.30~3.20(m,1H),2.92~2.66(m,5H),2.14~2.04(m,1H),1.88~1.77(m,1H),1.74~1.65(m,1H),1.61~1.54(m,1H),1.45~1.36(m,1H),1.04(d,3H),0.99(d,3H)
实施例122.(S)-奎宁环-3-基(7-(2-氟-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.71~7.63(m,1H),7.58~7.52(m,1H),7.50~7.42(m,1H),7.25~7.16(m,1H),7.02~6.88(m,1H),6.84~6.74(m,1H)4.91~4.84(m,1H),4.82~4.76(m,1H),4.70(d,1H),3.94~3.79(m,5H),3.33~3.22(m,1H),2.95~2.68(m,5H),2.12~2.05(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.47~1.36(m,1H),1.08(d,3H),1.04(d,3H)
实施例123.(S)-奎宁环-3-基(7-(2,5-二氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.21(m,1H),7.14(dd,1H),7.05(t,1H),6.95(s,1H),6.76(dd,1H)5.01(t,1H),4.82~4.75(m,1H),4.69(d,1H),3.94~3.79(m,5H),3.30~3.20(m,1H),2.91~2.66(m,5H),2.13~2.05(m,1H),1.86~1.77(m,1H),1.74~1.65(m,1H),1.61~1.53(m,1H),1.46~1.36(m,1H),1.05(d,3H),1.01(d,3H)
实施例124.(S)-奎宁环-3-基(7-(4-乙氧基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.19(m,3H),7.09(t,1H),7.02~7.95(m,2H),4.95(t,1H),4.82~4.75(m,1H),4.69(d,1H),4.14(q,2H),3.93~3.79(m,2H),3.31~3.20(m,1H),2.93~2.68(m,5H),2.12~2.06(m,1H),1.88~1.77(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.46(t,3H),1.42~1.35(m,1H),1.05(d,3H),1.01(d,3H)
实施例125.(S)-奎宁环-3-基(7-(2,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.25~7.17(m,2H),7.08(t,1H),6.98(s,1H),6.59~6.52(m,2H),4.95(t,1H),4.82~4.75(m,1H),4.68(d,1H),3.91~3.76(m,8H),3.32~3.20(m,1H),2.95~2.67(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例126.(S)-奎宁环-3-基(7-(2,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.20(m,1H),7.12(t,1H),7.01(s,1H),6.93~6.82(m,3H),4.85~4.77(m,2H),4.70(d,1H),3.93~3.80(m,2H),3.78(s,3H),3.77(s,3H),3.32~3.23(m,1H),2.94~2.69(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.74~1.67(m,1H),1.62~1.55(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.04(d,3H)
实施例127.(S)-奎宁环-3-基(7-(2,3-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.28~7.19(m,1H),7.15~7.05(m,2H),7.00(s,1H),6.93~6.89(m,2H),5.02~4.93(m,1H),4.83~4.76(m,1H),4.71(d,1H),3.95~3.87(m,4H),3.86~3.79(m,1H),3.63(d,3H),3.32~3.22(m,1H),2.94~2.67(m,5H),2.13~2.06(m,1H),1.89~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例128.(S)-奎宁环-3-基(7-(3,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.21(m,1H),7.16~7.12(m,2H),7.08(s,1H),7.02(s,1H),6.93(d,1H),4.85~4.77(m,2H),4.71(d,1H),3.96~3.89(m,7H),3.87~3.81(m,1H),3.34~3.23(m,1H),2.95~2.69(m,5H),2.13~2.05(m,1H),1.89~1.80(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例129.(S)-奎宁环-3-基(7-(2,6-二甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(dd,1H),7.22(dd,1H),7.11(t,1H),7.01(s,1H),6.38(d,1H),4.88(t,1H),4.86~4.78(m,1H),4.69(d,1H),3.96(d,6H),3.88(dd,1H),3.82(dd,1H),3.32~3.22(m,1H),2.93~2.67(m,5H),2.12~2.05(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.61~1.53(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例130.(S)-奎宁环-3-基(3,3-二甲基-7-(萘-2-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.02(s,1H),7.94~7.84(m,3H),7.71(d,1H),7.54~7.45(m,2H),7.36~7.28(m,2H),7.19(s,1H),4.93(t,1H),4.86~4.78(m,1H),4.74(d,1H),3.94(dd,1H),3.88(dd,1H),3.34~3.22(m,1H),2.97~2.68(m,5H),2.16~2.07(m,1H),1.91~1.80(m,1H),1.76~1.67(m,1H),1.65~1.55(m,1H),1.48~1.30(m,1H),1.09(d,3H),1.05(d,3H)
实施例131.(S)-奎宁环-3-基(3,3-二甲基-7-(萘-1-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.95~7.89(m,2H),7.86(d,1H),7.53~7.40(m,4H),7.32(dd,1H),7.07(t,1H),6.98(s,1H),4.93(t,1H),4.85~4.76(m,2H),3.96(dd,1H),3.89(dd,1H),3.35~3.23(m,1H),2.96~2.71(m,5H),2.16~2.08(m,1H),1.91~1.82(m,1H),1.77~1.67(m,1H),1.64~1.54(m,1H),1.48~1.38(m,1H),1.11(d,3H),1.08(d,3H)
实施例132.(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.89(d,1H),8.19(d,1H),8.15(d,1H),8.00~7.89(m,2H),7.17(s,1H),5.01(t,1H),4.85~4.78(m,1H),4.74(d,1H),3.93(dd,1H),3.87(dd,1H),3.35~3.21(m,1H),2.97~2.67(m,5H),2.17~2.07(m,1H),1.89~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.47~1.36(m,1H),1.08(d,3H),1.04(d,3H)
实施例133.(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.26~7.18(m,3H),7.11(t,1H),7.00(s,1H),4.86(t,1H),4.83~4.77(m,1H),4.70(d,1H),3.90~3.80(m,4H),3.33~3.23(m,1H),2.95~2.69(m,5H),2.32(s,6H),2.13~2.06(m,1H),1.86~1.79(m,1H),1.76~1.67(m,1H),1.63~1.55(m,1H),1.48~1.37(m,4H),1.06(d,3H),1.02(d,3H)
实施例134.(S)-奎宁环-3-基(7-(2,4-二氯-5-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45(s,1H),7.30~7.22(m,1H),7.03~6.95(m,1H),6.89~6.82(m,2H),4.99(t,1H),4.84~4.76(m,1H),4.72(d,1H),4.11~4.06(m,2H),3.95~3.81(m,2H),3.32~3.19(m,1H),2.93~2.67(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.50~1.37(m,4H),1.07(d,3H),1.03(d,3H)
实施例135.(S)-奎宁环-3-基(7-(2-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.26(dd,1H),7.11(t,1H),7.06~6.98(m,2H),6.95~6.89(m,1H),6.85~6.77(m,1H),4.96(t,1H),4.82~4.76(m,1H),4.71(d,1H),4.53~4.44(m,1H),3.90(dd,1H),3.83(dd,1H),3.31~3.20(m,1H),2.93~2.67(m,5H),2.13~2.05(m,1H),1.87~1.78(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.45~1.37(m,1H),1.33(d,6H),1.06(d,3H),1.02(d,3H)
实施例136.(S)-奎宁环-3-基(7-(3-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.26(dd,1H),7.11(t,1H),7.01(s,1H),6.86(s,1H),6.82(d,1H),6.57(d,1H),4.89(t,1H),4.83~4.77(m,1H),4.72(d,1H),4.60~4.52(m,1H),3.91(dd,1H),3.84(dd,1H),3.33~3.22(m,1H),2.94~2.69(m,5H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.47~1.39(m,1H),1.36(d,6H),1.06(d,3H),1.02(d,3H)
实施例137.(S)-奎宁环-3-基(7-(2-氯-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.73(s,1H),7.56(d,1H),7.44(d,1H),7.34~7.24(m,1H),6.99(t,1H),6.89(s,1H),4.96(t,1H),4.84~4.78(m,1H),4.74(d,1H),3.93(dd,1H),3.86(dd,1H),3.32~3.22(m,1H),2.95~2.67(m,5H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.47~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例138.(S)-奎宁环-3-基(7-(2-氯-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.70(d,1H),7.48(d,1H),7.40(t,1H),7.28(dd,1H),6.98~6.92(m,1H),6.84(s,1H),5.00(t,1H),4.83~4.78(m,1H),4.74(d,1H),3.92(dd,1H),3.85(dd,1H),3.32~3.20(m,1H),2.95~2.67(m,5H),2.13~2.06(m,1H),1.87~1.79(m,1H),1.75~1.65(m,1H),1.63~1.53(m,1H),1.47~1.36(m,1H),1.08(d,3H),1.04(d,3H)
实施例139.(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.63~7.49(m,3H),7.35~7.24(m,1H),7.00(t,1H),6.89(s,1H),5.08~4.92(m,1H),4.84~4.77(m,1H),4.73(d,1H),3.98~3.81(m,2H),3.34~3.18(m,1H),2.96~2.64(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.11(d,3H),0.96(d,3H)
实施例140.(S)-奎宁环-3-基(7-(3,5-二甲基-4-丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.26~7.18(m,3H),7.11(t,1H),7.00(s,1H),4.84~4.77(m,2H),4.70(d,1H),3.94~3.81(m,2H),3.76(t,2H),3.33~3.23(m,1H),2.95~2.69(m,5H),2.32(s,6H),2.13~2.05(m,1H),1.90~1.81(m,3H),1.77~1.69(m,1H),1.63~1.54(m,1H),1.47~1.37(m,1H),1.09(t,3H),1.06(d,3H),1.02(d,3H)
实施例141.(S)-奎宁环-3-基(7-(4-(叔丁氧基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.53(d,2H),7.40(d,2H),7.30~7.22(m,1H),7.15(t,1H),7.04(s,1H),4.89~4.77(m,2H),4.71(d,1H),4.48(s,1H),3.91(dd,1H),3.84(dd,1H),3.33~3.23(m,1H),2.94~2.69(m,5H),2.14~2.05(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.64~1.54(m,1H),1.48~1.37(m,1H),1.32(s,9H),1.07(d,3H),1.03(d,3H)
实施例142.(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47(d,1H),7.27(dd,1H),7.19(s,1H),7.14(d,1H),7.00(dd,1H),6.89(s,1H),5.02(t,1H),4.84~4.77(m,1H),4.74(d,1H),3.97~3.80(m,2H),3.34~3.20(m,1H),2.95~2.67(m,5H),2.15~2.01(m,1H),1.89~1.78(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例143.(S)-奎宁环-3-基(7-(2-丁氧基-6-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.70~7.60(m,1H),7.49~7.41(m,1H),7.33~7.14(m,2H),7.01~6.87(m,1H),6.83~6.71(m,1H),5.19~4.91(m,1H),4.83~4.75(m,1H),4.74~4.64(m,1H),4.00~3.78(m,4H),3.31~3.20(m,1H),2.93~2.66(m,5H),2.12~2.05(m,1H),1.88~1.76(m,1H),1.73~1.63(m,3H),1.61~1.52(m,1H),1.45~1.31(m,3H),1.10~0.84(m,9H)
实施例144.(S)-奎宁环-3-基(3,3-二甲基-7-(6-(2,2,2-tri氟乙氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.33(s,1H),7.82(d,1H),7.29(dd,1H),7.09(t,1H),6.98(s,1H),6.92(d,1H),4.90~4.68(m,5H),3.92(dd,1H),3.85(dd,1H),3.34~3.22(m,1H),2.95~2.69(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.64~1.54(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例145.(S)-奎宁环-3-基(7-(6-甲氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.95(s,1H),7.81~7.75(m,2H),7.68(d,1H),7.34~7.26(m,2H),7.21~7.12(m,3H),4.96(t,1H),4.85~4.78(m,1H),4.74(d,1H),3.98~3.90(m,4H),3.86(dd,1H),3.34~3.21(m,1H),2.95~2.68(m,5H),2.16~2.06(m,1H),1.90~1.80(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.08(d,3H),1.04(d,3H)
实施例146.(S)-奎宁环-3-基(7-(4-乙氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.76(s,1H),7.66(d,1H),7.27(dd,1H),7.11(t,1H),7.04(d,1H),7.00(s,1H),4.89~4.77(m,2H),4.72(d,1H),4.17(q,2H),3.92(dd,1H),3.85(dd,1H),3.34~3.22(m,1H),2.96~2.69(m,5H),2.14~2.05(m,1H),1.88~1.79(m,1H),1.76~1.68(m,1H),1.63~1.54(m,1H),1.47(t,3H),1.43~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例147.(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.84(d,1H),7.78(s,1H),7.54(d,1H),7.39~7.27(m,3H),7.21(t,1H),7.12(s,1H),4.94(t,1H),4.85~4.78(m,1H),4.73(d,1H),3.94~3.84(m,2H),3.35~3.21(m,1H),2.96~2.68(m,5H),2.14~2.06(m,1H),1.90~1.79(m,1H),1.75~1.66(m,1H),1.64~1.55(m,1H),1.47~1.38(m,1H),1.08(d,3H),1.04(d,3H)
实施例148.(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.22(m,2H),7.17(t,1H),7.06(s,1H),6.94~6.86(m,2H),6.74(d,1H),4.94(t,1H),4.83~4.77(m,1H),4.71(d,1H),3.92~3.82(m,2H),3.31~3.22(m,1H),2.99(s,6H),2.91~2.68(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例149.(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.21(m,3H),7.12~7.03(m,2H),6.96(s,1H),4.91(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.93~3.83(m,2H),3.33~3.20(m,1H),2.95~2.67(m,5H),2.14~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例150.(S)-奎宁环-3-基(7-(2,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.37(d,1H),7.31(s,1H),729~7.21(m,2H),6.97(t,1H),6.87(s,1H),5.05(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.93~3.82(m,2H),3.33~3.18(m,1H),2.94~2.66(m,5H),2.14~2.05(m,1H),1.88~1.77(m,1H),1.75~1.64(m,1H),1.62~1.53(m,1H),1.46~1.35(m,1H),1.06(d,3H),1.02(d,3H)
实施例151.(S)-奎宁环-3-基(7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41(s,1H),7.40~7.33(m,2H),7.30~7.21(m,2H),7.17(t,1H),7.06(s,1H),4.91(t,1H),4.83~4.77(m,1H),4.72(d,1H),3.93~3.83(m,2H),3.34~3.22(m,1H),3.00~2.93(m,1H),2.91~2.70(m,5H),2.14~2.07(m,1H),1.89~1.79(m,1H),1.75~1.67(m,1H),1.63~1.54(m,1H),1.48~1.38(m,1H),1.30(d,6H),1.07(d,3H),1.03(d,3H)
实施例152.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.42~7.34(m,3H),7.27(dd,1H),7.15(t,1H),7.06(s,1H),4.93(t,1H),4.84~4.77(m,1H),4.72(d,1H),3.93~3.83(m,2H),3.35~3.21(m,1H),2.94~2.67(m,5H),2.14~2.07(m,1H),1.88~1.78(m,1H),1.76~1.66(m,1H),1.63~1.54(m,1H),1.47~1.40(m,1H),1.37(s,9H),1.07(d,3H),1.03(d,3H)
实施例153.(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(d,1H),7.29~7.21(m,1H),7.01(t,1H),6.90(s,1H),6.87~6.78(m,2H),5.06(t,1H),4.83~4.75(m,1H),4.72(d,1H),3.94~3.82(m,2H),3.79(s,3H),3.31~3.20(m,1H),2.92~2.65(m,5H),2.14~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.62~1.53(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例154.(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.79(s,1H),7.65~7.63(m,2H),7.59~7.43(m,5H),7.37(t,1H),7.33~7.19(m,2H),7.12(s,1H),4.99(t,1H),4.85~4.78(m,1H),4.73(d,1H),3.94~3.83(m,2H),3.35~3.21(m,1H),2.95~2.69(m,5H),2.16~2.07(m,1H),1.90~1.79(m,1H),1.76~1.66(m,1H),1.63~1.54(m,1H),1.47~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例155.(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.22(s,1H),8.30(s,1H),8.02(d,1H),7.93(d,1H),7.70~7.58(m,2H),7.35(dd,1H),7.05(t,1H),6.96(s,1H),5.59(t,1H),4.86~4.72(m,2H),3.96~3.87(m,2H),3.34~3.22(m,1H),2.95~2.67(m,5H),2.16~2.08(m,1H),1.90~1.79(m,1H),1.76~1.67(m,1H),1.63~1.55(m,1H),1.47~1.37(m,1H),1.11(d,3H),1.06(d,3H)
实施例156.(S)-奎宁环-3-基(7-(2-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41(t,1H),7.34~7.25(m,2H),7.22~7.09(m,3H),7.02(s,1H),4.90(t,1H),4.83~4.7(m,1H),4.72(d,1H),3.93~3.82(m,2H),3.35~3.20(m,1H),2.95~2.67(m,5H),2.14~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.48~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例157.(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.43~7.30(m,4H),7.28~7.20(m,1H),7.02(t,1H),6.92(s,1H),5.06(t,1H),4.84~4.77(m,1H),4.73(d,1H),3.93~3.82(m,2H),3.32~3.19(m,1H),2.95~2.67(m,5H),2.19~2.06(m,1H),1.90~1.79(m,1H),1.76~1.66(m,1H),1.63~1.53(m,1H),1.47~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例158.(S)-奎宁环-3-基(7-(3-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32(t,1H),7.28~7.22(m,1H),7.19~7.11(m,2H),7.09(s,1H),7.04(s,1H),6.88(dd,1H),4.95(t,1H),4.83~4.77(m,1H),4.71(d,1H),4.08(q,2H),3.92~3.82(m,2H),3.30~3.20(m,1H),2.94~2.66(m,5H),2.16~2.06(m,1H),1.89~1.79(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.48~1.36(m,4H),1.06(d,3H),1.02(d,3H)
实施例159.(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.12(s,1H),7.44(t,1H),7.39~7.30(m,2H),7.29~7.23(m,1H),7.20(d,1H),7.15(s,1H),5.22(dd,1H),4.85~4.79(m,1H),4.75(d,1H),4.05(s,3H),3.97~3.83(m,2H),3.34~3.21(m,1H),2.92~2.66(m,5H),2.15~2.05(m,1H),1.87~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.09(d,3H),1.05(d,3H)
实施例160.(S)-奎宁环-3-基(7-(异喹啉-8-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.32(d,1H),8.45~8.36(m,1H),7.81(d,1H),7.75~7.64(m,2H),7.49(dd,1H),7.34(t,1H),7.05(dd,1H),6.98(d,1H),6.04~5.87(m,1H),4.90~4.71(m,2H),3.98~3.82(m,2H),3.33~3.18(m,1H),2.93~2.65(m,5H),2.21~2.06(m,1H),1.91~1.77(m,1H),1.75~1.66(m,1H),1.62~1.55(m,1H),1.45~1.36(m,1H),1.10~1.06(m,6H)
实施例161.(S)-奎宁环-3-基(7-(4-环丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.46(d,2H),7.29~7.21(m,1H),7.18~7.09(m,3H),7.03(s,1H),4.96(t,1H),4.83~4.75(m,1H),4.70(d,1H),3.91~3.81(m,2H),3.33~3.20(m,1H),2.94~2.68(m,5H),2.13~2.06(m,1H),1.98~1.89(m,1H),1.87~1.78(m,1H),1.75~1.65(m,1H),1.63~1.54(m,1H),1.47~1.36(m,1H),1.10~0.94(m,8H),0.75~0.71(m,2H)
实施例162.(S)-奎宁环-3-基(7-(2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35(m,3H),7.11(t,1H),7.05~6.95(m,3H),4.94~4.86(m,1H),4.83~4.76(m,1H),4.71~4.69(d,1H),3.93~3.87(m,1H),3.85~3.77(m,4H),3.32~3.21(m,1H),2.94~2.68(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.47~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例163.(S)-奎宁环-3-基(3',3'-二甲基-[6,7'-二苯并二氢吡喃]-4'-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32~7.18(m,3H),7.10(t,1H),6.99(s,1H),6.84(d,1H),4.89(t,1H),4.83~4.76(m,1H),4.69(d,1H),4.21(t,2H),3.91~3.81(m,2H),3.32~3.20(m,1H),2.94~2.67(m,7H),2.13~2.00(m,3H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例164.(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.72~7.65(m,2H),7.57(s,1H),7.38~7.29(m,1H),7.12(t,1H),7.02(s,1H),4.92(t,1H),4.84~4.78(m,1H),4.74(d,1H),3.98~3.81(m,2H),3.34~3.22(m,1H),2.94~2.69(m,5H),2.15~2.07(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.54(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.02(d,3H)
实施例165.(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.98~8.93(m,1H),8.21(d,1H),7.84(d,1H),7.72(d,1H),7.59(t,1H),7.42(dd,1H),7.10~7.02(m,2H),6.99(s,1H),4.92~4.72(m,2H),4.63(d,1H),3.95~3.75(m,2H),3.33~3.20(m,1H),2.95~2.67(m,5H),2.13~2.04(m,1H),1.87~1.77(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.02(d,3H),0.98(d,3H)
实施例166.(S)-奎宁环-3-基(7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(t,1H),7.27(t,1H),7.19~7.13(m,2H),7.09(s,1H),7.05(s,1H),6.90(dd,1H),4.89~4.77(m,2H),4.72(d,1H),3.95~3.80(m,5H),3.34~3.23(m,1H),2.95~2.68(m,5H),2.15~2.05(m,1H),1.90~1.79(m,1H),1.74~1.67(m,1H),1.63~1.54(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例167.(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.38(d,1H),7.24(dd,1H),7.09(t,1H),7.02~6.95(m,2H),4.89~4.77(m,2H),4.71(d,1H),4.62~4.56(m,1H),3.92~3.82(m,2H),3.33~3.23(m,1H),2.95~2.67(m,5H),2.14~2.04(m,1H),1.89~1.81(m,1H),1.76~1.67(m,1H),1.63~1.54(m,1H),1.47~1.36(m,7H),1.06(d,3H),1.02(d,3H)
实施例168.(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.28(m,2H),6.92(t,1H),6.83(s,1H),6.67~6.61(m,2H),4.89(t,1H),4.82~4.76(m,1H),4.71(d,1H),3.91~3.79(m,2H),3.74(s,6H),3.34~3.22(m,1H),2.93~2.69(m,5H),2.13~2.06(m,1H),1.89~1.83(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例169.(S)-奎宁环-3-基(7-(2-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47~7.45(m,1H),7.35~7.22(m,4H),7.01(t,1H),6.91(s,1H),4.91(t,1H),4.84~4.77(m,1H),4.74(d,1H),3.94~3.83(m,2H),3.33~3.23(m,1H),2.96~2.69(m,5H),2.13~2.06(m,1H),1.90~1.81(m,1H),1.74~1.66(m,1H),1.64~1.55(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例170.(S)-奎宁环-3-基(7-(3-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.83(s,1H),7.78(d,1H),7.63(d,1H),7.53(t,1H),7.33~7.27(m,1H),7.10(dd,1H),7.01(s,1H),4.93~4.78(m,2H),4.74(d,1H),3.95~3.84(m,2H),3.34~3.23(m,1H),2.95~2.69(m,5H),2.14~2.06(m,1H),1.88~1.80(m,1H),1.74~1.66(m,1H),1.63~1.55(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例171.(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.21(m,1H),7.15~7.02(m,4H),7.00(s,1H),4.8~4.78(m,2H),4.72(d,1H),3.93~3.83(m,2H),3.33~3.23(m,1H),2.94~2.85(m,8H),2.83~2.70(m,3H),2.14~2.06(m,1H),1.89~1.80(m,1H),1.74~1.66(m,1H),1.64~1.55(m,1H),1.48~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例172.(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.26~7.19(m,1H),7.13~7.03(m,3H),6.99(s,1H),6.91(d,1H),4.86~4.77(m,2H),4.70(d,1H),4.29(s,4H),3.92~3.81(m,2H),3.33~3.23(m,1H),2.95~2.68(m,5H),2.14~2.06(m,1H),1.90~1.79(m,1H),1.77~1.67(m,1H),1.64~1.55(m,1H),1.48~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例173.(S)-奎宁环-3-基(7-(1H-吲哚-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.75(brs,1H),7.69~7.61(m,1H),7.37~7.15(m,5H),7.11(s,1H),6.61(s,1H),5.18~5.05(m,1H),4.85~4.65(m,2H),3.96~3.80(m,2H),3.30~3.16(m,1H),2.92~2.64(m,5H),2.15~2.07(m,1H),1.87~1.78(m,1H),1.75~1.65(m,1H),1.63~1.54(m,1H),1.48~1.37(m,1H),1.09(d,3H),1.05(d,3H)
实施例174.(S)-奎宁环-3-基(7-(4-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50(m,2H),7.32~7.23(m,3H),7.15(t,1H),7.04(s,1H),4.86(t,1H),4.83~4.78(m,1H),4.72(d,1H),3.93~3.82(m,2H),3.34~3.23(m,1H),3.00~2.69(m,6H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.37(m,1H),1.29(d,6H),1.07(d,3H),1.03(d,3H)
实施例175.(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.76(d,1H),7.73~7.67(m,1H),7.33~7.21(m,2H),7.01(t,1H),6.99(s,1H),4.88(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.94~3.84(m,2H),3.35~3.22(m,1H),2.96~2.67(m,5H),2.14~2.05(m,1H),1.88~1.79(m,1H),1.76~1.67(m,1H),1.63~1.54(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例176.(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.21(m,2H),7.00(t,1H),6.97~6.91(m,2H),6.89(s,1H),4.97~4.89(m,1H),4.83~4.77(m,1H),4.73(d,1H),3.98~3.82(m,5H),3.33~3.21(m,1H),2.94~2.68(m,5H),2.12~2.06(m,1H),1.89~1.80(m,1H),1.75~1.65(m,1H),1.53~1.53(m,1H),1.47~1.37(m,1H),1.07(d,3H),1.04(d,3H)
实施例177.(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.40(d,1H),7.30~7.25(m,1H),7.18~7.06(m,3H),7.02(s,1H),4.89~4.78(m,2H),4.73(d,1H),3.99~3.84(m,5H),3.35~3.23(m,1H),2.95~2.70(m,5H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.74~1.66(m,1H),1.63~1.55(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例178.(S)-奎宁环-3-基(7-(1H-吲唑-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.10(s,1H),7.73(d,1H),7.39~7.31(m,2H),7.25~7.16(m,2H),7.09(s,1H),5.43(dd,1H),4.83~4.71(m,2H),3.96~3.82(m,2H),3.22~3.00(m,1H),2.89~2.48(m,5H),2.17~2.06(m,1H),1.85~1.77(m,1H),1.73~1.65(m,1H),1.61~1.51(m,1H),1.46~1.36(m,1H),1.08(d,3H),1.04(d,3H)
实施例179.(S)-奎宁环-3-基(7-(3,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.38(m,2H),7.34~7.25(m,2H),7.12~7.04(m,1H),6.98(s,1H),4.91~4.78(m,2H),4.74(t,1H),3.97~3.82(m,2H),3.35~3.20(m,1H),2.96~2.67(m,5H),2.15~2.07(m,1H),1.89~1.79(m,1H),1.77~1.67(m,1H),1.64~1.55(m,1H),1.49~1.37(m,1H),1.08~1.01(m,6H)
实施例180.(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.78(s,1H),7.58(s,1H),7.40~7.30(m,3H),7.28~7.22(m,2H),7.16(dd,1H),7.02(t,1H),6.91(s,1H),5.33(s,2H),4.85~4.75(m,2H),4.66(d,1H),3.89~3.79(m,2H),3.33~3.21(m,1H),2.94~2.69(m,5H),2.14~2.04(m,1H),1.87~1.77(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.04(d,3H),1.00(d,3H)
实施例181.(S)-奎宁环-3-基(7-(2,3-二氢苯并呋喃-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.40(s,1H),7.32(d,1H),7.26~7.19(m,1H),7.10(t,1H),6.98(s,1H),6.83(d,1H),4.90~4.7(m,2H),4.70(d,1H),4.61(t,2H),3.92~3.81(m,2H),3.33~3.21(m,3H),2.95~2.69(m,5H),2.13~2.05(m,1H),1.89~1.81(m,1H),1.74~1.66(m,1H),1.63~1.55(m,1H),1.48~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例182.(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.33(s,1H),7.75(d,1H),7.32~7.22(m,1H),7.09(t,1H),6.98(s,1H),6.83(d,1H),4.88~4.77(m,2H),4.72(d,1H),4.17(d,2H),3.93~3.83(m,2H),3.36~3.23(m,1H),2.95~2.68(m,5H),2.13~2.06(m,1H),1.88~1.80(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.47~1.38(m,1H),1.36~1.25(m,1H),1.07(d,3H),1.03(d,3H),0.68~0.59(m,2H),0.41~0.32(m,2H)
实施例183.(S)-奎宁环-3-基(7-(苯并呋喃-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(d,1H),7.51(d,1H),7.43(t,1H),7.34~7.20(m,4H),7.00(s,1H),4.87(t,1H),4.83~4.78(m,1H),4.72(d,1H),3.95~3.84(m,2H),3.34~3.23(m,1H),2.95~2.69(m,5H),2.14~2.07(m,1H),1.90~1.82(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例184.(S)-奎宁环-3-基(3,3-二甲基-7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.01(s,1H),7.80~7.76(m,2H),7.58(t,1H),7.35~7.25(m,1H),7.17(t,1H),7.07(s,1H),4.88(t,1H),4.83~4.78(m,1H),4.74(d,1H),3.95~3.85(m,2H),3.32~3.22(m,5H),2.93~2.69(m,5H),2.14~2.06(m,1H),1.89~1.67(m,6H),1.63~1.56(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例185.(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.72(d,1H),7.54(t,1H),7.45(t,1H),7.31(d,1H),7.21(dd,1H),6.88(t,1H),6.78(s,1H),5.17(t,1H),4.83~4.76(m,1H),4.74(d,1H),3.92~3.82(m,2H),3.30~3.19(m,1H),2.93~2.67(m,5H),2.12~2.05(m,1H),1.89~1.79(m,1H),1.75~1.65(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例186.(S)-奎宁环-3-基(7-(2-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35~7.27(m,2H),7.22(t,1H),7.19~7.13(m,1H),7.05~6.94(m,3H),4.93(t,1H),4.83~4.77(m,1H),4.71(d,1H),4.09~4.04(q,2H),3.91~3.80(m,2H),3.36~3.21(m,1H),2.94~2.70(m,5H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.66(m,1H),1.63~1.53(m,1H),1.46~1.36(m,4H),1.07(d,3H),1.03(d,3H)
实施例187.(S)-奎宁环-3-基(3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.44(s,1H),7.40~7.34(m,2H),7.26~7.15(m,2H),7.06(s,1H),4.89~4.77(m,2H),4.70(d,1H),3.92~3.82(m,2H),3.35~3.20(m,1H),2.94~2.69(m,5H),2.14~2.05(m,1H),1.89~1.83(m,1H),1.81~1.75(m,1H),1.66~1.55(m,1H),1.48~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例188.(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.76(s,1H),7.68(d,1H),7.32~7.22(m,1H),7.15~7.04(m,2H),7.00(s,1H),4.87~4.77(m,1H),4.72(d,1H),3.98~3.83(m,5H),3.35~3.23(m,1H),2.94~2.70(m,5H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.74~1.68(m,1H),1.64~1.54(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例189.(S)-奎宁环-3-基(7-(2-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.75(d,1H),7.63(t,1H),7.51~7.41(m,2H),7.36~7.28(m,1H),7.13(d,1H),6.98(s,1H),5.08~4.99(m,1H),4.83~4.77(m,1H),4.74(d,1H),3.94~3.84(m,2H),3.32~3.22(m,1H),2.92~2.68(m,5H),2.14~2.06(m,1H),1.90~1.80(m,1H),1.76~1.67(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例190.(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.17(m,2H),7.16~7.06(m,2H),7.03~6.95(m,2H),4.91(t,1H),4.83~4.75(m,1H),4.70(d,1H),4.30~4.20(m,4H),3.91~3.81(m,2H),3.31~3.21(m,1H),2.93~2.67(m,5H),2.23~2.20(m,2H),2.23~2.20(m,2H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.01(d,3H)
实施例191.(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.11(s,1H),8.02(d,1H),7.83(d,1H),7.35~7.30(m,1H),7.27~7.24(m,1H),7.14(s,1H),5.06(t,1H),4.84~4.78(m,1H),4.74(d,1H),3.95~3.85(m,2H),3.33~3.21(m,1H),2.93~2.68(m,5H),2.16~2.06(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.47~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例192.(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ9.03(s,1H),8.25(s,1H),8.13(d,1H),7.86(d,1H),7.71(t,1H),7.57(t,1H),7.35(dd,1H),7.28~7.24(m,1H),7.14(s,1H),5.38~5.35(m,1H),4.86~4.79(m,1H),4.75(d,1H),3.93~3.84(m,2H),3.32~3.22(m,1H),2.93~2.67(m,5H),2.15~2.07(m,1H),1.87~1.77(m,1H),1.74~1.65(m,1H),1.63~1.54(m,1H),1.45~1.35(m,1H),1.08(d,3H),1.03(d,3H)
实施例193.(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.52~7.50(m,2H),7.46~7.44(m,2H),7.30~7.22(m,1H),7.16(t,1H),7.05(s,1H),4.98(t,1H),4.83~4.76(m,1H),4.71(d,1H),3.92~3.82(m,2H),3.32~3.21(m,1H),2.95~2.67(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.63~1.55(m,1H),1.47~1.38(m,1H),1.36(s,9H),1.07(d,3H),1.03(d,3H)
实施例194.(S)-奎宁环-3-基(3,3-二甲基-7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.43~7.34(m,2H),7.28~7.19(m,1H),7.12(t,1H),7.07~6.99(m,2H),5.03(t,1H),4.83~4.75(m,1H),4.70(d,1H),3.87~3.85(m,6H),3.33~3.20(m,1H),2.94~2.92(m,4H),2.90~2.66(m,5H),2.36(s,3H),2.14~2.05(m,1H),1.88~1.78(m,1H),1.75~1.65(m,1H),1.62~1.53(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例195.(S)-奎宁环-3-基(7-(3,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.65~7.60(m,1H),7.54~7.44(m,2H),7.40~7.34(m,1H),7.31~7.21(m,1H),6.98(s,1H),4.96(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.93~3.82(m,2H),3.32~3.21(m,1H),2.92~2.68(m,5H),2.13~2.05(m,1H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例196.(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.97(s,1H),7.75(d,1H),7.52(s,1H),7.36(d,1H),7.32~7.21(m,2H),7.12(s,1H),5.05(t,1H),4.84~4.78(m,1H),4.73(d,1H),4.09(s,2H),3.94~3.84(m,2H),3.35~3.20(m,1H),2096~2.67(m,5H),2.15~2.06(m,1H),1.89~1.78(m,1H),1.75~1.65(m,1H),1.64~1.55(m,1H),1.45~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例197.(S)-奎宁环-3-基(7-(1H-吲哚-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.57(d,1H),7.68(d,1H),7.57(s,1H),7.35(d,1H),7.30~7.21(m,3H),7.12(s,1H),6.57(s,1H),4.93(t,1H),4.84~4.78(m,1H),4.73(d,1H),3.92~3.82(m,2H),3.34~3.24(m,1H),2.95~2.71(m,5H),2.16~2.08(m,1H),1.91~1.80(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例198.(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.20(dd,1H),7.12~7.07(m,2H),7.02(s,1H),6.99(s,1H),6.71(d,1H),4.95(t,1H),4.82~4.76(m,1H),4.68(d,1H),4.32(t,2H),3.90~3.79(m,2H),3.30~3.20(m,3H),2.91(s,3H),2.89~2.68(m,5H),2.12~2.06(m,1H),1.87~1.77(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.35(m,1H),1.05(d,3H),1.01(d,3H)
实施例199.(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.75(s,1H),7.64(d,1H),7.35(d,1H),7.28(dd,1H),7.08(t,1H),6.98(s,1H),5.03(t,1H),4.82~4.75(m,1H),4.71(d,1H),3.92~3.82(m,2H),3.29~3.19(m,1H),2.92~2.65(m,5H).2.56(s,3H),2.12~2.05(m,1H),1.89~1.77(m,1H),1.72~1.65(m,1H),1.62~1.53(m,1H),1.46~1.36(m,1H),1.05(d,3H),1.01(d,3H)
实施例200.(S)-奎宁环-3-基(3,3-二甲基-7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.20(m,2H),7.07~6.97(m,2H),6.94(s,1H),4.95(t,1H),4.83~4.77(m,1H),4.72(d,1H),3.93~3.82(m,2H),3.33~3.20(m,1H),2.94~2.68(m,5H),2.13~2.06(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例201.(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.61~7.52(m,2H),7.31~7.22(m,3H),7.12(t,1H),7.01(s,1H),4.96(t,1H),4.84~4.76(m,1H),4.72(d,1H),3.93~3.83(m,2H),3.32~3.20(m,1H),2.93~2.68(m,5H),2.13~2.06(m,1H),1.87~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.02(d,3H)
实施例202.(S)-奎宁环-3-基(3,3-二甲基-7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.52~7.50(m,2H),7.31~7.22(m,3H),7.15(t,1H),7.04(s,1H),4.97(t,1H),4.85~4.76(m,1H),4.71(d,1H),4.15~4.05(m,2H),3.92~3.82(m,2H),3.60~3.49(m,2H),3.34~3.21(m,1H),2.93~2.68(m,6H),2.16~2.06(m,1H),1.91~1.77(m,5H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例203.(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.17(d,1H),7.28(dd,1H),7.16(t,1H),7.08~7.02(m,2H),6.90(s,1H),5.04(t,1H),4.83~4.75(m,1H),4.71(d,1H),3.96(s,3H),3.93~3.81(m,2H),3.31~3.18(m,1H),2.91~2.06(m,5H),2.13~2.03(m,1H),1.86~1.76(m,1H),1.73~1.64(m,1H),1.60~1.52(m,1H),1.45~1.36(m,1H),1.05(d,3H),1.01(d,3H)
实施例204.(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.19(m,3H),7.09(t,1H),7.01~6.91(m,2H),5.05(t,1H),4.82~4.74(m,1H),4.69(d,1H),3.92~3.79(m,6H),3.29~3.19(m,1H),3.15~3.06(m,4H),2.91~2.64(m,5H),2.11~2.05(m,1H),1.85~1.77(m,1H),1.73~1.65(m,1H),1.61~1.53(m,1H),1.44~1.35(m,1H),1.05(d,3H),1.01(d,3H)
实施例205.(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.42(d,1H),7.29~7.20(m,1H),7.11~7.06(m,2H),6.98(s,1H),4.97(t,1H),4.83~4.76(m,1H),4.70(d,1H),3.95~3.80(m,6H),3.32~3.20(m,1H),3.14~3.02(m,4H),2.94~2.68(m,5H),2.12~2.06(m,1H),1.87~1.77(m,1H),1.74~1.66(m,1H),1.62~1.53(m,1H),1.45~1.37(m,1H),1.06(d,3H),1.01(d,3H)
实施例206.(S)-奎宁环-3-基(7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50(d,2H),7.28~7.19(m,1H),7.12(t,1H),7.00(s,1H),6.95(d,2H),5.03(t,1H),4.82~4.76(m,1H),4.69(d,1H),3.93~3.79(m,5H),3.30~3.20(m,1H),2.92~2.68(m,5H),2.13~2.05(m,1H),1.87~1.77(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.01(d,3H)
实施例207.(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.43(s,1H),8.23(s,1H),7.33~7.24(m,2H),7.10(t,1H),7.00(s,1H),5.32(t,1H),4.83~4.75(m,1H),4.71(d,1H),3.95~3.82(m,5H),3.31~3.18(m,1H),2.91~2.65(m,5H),2.13~2.05(m,1H),1.86~1.77(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.44~1.36(m,1H),1.05(d,3H),1.01(d,3H)
实施例208.(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.82(d,1H),7.77(d,1H),7.52(s,1H),7.38~7.22(m,4H),7.12(s,1H),4.88~4.77(m,2H),4.72(d,1H),3.94~3.84(m,2H),3.35~3.20(m,1H),2.95~2.69(m,5H),2.14~2.06(m,1H),1.90~1.80(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例209.(S)-奎宁环-3-基(7-(4-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49(d,2H),7.29~7.19(m,1H),7.12(t,1H),7.01(s,1H),6.95(d,2H),4.89(t,1H),4.83~4.77(m,1H),4.70(d,1H),4.07(q,2H),3.92~3.81(m,2H),3.35~3.20(m,1H),2.95~2.69(m,5H),2.12~2.04(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.45~1.34(m,4H),1.06(d,3H),1.02(d,3H)
实施例210.(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.49(s,1H),8.01(s,1H),7.30(t,1H),7.08(t,1H),6.97(s,1H),4.89(t,1H),4.83~4.77(m,1H),4.73(d,1H),4.08(s,3H),3.94~3.84(m,2H),3.34~3.23(m,1H),2.94~2.69(m,5H),2.14~2.05(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.63~1.53(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.02(d,3H)
实施例211.(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.72~7.60(m,4H),7.32~7.27(m,1H),7.16(t,1H),7.05(s,1H),4.99(t,1H),4.84~4.76(m,1H),4.73(d,1H),3.94~3.84(m,2H),3.32~3.21(m,1H),2.93~2.68(m,5H),2.14~2.04(m,1H),1.88~1.79(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例212.(S)-奎宁环-3-基(7-(1H-吲唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.22(s,1H),7.49~7.40(m,2H),7.33(t,1H),7.29~7.24(m,1H),7.21(d,1H),7.16(s,1H),5.18(d,1H),4.87~4.80(m,1H),4.76(d,1H),3.94~3.86(m,2H),3.38~3.24(m,1H),2.96~2.70(m,5H),2.16~2.09(m,1H),1.91~1.81(m,1H),1.77~1.68(m,1H),1.65~1.57(m,1H),1.48~1.39(m,1H),1.09(d,3H),1.05(d,3H)
实施例213.(S)-奎宁环-3-基(7-(4-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47(d,2H),7.37(d,2H),7.26(dd,1H),7.11(t,1H),7.00(s,1H),4.99(t,1H),4.84~4.75(m,1H),4.71(d,1H),3.92~3.82(m,2H),3.31~3.20(m,1H),2.92~2.68(m,5H),2.12~2.06(m,1H),1.86~1.78(m,1H),1.74~1.66(m,1H),1.61~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例214.(S)-奎宁环-3-基(7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.56~7.47(m,2H),7.29~7.23(m,1H),7.15~7.06(m,3H),7.00(s,1H),4.88(t,1H),4.83~4.78(m,1H),4.71(d,1H),3.93~3.82(m,2H),3.35~3.22(m,1H),2.96~2.68(m,5H),2.14~2.06(m,1H),1.87~1.79(m,1H),1.75~1.67(m,1H),1.62~1.55(m,1H),1.46~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例215.(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.31~8.23(m,1H),7.84~7.75(m,1H),7.34~7.24(m,1H),7.16~7.03(m,1H),6.94(s,1H),4.88~4.77(m,2H),4.73(d,1H),4.02(s,3H),3.95~3.82(m,2H),3.34~3.23(m,1H),2.93~2.69(m,5H),2.13~2.06(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.62~1.55(m,1H),1.45~1.37(m,1H),1.07(d,3H),1.02(d,3H)
实施例216.(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41~7.22(m,2H),7.17(s,1H),7.12(t,1H),7.09~7.07(m,2H),4.99(t,1H),4.83~4.76(m,1H),4.70(d,1H),4.61(s,2H),3.92~3.83(m,2H),3.37(s,3H),3.31~3.22(m,1H),2.93~2.68(m,5H),2.13~2.06(m,1H),1.87~1.79(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例217.(S)-奎宁环-3-基(3,3-二甲基-7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.25(m,1H),7.16~7.09(m,1H),7.08~6.98(m,2H),6.95(s,1H),4.94(t,1H),4.83~4.76(m,1H),4.73(d,1H),3.93~3.83(m,2H),3.32~3.21(m,1H),2.94~2.67(m,5H),2.13~2.06(m,1H),1.90~1.78(m,1H),1.74~1.67(m,1H),1.63~1.53(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例218.(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.56(d,2H),7.27(dd,1H),7.18(d,2H),7.11(t,1H),7.00(s,1H),6.54(t,1H),4.95(t,1H),4.83~4.76(m,1H),4.71(d,1H),3.92~3.82(m,2H),3.32~3.20(m,1H),2.93~2.68(m,5H),2.12~2.05(m,1H),1.87~1.78(m,1H),1.74~1.66(m,1H),1.62~1.53(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例219.(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.91(d,1H),8.28(d,1H),8.11(d,1H),7.73(t,1H),7.48(d,1H),7.39~7.30(m,2H),7.02(t,1H),6.93(s,1H),5.07(t,1H),4.86~4.74(m,2H),3.96~3.86(m,2H),3.34~3.22(m,1H),2.95~2.66(m,5H),2.15~2.07(m,1H),1.89~1.80(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.10(d,3H),1.06(d,3H)
实施例220.(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噁二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.94~7.85(m,2H),7.66(d,1H),7.36~7.31(m,1H),7.19(t,1H),7.09(s,1H),5.00(t,1H),4.84~4.78(m,1H),4.75(d,1H),3.96~3.86(m,2H),3.34~3.22(m,1H),2.94~2.67(m,5H),2.13~2.06(m,1H),1.90~1.78(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例221.(S)-奎宁环-3-基(3,3-二甲基-7-(5-甲基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.55(s,1H),8.40(s,1H),7.63(s,1H),7.35~7.24(m,1H),7.11(t,1H),7.01(s,1H),5.17(t,1H),4.84~4.76(m,1H),4.73(d,1H),3.97~3.80(m,2H),3.35~3.21(m,1H),2.94~2.67(m,5H),2.38(s,3H),2.12~2.05(m,1H),1.89~1.79(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例222.(S)-奎宁环-3-基(7-(2-氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.18(d,1H),7.85(t,1H),7.35~7.23(m,2H),7.12(t,1H),7.02(s,1H),4.95(t,1H),4.84~4.77(m,1H),4.73(d,1H),3.96~3.81(m,2H),3.33~3.20(m,1H),2.93~2.68(m,5H),2.13~2.05(m,1H),1.87~1.78(m,1H),1.74~1.66(m,1H),1.62~1.55(m,1H),1.45~1.36(m,1H),1.07(d,3H),1.02(d,3H)
实施例223.(S)-奎宁环-3-基(7-(2-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.17(m,3H),7.10(d,1H),6.99(t,1H),6.88(s,1H),5.14(t,1H),4.82~4.74(m,1H),4.71(d,1H),3.93~3.79(m,2H),3.30~3.19(m,1H),2.93~2.66(m,5H),2.36(s,3H),2.13~2.05(m,1H),1.88~1.77(m,1H),1.73~1.65(m,1H),1.60~1.52(m,1H),1.44~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例224.(S)-奎宁环-3-基(7-(2-氯-5-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33(d,1H),7.28~7.21(m,1H),7.13(s,1H),7.08(d,1H),7.00(t,1H),6.89(s,1H),4.98(t,1H),4.83~4.76(m,1H),4.73(d,1H),3.96~3.79(m,2H),3.31~3.21(m,1H),2.93~2.68(m,5H),2.34(s,3H),2.12~2.07(m,1H),1.89~1.79(m,1H),1.73~1.67(m,1H),1.62~1.54(m,1H),1.45~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例225.(S)-奎宁环-3-基(7-(2-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.21(m,2H),7.10(t,1H),7.03~6.90(m,3H),5.02(t,1H),4.83~4.75(m,1H),4.70(d,1H),3.94~3.77(m,2H),3.34~3.16(m,1H),2.95~2.66(m,5H),2.37(s,3H),2.13~2.04(m,1H),1.87~1.77(m,1H),1.73~1.65(m,1H),1.61~1.52(m,1H),1.46~1.34(m,1H),1.06(d,3H),1.02(d,3H)
实施例226.(S)-奎宁环-3-基(7-(3-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(s,1H),7.35(d,1H),7.30~7.22(m,2H),7.12(t,1H),7.01(s,1H),4.80(t,1H),4.82~4.77(m,1H),4.72(d,1H),3.95~3.82(m,2H),3.34~3.22(m,1H),2.94~2.69(m,5H),2.40(s,3H),2.15~2.07(m,1H),1.89~1.80(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例227.(S)-奎宁环-3-基(7-(4-氟-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.19(m,1H),7.14(t,1H),6.97~6.87(m,2H),6.83(t,1H),6.73(s,1H),5.00(t,1H),4.84~4.77(m,1H),4.73(d,1H),3.94~3.80(m,2H),3.32~3.20(m,1H),2.93~2.67(m,5H),2.26(s,3H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例228.(S)-奎宁环-3-基(7-(3-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.18(m,4H),7.12(t,1H),7.01(s,1H),4.94(t,1H),4.82~4.76(m,1H),4.71(d,1H),3.96~3.78(m,2H),3.32~3.21(m,1H),2.94~2.67(m,5H),2.30(s,3H),2.14~2.05(m,1H),1.87~1.79(m,1H),1.75~1.66(m,1H),1.64~1.53(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例229.(S)-奎宁环-3-基(7-(4-氟-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.30(m,2H),7.25(dd,1H),7.13~6.99(m,2H),6.98(s,1H),4.94(t,1H),4.83~4.76(m,1H),4.71(d,1H),3.94~3.81(m,2H),3.30~3.21(m,1H),2.92~2.67(m,5H),2.32(s,3H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.73~1.65(m,1H),1.63~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例230.(S)-奎宁环-3-基(7-(2,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.46(s,1H),7.31~7.19(m,3H),6.96(t,1H),6.86(s,1H),5.09(t,1H),4.82~4.75(m,1H),4.72(d,1H),3.95~3.78(m,2H),3.30~3.18(m,1H),2.92~2.68(m,5H),2.13~2.05(m,1H),1.88~1.78(m,1H),1.73~1.65(m,1H),1.61~1.52(m,1H),1.44~1.35(m,1H),1.06(d,3H),1.02(d,3H)
实施例231.(S)-奎宁环-3-基(7-(2-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.17(m,3H),7.04~6.93(m,2H),6.85(s,1H),5.15(t,1H),4.82~4.76(m,1H),4.72(d,1H),3.94~3.81(m,2H),3.30~3.18(m,1H),2.91~2.66(m,5H),2.13~2.05(m,1H),1.87~1.77(m,1H),1.73~1.64(m,1H),1.60~1.53(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例232.(S)-奎宁环-3-基(7-(2-氯-5-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.40(dd,1H),7.26(dd,1H),7.07~6.94(m,3H),6.88(s,1H),5.08(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.95~3.81(m,2H),3.30~3.21(m,1H),2.93~2.66(m,5H),2.13~2.06(m,1H),1.87~1.78(m,1H),1.74~1.65(m,1H),1.61~1.53(m,1H),1.45~1.35(m,1H),1.07(d,3H),1.03(d,3H)
实施例233.(S)-奎宁环-3-基(7-(2,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.37(dd,1H),7.26(dd,1H),7.05(t,1H),6.97~6.85(m,3H),5.02(t,1H),4.82~4.76(m,1H),4.71(d,1H),3.93~3.81(m,2H),3.31~3.19(m,1H),2.93~2.68(m,5H),2.13~2.05(m,1H),1.86~1.78(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.44~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例234.(S)-奎宁环-3-基(7-(2,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.27(dd,1H),7.14~7.05(m,3H),7.02~6.94(m,2H),4.96(t,1H),4.83~4.75(m,1H),4.72(d,1H),3.95~3.81(m,2H),3.32~3.18(m,1H),2.91~2.64(m,5H),2.14~2.02(m,1H),1.88~1.78(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例235.(S)-奎宁环-3-基(7-(2,3-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.44(dd,1H),7.31~7.15(m,3H),6.96(dd,1H),6.85(s,1H),5.11(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.95~3.80(m,2H),3.31~3.18(m,1H),2.93~2.67(m,5H),2.14~2.06(m,1H),1.87~1.77(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.45~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例236.(S)-奎宁环-3-基(7-(3-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(d,1H),7.44~7.36(m,1H),7.30~7.22(m,1H),7.18(t,1H),7.11~7.04(m,1H),6.97(s,1H),4.90(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.94~3.82(m,2H),3.32~3.22(m,1H),2.95~2.68(m,5H),2.13~2.06(m,1H),1.89~1.78(m,1H),1.75~1.66(m,1H),1.62~1.55(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例237.(S)-奎宁环-3-基(7-(2-氯-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31~7.22(m,2H),7.17~7.08(m,2H),6.99(t,1H),6.89(s,1H),5.08(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.95~3.81(m,2H),3.30~3.21(m,1H),2.93~2.67(m,5H),2.16~2.06(m,1H),1.88~1.78(m,1H),1.74~1.65(m,1H),1.61~1.53(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例238.(S)-奎宁环-3-基(7-(3,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(dd,1H),7.30~7.16(m,3H),7.08(t,1H),6.97(m,1H),4.87(t,1H),4.82~4.77(m,1H),4.72(d,1H),3.96~3.81(m,2H),3.34~3.21(m,1H),2.94~2.68(m,5H),2.13~2.05(m,1H),1.87~1.78(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例239.(S)-奎宁环-3-基(7-(2,3-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.27(dd,1H),7.18~7.07(m,4H),6.99(s,1H),5.06(t,1H),4.82~4.75(m,1H),4.72(d,1H),3.95~3.81(m,2H),3.29~3.20(m,1H),2.92~2.68(m,5H),2.13~2.05(m,1H),1.86~1.76(m,1H),1.73~1.64(m,1H),1.62~1.52(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例240.(S)-奎宁环-3-基(7-(3,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.27(dd,1H),7.13~7.03(m,3H),6.99(s,1H),6.77(t,1H),4.98(t,1H),4.84~4.76(m,1H),4.72(d,1H),3.95~3.80(m,2H),3.32~3.20(m,1H),2.93~2.06(m,5H),2.13~2.06(m,1H),1.86~1.78(m,1H),1.74~1.65(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.01(d,3H)
实施例241.(S)-奎宁环-3-基(7-(6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.35(s,1H),7.75(d,1H),7.27(t,1H),7.08(t,1H),6.97(s,1H),6.79(d,1H),4.94(t,1H),4.83~4.75(m,1H),4.71(d,1H),3.97(s,3H),3.93~3.81(m,2H),3.33~3.20(m,1H),2.96~2.65(m,5H),2.13~2.04(m,1H),1.86~1.76(m,1H),1.74~1.66(m,1H),1.61~1.53(m,1H),1.47~1.33(m,1H),1.06(d,3H),1.02(d,3H)
实施例242.(S)-奎宁环-3-基(7-([1,1'-联苯]-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.69~7.62(m,6H),7.50~7.43(m,2H),7.37(t,1H),7.31(d,1H),7.23(d,1H),7.11(s,1H),4.90~4.88(m,1H),4.85~4.78(m,1H),4.74(d,1H),3.96~3.82(m,2H),3.34~3.24(m,1H),2.95~2.71(m,5H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.47~1.37(m,1H),1.07(s,3H),1.03(s,3H)
实施例243.(S)-奎宁环-3-基(3,3-二甲基-7-(噻唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.68~7.51(m,2H),7.48~7.39(m,1H),7.33~7.10(m,sH),6.96~6.77(m,1H),5.04~4.90(m,1H),4.83~4.74(m,1H),4.73~4.63(m,1H),3.97~3.75(m,2H),3.31~3.18(m,1H),2.93~2.65(m,5H),2.12~2.02(m,1H),1.88~1.76(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.45~1.35(m,1H),1.09~0.84(m,6H)
实施例244.(S)-奎宁环-3-基(3,3-二甲基-7-(3-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.59(s,1H),7.48~7.43(m,1H),7.41~7.36(m,2H),7.27(dd,1H),7.17(t,1H),7.06(s,1H),6.77(dd,1H),5.80(d,1H),5.30(d,1H),4.99(t,1H),4.83~4.77(m,1H),4.72(d,1H),3.95~3.81(m,2H),3.33~3.20(m,1H),2.93~2.68(m,5H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.65(m,1H),1.63~1.54(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例245.(S)-奎宁环-3-基(7-(2-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.15(d,1H),7.59(d,1H),7.29~7.21(m,1H),7.13(t,1H),7.03(s,1H),6.96(dd,1H),4.90(t,1H),4.82~4.75(m,1H),4.71(d,1H),3.97(s,3H),3.92~3.80(m,2H),3.33~3.22(m,1H),2.93~2.69(m,5H),2.11~2.03(m,1H),1.89~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.37(m,1H),1.06(d,3H),1.03(d,3H)
实施例246.(S)-奎宁环-3-基(7-(6-甲氧基吡啶-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.64~7.56(m,2H),7.54(s,1H),7.33~7.24(m,2H),6.68(d,1H),4.96(t,1H),4.83~4.76(m,1H),4.72(d,1H),4.01(s,3H),3.95~3.82(m,2H),3.30~3.20(m,1H),2.93~2.68(m,5H),2.14~2.05(m,1H),1.88~1.79(m,1H),1.74~1.65(m,1H),1.61~1.54(m,1H),1.45~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例247.(S)-奎宁环-3-基(7-(4-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.73~7.60(m,rH),7.34~7.25(m,1H),7.14(t,1H),7.03(s,1H),4.98(t,1H),4.83~4.76(m,1H),4.73(d,1H),3.95~3.83(m,2H),3.30~3.20(m,1H),2.91~2.67(m,5H),2.13~2.05(m,1H),1.86~1.78(m,1H),1.73~1.65(m,1H),1.61~1.54(m,1H),1.46~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例248.(S)-奎宁环-3-基(7-(2-氟-6-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.73(t,1H),7.28(dd,1H),7.15~7.06(m,2H),7.01(s,1H),4.92(t,1H),4.82~4.76(m,1H),4.72(d,1H),3.94~3.81(m,2H),3.32~3.20(m,1H),2.93~2.66(m,5H),2.53(s,3H),2.12~2.04(m,1H),1.86~1.78(m,1H),1.74~1.66(m,1H),1.61~1.53(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例249.(S)-奎宁环-3-基(7-(苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.19(m,1H),7.12~7.00(m,3H),6.97(s,1H),6.86(d,1H),5.99(s,2H),4.86(t,1H),4.82~4.77(m,1H),4.70(d,1H),3.93~3.80(m,2H),3.32~3.23(m,1H),2.92~2.68(m,5H),2.14~2.04(m,1H),1.86~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例250.(S)-奎宁环-3-基(7-(6-环丙基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.63(s,1H),7.69(d,1H),7.28(dd,1H),7.17(d,1H),7.11(t,1H),7.00(s,1H),4.93~4.90(m,1H),4.82~4.76(m,1H),4.72(d,1H),3.96~3.81(m,2H),3.32~3.21(m,1H),2.94~2.67(m,5H),2.13~2.02(m,2H),1.86~1.78(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.36(m,1H),1.11~0.95(m,10H)
实施例251.(S)-奎宁环-3-基(7-(6-(二甲氨基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.41(s,1H),7.66(d,1H),7.24(dd,1H),7.09(t,1H),6.97(s,1H),6.57(d,1H),4.92~4.85(m,1H),4.83~4.75(m,1H),4.69(d,1H),3.94~3.78(m,2H),3.34~3.21(m,1H),3.13(s,6H),2.93~2.66(m,5H),2.13~2.05(m,1H),1.88~1.77(m,1H),1.74~1.66(m,1H),1.63~1.53(m,1H),1.45~1.35(m,1H),1.06(d,3H),1.02(d,3H)
实施例252.(S)-奎宁环-3-基(7-(5-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.24(dd,1H),7.12~6.94(m,4H),6.90~6.87(m,1H),4.93(t,1H),4.82~4.75(m,1H),4.70(d,1H),3.94~3.81(m,2H),3.78(s,3H),3.32~3.21(m,1H),2.94~2.66(m,5H),2.15~2.06(m,1H),1.87~1.79(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例253.(S)-奎宁环-3-基(7-(6-乙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.34(s,1H),7.75(dd,1H),7.27(dd,1H),7.09(t,1H),6.98(s,1H),6.78(d,1H),4.91~4.84(m,1H),4.82~4.77(m,1H),4.72(d,1H),4.39(q,2H),3.94~3.81(m,2H),3.33~3.22(m,1H),2.92~2.68(m,5H),2.13~2.05(m,1H),1.85~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.35(m,4H),1.07(d,3H),1.02(d,3H)
实施例254.(S)-奎宁环-3-基(7-(6-甲氧基-5-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.18(s,1H),7.56(s,1H),7.28~7.23(m,1H),7.08(t,1H),6.97(s,1H),4.92(t,1H),4.83~4.75(m,1H),4.70(d,1H),3.99(s,3H),3.94~3.79(m,2H),3.32~3.21(m,1H),2.93~2.67(m,5H),2.23(s,3H),2.13~2.00(m,1H),1.87~1.78(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.45~1.35(m,1H),1.06(d,3H),1.02(d,3H)
实施例255.(S)-奎宁环-3-基(7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.28~7.18(m,3H),7.10(t,1H),6.99(s,1H),4.90(t,1H),4.83~4.76(m,1H),4.70(d,1H),3.94~3.81(m,2H),3.75(s,3H),3.33~3.22(m,1H),2.94~2.69(m,5H),2.33(s,6H),2.13~2.06(m,1H),1.89~1.79(m,1H),1.74~1.66(m,1H),1.62~1.53(m,1H),1.46~1.35(m,1H),1.06~(d,3H),1.02(d,3H)
实施例256.(S)-奎宁环-3-基(7-(4-丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.47(m,2H),7.29~7.21(m,3H),7.15(t,1H),7.04(s,1H),4.91(t,1H),4.83~4.77(m,1H),4.71(d,1H),3.94~3.80(m,2H),3.32~3.22(m,1H),2.96~2.70(m,5H),2.65(t,2H),2.13~2.05(m,1H),1.88~1.78(m,1H),1.74~1.54(m,4H),1.46~1.34(m,3H),1.07(d,3H),1.03(d,3H),0.95(t,3H)
实施例257.(S)-奎宁环-3-基(7-(4-异丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.48~7.47(m,2H),7.28~7.14(m,4H),7.05(s,1H),4.96(t,1H),4.82~4.76(m,1H),4.71(d,1H),3.94~3.79(m,2H),3.32~3.20(m,1H),2.93~2.67(m,5H),2.51(d,2H),2.13~2.04(m,1H),1.94~1.78(m,2H),1.75~1.65(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.06(d,3H),1.02(d,3H),0.94(d,6H)
实施例258.(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.34(s,1H),7.73(d,1H),7.27(dd,1H),7.09(t,1H),6.97(s,1H),6.73(d,1H),5.37~5.28(m,1H),4.87(t,1H),4.82~4.77(m,1H),4.71(d,1H),3.94~3.80(m,2H),3.32~3.21(m,1H),2.93~2.69(m,5H),2.13~2.05(m,1H),1.89~1.79(m,1H),1.73~1.66(m,1H),1.62~1.53(m,1H),1.47~1.39(m,1H),1.37(d,6H),1.06(d,3H),1.02(d,3H)
实施例259.(S)-奎宁环-3-基(7-(4-(异噁唑-3-基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.47(s,1H),7.91~7.84(m,2H),7.70~7.61(m,2H),7.29(dd,1H),7.20(t,1H),7.09(s,1H),6.69(s,1H),4.98(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.97~3.81(m,2H),3.33~3.22(m,1H),2.94~2.68(m,5H),2.14~2.05(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.47~1.35(m,1H),1.07(d,3H),1.03(d,3H)
实施例260.(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.53~7.42(m,2H),7.25~7.19(m,1H),7.12(t,1H),7.01(s,1H),6.98~6.91(m,2H),4.85(t,1H),4.82~4.76(m,1H),4.70(d,1H),3.95~3.81(m,2H),3.76(d,2H),3.34~3.22(m,1H),2.96~2.67(m,5H),2.16~2.04(m,2H),1.87~1.79(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.38(m,1H),1.11~0.92(m,12H)
实施例261.(S)-奎宁环-3-基(7-(3-氟-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.33~7.19(m,3H),7.09(t,1H),7.04~6.96(m,2H),4.95(t,1H),4.83~4.76(m,1H),4.70(d,1H),4.60~4.54(m,1H),3.92~3.81(m,2H),3.31~3.21(m,1H),2.93~2.68(m,5H),2.13~2.05(m,1H),1.87~1.78(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.45~1.33(m,7H),1.06(d,3H),1.01(d,3H)
实施例262.(S)-奎宁环-3-基(7-(2-氟-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(t,1H),7.47(d,1H),7.41(d,1H),7.35~7.25(m,1H),7.11(t,1H),7.01(s,1H),4.97(t,1H),4.84~4.77(m,1H),4.73(d,1H),3.96~3.81(m,2H),3.32~3.22(m,1H),2.94~2.69(m,5H),2.17~2.05(m,1H),1.88~1.79(m,1H),1.74~1.67(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例263.(S)-奎宁环-3-基(7-(4-异丙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.18(m,3H),7.12(t,1H),7.01(s,1H),4.88(t,1H),4.83~4.76(m,1H),4.70(d,1H),4.20(m,1H),3.94~3.79(m,2H),3.33~3.22(m,1H),2.96~2.69(m,5H),2.31(s,6H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.75~1.66(m,1H),1.63~1.55(m,1H),1.47~1.38(m,1H),1.32(d,6H),1.06(d,3H),1.02(d,3H)
实施例264.(S)-奎宁环-3-基(3,3-二甲基-7-苯基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.60~7.53(m,2H),7.47~7.39(m,2H),7.36~7.29(m,1H),7.27(t,1H),7.16(t,1H),7.06(s,1H),4.99(t,1H),4.83~4.77(m,1H),4.72(d,1H),3.94~3.82(m,2H),3.33~3.20(m,1H),2.92~2.68(m,5H),2.13~2.06(m,1H),1.87~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.45~1.35(m,1H),1.07(d,3H),1.03(d,3H)
实施例265.(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.71(s,1H),8.55(d,1H),7.82(d,1H),7.38~7.23(m,2H),7.11(t,1H),7.01(s,1H),5.30(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.95~3.82(m,2H),3.32~3.20(m,1H),2.92~2.67(m,5H),2.14~2.05(m,1H),1.86~1.77(m,1H),1.74~1.65(m,1H),1.61~1.53(m,1H),1.44~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例266.(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-2-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.69~7.60(m,1H),7.48~7.40(m,1H),7.23~7.13(m,3H),6.91(dd,1H),6.81(d,1H),4.93(t,1H),4.81~4.74(m,1H),4.67(d,1H),3.90~3.75(m,2H),3.26~3.18(m,1H),2.94~2.66(m,5H),2.11~2.03(m,1H),1.88~1.77(m,1H),1.76~1.65(m,1H),1.61~1.52(m,1H),1.44~1.35(m,1H),1.03(d,3H),0.99(d,3H)
实施例267.(S)-奎宁环-3-基(7-苄基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32~7.25(m,2H),7.23~7.16(m,3H),7.13~7.07(m,1H),6.76(t,1H),6.64(s,1H),4.87~4.73(m,2H),4.63(d,1H),3.90(s,2H),3.86~3.73(m,2H),3.31~3.20(m,1H),2.91~2.66(m,5H),2.11~2.02(m,1H),1.87~1.76(m,1H),1.73~1.66(m,1H),1.61~1.53(m,1H),1.45~1.36(m,1H),1.02(d,3H),0.98(d,3H)
实施例268.(S)-奎宁环-3-基(3,3-二甲基-7-(间甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.41~7.21(m,4H),7.19~7.12(m,2H),7.05(s,1H),4.96(t,1H),4.84~4.76(m,1H),4.71(d,1H),3.94~3.80(m,2H),3.33~3.22(m,1H),2.92~2.69(m,5H),2.41(s,3H),2.13~2.05(m,1H),1.88~1.79(m,1H),1.74~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例269.(S)-奎宁环-3-基(3,3-二甲基-7-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.39(m,2H),7.30~7.20(m,3H),7.15(t,1H),7.04(s,1H),4.98(t,1H),4.83~4.76(m,1H),4.71(d,1H),3.94~3.80(m,2H),3.32~3.21(m,1H),2.93~2.68(m,5H),2.39(s,3H),2.15~2.05(m,1H),1.87~1.78(m,1H),1.74~1.66(m,1H),1.62~1.53(m,1H),1.45~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例270.(S)-奎宁环-3-基(3,3-二甲基-7-(邻甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.16(m,5H),6.88(t,1H),6.78(s,1H),5.05(t,1H),4.83~4.77(m,1H),4.73(d,1H),3.93~3.79(m,2H),3.33~3.20(m,1H),2.94~2.67(m,5H),2.28(s,3H),2.14~2.06(m,1H),1.90~1.78(m,1H),1.75~1.65(m,1H),1.62~1.54(m,1H),1.46~.135(m,1H),1.07(d,3H),1.03(d,3H)
实施例271.(S)-奎宁环-3-基(3,3-二甲基-7-((E)-2-(噻吩-3-基)乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36~7.29(m,2H),7.28~7.24(m,1H),7.21~7.14(m,1H),7.08~7.01(m,2H),6.93~6.83(m,2H),4.92(t,1H),4.83~4.73(m,1H),4.67(d,1H),3.92~3.77(m,2H),3.34~3.20(m,1H),2.92~2.67(m,5H),2.14~2.04(m,1H),1.90~1.78(m,1H),1.74~1.65(m,1H),1.62~1.52(m,1H),1.47~1.36(m,1H),1.04(d,3H),1.00(d,3H)
实施例272.(S)-奎宁环-3-基(3,3-二甲基-7-(4-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.57~7.51(m,2H),7.49~7.44(m,2H),7.27(dd,1H),7.17(t,1H),7.06(s,1H),6.75(dd,1H),5.79(d,1H),5.27(d,1H),4.95(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.94~3.81(m,2H),3.32~3.22(m,1H),2.93~2.68(m,5H),2.14~2.06(m,1H),1.87~1.79(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.47~1.37(m,1H),1.07(d,3H),1.02(d,3H)
实施例273.(S)-奎宁环-3-基(7-(4-乙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54~7.44(m,2H),7.31~7.23(m,3H),7.16(t,1H),7.04(s,1H),4.89(t,1H),4.84~4.77(m,1H),4.71(d,1H),3.95~3.80(m,2H),3.34~3.21(m,1H),2.94~2.62(m,7H),2.14~2.05(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.38(m,1H),1.28(t,3H),1.07(d,3H),1.03(d,3H)
实施例274.(S)-奎宁环-3-基(3,3-二甲基-7-(2-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.63(d,1H),7.37~7.29(m,2H),7.28~7.19(m,2H),6.90(t,1H),6.81(s,1H),6.74(dd,1H),5.69(d,1H),5.19(d,1H),5.00(t,1H),4.84~4.78(m,1H),4.73(d,1H),3.95~3.80(m,2H),3.33~3.20(m,1H),2.94~2.68(m,5H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.74~1.65(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例275.(S)-奎宁环-3-基(7-(4-乙氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.20(d,1H),7.12(d,1H),6.86(d,1H),6.81~6.73(m,3H),4.98(t,1H),4.83~4.76(m,1H),4.72(d,1H),4.05(q,2H),3.92~3.79(m,2H),3.30~3.21(m,1H),2.95~2.68(m,5H),2.26(S,3H),2.14~2.05(m,1H),1.89~1.80(m,1H),1.74~1.67(m,1H),1.62~1.54(m,1H),1.48~1.36(m,4H),1.07(d,3H),1.03(d,3H)
实施例276.(S)-奎宁环-3-基(7-(4-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.53~7.44(m,4H),7.42~7.38(m,2H),7.36~7.32(m,1H),7.26~7.20(m,1H),7.15~7.12(m,1H),7.11~7.09(m,3H),5.11(s,2H),4.90(t,1H),4.83~4.77(m,1H),4.71(d,1H),3.95~3.78(m,2H),3.32~3.22(m,1H),2.93~2.70(m,5H),2.14~2.05(m,1H),1.88~1.80(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例277.(S)-奎宁环-3-基(7-(3-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.44(m,2H),7.43~7.38(m,2H),7.36~7.32(m,2H),7.29~7.23(m,1H),7.21~7.11(m,3H),7.05(s,1H),6.96(d,1H),,5.12(S,2H),4.90(t,1H),4.84~4.77(m,1H),4.72(d,1H),3.96~3.81(m,2H),3.34~3.22(m,1H),2.94~2.69(m,5H),2.15~2.06(m,1H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.63~1.54(m,1H),1.47~1.38(m,1H),1.07~(d,3H),1.03(d,3H)
实施例278.(S)-奎宁环-3-基(7-(2,6-二氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.94(dd,1H),7.35~7.23(m,2H),7.15~7.04(m,1H),6.98(s,1H),6.92(dd,1H),4.85(t,1H),4.82~4.78(m,1H),4.74(d,1H),3.91~3.80(m,2H),3.35~3.20(m,1H),2.96~2.69(m,5H),2.14~2.05(m,1H),1.89~1.78(m,1H),1.75~1.66(m,1H),1.62~1.54(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例279.(S)-奎宁环-3-基(7-(2-烯丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34~7.18(m,5H),6.88(t,1H),6.78(s,1H),5.96~5.84(m,1H),5.03(d,1H),4.99~4.90(m,2H),4.83~4.77(m,1H),4.73(d,1H),3.96~3.79(m,2H),3.35(d,2H),3.29~3.24(m,1H),2.94~2.68(m,5H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.54(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例280.(S)-奎宁环-3-基(7-(4-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.59~7.53(m,2H),7.41~7.35(m,2H),7.27(dd,1H),7.14(t,1H),7.03(s,1H),4.95(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.95~3.82(m,2H),3.78(s,2H),3.32~3.21(m,1H),2.93~2.68(m,5H),2.14~2.06(m,1H),1.88~1.77(m,1H),1.74~1.67(m,1H),1.63~1.54(m,1H),1.48~1.36(m,1H),1.06(d,3H),1.02(d,3H)
实施例281.(S)-奎宁环-3-基(7-(3-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.57~7.48(m,2H),7.43(t,1H),7.33~7.23(m,2H),7.14(t,1H),7.03(s,1H),4.93(t,1H),4.84~4.76(m,1H),4.72(d,1H),3.95~3.83(m,2H),3.80(s,2H),3.33~3.21(m,1H),2.94~2.67(m,5H),2.15~2.05(m,1H),1.88~1.78(m,1H),1.74~1.67(m,1H),1.62~1.53(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.02(d,3H)
实施例282.(S)-奎宁环-3-基(7-((E)-2-([1,1'-二苯基]-4-基)乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.68~7.52(m,6H),7.48~7.41(m,3H),7.35(t,1H),7.24~7.16(m,1H),7.14~7.05(m,2H),6.98(s,1H),5.03~4.93(m,1H),4.83~4.75(m,1H),4.69(d,1H),3.93~3.78(m,2H),3.32~3.20(m,1H),2.93~2.67(m,5H),2.14~2.05(m,1H),1.88~1.78(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.46~1.36(m,1H),1.09~0.95(m,6H)
实施例283.(S)-奎宁环-3-基(7-(2-环丙基嘧啶-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.72~7.64(m,2H),7.32(dd,1H),7.07(t,1H),6.96(s,1H),5.10(dd,1H),4.84~4.75(m,1H),4.72(d,1H),3.95~3.80(m,2H),3.30~3.20(m,1H),2.91~2.66(m,5H),2.33~2.24(m,1H),2.11~2.03(m,1H),1.86~1.77(m,1H),1.73~1.65(m,1H),1.61~1.52(m,1H),1.45~1.36(m,1H),1.20~1.09(m,4H),1.06(d,3H),1.01(d,3H)
实施例284.(S)-奎宁环-3-基(3,3-二甲基-7-((E)-4-(三氟甲基)苯乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.62~7.55(m,4H),7.21(dd,1H),7.14~7.06(m,3H),6.97(s,1H),4.91(t,1H),4.83~4.76(m,1H),4.69(d,1H),3.94~3.80(m,2H),3.32~3.21(m,1H),2.93~2.67(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.53(m,1H),1.47~1.37(m,1H),1.05(d,3H),1.01(d,3H)
实施例285.(S)-奎宁环-3-基(7-(2-氯-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.29~7.19(m,1H),7.04(s,1H),7.01~6.93(m,2H),6.86(s,1H),5.04(t,1H),4.83~4.76(m,1H),4.72(d,1H),3.94~3.79(m,2H),3.31~3.20(m,1H),2.93~2.68(m,5H),2.40(s,3H),2.30(s,3H),2.12~2.05(m,1H),1.8~1.79(m,1H),1.73~1.66(m,1H),1.62~1.54(m,1H),1.46~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例286.(S)-奎宁环-3-基(7-((E)-2,4-二氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(dd,1H),7.23~7.12(m,2H),7.09~6.98(m,2H),6.95(s,1H),6.91~6.78(m,2H),4.94(t,1H),4.83~4.75(m,1H),4.68(d,1H),3.94~3.79(m,2H),3.35~3.21(m,1H),2.93~2.67(m,5H),2.12~2.05(m,1H),1.88~1.78(m,1H),1.74~1.66(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.04(d,3H),1.00(d,3H)
实施例287.(S)-奎宁环-3-基(7-((E)-4-乙基苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
7.47~7.38(m,2H),7.23~7.14(m,3H),7.11~6.98(m,3H),6.95(s,1H),4.93(t,1H),4.83~4.76(m,1H),4.67(d,1H),3.93~3.77(m,2H),3.32~3.20(m,1H),2.94~2.71(m,5H),2.66(q,2H),2.12~2.04(m,1H),1.87~1.79(m,1H),1.74~1.65(m,1H),1.62~1.53(m,1H),1.45~1.37(m,1H),1.25(t,3H),1.05(d,3H),1.00(d,3H)
实施例288.(S)-奎宁环-3-基(7-(6-乙氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.94(s,1H),7.81~7.74(m,2H),7.67(d,1H),7.32~7.24(m,2H),7.21~7.11(m,3H),4.95(t,1H),4.84~4.78(m,1H),4.73(d,1H),4.17(q,2H),3.96~3.81(m,2H),3.33~3.23(m,1H),2.93~2.69(m,5H),2.13~2.05(m,1H),1.91~1.76(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.49(t,3H),1.45~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例289.(S)-奎宁环-3-基(7-((E)-3-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34~7.16(m,4H),7.10~7.06(m,1H),7.04~7.00(m,2H),6.98~6.93(m,2H),4.90~4.76(m,2H),4.69(d,1H),3.94~3.80(m,2H),3.32~3.22(m,1H),2.95~2.70(m,5H),2.13~2.06(m,1H),1.86~1.78(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.46~1.37(m,1H),1.05(d,3H),1.01(d,3H)
实施例290.(S)-奎宁环-3-基(7-(二苯并[b,d]呋喃-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.99(d,1H),7.94(d,1H),7.64~7.56(m,2H),7.54~7.44(m,2H),7.42~7.32(m,4H),4.96(t,1H),4.85~4.81(m,1H),4.77(d,1H),4.00~3.85(m,2H),3.37~3.23(m,1H),2.96~2.69(m,5H),2.18~2.07(m,1H),1.92~1.80(m,1H),1.77~1.67(m,1H),1.64~1.55(m,1H),1.48~1.37(m,1H),1.11(d,3H),1.07(d,3H)
实施例291.(S)-奎宁环-3-基(7-(4-氰基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.65(t,1H),7.44~7.28(m,3H),7.17~7.07(m,1H),7.02(s,1H),4.97(t,1H),4.84~4.77(m,1H),4.73(d,1H),3.98~3.80(m,2H),3.32~3.20(m,1H),2.93~2.67(m,5H),2.12~2.05(m,1H),1.88~1.78(m,1H),1.75~1.66(m,1H),1.63~1.54(m,1H),1.47~1.37(m,1H),1.06(d,3H),1.02(d,3H)
实施例292.(S)-奎宁环-3-基(7-(1-苄基-6-氧代-1,6-二氢吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(d,1H),7.43(s,1H),7.37~7.25(m,5H),7.20(dd,1H),6.88(t,1H),6.76(s,1H),6.64(d,1H),5.17(s,2H),5.07(q,1H),4.82~4.74(m,1H),4.66(d,1H),3.90~3.79(m,2H),3.31~3.18(m,1H),2.90~2.63(m,5H),2.11~2.04(m,1H),1.87~1.76(m,1H),1.73~1.65(m,1H),1.61~1.52(m,1H),1.45~1.35(m,1H),1.03(d,3H),0.99(d,3H)
实施例293.(S)-奎宁环-3-基(7-((E)-4-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.66(dd,1H),7.51~7.40(m,2H),7.30~7.13(m,2H),7.10~6.99(m,2H),6.96~6.79(m,2H),4.89(t,1H),4.82~4.74(m,1H),4.68(d,1H),3.97~3.76(m,2H),3.32~3.65(m,1H),2.93~2.65(m,5H),2.14~2.04(m,1H),1.87~1.78(m,1H),1.73~1.65(m,1H),1.62~1.53(m,1H),1.46~1.35(m,1H),1.09(d,3H),0.92(d,3H)
实施例294.(S)-奎宁环-3-基(6-(3-氟苯基)-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
使用制备例6的(S)-奎宁环-3-基(6-溴-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯和3-氟苯基硼酸,按照与制备实施例1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.52~7.48(d,1H),7.41~7.21(m,4H),7.02~6.98(t,1H),6.89~6.87(d,1H),5.06~5.04(m,1H),4.97~4.95(m,1H),4.81(m,1H),3.30~3.25(m,1H),2.87~2.72(m,5H),2.31~2.27(m,1H),2.13~2.06(m,1H),1.93~1.69(m,3H),1.64(m,1H),1.47(s,3H),1.47~1.37(m,1H),1.34(s,3H)
实施例295至实施例296
分别使用制备例5中制备的(S)-奎宁环-3-基(7-溴-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例295至实施例296的标题化合物。
实施例295.(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.81(s,1H),7.51~7.32(d,1H),7.60~7.58(d,1H),7.55~7.51(t,1H),7.41~7.36(m,1H),7.16~7.12(t,1H),7.05(s,1H),5.06~5.03(m,2H),4.82~4.80(m,1H),3.26(m,1H),2.89~2.71(m,5H),2.27~2.25(m,1H),2.14~2.05(m,2H),1.80~1.69(m,3H),1.60~1.59(m,1H),1.47(s,3H),1.44~1.41(m,1H),1.37(s,3H)
实施例296.(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.48(d,1H),7.44~7.34(m,3H),7.19~7.17(d,1H),7.13~7.09(t,1H),7.02(s,1H),5.10~5.02(m,2H),4.81~4.79(m,1H),3.28~3.24(m,1H),2.88~2.70(m,5H),2.38(m,1H),2.28~2.24(m,1H),2.11~2.05(m,1H),1.79~1.68(m,3H),1.59~1.58(m,1H),1.46(s,3H),1.44~1.40(m,1H),1.36(s,3H)
实施例297至实施例311
分别使用制备例7中制备的(S)-奎宁环-3-基(7-溴-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例297至实施例311的标题化合物。
实施例297.(S)-奎宁环-3-基(7-(3-氯苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.53(s,1H),7.48~7.40(m,2H),7.38~7.28(m,2H),7.13(d,1H),7.03(s,1H),5.07~5.06(m,1H),4.71~4.60(m,1H),4.37~4.18(m,2H),3.28~3.13(m,1H),2.92~2.58(m,6H),2.07~1.92(m,2H),1.86~1.59(m,5H),1.57~1.46(m,1H),1.40~1.30(m,1H)
实施例298.(S)-奎宁环-3-基(7-(3-氟苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45(d,1H),7.41~7.31(m,2H),7.26~7.23(m,1H),7.14(d,1H),7.07~6.99(m,2H),5.07(s,1H),4.71~4.62(m,1H),4.36~4.18(m,2H),3.28~3.12(m,1H),2.94~2.58(m,6H),2.08~1.91(m,2H),1.86~1.59(m,5H),1.56~1.46(m,1H),1.41~1.30(m,1H)
实施例299.(S)-奎宁环-3-基(7-(3-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47~7.40(m,1H),7.34(t,1H),7.20~7.12(m,2H),7.10~7.03(m,2H),6.89(d,1H),5.14~5.04(m,1H),4.72~4.61(m,1H),4.34~4.20(m,2H),3.85(s,3H),3.26~3.15(m,1H),2.89~2.59(m,6H),2.09~1.91(m,2H),1.84~1.60(m,5H),1.56~1.47(m,1H),1.40~1.30(m,1H)
实施例300.(S)-奎宁环-3-基(7-(3-异丙基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.48~7.32(m,4H),7.23(d,1H),7.17(d,1H),7.07(s,1H),5.15~5.07(m,1H),4.72~4.63(m,1H),4.35~4.19(m,2H),3.27~3.13(m,1H),3.02~2.92(m,1H),2.89~2.60(m,6H),2.09~1.91(m,2H),1.85~1.60(m,5H),1.57~1.45(m,1H),1.41~1.33(m,1H),1.31~1.29(d,6H)
实施例301.(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47~7.39(m,1H),7.34(d,1H),7.03(d,1H),6.92(s,1H),6.87~6.79(m,2H),5.12(s,1H),4.72~4.62(m,1H),4.36~4.17(m,2H),3.80(s,3H),3.28~3.13(m,1H),2.90~2.57(m,6H),2.11~1.92(m,2H),1.87~1.62(m,5H),1.57~1.47(m,1H),1.41~1.29(m,1H)
实施例302.(S)-奎宁环-3-基(7-(4-乙氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.45(m,2H),7.44~7.37(m,1H),7.13(d,1H),7.02(s,1H),6.98~6.90(m,2H),5.13~5.05(m,1H),4.71~4.63(m,1H),4.33~4.18(m,2H),4.07(q,2H),3.25~3.13(m,1H),2.91~2.59(m,6H),2.08~1.92(m,2H),1.85~1.60(m,5H),1.56~1.48(m,1H),1.45~1.44(m,1H),1.38(t,3H)
实施例303.(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.39(m,1H),7.30(d,1H),7.18(d,1H),7.08(s,1H),6.95~6.85(m,2H),6.74(d,1H),5.16~5.05(m,1H),4.72~4.63(m,1H),4.34~4.19(m,2H),3.27~3.12(m,1H),3.00(s,6H),2.89~2.58(m,6H),2.10~1.93(m,2H),1.86~1.59(m,5H),1.56~1.46(m,1H),1.42~1.31(m,1H)
实施例304.(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.84(d,1H),7.78(s,1H),7.55(d,1H),7.47(d,1H),7.39~7.28(m,2H),7.22(d,1H),7.14(s,1H),5.14~5.07(m,1H),4.72~4.65(m,1H),4.36~4.20(m,2H),3.28~3.14(m,1H),2.91~2.59(m,6H),2.10~1.91(m,2H),1.87~1.62(m,5H),1.57~1.47(m,1H),1.41~1.30(m,1H)
实施例305.(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.79(s,1H),7.72(d,1H),7.60(d,1H),7.54(t,1H),7.47(d,1H),7.16(d,1H),7.06(s,1H),5.16~5.04(m,1H),4.70~4.62(m,1H),4.36~4.20(m,2H),3.26~3.13(m,1H),2.91~2.56(m,6H),2.07~1.90(m,2H),1.85~1.60(m,5H),1.56~1.44(m,1H),1.40~1.30(m,1H)
实施例306.(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.36(m,4H),7.19(d,1H),7.13(d,1H),7.04(s,1H),5.11(s,1H),4.70~4.61(m,1H),4.34~4.21(m,2H),3.26~3.13(m,1H),2.91~2.59(m,6H),2.08~1.89(m,2H),1.85~1.59(m,5H),1.56~1.46(m,1H),1.41~1.29(m,1H)
实施例307.(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.44(d,1H),7.29~7.19(m,2H),7.13~7.03(m,2H),6.97(s,1H),5.10(s,1H),4.72~4.61(m,1H),4.35~4.19(m,2H),3.25~3.13(m,1H),2.90~2.56(m,6H),2.06~1.90(m,2H),1.83~1.59(m,5H),1.56~1.46(m,1H),1.41~1.19(m,1H)
实施例308.(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45~7.37(m,1H),7.22~7.16(m,2H),7.11(d,1H),7.01(s,1H),5.11~5.04(m,1H),4.72~4.60(m,1H),4.31~4.16(m,2H),3.88(q,2H),3.27~3.13(m,1H),2.92~2.56(m,6H),2.32(s,6H),2.06~1.90(m,2H),1.83~1.59(m,5H),1.56~1.46(m,1H),1.44(t,3H),1.41~1.19(m,1H)
实施例309.(S)-奎宁环-3-基(7-(2-氰基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.76(d,1H),7.63(t,1H),7.52~7.41(m,3H),7.15(d,1H),7.00(s,1H),5.08(s,1H),4.72~4.63(m,1H),4.35~4.17(m,2H),3.26~3.15(m,1H),2.91~2.58(m,6H),2.16~1.92(m,2H),1.88~1.61(m,5H),1.58~1.48(m,1H),1.42~1.31(m,1H)
实施例310.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.57(s,1H),7.48~7.33(m,4H),7.17(d,1H),7.07(s,1H),5.11(s,1H),4.72~4.63(m,1H),4.35~4.20(m,2H),3.27~3.12(m,1H),2.91~2.59(m,6H),2.10~1.92(m,2H),1.86~1.60(m,5H),1.57~1.47(m,1H),1.41~1.28(m,10H)
实施例311.(S)-奎宁环-3-基(4-甲基-7-(4-甲基噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45~7.35(m,1H),7.18(d,1H),7.04~6.93(m,2H),6.87(s,1H),5.09(s,1H),4.70~4.62(m,1H),4.34~4.17(m,2H),3.27~3.12(m,1H),2.91~2.58(m,6H),2.28(s,3H),2.09~1.91(m,2H),1.87~1.60(m,5H),1.56~1.47(m,1H),1.41~1.29(m,1H)
实施例312至实施例313
分别使用制备例8中制备的(S)-奎宁环-3-基(7-溴异苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例312至实施例313的标题化合物。
实施例312.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)异苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(s,1H),7.52~7.46(m,2H),7.43~7.33(m,3H),7.22(s,1H),5.42~5.33(m,1H),4.93~4.71(m,4H),4.17~4.07(m,1H),3.98~3.87(m,1H),3.32~3.19(m,1H),2.92~2.65(m,5H),2.08~1.98(m,1H),1.85~1.75(m,1H),1.73~1.64(m,1H),1.62~1.52(m,1H),1.43~1.21(m,10H)
实施例313.(S)-奎宁环-3-基(7-(3-异丙基苯基)异苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.52~7.46(m,2H),7.41~7.33(m,3H),7.26~7.19(m,2H),5.42~5.35(m,1H),4.92~4.72(m,4H),4.16~4.08(m,1H),3.98~3.88(m,1H),3.32~3.20(m,1H),3.03~2.93(m,1H),2.90~2.67(m,5H),2.07~1.99(m,1H),1.84~1.75(m,1H),1.72~1.65(m,1H),1.61~1.53(m,1H),1.42~1.34(m,1H),1.31(d,6H)
实施例314至实施例315
分别使用制备例9中制备的(S)-奎宁环-3-基(7-溴-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例314至实施例315的标题化合物。
实施例314.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.58(s,1H),7.43~7.34(m,3H),7.27(t,1H),6.90(t,1H),6.81(s,1H),5.07(d,1H),4.92~4.84(m,1H),4.81~4.72(m,1H),3.34~3.19(m,3H),2.99(s,3H),2.92~2.66(m,5H),2.18~2.09(m,2H),2.07~2.00(m,1H),1.87~1.76(m,1H),1.73~1.65(m,1H),1.62~1.52(m,1H),1.45~1.31(m,10H)
实施例315.(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.84(d,1H),7.78(s,1H),7.55(d,1H),7.39~7.24(m,3H),6.95(t,1H),6.88(s,1H),5.08(d,1H),4.93~4.85(m,1H),4.82~4.73(m,1H),3.34~3.19(m,3H),2.99(s,3H),2.94~2.66(m,5H),2.18~2.09(m,2H),2.08~2.00(m,1H),1.85~1.76(m,1H),1.73~1.65(m,1H),1.61~1.53(m,1H),1.43~1.34(m,1H)
实施例316.(S)-奎宁环-3-基(6-(4-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
使用制备例10中制备的(S)-奎宁环-3-基(6-溴硫代苯并二氢吡喃-4-基)氨基甲酸酯和4-氯苯基硼酸,按照与实施例1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.52~7.44(m,3H),7.43~7.34(m,3H),7.20(d,1H),5.09(br,1H),4.99(br,1H),4.77(br,1H),3.32~3.11(m,2H),3.09~2.97(m,1H),2.90~2.68(m,5H),2.53~2.38(m,1H),2.21~1.97(m,2H),1.89~1.77(m,1H),1.70(br,2H),1.64~1.50(m,1H),1.44~1.34(m,1H)
实施例317至实施例328
分别使用制备例11中制备的(S)-奎宁环-3-基(7-溴硫代苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例317至实施例328的标题化合物。
实施例317.(S)-奎宁环-3-基(7-(3-氟苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.61~7.58(m,1H),7.56~7.51(m,1H),7.45(s,1H),7.34(s,3H),7.27(d,1H),4.84~4.76(m,2H),3.29~3.11(m,2H),3.07(d,1H),2.89~2.72(m,6H),2.37~2.26(m,1H),2.26~2.14(m,1H),2.09~2.06(m,1H),1.99~1.89(m,1H),1.79~1.77(m,1H),1.66(m,1H),1.51~1.49(m,1H)
实施例318.(S)-奎宁环-3-基(7-(3-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.58(brs,1H),7.52~7.49(m,1H),7.44~7.29(m,5H),4.84~4.75(m,2H),3.29~3.11(m,3H),3.07~3.04(m,1H),2.89~2.71(m,5H),2.28(brs,1H),2.19(dd,1H),2.09~2.05(m,1H),1.96~1.93(m,1H),1.80~1.75(m,1H),1.68~1.64(m,1H),1.50(brs,1H)
实施例319.(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.86~7.82(m,2H),7.66~7.63(m,2H),7.41~7.34(m,3H),4.85~4.76(m,2H),3.30~3.11(m,2H),3.09~3.06(m,1H),2.93~2.67(m,6H),2.31~2.28(m,1H),2.21~2.19(m,1H),2.10~2.06(m,1H),1.95(s,1H),1.80~1.76(m,1H),1.68~1.64(m,1H),1.52~1.48(m,1H)
实施例320.(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CD3OD)δ7.61~7.58(m,1H),7.56~7.51(m,1H),7.45(s,1H),7.34(s,3H),7.27(d,1H),4.84~4.76(m,2H),3.29~3.11(m,2H),3.07(d,1H),2.89~2.72(m,6H),2.37~2.26(m,1H),2.26~2.14(m,1H),2.09~2.06(m,1H),1.99~1.89(m,1H),1.79~1.77(m,1H),1.66(dd,1H),1.51~1.49(m,1H)
实施例321.(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.38~7.32(m,3H),7.29~7.25(m,1H),7.22~7.17(m,2H),7.04(d,1H),5.31(brd,1H),5.22(s,2H),4.98~4.94(m,1H),4.79~4.74(m,1H),3.77~3.73(m,1H),3.50(s,3H),3.24(dd,1H),3.15~3.10(m,1H),3.01(ddd,1H),2.86~2.67(m,5H),2.46~2.41(m,1H),2.23~2.14(m,1H),1.82~1.76(m,1H),1.70~1.66(m,1H),1.60~1.55(m,1H),1.38(d,1H)
实施例322.(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(s,1H),7.42~7.28(m,5H),6.99(s,1H),5.13~4.88(m,2H),4.77(br,1H),3.33~3.09(m,2H),3.03(m,1H),2.93~2.68(m,5H),2.57~2.36(m,1H),2.23~2.09(m,1H),2.05~2.01(m,1H),1.98~1.89(m,1H),1.84~1.75(m,1H),1.74~1.65(m,1H),1.63~1.50(m,1H),1.37(s,9H)
实施例323.(S)-奎宁环-3-基(7-(2,5-二氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.43~7.33(m,1H),7.33~7.21(m,2H),7.19~7.04(m,2H),7.01~6.93(m,1H),5.17(br,1H),5.10~4.90(m,1H),4.76(br,1H),3.26(br,1H),3.18~2.96(m,2H),2.91~2.68(m,4H),2.53~2.40(m,1H),2.21~2.12(m,1H),2.12~2.00(m,1H),1.94~1.89(m,1H),1.83~1.76(m,1H),1.70(qd,1H),1.62~1.50(m,1H),1.42~1.34(m,1H)
实施例324.(S)-奎宁环-3-基(7-(3-乙氧基苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.28(m,3H),7.12(d,1H),7.07(s,1H),6.99(s,1H),6.89(m,1H),5.16~5.01(m,1H),5.00~4.87(m,1H),4.87~4.69(m,1H),4.14~4.02(m,2H),3.34~3.21(m,1H),3.20~3.09(m,1H),3.07~2.96(m,1H),2.92~2.68(m,5H),2.56~2.38(m,1H),2.23~2.09(m,1H),2.06~2.00(m,1H),1.94~1.86(m,1H),1.83~1.75(m,1H),1.74~1.66(m,1H),1.63~1.51(m,1H),1.44(m,3H)
实施例325.(S)-奎宁环-3-基(7-(3-(甲硫基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.42~7.22(m,6H),6.99(s,1H),5.16~5.01(m,1H),5.01~4.88(m,1H),4.88~4.69(m,1H),3.30~3.10(m,2H),3.03(m,1H),2.92~2.68(m,5H),2.53(s,3H),2.50~2.39(m,1H),2.23~2.09(m,1H),2.03(br,1H),1.83~1.65(m,2H),1.62~1.52(m,1H),1.42~1.35(m,1H)
实施例326.(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.37~7.27(m,3H),6.99(s,1H),6.93~6.84(m,2H),6.76(s,1H),5.17~5.01(m,1H),5.00~4.87(m,1H),4.77(br,1H),3.33~3.21(m,1H),3.21~3.08(m,1H),3.08~3.02(m,1H),3.02~2.98(m,6H),2.95~2.68(m,5H),2.57~2.39(m,1H),2.23~2.09(m,1H),2.03(br,1H),1.83~1.74(m,1H),1.70(m,1H),1.58~1.49(m,1H),1.43~1.38(m,1H)
实施例327.(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.44~7.31(m,1H),7.27~7.17(m,3H),7.11(d,1H),6.99(s,1H),5.13~5.01(m,1H),4.98(d,1H),4.87~4.69(m,1H),3.26(m,1H),3.19~3.08(m,1H),3.08~2.99(m,1H),2.92~2.68(m,4H),2.56~2.38(m,1H),2.23~2.09(m,1H),2.04(d,1H),1.94~1.88(m,1H),1.84~1.74(m,1H),1.70(qd,1H),1.63~1.50(m,1H),1.42~1.35(m,1H)
实施例328.(S)-奎宁环-3-基(7-(苯并呋喃-3-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.85~7.74(m,2H),7.55(d,1H),7.44~7.30(m,4H),6.99(s,1H),5.11(br d,1H),5.06~4.89(m,1H),4.89~4.70(m,1H),3.49~3.21(m,1H),3.15(br m,1H),3.05(m,1H),2.93~2.82(m,2H),2.82~2.69(m,3H),2.56~2.36(m,1H),2.23~2.11(m,1H),2.10~1.96(m,1H),1.81(m,1H),1.69(m,1H),1.63~1.52(m,1H),1.42~1.39(m,1H)
实施例329.(S)-奎宁环-3-基(3,3-二甲基-6-(4-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯
使用制备例12中制备的(S)-奎宁环-3-基(6-溴-3,3-di甲硫基苯并二氢吡喃-4-基)氨基甲酸酯和4-(三氟甲基)苯基硼酸,按照与实施例1相同的程序制备标题化合物。
1H-NMR(400MHz,CDCl3)δ7.45~7.32(m,2H),7.29(d,1H),7.21~7.15(m,2H),7.15~7.09(m,1H),6.97(s,1H),4.90~4.84(m,1H),4.75~4.70(m,1H),4.60(d,1H),3.30~3.16(m,1H),3.01~2.92(m,1H),2.90~2.64(m,6H),2.04~1.97(m,1H),1.72~1.61(m,2H),1.58~1.49(m,1H),1.40~1.30(m,1H),1.17(d,3H),1.11~1.08(m,3H)
实施例330至实施例348
分别使用制备例13中制备的(S)-奎宁环-3-基(7-溴-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例330至实施例348的标题化合物。
实施例330.(S)-奎宁环-3-基(6-氟-7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39(dd,1H),7.33~7.21(m,2H),7.10~6.97(m,2H),6.87(d,1H),4.92~4.85(m,1H),4.83~4.78(m,1H),4.73(d,1H),3.95~3.80(m,2H),3.35~3.23(m,1H),2.97~2.68(m,5H),2.17~2.07(m,1H),1.89~1.78(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.49~1.39(m,1H),1.06(d,3H),1.02(d,3H)
实施例331.(S)-奎宁环-3-基(6-氟-7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54~7.45(m,2H),7.16~7.08(m,2H),7.00(dd,1H),6.84(d,1H),4.91~4.78(m,2H),4.72(d,1H),3.93~3.81(m,2H),3.34~3.23(m,1H),2.96~2.70(m,5H),2.14~2.06(m,1H),1.88~1.78(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.48~1.38(m,1H),1.06(d,3H),1.02(d,3H)
实施例332.(S)-奎宁环-3-基(6-氟-7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.52(s,1H),7.43~7.31(m,3H),7.02(dd,1H),6.86(d,1H),4.89~4.78(m,2H),4.73(d,1H),3.94~3.79(m,2H),3.35~3.23(m,1H),2.98~2.69(m,5H),2.16~2.06(m,1H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.64~1.56(m,1H),1.49~1.39(m,1H),1.06(d,3H),1.02(d,3H)
实施例333.(S)-奎宁环-3-基(7-(3-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.31(m,3H),7.24~7.18(m,1H),7.00(dd,1H),6.89(d,1H),4.89~4.78(m,2H),4.73(d,1H),3.94~3.79(m,2H),3.35~3.23(m,1H),2.97~2.66(m,7H),2.16~2.06(m,1H),1.90~1.80(m,1H),1.76~1.67(m,1H),1.64~1.56(m,1H),1.48~1.38(m,1H),1.28(t,3H),1.07(d,3H),1.03(d,3H)
实施例334.(S)-奎宁环-3-基(7-(4-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.40(m,2H),7.31~7.22(m,2H),6.99(dd,1H),6.88(d,1H),4.92~4.76(m,2H),4.72(d,1H),3.93~3.78(m,2H),3.36~3.21(m,1H),2.98~2.64(m,7H),2.16~2.06(m,1H),1.91~1.79(m,1H),1.76~1.67(m,1H),1.63~1.55(m,1H),1.48~1.38(m,1H),1.28(t,3H),1.06(d,3H),1.02(d,3H)
实施例335.(S)-奎宁环-3-基(6-氟-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.34(t,1H),7.11(d,1H),7.06(s,1H),7.00(dd,1H),6.94~6.86(m,2H),4.91~4.77(m,2H),4.72(d,1H),3.95~3.79(m,5H),3.34~3.24(m,1H),2.96~2.69(m,5H),2.14~2.07(m,1H),1.88~1.79(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.02(d,3H)
实施例336.(S)-奎宁环-3-基(6-氟-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.43(m,2H),7.02~6.93(m,3H),6.86(d,1H),4.90~-4.77(m,2H),4.72(d,1H),3.93~3.78(m,5H),3.35~3.23(m,1H),2.96~2.69(m,5H),2.15~2.07(m,1H),1.89~1.80(m,1H),1.75~1.68(m,1H),1.64~1.55(m,1H),1.48~1.39(m,1H),1.06(d,3H),1.02(d,3H)
实施例337.(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.40(m,2H),7.03~6.92(m,3H),6.86(d,1H),4.90~4.78(m,2H),4.71(d,1H),4.08(q,2H),3.93~3.78(m,2H),3.34~3.23(m,1H),2.97~2.70(m,5H),2.15~2.07(m,1H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.64~1.54(m,1H),1.49~1.38(m,4H),1.06(d,3H),1.02(d,3H)
实施例338.(S)-奎宁环-3-基(6-氟-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.60(s,1H),7.42~7.35(m,2H),7.05~6.93(m,2H),4.91~4.76(m,2H),4.71(d,1H),3.95~3.79(m,2H),3.35~3.23(m,1H),2.96~2.69(m,5H),2.16~2.07(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.63~1.56(m,1H),1.47~1.38(m,1H),1.06(d,3H),1.01(d,3H)
实施例339.(S)-奎宁环-3-基(6-氟-7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.39~7.32(m,3H),7.26~7.21(m,1H),7.00(dd,1H),6.90(d,1H),4.91~4.78(m,2H),4.72(d,1H),3.93~3.80(m,2H),3.35~3.24(m,1H),3.00~2.70(m,6H),2.16~2.06(m,1H),1.89~1.80(m,1H),1.76~1.68(m,1H),1.64~1.56(m,1H),1.49~1.39(m,1H),1.29(d,6H),1.07(d,3H),1.03(d,3H)
实施例340.(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36(d,1H),7.00(dd,1H),6.87(dd,1H),6.84(s,1H),6.75(d,1H),5.03~4.93(m,1H),4.84~4.78(m,1H),4.74(d,1H),3.94~3.76(m,5H),3.32~3.22(m,1H),2.95~2.69(m,5H),2.14~2.06(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.62~1.55(m,1H),1.47~1.39(m,1H),1.07(d,3H),1.03(d,3H)
实施例341.(S)-奎宁环-3-基(6-氟-7-(2-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.30~7.22(m,2H),7.00(dd,1H),6.81(d,1H),6.74(dd,1H),4.91~4.85(m,1H),4.83~4.78(m,1H),4.72(d,1H),3.93~3.79(m,5H),3.34~3.22(m,1H),2.94~2.70(m,5H),2.14~2.06(m,1H),1.87~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.47~1.38(m,1H),1.06(d,3H),1.02(d,3H)
实施例342.(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.11(d,1H),6.96(dd,1H),6.82(s,1H),6.79(d,1H),6.68(d,1H),4.91~4.85(m,1H),4.83~4.78(m,1H),4.73(d,1H),3.93~3.78(m,5H),3.34~3.23(m,1H),2.93~2.69(m,5H),2.20(s,3H),2.14~2.07(m,1H),1.89~1.80(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.48~1.39(m,1H),1.07(d,3H),1.03(d,3H)
实施例343.(S)-奎宁环-3-基(7-(4-丁基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47~7.41(m,2H),7.28~7.20(m,2H),6.99(dd,1H),6.88(d,1H),4.91~4.85(m,1H),4.83~4.78(m,1H),4.72(d,1H),3.92~3.79(m,2H),3.33~3.24(m,1H),2.96-2.71(m,5H),2.65(t,2H),2.14~2.07(m,1H),1.89~1.79(m,1H),1.76~1.68(m,1H),1.67~1.55(m,3H),1.47~1.35(m,3H),1.06(d,3H),1.02(d,3H),0.95(t,3H)
实施例344.(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.55(s,1H),7.36(d,1H),7.03~6.94(m,2H),6.84(d,1H),4.90~4.77(m,2H),4.71(d,1H),4.63~4.57(m,1H),3.93~3.79(m,2H),3.33~3.23(m,1H),2.96~2.69(m,5H),2.15~2.07(m,1H),1.88-1.79(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.47~1.37(m,7H),1.06(d,3H),1.01(d,3H)
实施例345.(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50~7.43(m,4H),7.00(dd,1H),6.89(d,1H),4.89~4.77(m,2H),4.72(d,1H),3.94~3.79(m,2H),3.35~3.23(m,1H),2.97~2.70(m,5H),2.16~2.07(m,1H),1.90~1.79(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.47~1.39(m,1H),1.36(s,9H),1.06(d,3H),1.02(d,3H)
实施例346.(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.20~7.13(m,2H),6.97(dd,1H),6.84(d,1H),4.90~4.78(m,2H),4.71(d,1H),3.93~3.80(m,2H),3.76(s,3H),3.35~3.24(m,1H),2.96~2.70(m,5H),2.33(s,6H),2.15~2.07(m,1H),1.91~1.80(m,1H),1.76~1.66(m,1H),1.64~1.54(m,1H),1.48~1.39(m,1H),1.06(d,3H),1.02(d,3H)
实施例347.(S)-奎宁环-3-基(6-氟-7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.48~7.41(m,2H),7.02~6.92(m,3H),6.86(d,1H),4.86~4.77(m,2H),4.71(d,1H),3.92~3.80(m,2H),3.76(d,2H),3.35~3.24(m,1H),2.95~2.69(m,5H),2.16~2.06(m,2H),1.89~1.79(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.47~1.38(m,1H),1.09~0.96(m,12H)
实施例348.(S)-奎宁环-3-基(6-氟-7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.29(s,1H),7.72(d,1H),7.01(dd,1H),6.84(d,1H),6.74(d,1H),5.37~5.31(m,1H),4.90~4.77(m,2H),4.72(d,1H),3.94~3.79(m,2H),3.33~3.22(m,1H),2.95~2.70(m,5H),2.14~2.07(m,1H),1.87~1.78(m,1H),1.74~1.67(m,1H),1.64~1.55(m,1H),1.48~1.41(m,1H),1.38(d,6H),1.06(d,3H),1.02(d,3H)
实施例349至实施例367
分别使用制备例14中制备的(S)-奎宁环-3-基(7-溴-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯和相应的取代硼酸,按照与实施例1相同的程序制备实施例349至实施例367的标题化合物。
实施例349.(S)-奎宁环-3-基(7-(3-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.35(dd,1H),7.30~7.21(m,2H),7.02(t,1H),6.83~6.75(m,2H),4.92~4.78(m,2H),4.69(d,1H),3.89~3.70(m,5H),3.36~3.23(m,1H),2.95~2.70(m,5H),2.15~2.07(m,1H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.64-1.56(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.04(d,3H)
实施例350.(S)-奎宁环-3-基(7-(4-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.51~7.43(m,2H),7.13~7.03(m,2H),6.82~6.72(m,2H),4.91~4.78(m,2H),4.68(d,1H),3.89~3.68(m,5H),3.36~3.23(m,1H),2.93~2.70(m,5H),2.14~2.07(m,1H),1.87~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.38(m,1H),1.07(d,3H),1.04(d,3H)
实施例351.(S)-奎宁环-3-基(7-(3-氯苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.50(s,1H),7.40~7.24(m,3H),6.82~6.74(m,2H),4.92~4.78(m,2H),4.69(d,1H),3.88~3.68(m,5H),3.35~3.24(m,1H),2.94~2.70(m,5H),2.14~2.07(m,1H),1.89~1.79(m,1H),1.75~1.68(m,1H),1.64~1.55(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例352.(S)-奎宁环-3-基(7-(3-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.36~7.29(m,3H),7.17(d,1H),6.84~6.74(m,2H),4.91~4.77(m,2H),4.68(d,1H),3.88~3.68(m,5H),3.34~3.23(m,1H),2.94~2.65(m,7H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.37(m,1H),1.27(t,3H),1.08(d,3H),1.04(d,3H)
实施例353.(S)-奎宁环-3-基(7-(4-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.46~7.40(m,2H),7.28~7.20(m,2H),6.81(s,1H),6.77(d,1H),4.93~4.86(m,1H),4.83~4.77(m,1H),4.67(d,1H),3.87~3.68(m,5H),3.35~3.22(m,1H),2.94~2.64(m,7H),2.14~2.06(m,1H),1.88~1.79(m,1H),1.76~1.67(m,1H),1.64-1.55(m,1H),1.47~1.37(m,1H),1.28(t,3H),1.07(d,3H),1.04(d,3H)
实施例354.(S)-奎宁环-3-基(6-甲氧基-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.31(t,1H),7.11~7.04(m,2H),6.88(dd,1H),6.82(s,1H),6.79(d,1H),4.91~4.77(m,2H),4.68(d,1H),3.89~3.76(m,5H),3.73(d,3H),3.35~3.23(m,1H),2.96~2.70(m,5H),2.15~2.06(m,1H),1.91~1.79(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例355.(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.40(m,2H),6.97~6.90(m,2H),6.82~6.73(m,2H),4.92~4.77(m,2H),4.67(d,1H),3.88~3.76(m,5H),3.72(d,3H),3.36~3.23(m,1H),2.94~2.69(m,5H),2.15~2.07(m,1H),1.89~1.78(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例356.(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.47~7.41(m,2H),6.95~6.89(m,2H),6.81~6.72(m,2H),4.90~4.77(m,2H),4.67(d,1H),4.07(q,2H),3.87~3.75(m,2H),3.72(d,3H),3.34~3.23(m,1H),2.94~2.69(m,5H),2.13~2.06(m,1H),1.88~1.79(m,1H),1.75~1.67(m,1H),1.64~1.55(m,1H),1.47~1.38(m,4H),1.07(d,3H),1.03(d,3H)
实施例357.(S)-奎宁环-3-基(6-甲氧基-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.61(s,1H),7.41(d,1H),7.34(d,1H),6.98(s,1H),6.78(d,1H),4.90~4.78(m,2H),4.67(d,1H),3.90-3.73(m,5H),3.37~3.24(m,1H),2.96~2.70(m,5H),2.14~2.07(m,1H),1.89~1.80(m,1H),1.76~1.68(m,1H),1.65~1.55(m,1H),1.47~1.38(m,1H),1.07(d,3H),1.03(d,3H)
实施例358.(S)-奎宁环-3-基(7-(3-异丙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.38~7.30(m,3H),7.20(d,1H),6.83(s,1H),6.81~6.74(m,1H),4.91~4.76(m,2H),4.68(d,1H),3.88~3.69(m,5H),3.36~3.23(m,1H),2.99~2.70(m,6H),2.15~2.06(m,1H),1.87~1.79(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.37(m,1H),1.28(d,6H),1.08(d,3H),1.04(d,3H)
实施例359.(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.32(d,1H),6.87~6.73(m,3H),6.69(s,1H),5.05~4.94(m,1H),4.83~4.78(m,1H),4.70(d,1H),3.90~3.76(m,5H),3.71(d,3H),3.35~3.22(m,1H),2.94~2.69(m,5H),2.14~2.06(m,1H),1.89~1.79(m,1H),1.75~1.67(m,1H),1.63~1.54(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例360.(S)-奎宁环-3-基(7-(2-氟-4-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.23(t,1H),6.81~6.72(m,3H),6.68(d,1H),4.93~4.87(m,1H),4.83~4.77(m,1H),4.68(d,1H),3.87~3.76(m,5H),3.72(d,3H),3.35~3.22(m,1H),2.92~2.68(m,5H),2.13~2.07(m,1H),1.87~1.79(m,1H),1.75~1.67(m,1H),1.63~1.56(m,1H),1.46~1.37(m,1H),1.07(d,3H),1.03(d,3H)
实施例361.(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.07(d,1H),6.79(s,1H),6.78~6.71(m,2H),6.62(s,1H),4.97~4.88(m,1H),4.84~4.78(m,1H),4.69(d,1H),3.88~3.73(m,5H),3.67(d,3H),3.35~3.22(m,1H),2.94~2.69(m,5H),2.13(s,3H),2.12~2.07(m,1H),1.88~1.80(m,1H),1.75~1.67(m,1H),1.63~1.55(m,1H),1.46~1.37(m,1H),1.08(d,3H),1.04(d,3H)
实施例362.(S)-奎宁环-3-基(7-(4-丁基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.45~7.38(m,2H),7.24~7.18(m,2H),6.81(s,1H),6.77(d,1H),4.91~4.86(m,1H),4.84~4.78(m,1H),4.68(d,1H),3.87~3.76(m,2H),3.72(d,3H),3.35~3.23(m,1H),2.94~2.70(m,5H),2.64(t,2H),2.13~2.06(m,1H),1.90~1.78(m,1H),1.75~1.68(m,1H),1.67~1.54(m,3H),1.46~1.35(m,3H),1.07(d,3H),1.03(d,3H),0.95(t,3H)
实施例363.(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.54(s,1H),7.34(d,1H),6.96(d,1H),6.80~6.72(m,2H),4.91~4.84(m,1H),4.83~4.77(m,1H),4.67(d,1H),4.61~4.54(m,1H),3.87~3.77(m,2H),3.73(d,3H),3.35~3.22(m,1H),2.93~2.68(m,5H),2.14~2.06(m,1H),1.87~1.79(m,1H),1.74~1.67(m,1H),1.63~1.54(m,1H),1.46~1.36(m,7H),1.07(d,3H),1.03(d,3H)
实施例364.(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.49~7.39(m,4H),6.83(s,1H),6.77(d,1H),4.93~4.86(m,1H),4.84~4.78(m,1H),4.68(d,1H),3.87~3.78(m,2H),3.73(d,3H),3.37~3.22(m,1H),2.96~2.69(m,5H),2.14~2.06(m,1H),1.91~1.79(m,1H),1.75~1.67(m,1H),1.64~1.54(m,1H),1.47~1.40(m,1H),1.36(s,9H),1.07(d,3H),1.04(d,3H)
实施例365.(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.19~7.11(m,2H),6.80~6.71(m,2H),4.93~4.85(m,1H),4.83~4.78(m,1H),4.67(d,1H),3.87~3.69(m,8H),3.35~3.22(m,1H),2.94~2.70(m,5H),2.31(s,6H),2.14~2.06(m,1H),1.88~1.78(m,1H),1.76~1.66(m,1H),1.64~1.54(m,1H),1.47~1.36(m,1H),1.07(d,3H),1.03(d,3H)
实施例366.(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ7.48~7.39(m,2H),6.96~6.89(m,2H),6.82~6.72(m,2H),4.91~4.84(m,1H),4.83~4.78(m,1H),4.67(d,1H),3.87~3.67(m,7H),3.35~3.22(m,1H),2.93~2.69(m,5H),2.16~2.06(m,2H),1.89~1.79(m,1H),1.76~1.67(m,1H),1.64~1.55(m,1H),1.45~1.37(m,1H),1.12~0.97(m,12H)
实施例367.(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯
1H-NMR(400MHz,CDCl3)δ8.27(s,1H),7.23(d,1H),6.81~6.74(m,2H),6.70(d,1H),5.38~5.29(m,1H),4.93~4.85(m,1H),4.83~4.77(m,1H),4.68(d,1H),3.88~3.77(m,2H),3.73(d,3H),3.34-3.23(m,1H),2.94~2.69(m,5H),2.13~2.06(m,1H),1.87~1.77(m,1H),1.74~1.67(m,1H),1.62~1.55(m,1H),1.46~1.40(m,1H),1.37(d,6H),1.07(d,3H),1.03(d,3H)
实验例1:对GCS的抑制活性的评价
根据已知文献中描述的方法(Hayashi Y et al.,A sensitive andreproducible assay to measure the activity of glucosylceramide synthase andlactosylceramide synthase using HPLC and fluorescent substrates,AnalyticalBiochemistry 345(2005)181-186),对本发明的化合物对GCS的抑制活性进行如下评价。将已知作为GCS抑制剂的Ibiglustat用作对照。
(1)材料
A549细胞(ATCC,CCL-185)
NBD C6-神经酰胺(Thermo Fisher,N1154)
UDP-葡萄糖(Sigma,U4625)
氯化钾(Sigma,P9333)
超级纯TM(UltraPure TM)0.5M EDTA(英杰公司(Invitrogen),15575-038)
BCA蛋白检测试剂盒(Thermo Fisher,23227)
Ibiglustat(上海双福生物科技有限公司(Shanghai Systeam Biochem Co.,ltd),Genz-682452)
HEPES(sigma,H3375)
蛋白酶/磷酸酶抑制剂混合物(protease/phosphatase inhibitor cocktail)(CST,5872s)
DMEM(GIBCO,11995-065)
FBS(GIBCO,16000-044)
抗生素-抗真菌剂(Antibiotic-Antimycotic)(100X)(GIBCO,15240-112)
200mM L-谷氨酰胺(GIBCO,25030081)
PBS(GIBCO,10010-023)
0.25%胰蛋白酶-EDTA(GIBCO,25200-056)
二甲基亚砜(Sigma,34869)
2-丙醇,HPLC级(Burdick&Jackson,AH323-4)
己烷,HPLC级(Burdick&Jackson,AH216-4)
氯仿(Sigma,C2432)
甲醇(Merck,1.06009.1011)
(2)方案(Protocol)
<1>细胞裂解物(cell lysate)的制备
在37℃和5%CO2的培养箱中,将A549细胞(ATCC,CCL-185)在补充有10%胎牛血清(FBS)、1x抗生素-抗真菌剂和1x L-谷氨酰胺的DMEM培养基中培养。将附着在培养皿上的细胞用磷酸盐缓冲液(PBS)洗涤后,用细胞刮刀刮去细胞,然后离心(4000rpm,3分钟,4℃)收集细胞于50ml管中。将细胞团块(cell pellets)悬浮在裂解缓冲液(50mM HEPES,pH 7.3,含有1x蛋白酶/磷酸酶抑制剂混合物)中,通过超声裂解,然后将裂解物(lysate)离心(13000rpm,10分钟,4℃)。获得的上清液用于蛋白质的定量分析。使用牛血清白蛋白作为标准物(standard),使用BCA蛋白检测试剂盒测量蛋白质的量。
<2>GCS酶反应(enzyme reaction)
通过将以下反应材料依次加入96深孔板(deep-well plate)中来引发酶促反应(Enzymatic reaction)。此后,酶促反应在37℃进行90分钟。
酶反应混合物(Enzyme reaction Mix)(总计50μl)
<3>脂质提取
通过加入100μl的氯仿/甲醇(2:1,v/v)停止酶促反应。涡旋(vortexing)15秒后,将每种混合物离心(4000rpm,10分钟,18℃)。将下层(50μl)转移到新的96深孔板中,并用减压浓缩器(reduced concentrator)干燥。
<4>HPLC分析
将脂质溶解在100μl的异丙醇/正己烷/H2O(55:44:1,v/v/v)中,然后转移到玻璃小瓶中用于HPLC(Agilent,8004-HP-H/i3u)。将样品(100μl)自动加载到正相色谱柱(Intersil SIL 150A-5,4.6x250mm,GL Sciences,日本)上,然后用异丙醇/正己烷/H2O(55:44:1,v/v/v)以2.0ml/分钟的流速洗脱。分别使用470nm和530nm作为激发波长和发射波长,用荧光检测器(安捷伦(Agilent),1260FLD Spectra)测量其荧光。
<5>数据分析
通过以下等式进行数据分析。
%面积(样品)=面积(GlcCer)/[面积(Cer)+面积(GlcCer)]×100
%GCS活性=[面积(样品)-面积(ibiglustat)]/[面积(DMSO)-面积(ibiglustat)]×100
使用软件GraphPad Prism(Ver 5.01)分析获得的%GCS活性数据以计算IC50值。结果示于下表1至表4中。
表1
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
1 | 2.6 | 41 | 0.52 | 81 | 0.94 |
2 | 0.7 | 42 | 14.01 | 82 | 2.86 |
3 | 0.7 | 43 | 0.58 | 83 | 3.93 |
4 | 0.7 | 44 | 9.17 | 84 | 2.79 |
5 | 3.71 | 45 | 4.13 | 85 | 9.67 |
6 | 0.67 | 46 | 4.08 | 86 | 9.68 |
7 | 3.28 | 47 | 2.55 | 87 | 3.57 |
8 | 0.48 | 48 | 6.27 | 88 | 9.41 |
9 | 1.81 | 49 | 3.80 | 89 | 6.63 |
10 | 2.02 | 50 | 3.98 | 90 | 4.27 |
11 | 10.44 | 51 | 1.02 | 91 | 5.38 |
12 | 4.28 | 52 | 7.06 | 92 | 29.59 |
13 | 8.54 | 53 | 1.77 | 93 | 4.25 |
14 | 9.67 | 54 | 2.14 | 94 | 8.13 |
15 | 11.75 | 55 | 3.58 | 95 | 19.75 |
16 | 9.40 | 56 | 1.38 | 96 | 8.55 |
17 | 1.41 | 57 | 3.52 | 97 | 11.49 |
18 | 1.54 | 58 | 2.00 | 98 | 14.95 |
19 | 8.32 | 59 | 0.30 | 99 | 19.18 |
20 | 2.86 | 60 | 2.39 | 100 | 7.1 |
21 | 0.67 | 61 | 1.36 | 101 | 9.2 |
22 | 4.00 | 62 | 1.03 | 102 | 0.8 |
23 | 0.48 | 63 | 1.33 | 103 | 1 |
24 | 4.88 | 64 | 1.32 | 104 | 1 |
25 | 0.65 | 65 | 0.22 | 105 | 1.11 |
26 | 10.18 | 66 | 1.75 | 106 | 1.17 |
27 | 0.75 | 67 | 0.93 | 107 | 1.17 |
28 | 5.19 | 68 | 3.65 | 108 | 0.69 |
29 | 2.28 | 69 | 1.91 | 109 | 2.14 |
30 | 3.92 | 70 | 0.59 | 110 | 1.30 |
31 | 3.26 | 71 | 5.30 | 111 | 1.93 |
32 | 3.34 | 72 | 0.92 | 112 | 0.53 |
33 | 1.43 | 73 | 1.47 | 113 | 2.92 |
34 | 1.97 | 74 | 5.03 | 114 | 0.75 |
35 | 2.77 | 75 | 2.44 | 115 | 1.88 |
36 | 1.53 | 76 | 1.94 | 116 | 1.39 |
37 | 1.40 | 77 | 3.33 | 117 | 1.66 |
38 | 3.02 | 78 | 1.26 | 118 | 1.63 |
39 | 1.82 | 79 | 2.57 | 119 | 0.65 |
40 | 3.78 | 80 | 5.75 | 120 | 0.71 |
表2
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
121 | 2.67 | 161 | 0.38 | 201 | 0.41 |
122 | 0.96 | 162 | 0.52 | 202 | 0.28 |
123 | 0.79 | 163 | 0.59 | 203 | 0.72 |
124 | 0.75 | 164 | 1.59 | 204 | 0.52 |
125 | 0.86 | 165 | 0.82 | 205 | 0.65 |
126 | 0.58 | 166 | 0.31 | 206 | 0.50 |
127 | 2.11 | 167 | 0.71 | 207 | 1.12 |
128 | 2.84 | 168 | 1.40 | 208 | 1.41 |
129 | 1.15 | 169 | 0.37 | 209 | 0.34 |
130 | 0.71 | 170 | 0.42 | 210 | 1.57 |
131 | 1.02 | 171 | 0.79 | 211 | 0.71 |
132 | 1.55 | 172 | 0.37 | 212 | 0.87 |
133 | 1.35 | 173 | 1.17 | 213 | 0.78 |
134 | 2.83 | 174 | 0.35 | 214 | 0.55 |
135 | 0.44 | 175 | 0.71 | 215 | 1.57 |
136 | 0.61 | 176 | 0.59 | 216 | 1.51 |
137 | 0.62 | 177 | 1.39 | 217 | 0.55 |
138 | 0.63 | 178 | 1.14 | 218 | 0.40 |
139 | 0.62 | 179 | 1.31 | 219 | 2.26 |
140 | 0.88 | 180 | 0.44 | 220 | 0.80 |
141 | 0.19 | 181 | 0.50 | 221 | 0.74 |
142 | 0.67 | 182 | 0.25 | 222 | 0.79 |
143 | 0.78 | 183 | 1.22 | 223 | 1.58 |
144 | 0.17 | 184 | 0.91 | 224 | 0.62 |
145 | 0.69 | 185 | 0.67 | 225 | 0.45 |
146 | 0.98 | 186 | 0.38 | 226 | 0.71 |
147 | 0.40 | 187 | 0.32 | 227 | 0.56 |
148 | 0.74 | 188 | 0.75 | 228 | 0.55 |
149 | 0.41 | 189 | 0.36 | 229 | 0.71 |
150 | 0.72 | 190 | 0.29 | 230 | 0.86 |
151 | 0.53 | 191 | 0.63 | 231 | 0.62 |
152 | 0.91 | 192 | 0.92 | 232 | 0.41 |
153 | 0.48 | 193 | 0.51 | 233 | 0.49 |
154 | 0.74 | 194 | 0.60 | 234 | 0.40 |
155 | 0.60 | 195 | 1.14 | 235 | 0.75 |
156 | 0.29 | 196 | 1.25 | 236 | 0.75 |
157 | 0.48 | 197 | 0.90 | 237 | 0.63 |
158 | 0.42 | 198 | 0.66 | 238 | 0.47 |
159 | 0.57 | 199 | 0.51 | 239 | 0.47 |
160 | 0.52 | 200 | 0.49 | 240 | 0.92 |
表3
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
241 | 0.81 | 281 | 0.65 | 321 | 1.00 |
242 | 0.53 | 282 | 1.64 | 322 | 1.78 |
243 | 1.90 | 283 | 2.20 | 323 | 0.63 |
244 | 0.42 | 284 | 0.91 | 324 | 1.25 |
245 | 0.95 | 285 | 1.96 | 325 | 0.58 |
246 | 0.75 | 286 | 0.93 | 326 | 0.64 |
247 | 0.58 | 287 | 0.79 | 327 | 2.70 |
248 | 0.86 | 288 | 1.11 | 328 | 1.18 |
249 | 0.39 | 289 | 0.61 | 329 | 14.93 |
250 | 0.35 | 290 | 1.54 | 330 | 0.28 |
251 | 1.64 | 291 | 1.03 | 331 | 0.36 |
252 | 0.54 | 292 | 1.38 | 332 | 0.39 |
253 | 0.76 | 293 | 1.23 | 333 | 0.45 |
254 | 1.70 | 294 | 144.6 | 334 | 0.33 |
255 | 1.20 | 295 | 18.1 | 335 | 0.35 |
256 | 0.39 | 296 | 11.4 | 336 | 0.27 |
257 | 0.36 | 297 | 0.80 | 337 | 0.23 |
258 | 0.45 | 298 | 0.70 | 338 | 0.19 |
259 | 1.14 | 299 | 0.60 | 339 | 0.61 |
260 | 0.51 | 300 | 0.23 | 340 | 0.48 |
261 | 0.65 | 301 | 0.80 | 341 | 0.17 |
262 | 0.52 | 302 | 0.80 | 342 | 0.45 |
263 | 1.44 | 303 | 0.50 | 343 | 0.12 |
264 | 0.35 | 304 | 0.38 | 344 | 0.58 |
265 | 2.03 | 305 | 0.70 | 345 | 0.37 |
266 | 4.07 | 306 | 0.50 | 346 | 1.18 |
267 | 1.48 | 307 | 1.07 | 347 | 0.23 |
268 | 0.62 | 308 | 1.06 | 348 | 0.24 |
269 | 0.66 | 309 | 5.77 | 349 | 0.32 |
270 | 0.78 | 310 | 0.23 | 350 | 0.47 |
271 | 1.26 | 311 | 0.17 | 351 | 0.45 |
272 | 0.89 | 312 | 5.62 | 352 | 0.38 |
273 | 0.46 | 313 | 3.89 | 353 | 0.33 |
274 | 0.58 | 314 | 6.47 | 354 | 0.63 |
275 | 0.84 | 315 | 14.70 | 355 | 0.58 |
276 | 0.54 | 316 | 36.45 | 356 | 0.48 |
277 | 0.65 | 317 | 2.94 | 357 | 0.45 |
278 | 2.19 | 318 | 1.29 | 358 | 0.61 |
279 | 0.73 | 319 | 1.07 | 359 | 0.62 |
280 | 0.62 | 320 | 1.5 | 360 | 0.55 |
表4
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
361 | 0.99 | 364 | 0.43 | 367 | 0.22 |
362 | 0.11 | 365 | 1.20 | ||
363 | 0.75 | 366 | 0.19 |
由表1至表4的结果可见,本发明的化合物对GCS表现出优异的抑制活性。
实验例2:对GM1产生的抑制活性的评价
GM1是鞘脂代谢的最终产物,在细胞膜上表达,因此易于检测。此外,GM1的量代表神经酰胺转化为葡萄糖神经酰胺。因此,根据已知文献(Dijkhuis et al.,Gangliosidesdo not affect ABC transporter function in human neuroblastoma cells.TheJournal of Lipid Research 47(2006).1187-1195)中描述的方法,如下评价本发明化合物对GM1产生的抑制活性。将已知作为GCS抑制剂的Ibiglustat用作对照。
(1)材料
白血病细胞(Jurkat cells),克隆E6-1(ATCC,TIB-152)
霍乱毒素亚基B(Cholera toxin subunit B,CTB),FITC(Sigma,C1655)
Ibiglustat(上海双福生物科技有限公司,Genz-682452)
DMSO(Sigma,D2650)
固定缓冲液(Fixation buffer)(BD,554655)
RPMI 1640(Gibco,A1049101)
FBS(Gibco,16000-044)
抗生素-抗真菌剂(100X)(Gibco,15240-122)
FACS鞘液(Sheath Fluid)(BD,342003)
白血病细胞在补充有10%FBS和1X抗生素-抗真菌剂的RPMI 1640培养基中培养。通过将10ml FBS加入到490ml FACS鞘液中制备洗涤液(washing solution)。通过用洗涤液稀释CTB-FITC储备溶液(10mg/ml)至最终浓度为2μg/ml来制备CTB-FITC溶液。
(2)方案
用培养基(补充有10%FBS和1X抗生素-抗真菌剂的RPMI 1640培养基)制备细胞混悬剂(1×105个细胞/ml)。将细胞混悬剂(200μl)加入到96孔板的每个孔中(20,000个细胞/孔),然后以每孔0.05至3000nM(3倍(fold),11个点)的最终浓度对混合物(compounds)进行处理。每种混合物(mixture)在CO2培养箱中于37℃培养72小时。以1500rpm离心3分钟以除去培养基后,将细胞重新悬浮在每孔200μl洗涤液中。在以1500rpm离心3分钟以除去洗涤液后,将细胞重新悬浮在200μl的2ug/ml CTB-FITC溶液中。将得到的混悬剂在4℃培养60分钟,同时不暴露于光。以1500rpm离心3分钟以除去CTB-FITC溶液后,用200μl洗涤液洗涤细胞。洗涤过程另外重复两次。将洗涤后的板以1500rpm离心3分钟以除去洗涤液,然后将细胞完全重新悬浮于200μl固定缓冲液中。由通过用GuavaTM easyCyte 5HT(Merck Milipore,0500-4005)量化FITC荧光获得的值确定IC50。
通过以下等式进行数据分析。
%MFI(中位荧光强度)=(药物处理组的荧光值/DMSO处理组的荧光值)×100
%细胞=(孔中的细胞浓度/DMSO处理组中的细胞浓度)×100
使用软件GraphPad Prism(Ver 5.01)分析%MFI和%细胞数据以计算IC50值。结果示出于下表5至表8中。
表5
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
1 | 1.686 | 41 | 0.45 | 81 | 14.79 |
2 | 3.474 | 42 | 34.06 | 82 | 7.00 |
3 | 2.127 | 43 | 0.02 | 83 | 19.61 |
4 | 1.084 | 44 | 15.59 | 84 | 7.18 |
5 | 29.21 | 45 | 26.23 | 85 | 222 |
6 | 7.18 | 46 | 20.46 | 86 | 181.4 |
7 | 34.13 | 47 | 10.54 | 87 | 98.71 |
8 | 3.59 | 48 | 42.03 | 88 | 159.6 |
9 | 2.83 | 49 | 12.32 | 89 | 216.5 |
10 | 7.23 | 50 | 25.93 | 90 | 140.9 |
11 | 18.22 | 51 | 4.99 | 91 | 171.2 |
12 | 3.28 | 52 | 24.77 | 92 | 494.6 |
13 | 42.76 | 53 | 2.66 | 93 | 79.77 |
14 | 42.11 | 54 | 14.06 | 94 | 407.5 |
15 | 38.94 | 55 | 22.34 | 95 | 513 |
16 | 27.80 | 56 | 6.03 | 96 | 78.93 |
17 | 5.50 | 57 | 36.60 | 97 | 502.4 |
18 | 6.98 | 58 | 21.17 | 98 | 525.1 |
19 | 30.49 | 59 | 2.22 | 99 | 322.3 |
20 | 19.10 | 60 | 16.49 | 100 | 289.3 |
21 | 4.56 | 61 | 40.07 | 101 | 65.94 |
22 | 34.24 | 62 | 21.20 | 102 | 2.812 |
23 | 0.57 | 63 | 27.02 | 103 | 1.434 |
24 | 10.69 | 64 | 19.20 | 104 | 1.024 |
25 | 1.07 | 65 | 1.18 | 105 | 1.409 |
26 | 23.26 | 66 | 11.35 | 106 | 0.22 |
27 | 0.54 | 67 | 11.30 | 107 | 0.10 |
28 | 24.07 | 68 | 28.29 | 108 | 0.46 |
29 | 12.40 | 69 | 8.93 | 109 | 2.00 |
30 | 48.23 | 70 | 5.78 | 110 | 0.12 |
31 | 27.63 | 71 | 38.79 | 111 | 1.27 |
32 | 48.65 | 72 | 12.84 | 112 | 0.55 |
33 | 10.75 | 73 | 28.20 | 113 | 13.01 |
34 | 5.97 | 74 | 44.27 | 114 | 2.81 |
35 | 5.44 | 75 | 23.60 | 115 | 3.72 |
36 | 11.07 | 76 | 29.18 | 116 | 1.16 |
37 | 9.47 | 77 | 28.68 | 117 | 4.43 |
38 | 14.49 | 78 | 27.27 | 118 | 3.63 |
39 | 7.73 | 79 | 33.42 | 119 | 1.25 |
40 | 19.71 | 80 | 44.16 | 120 | 6.41 |
表6
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
121 | 15.92 | 161 | 0.18 | 201 | 1.12 |
122 | 3.75 | 162 | 0.02 | 202 | 0.47 |
123 | 4.24 | 163 | 0.50 | 203 | 8.03 |
124 | 4.47 | 164 | 3.22 | 204 | 0.31 |
125 | 3.85 | 165 | 0.66 | 205 | 0.25 |
126 | 0.85 | 166 | 0.07 | 206 | 0.01 |
127 | 14.18 | 167 | 3.28 | 207 | 1.06 |
128 | 23.16 | 168 | 2.05 | 208 | 2.47 |
129 | 4.56 | 169 | 0.25 | 209 | 0.01 |
130 | 1.40 | 170 | 5.83 | 210 | 17.99 |
131 | 1.21 | 171 | 5.23 | 211 | 1.41 |
132 | 8.95 | 172 | 1.92 | 212 | 2.45 |
133 | 0.10 | 173 | 2.95 | 213 | 0.03 |
134 | 12.66 | 174 | 1.37 | 214 | 1.81 |
135 | 3.46 | 175 | 2.20 | 215 | 2.51 |
136 | 2.73 | 176 | 3.20 | 216 | 8.58 |
137 | 0.11 | 177 | 9.73 | 217 | 7.35 |
138 | 1.57 | 178 | 4.36 | 218 | 2.69 |
139 | 0.30 | 179 | 4.42 | 219 | 7.58 |
140 | 0.15 | 180 | 3.42 | 220 | 2.42 |
141 | 0.20 | 181 | 5.55 | 221 | 2.80 |
142 | 0.19 | 182 | 0.79 | 222 | 6.59 |
143 | 1.46 | 183 | 6.43 | 223 | 1.60 |
144 | 1.20 | 184 | 4.16 | 224 | 0.60 |
145 | 0.08 | 185 | 0.98 | 225 | 1.70 |
146 | 2.35 | 186 | 2.81 | 226 | 1.30 |
147 | 1.00 | 187 | 2.06 | 227 | 4.50 |
148 | 0.03 | 188 | 4.59 | 228 | 1.30 |
149 | 0.03 | 189 | 0.04 | 229 | 2.10 |
150 | 0.40 | 190 | 0.03 | 230 | 0.80 |
151 | 0.31 | 191 | 0.31 | 231 | 1.50 |
152 | 0.22 | 192 | 1.35 | 232 | 0.30 |
153 | 0.06 | 193 | 0.46 | 233 | 3.00 |
154 | 0.41 | 194 | 1.81 | 234 | 1.10 |
155 | 0.77 | 195 | 1.39 | 235 | 7.10 |
156 | 0.27 | 196 | 6.13 | 236 | 3.60 |
157 | 0.12 | 197 | 1.99 | 237 | 5.10 |
158 | 1.50 | 198 | 1.83 | 238 | 5.90 |
159 | 0.55 | 199 | 3.63 | 239 | 4.80 |
160 | 0.54 | 200 | 1.94 | 240 | 5.00 |
表7
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
241 | 24.10 | 281 | 6.90 | 322 | 5.88 |
242 | 3.80 | 282 | 2.00 | 323 | 26.34 |
243 | 24.10 | 283 | 25.60 | 324 | 14.44 |
244 | 0.60 | 284 | 0.50 | 325 | 6.13 |
245 | 4.70 | 285 | 9.70 | 326 | 10.28 |
246 | 1.30 | 286 | 3.30 | 327 | 37.62 |
247 | 10.70 | 287 | 1.00 | 328 | 13.76 |
248 | 29.60 | 288 | 0.70 | 329 | 33.76 |
249 | 4.00 | 289 | 1.40 | 330 | 1.8 |
250 | 5.40 | 290 | 0.90 | 331 | 3.7 |
251 | 17.50 | 291 | 8.90 | 332 | 0.9 |
252 | 1.40 | 292 | 30.20 | 333 | 0.8 |
253 | 6.40 | 293 | 3.00 | 334 | 0.4 |
254 | 17.40 | 295 | 11.16 | 335 | 2.0 |
255 | 5.10 | 296 | 1.256 | 336 | 3.5 |
256 | 0.20 | 297 | 5.60 | 337 | 1.2 |
257 | 0.70 | 298 | 5.50 | 338 | 3.3 |
258 | 1.00 | 299 | 9.70 | 339 | 0.2 |
259 | 6.90 | 300 | 0.90 | 340 | 2.4 |
260 | 0.30 | 301 | 17.50 | 341 | 4.1 |
261 | 2.60 | 302 | 2.60 | 342 | 3.5 |
262 | 3.70 | 303 | 3.20 | 343 | 0.1 |
263 | 4.00 | 304 | 2.10 | 344 | 7.3 |
264 | 0.70 | 305 | 5.40 | 345 | 1.6 |
265 | 38.70 | 306 | 3.00 | 346 | 9.5 |
266 | 26.90 | 307 | 3.10 | 347 | 0.02 |
267 | 9.10 | 308 | 4.10 | 348 | 0.5 |
268 | 1.40 | 309 | 37.20 | 349 | 3.2 |
269 | 1.90 | 310 | 0.20 | 350 | 7.5 |
270 | 1.00 | 311 | 0.70 | 351 | 1.7 |
271 | 9.00 | 312 | 28.8 | 352 | 2 |
272 | 4.40 | 313 | 34.5 | 353 | 2.3 |
273 | 2.90 | 314 | 56.30 | 354 | 3.1 |
274 | 1.70 | 315 | 58.10 | 355 | 5.8 |
275 | 2.60 | 316 | 251.1 | 356 | 3.4 |
276 | 1.30 | 317 | 13.83 | 357 | 4 |
277 | 0.90 | 318 | 27.24 | 358 | 2 |
278 | 12.40 | 319 | 6.703 | 359 | 2.4 |
279 | 6.20 | 320 | 13.77 | 360 | 10 |
280 | 9.30 | 321 | 3.64 | 361 | 8.5 |
表8
实施例 | IC<sub>50</sub>(nM) | 实施例 | IC<sub>50</sub>(nM) |
362 | 0.7 | 365 | 14.5 |
363 | 8.7 | 366 | 0.7 |
364 | 2 | 367 | 3.2 |
从表5至表8的结果可见,本发明的化合物对GM1的产生表现出优异的抑制活性。
Claims (17)
1.一种式1的化合物或其药学上可接受的盐:
<式1>
其中,
L为-O-、-CO-、-CR1R2-或-NR3-,
X是氢;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C1~C6烷氧基;或被1至3个卤素原子取代的C1~C6烷氧基,
Y是-CR4R5-;-NR3-;-O-;或-S-,
P是-CR4R5-,
Q是-O-或-CR4R5-,
Z是-CR6-,
R1和R2彼此独立地是氢;卤素;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基;或R1和R2与它们所连接的碳原子一起形成C3~C10环烷基,
R3是氢;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基,
R4和R5彼此独立地是氢;卤素;C1~C6烷基;具有氮原子、氧原子或硫原子的C1~C6烷基;C3~C10环烷基;3-元至12-元杂环;或C1~C6烷氧基;或R4和R5与它们所连接的P或Q的碳原子一起形成C3~C10环烷基,
R6是氢;C1~C6烷基;或具有氮原子、氧原子或硫原子的C1~C6烷基,
W是一个键、-CH2-、-O-、-NH-、-CH2CH2-、-CH=CH-、或-C≡C-,
A环是6-元至12-元芳基;5-元至12-元杂芳基;C3~C10环烷基;或3-元至12-元杂环,并且
X1、X2、X3和X4彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;3-元至12-元杂环;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;C1~C6烷硫基;氨基;单或双C1~C6烷基氨基;吗啉基;吡咯烷基-磺酰基;苄基;羟基;或硝基。
2.根据权利要求1所述的化合物或其药学上可接受的盐,其中L为-O-。
3.根据权利要求1所述的化合物或其药学上可接受的盐,其中X是氢;卤素;或C1~C6烷氧基。
4.根据权利要求1所述的化合物或其药学上可接受的盐,其中R3是C1~C6烷基。
5.根据权利要求1所述的化合物或其药学上可接受的盐,其中R4、R5和R6彼此独立地是氢或C1~C6烷基。
6.根据权利要求1所述的化合物或其药学上可接受的盐,其中Y是-O-。
7.根据权利要求1所述的化合物或其药学上可接受的盐,其中Q是-O-。
8.根据权利要求1所述的化合物或其药学上可接受的盐,其中Y是-S-。
9.根据权利要求1所述的化合物或其药学上可接受的盐,其中Y是-NR3-。
10.根据权利要求1所述的化合物或其药学上可接受的盐,其中W是一个键、-CH2-或-CH=CH-。
11.根据权利要求1所述的化合物或其药学上可接受的盐,其中A环是苯基、联苯基、噻吩基、吡唑基、噻唑基、萘基、苯并噻二唑基、苯并二氧杂环戊烯基、2,3-二氢苯并二噁英基、苯并呋喃基、2,3-二氢苯并呋喃基、1,3-二氢异苯并呋喃基、3,4-二氢-1,4-苯并噁嗪基、3-氧代-3,4-二氢-1,4-苯并噁嗪基、苯并噻吩基、吲哚基、吲唑基、异喹啉基、喹啉基、3,4-二氢-苯并二氧杂环庚三烯基、苯并[c][1,2-5]噁二唑基、吡啶基、6-氧代-1,6-二氢吡啶基、苯并二氢吡喃基、二苯并呋喃基或嘧啶基。
12.根据权利要求1所述的化合物或其药学上可接受的盐,其中,X1、X2、X3和X4彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;吗啉基;单或双C1~C6烷基氨基;吡咯烷基-磺酰基;苄基;四氢吡喃基;C1~C6烷硫基;或异噁唑基。
13.根据权利要求1所述的化合物或其药学上可接受的盐,其中
L是-O-,
X是氢;卤素;或C1~C6烷氧基,
Y是-CR4R5-;-NR3-;-O-;或-S-,
P是-CR4R5-,
Q是-O-或-CR4R5-,
Z是-CR6-,
R3是C1~C6烷基,
R4、R5和R6彼此独立地是氢或C1~C6烷基,
W是一个键、-CH2-或-CH=CH-,
A环是苯基、联苯基、噻吩基、吡唑基、噻唑基、萘基、苯并噻二唑基、苯并二氧杂环戊烯基、2,3-二氢苯并二噁英基、苯并呋喃基、2.3-二氢苯并呋喃基、1,3-二氢异苯并呋喃基、3,4-二氢-1,4-苯并噁嗪基、3-氧代-3,4-二氢-1,4-苯并噁嗪基、苯并噻吩基、吲哚基、吲唑基、异喹啉基、喹啉基、3,4-二氢-苯并二氧杂环庚三烯基、苯并[c][1,2-5]噁二唑基、吡啶基、6-氧代-1,6-二氢吡啶基、苯并二氢吡喃基、二苯并呋喃基或嘧啶基,并且
X1、X2、X3和X4彼此独立地是氢;氰基;卤素;C1~C6烷基;被1至3个卤素原子取代的C1~C6烷基;被氰基或C1~C6烷氧基取代的C1~C6烷基;C3~C10环烷基;C1~C6烯基;C1~C6烷氧基;C1~C6烷氧基-C1~C6烷氧基;被1至3个卤素原子取代的C1~C6烷氧基;被C3~C10环烷基或苄基取代的C1~C6烷氧基;吗啉基;单或双C1~C6烷基氨基;吡咯烷基-磺酰基;苄基;四氢吡喃基;C1~C6烷硫基;或异噁唑基。
14.根据权利要求1所述的化合物或其药学上可接受的盐,其选自以下化合物:
(S)-奎宁环-3-基(7-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-环丙基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-甲基-1H-吲哚-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(喹啉-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1,3-二氢异苯并呋喃-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基[6,7'-二苯并二氢吡喃]-4'-基氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基-5-(三氟甲基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-氯苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-(甲硫基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氰基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(甲氧基甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(2-甲氧基乙氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(8-甲基喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-6-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(萘-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(萘-1-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氯-5-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-5-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二甲基-4-丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁氧基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-(三氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-丁氧基-6-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(6-(2,2,2-三氟乙氧基)吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-4-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-8-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-环丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3',3'-二甲基-[6,7'-二苯并二氢吡喃]-4'-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-5-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-8-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并[b][1,4]二噁英-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯-3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-1H-吡唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氢苯并呋喃-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(环丙基甲氧基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-(吡咯烷-1-基磺酰基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氢-2H-苯并[b][1,4]二氧杂环庚三烯-7-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噻二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(异喹啉-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-甲基-4-吗啉代苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(1-甲基-1H-吲唑-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲哚-6-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3,4-二氢-2H-苯并[b][1,4]噁嗪-7-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氰基-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2,4,5-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(四氢-2H-吡喃-4-基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-吗啉代苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[b]噻吩-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1H-吲唑-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氯-6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-甲基-3-氧代-3,4-二氢-2H-苯并[b][1,4]噁嗪-6-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2,3,4-三氟苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(二氟甲氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(喹啉-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[c][1,2,5]噁二唑-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(5-甲基吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟-3-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,4-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,3-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3,5-二氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-([1,1'-联苯]-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(噻唑-5-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(3-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-甲氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基吡啶-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氰基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-6-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并[d][1,3]二氧杂环戊烯-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-环丙基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-(二甲氨基)吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(5-氟-2-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-乙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-甲氧基-5-甲基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(异噁唑-3-基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟-4-异丙氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-(三氟甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丙氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-苯基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(吡啶-2-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-苄基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(间甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(对甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(邻甲苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-((E)-2-(噻吩-3-基)乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(4-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-(2-乙烯基苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(苄氧基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,6-二氟吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-烯丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(氰基甲基)苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-2-([1,1'-二苯基]-4-基)乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-环丙基嘧啶-5-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-7-((E)-4-(三氟甲基)苯乙烯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-2,4-二氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-4-乙基苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(6-乙氧基萘-2-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-3-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(二苯并[b,d]呋喃-4-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氰基-3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(1-苄基-6-氧代-1,6-二氢吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-((E)-4-氟苯乙烯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(3-氟苯基)-2,2-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(2,2-二甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(3-(三氟甲氧基)苯基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基-3,5-二甲基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氰基苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-4-甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(4-甲基-7-(4-甲基噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)异苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)异苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)-1-甲基-1,2,3,4-四氢喹啉-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-(4-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(三氟甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲氧基甲氧基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(叔丁基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,5-二氯苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙氧基苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(甲硫基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-(二甲氨基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2,2-二氟苯并[d][1,3]二氧杂环戊烯-5-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(苯并呋喃-3-基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(3,3-二甲基-6-(4-(三氟甲基)苯基)硫代苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-氟苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-氯苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(3-异丙基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(2-氟-4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-氟-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(4-异丁氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-氟-7-(6-异丙氧基吡啶-3-基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-氟苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(3-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-乙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-3,3-二甲基-7-(噻吩-3-基)苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-异丙基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氯-5-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(2-氟-4-甲氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-2-甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-丁基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(3-氯-4-异丙氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-(叔丁基)苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(6-甲氧基-7-(4-甲氧基-3,5-二甲基苯基)-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;
(S)-奎宁环-3-基(7-(4-异丁氧基苯基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯;和
(S)-奎宁环-3-基(7-(6-异丙氧基吡啶-3-基)-6-甲氧基-3,3-二甲基苯并二氢吡喃-4-基)氨基甲酸酯。
15.一种用于抑制葡萄糖神经酰胺合酶的药物组合物,其包含权利要求1至14中任一项所述的化合物或其药学上可接受的盐作为活性成分。
16.根据权利要求15所述的药物组合物,其用于预防或治疗戈谢病、法布里病、泰-萨克斯病或帕金森病。
17.一种在哺乳动物中抑制葡萄糖神经酰胺合酶的方法,该方法包括将治疗有效量的如权利要求1至14中任一项所述的化合物或其药学上可接受的盐施用于有需要的哺乳动物。
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CA3080677A1 (en) | 2017-11-06 | 2019-05-09 | Jubilant Prodel LLC | Pyrimidine derivatives as inhibitors of pd1/pd-l1 activation |
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