(2S,3R)-1-(3-Chloro-4-cyano-2-methyl-phenylsulfamoyl)-3-hydroxy-2-methyl-pyrrolidine-2-carboxylic acid methyl ester | 863204-64-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3R)-1-(3-Chloro-4-cyano-2-methyl-phenylsulfamoyl)-3-hydroxy-2-methyl-pyrrolidine-2-carboxylic acid methyl ester
• 英文别名: methyl (2S,3R)-1-[(3-chloro-4-cyano-2-methylphenyl)sulfamoyl]-3-hydroxy-2-methylpyrrolidine-2-carboxylate
• CAS: 863204-64-2
• 化学式: C₁₅H₁₈ClN₃O₅S
• 分子量: 387.844
• InChiKey: PUDDUWOJZITHGQ-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-(3-Chloro-4-cyano-2-methyl-phenylsulfamoyl)-3-hydroxy-2-methyl-pyrrolidine-2-carboxylic acid methyl ester 在 sodium hydroxide 、 对硝基苯酚 、 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 生成 4-[(3aS,4R)-4-hydroxy-3a-methyl-1,1,3-trioxohexahydrothia-2,6a-diazapentalen-2-yl]-2-chloro-3-methylbenzonitrile
  参考文献：
  名称：

  Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators

  摘要：

  Replacement of the 3-oxo group of 2-chloro-4-[(7R,7aS)-7-hydroxy-1,3-dioxotetrahydro-IH-pyrrolo[1,2c]imidazol2(3H)-yl]-3-methylbenzonitrile resulted in a sulfamide series of selective androgen receptor modulator (SARM) agonists. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.007
• 作为产物：
  描述：

  4-氨基-2-氯-3-甲基苯甲腈 在 氯磺酸 、 五氯化磷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (2S,3R)-1-(3-Chloro-4-cyano-2-methyl-phenylsulfamoyl)-3-hydroxy-2-methyl-pyrrolidine-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators

  摘要：

  Replacement of the 3-oxo group of 2-chloro-4-[(7R,7aS)-7-hydroxy-1,3-dioxotetrahydro-IH-pyrrolo[1,2c]imidazol2(3H)-yl]-3-methylbenzonitrile resulted in a sulfamide series of selective androgen receptor modulator (SARM) agonists. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.007

文献信息

• Sulfonylpyrrolidine modulators of androgen receptor function and method
  申请人：Hamann G. Lawrence

  公开号：US20050187267A1

  公开（公告）日：2005-08-25

  Compounds are provided which are useful in the treatment of androgen receptor-associated conditions, such as age-related diseases, which compounds have the structure wherein R 1 is hydrogen (H), alkyl or substituted alkyl, alkenyl or substituted alkenyl, arylalkyl or substituted arylalkyl, CO 2 R 4a , CONR 4a R 4b , and CH 2 OR 4a ; R 2 is hydrogen (H), OR 3 , SR 3 , halo, NHR 3 , NHCOR 4c 1 , NHCO 2 R 4c 1 , NHCONR 4c R 4d and NHSO 2 R 4c ; R 3 in each functional group is hydrogen (H), alkyl or substituted alkyl, CHF 2 , CF 3 and CON 4e ; R 4 , R 4a , R 4b , R 4c , R 4c 1 , R 4d , R 4e , R 4f , R 4g , or R 4h in each functional group are the same or different and are hydrogen(H), alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, arylalkyl or substituted arylalkyl, aryl or substituted aryl, or heteroaryl or substituted heteroaryl; R 5 and R 5 ′ are the same or different and are hydrogen(H), alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, arylalkyl or substituted arylalkyl, aryl or substituted aryl, or heteroaryl or substituted heteroaryl, wherein at least one of R 5 and R 5 ′ is hydrogen, or R 5 and R 5 ′ taken together form a double bond with oxygen (O), sulfur (S), NR 7 or CR 7 R 7 ′; where R 7 and R 7 ′ are as defined herein; G is an aryl, heterocyclo or heteroaryl group, wherein said group is mono- or polycyclic, and which is optionally substituted; and n is an integer of 1 or 2, m is an integer of 1 or 2, Z is oxygen (—O—) or NR 4h , a prodrug ester, all stereoisomers thereof and a pharmaceutically acceptable salt. A method for treating androgen receptor-associated conditions such as age-related diseases is also provided.

  提供了一些化合物，用于治疗与雄激素受体相关的疾病，如与年龄相关的疾病，这些化合物具有以下结构： 其中 R1是氢（H），烷基或取代烷基，烯基或取代烯基，芳基烷基或取代芳基烷基，CO2R4a，CONR4aR4b和CH2OR4a； R2是氢（H），OR3，SR3，卤素，NHR3，NHCOR4c1，NHCO2R4c1，NHCONR4cR4d和NHSO2R4c； 每个功能基团中的R3是氢（H），烷基或取代烷基，CHF2，CF3和CON4e； 在每个功能基团中，R4，R4a，R4b，R4c，R4c1，R4d，R4e，R4f，R4g或R4h是相同或不同的，可以是氢（H），烷基或取代烷基，烯基或取代烯基，炔基或取代炔基，环烷基或取代环烷基，芳基烷基或取代芳基烷基，芳基或取代芳基，或杂环芳基或取代杂环芳基； R5和R5'是相同或不同的，可以是氢（H），烷基或取代烷基，烯基或取代烯基，炔基或取代炔基，环烷基或取代环烷基，芳基烷基或取代芳基烷基，芳基或取代芳基，或杂环芳基或取代杂环芳基，其中R5和R5'中至少有一个是氢，或者R5和R5'一起形成与氧（O），硫（S），NR7或CR7R7'的双键； 其中R7和R7'如本文所定义；G是一个芳基，杂环或杂环芳基，其中该基团是单环或多环的，可以选择性地取代；n是1或2的整数，m是1或2的整数，Z是氧（—O—）或NR4h，一个前药酯，所有立体异构体及药学上可接受的盐。还提供了一种治疗与雄激素受体相关疾病，如与年龄相关的疾病的方法。
• SULFONYLPYRROLIDINE MODULATORS OF ANDROGEN RECEPTOR FUNCTION AND METHOD
  申请人：Hamann Lawrence G.

  公开号：US20110015408A1

  公开（公告）日：2011-01-20

  Compounds are provided which are useful in the treatment of androgen receptor-associated conditions, such as age-related diseases, which compounds have the structure wherein R 1 , R 2 and R 4 , are as defined herein; G is an aryl, heterocyclo or heteroaryl group, wherein said group is mono- or polycyclic, and which is optionally substituted; n is an integer of 1 or 2; m is an integer of 1 or 2; Z is oxygen (—O—) or NR 4h ; a prodrug ester, all stereoisomers thereof and a pharmaceutically acceptable salt thereof. A method for treating androgen receptor-associated conditions such as age-related diseases is also provided.

  提供了一些化合物，这些化合物在治疗与雄激素受体相关的疾病，如与年龄相关的疾病中非常有用。这些化合物的结构如下： 其中，R1、R2和R4如定义所述；G是芳香基、杂环基或杂芳基，该基团是单环或多环的，并且可以选择性地取代；n是1或2的整数；m是1或2的整数；Z是氧（—O—）或NR4h；a是前药酯，其所有立体异构体及其药学上可接受的盐也在其中。还提供了一种治疗与雄激素受体相关的疾病，如与年龄相关的疾病的方法。
• US7820702B2
  申请人：——

  公开号：US7820702B2

  公开（公告）日：2010-10-26
• US7989640B2
  申请人：——

  公开号：US7989640B2

  公开（公告）日：2011-08-02
• Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators
  作者：Mark C. Manfredi、Yingzhi Bi、Alexandra A. Nirschl、James C. Sutton、Ramakrishna Seethala、Rajasree Golla、Blake C. Beehler、Paul G. Sleph、Gary J. Grover、Jacek Ostrowski、Lawrence G. Hamann

  DOI：10.1016/j.bmcl.2007.06.007

  日期：2007.8

  Replacement of the 3-oxo group of 2-chloro-4-[(7R,7aS)-7-hydroxy-1,3-dioxotetrahydro-IH-pyrrolo[1,2c]imidazol2(3H)-yl]-3-methylbenzonitrile resulted in a sulfamide series of selective androgen receptor modulator (SARM) agonists. (c) 2007 Elsevier Ltd. All rights reserved.