4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile
• 英文别名: 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidine-1-yl]benzonitrile
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: LNJKCZNHWLTNIS-CABZTGNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile 在 1,1'-双(二苯基膦)二茂铁 、 正丁基锂 、 水 、 palladium diacetate 、 三氧化硫吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 5-[(2S,3R)-1-(4-cyanophenyl)-3-hydroxy-2-methylpyrrolidin-3-yl]-N-methylpyridine-2-carboxamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives as novel androgen receptor antagonists

  摘要：

  We designed and synthesized a series of 3-aryl-3-hydroxy-1-phenylpyrrolidine derivatives D and evaluated their potential as novel androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a methyl group at the 2-position (R-2) of the pyrrolidine ring increased the AR binding affinity. The (2S, 3R) configuration of the pyrrolidine ring was favorable for the AR antagonistic activity. It was found that introduction of an amide substituent (R-1) and a pyridin-3-yl group (Q) was effective for reducing the AR agonistic activity which appeared during the optimization of lead compound 6. Compound 54 showed potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft, in which bicalutamide exhibited only partial suppression of tumor growth. Thus, the pyrrolidine derivatives such as 54 are novel AR antagonists, and their properties having efficacy against CRPC are distinct from those of a representative first-generation antagonist, bicalutamide. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.001
• 作为产物：
  描述：

  对氟苯腈 、 (4S,5S)-5-methyl-4-hydroxy-2-oxopyrrolidine 生成 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile
  参考文献：
  名称：

  Cyclic amine compound

  摘要：

  化合物的化学式为（I），其中环A是一个5到8个成员的环，可以选择性地具有除R6、R7和R8以外的其他取代基，R1是一个电子吸引基团，R2、R3、R4和R5分别是氢原子、卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，R6是卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，R7是氰基、硝基、可选择具有取代基的酰基、可选择酯化或酰胺化的羧基或可选择具有取代基的碳氢基团，或R6和R7可选择地与其键合的碳原子一起形成一个可选择具有取代基的环，R8是氢原子、卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，或其盐具有卓越的雄激素受体调节剂作用，并且用于预防或治疗性腺机能减退、男性更年期障碍、虚弱、消瘦、骨质疏松等。

  公开号：

  US20100152236A1

文献信息

• CYCLIC AMINE COMPOUND
  申请人：Hasuoka Atsushi

  公开号：US20100087506A1

  公开（公告）日：2010-04-08

  Provision of a compound having a superior androgen receptor regulating action. A compound represented by the formula (I) wherein R 1 is a hydrogen atom, a halogen atom, a group via a carbon atom, a group via a nitrogen atom, a group via an oxygen atom or a group via a sulfur atom; R 2 is a hydrogen atom, a halogen atom, a group via a carbon atom, a group via a nitrogen atom, a group via an oxygen atom or a group via a sulfur atom; R 3 is an electron-withdrawing group; R 4 is a hydrogen atom, a halogen atom, a group via a carbon atom, a group via a nitrogen atom, a group via an oxygen atom or a group via a sulfur atom; R 5 is a hydrogen atom, a halogen atom, a group via a carbon atom, a group via a nitrogen atom, a group via an oxygen atom or a group via a sulfur atom; R 6 is a hydrogen atom, a halogen atom, a group via a carbon atom, a group via a nitrogen atom, a group via an oxygen atom or a group via a sulfur atom; R 7 is alkyl optionally having substituent(s); R 8 is a hydrogen atom, alkyl optionally having substituent(s), alkenyl optionally having substituent(s) or cycloalkyl optionally having substituent(s); R 9 is a group via an oxygen atom; and ring A is a 5- or 6-membered ring optionally having substituent(s) other than R 6 to R 9 (excluding 2-chloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-3-methylbenzonitrile, 2-chloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile, 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile, 2-chloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-5-methylbenzonitrile, 2-chloro-3-ethyl-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile, 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile, 2,3-dichloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-5-methylbenzonitrile, 2,3-dichloro-4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]benzonitrile, 4-[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]-3-(trifluoromethyl)benzonitrile, 4-[(2S,3S)-3-hydroxy-2-isopropylpyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile, 4-[(2S,3R)-3-hydroxy-2-isopropylpyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile, and 2-chloro-4-[(2S)-3-hydroxy-2-methylpiperidin-1-yl]benzonitrile), or a salt thereof.

  提供具有优良雄激素受体调节作用的化合物。化合物由公式(I)表示，其中R1为氢原子、卤素原子、通过碳原子、氮原子、氧原子或硫原子连接的基团; R2为氢原子、卤素原子、通过碳原子、氮原子、氧原子或硫原子连接的基团; R3为电子吸引基团; R4为氢原子、卤素原子、通过碳原子、氮原子、氧原子或硫原子连接的基团; R5为氢原子、卤素原子、通过碳原子、氮原子、氧原子或硫原子连接的基团; R6为氢原子、卤素原子、通过碳原子、氮原子、氧原子或硫原子连接的基团; R7为可选带有取代基的烷基; R8为氢原子、可选带有取代基的烷基、烯基或环烷基; R9为通过氧原子连接的基团; 环A为5-或6-成员环，可选带有R6到R9之外的取代基团（不包括2-氯-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]-3-甲基苯甲腈、2-氯-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]苯甲腈、4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]苯甲腈、2-氯-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]-5-甲基苯甲腈、2-氯-3-乙基-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]苯甲腈、4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]-2-(三氟甲基)苯甲腈、2,3-二氯-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]-5-甲基苯甲腈、2,3-二氯-4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]苯甲腈、4-[(2S,3S)-3-羟基-2-甲基吡咯烷-1-基]-3-(三氟甲基)苯甲腈、4-[(2S,3S)-3-羟基-2-异丙基吡咯烷-1-基]-2-(三氟甲基)苯甲腈、4-[(2S,3R)-3-羟基-2-异丙基吡咯烷-1-基]-2-(三氟甲基)苯甲腈和2-氯-4-[(2S)-3-羟基-2-甲基哌啶-1-基]苯甲腈）或其盐。
• Cyclic amine compound
  申请人：Yamamoto Satoshi

  公开号：US20100152236A1

  公开（公告）日：2010-06-17

  A compound represented by the formula (I) wherein ring A is a 5- to 8-membered ring optionally having further substituent(s) other than R 6 , R 7 and R 8 , R 1 is an electron-withdrawing group, R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom, a halogen atom, a group bonded via a carbon atom, a group bonded via a nitrogen atom, a group bonded via an oxygen atom or a group bonded via a sulfur atom, R 6 is a halogen atom, a group bonded via a carbon atom, a group bonded via a nitrogen atom, a group bonded via an oxygen atom or a group bonded via a sulfur atom, R 7 is a cyano group, a nitro group, an acyl group optionally having substituent(s), an optionally esterified or amidated carboxyl group or a hydrocarbon group optionally having substituent(s), or R 6 and R 7 optionally form, together with the carbon atom bonded thereto, a ring optionally having substituent(s), and R 8 is a hydrogen atom, a halogen atom, a group bonded via a carbon atom, a group bonded via a nitrogen atom, a group bonded via an oxygen atom or a group bonded via a sulfur atom, or a salt thereof has a superior action as an androgen receptor modulator, and is useful for the prophylaxis or treatment of hypogonadism, male climacteric disorder, frailty, cachexia, osteoporosis and the like.

  化合物的化学式为（I），其中环A是一个5到8个成员的环，可以选择性地具有除R6、R7和R8以外的其他取代基，R1是一个电子吸引基团，R2、R3、R4和R5分别是氢原子、卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，R6是卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，R7是氰基、硝基、可选择具有取代基的酰基、可选择酯化或酰胺化的羧基或可选择具有取代基的碳氢基团，或R6和R7可选择地与其键合的碳原子一起形成一个可选择具有取代基的环，R8是氢原子、卤素原子、通过碳原子键合的基团、通过氮原子键合的基团、通过氧原子键合的基团或通过硫原子键合的基团，或其盐具有卓越的雄激素受体调节剂作用，并且用于预防或治疗性腺机能减退、男性更年期障碍、虚弱、消瘦、骨质疏松等。
• WO2007/15567
  申请人：——

  公开号：——

  公开（公告）日：——
• Cyclic amine compound as androgen receptor modulator
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2098507B1

  公开（公告）日：2014-11-12
• US8013008B2
  申请人：——

  公开号：US8013008B2

  公开（公告）日：2011-09-06