(2S,4S)-4-(3-chloro-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester | 686766-55-2

• 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,4S)-4-(3-chloro-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester
• 英文别名: methyl (2S,4S)-1-(tert-butoxycarbonyl)-4-(3-chlorophenoxy)pyrrolidine-2-carboxylate；(2S, 4S)-4-(3-Chloro-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester；1-O-tert-butyl 2-O-methyl (2S,4S)-4-(3-chlorophenoxy)pyrrolidine-1,2-dicarboxylate
• CAS: 686766-55-2
• 化学式: C₁₇H₂₂ClNO₅
• 分子量: 355.818
• InChiKey: PGJPHGLMCAEVGG-KBPBESRZSA-N

物化性质

• 沸点：
  438.4±45.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4S)-4-(3-chloro-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 在 盐酸 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 生成 4-(3-chlorophenoxy)pyrrolidine-2-carboxylic acid hydrochloride
  参考文献：
  名称：

  Part 2: Design, synthesis and evaluation of hydroxyproline-derived α2δ ligands

  摘要：

  Conformational constraint has been used to design a potent series of alpha(2)delta ligands derived from the readily available starting material (2S,4R)-hydroxy-L-proline. The ligands have improved physicochemistry and potency compared to their linear counterparts (described in our earlier publication) and the lead compound has been progressed to clinical development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.056
• 作为产物：
  描述：

  反式-4-羟基-L-脯氨酸甲酯盐酸盐 在 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,4S)-4-(3-chloro-phenoxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester
  参考文献：
  名称：

  Part 2: Design, synthesis and evaluation of hydroxyproline-derived α2δ ligands

  摘要：

  Conformational constraint has been used to design a potent series of alpha(2)delta ligands derived from the readily available starting material (2S,4R)-hydroxy-L-proline. The ligands have improved physicochemistry and potency compared to their linear counterparts (described in our earlier publication) and the lead compound has been progressed to clinical development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.056

文献信息

• [EN] PROLINE DERIVATIVES HAVING AFFINITY FOR THE CALCIUM CHANNEL ALPHA-2-DELTA SUBUNIT<br/>[FR] DERIVES DE PROLINE PRESENTANT UNE AFFINITE POUR LA SOUS-UNITE ALPHA-2-DELTA DU CANAL DE CALCIUM
  申请人：PFIZER LTD

  公开号：WO2004039367A1

  公开（公告）日：2004-05-13

  The compounds of formula (I) or a pharmaceutically acceptable salt, solvate or pro-drug thereof, are proline derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, fibromyalgia, arthritis, neuropathalogical disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. Wherein either X is O, S, NH or CH2 and Y is CH2 or a direct bond, or Y is O, S or NH and X is CH2; and R is a 3-12 membered cycloalkyl, 4-12 membered heterocycloalkyl, heteroaryl or aryl, where any ring may be optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, nitro, amino, hydroxycarbonyl, Cl-C6 alkyl, Cl-C6 alkenyl, CI-C6 alkynyl, Cl-C6 alkoxy, hydroxyC,-C6 alkyl, Cl-C6 alkoxyC,-C6 alkyl, perfluoro Cl-C6 alkyl, perfluoroC,-C6 alkoxy, Cl-C6 alkylamino, di- C1-C6 alkylamino, aminoC1-C6 alkyl, Cl-C6 alkylaminoC,-C6 alkyl, di-Cl-C6 alkylaminoC,-C6 alkyl, CI-C6acyl, C1-C6acyloxy, Cl-C6acyloxyC,-C6 alkyl, Cl-C6 acylamino, Cl-C6 alkylthio, C1-C6 alkylthiocarbonyl, C1-C6 alkylthioxo, C1-C6 alkoxycarbonyl, Cl-C6 alkylsulfonyl, C1-C6 alkylsulfonylamino, aminosulfonyl, Cl-C6 alkylaminosulfonyl, di-Cl-C6 alkylaminosulfonyl, 3-8 membered cycloalkyl, 4-8 membered heterocycloalkyl, phenyl and monocyclic heteroaryl; or a pharmaceutically acceptable salt, solvate or pro-drug thereof.

  化学式（I）的化合物或其药学上可接受的盐、溶剂化合物或前药是脯氨酸衍生物，在治疗癫痫、晕厥发作、运动减退、颅内疾病、神经退行性疾病、抑郁症、焦虑、恐慌、疼痛、纤维肌痛、关节炎、神经病理性疾病、睡眠障碍、内脏疼痛疾病和胃肠疾病的治疗中有用。包括制备最终产品和在过程中有用的中间体的方法。还包括含有一种或多种该化合物的药物组合物。其中X为O、S、NH或CH2，Y为 或直接键，或Y为O、S或NH，X为 ；R为3-12环状烷基、4-12环状杂环烷基、杂芳基或芳基，其中任何环都可以选择性地用一个或多个取代基独立选择自卤素、羟基、氰基、硝基、氨基、羟基羰基、Cl-C6烷基、Cl-C6烯基、Cl-C6炔基、Cl-C6烷氧基、羟基C1-C6烷基、Cl-C6烷氧基C1-C6烷基、全氟Cl-C6烷基、全氟C1-C6烷氧基、Cl-C6烷基氨基、二-Cl-C6烷基氨基、氨基C1-C6烷基、Cl-C6烷基氨基C1-C6烷基、二-Cl-C6烷基氨基C1-C6烷基、Cl-C6酰基、C1-C6酰氧基、Cl-C6酰氧基C1-C6烷基、Cl-C6酰胺基、Cl-C6烷基硫基、C1-C6烷基硫羰基、C1-C6烷基硫氧基、C1-C6烷氧羰基、Cl-C6烷基磺基、C1-C6烷基磺酰胺基、氨基磺基、Cl-C6烷基氨基磺基、二-Cl-C6烷基氨基磺基、3-8环状烷基、4-8环状杂环烷基、苯基和单环杂芳基；或其药学上可接受的盐、溶剂化合物或前药。
• Therapeutic proline derivatives
  申请人：——

  公开号：US20040132801A1

  公开（公告）日：2004-07-08

  The compounds of formula (I) or a pharmaceutically acceptable salt, solvate or pro-drug thereof, are proline derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, fibromyalgia, arthritis, neuropathalogical disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. 1 wherein either X is O, S, NH or CH 2 and Y is CH 2 or a direct bond, or Y is O, S or NH and X is CH 2 ; and R is a 3-12 membered cycloalkyl, 4-12 membered heterocycloalkyl, heteroaryl or aryl, where any ring may be optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, nitro, amino, hydroxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 alkoxy, hydroxyC 1 -C 6 alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl, perfluoro C 1 -C 6 alkyl, perfluoroC 1 -C 6 alkoxy, C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6 alkyl, C 1 -C 6 alkylaminoC 1 -C 6 alkyl, di-C 1 -C 6 alkylaminoC 1 -C 6 alkyl, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 acyloxyC 1 -C 6 alkyl, C 1 -C 6 acylamino, C 1 -C 6 alkylthio, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkylthioxo, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylsulfonylamino, aminosulfonyl, C 1 -C 6 alkylaminosulfonyl, di-C 1 -C 6 alkylaminosulfonyl, 3-8 membered cycloalkyl, 4-8 membered heterocycloalkyl, phenyl and monocyclic heteroaryl; or a pharmaceutically acceptable salt, solvate or pro-drug thereof.

  公式（I）的化合物或其药学上可接受的盐、溶剂合物或前药是脯氨酸衍生物，可用于治疗癫痫、晕厥发作、低动力症、头颅疾病、神经退行性疾病、抑郁症、焦虑症、惊恐症、疼痛、纤维肌痛、关节炎、神经病理学疾病、睡眠障碍、内脏疼痛疾病和胃肠疾病的治疗。包括用于制备最终产品和在过程中有用的中间体的过程。还包括含有一种或多种化合物的制药组合物。其中，X为O、S、NH或CH2，Y为 或直接键，或Y为O、S或NH，X为 ；R为3-12环烷基、4-12杂环烷基、杂环芳基或芳基，其中任何环都可以选择地用一个或多个取代基独立地选择自卤素、羟基、氰基、硝基、氨基、羟基羰基、C1-C6烷基、C1-C6烯基、C1-C6炔基、C1-C6烷氧基、羟基C1-C6烷基、C1-C6烷氧基C1-C6烷基、全氟C1-C6烷基、全氟C1-C6烷氧基、C1-C6烷基氨基、二C1-C6烷基氨基、氨基C1-C6烷基、C1-C6烷基氨基C1-C6烷基、二C1-C6烷基氨基C1-C6烷基、C1-C6酰基、C1-C6酰氧基、C1-C6酰氧基C1-C6烷基、C1-C6酰氨基、C1-C6烷硫基、C1-C6烷硫酰基、C1-C6烷基磺酰氨基、氨基磺酰基、C1-C6烷基氨基磺酰基、二C1-C6烷基氨基磺酰基、3-8环烷基、4-8杂环烷基、苯基和单环杂芳基；或其药学上可接受的盐、溶剂合物或前药。
• Therapeutic use of alpha-2-delta ligands
  申请人：Pfizer Inc

  公开号：US20040143014A1

  公开（公告）日：2004-07-22

  The instant invention relates to the use of an alpha-2-delta ligand in the treatment of chronic obstructive pulmonary disease (COPD) and diseases associated with a diagnosis of COPD, and particularly to the treatment of chronic cough, which may be unrelated to COPD.

  本发明涉及使用α-2-δ配体治疗慢性阻塞性肺疾病（COPD）及与COPD诊断相关的疾病，特别是治疗慢性咳嗽，该咳嗽可能与COPD无关。
• Method of treatment for sexual dysfunction
  申请人：——

  公开号：US20040176456A1

  公开（公告）日：2004-09-09

  Use of an alpha-2-delta ligand, or a pharmaceutically acceptable derivative thereof, for the manufacture of a medicament for the treatment of premature ejaculation.

  使用α-2-δ配体或其药学上可接受的衍生物，制造一种用于治疗早泄的药物。
• Method of treatment
  申请人：——

  公开号：US20040180958A1

  公开（公告）日：2004-09-16

  Use of an alpha-2-delta ligand, or a pharmaceutically acceptable derivative thereof, for the manufacture of a medicament for the treatment of LUTS, other than urinary incontinence, associated with OAB and/or BPH.

  使用α-2-δ配体或其药学上可接受的衍生物制造药物，用于治疗除尿失禁以外的与OAB和/或BPH相关的下尿路症状。