(2S,4R)-4-[(4-chlorophenyl)methoxy]-1-[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidine-2-carboxylic acid | 863221-25-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,4R)-4-[(4-chlorophenyl)methoxy]-1-[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4R)-4-[(4-chlorophenyl)methoxy]-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid
• CAS: 863221-25-4
• 化学式: C₂₇H₂₄ClNO₅
• 分子量: 477.944
• InChiKey: MFCXOTVODXNETA-CLOONOSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-[(4-chlorophenyl)methoxy]-1-[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidine-2-carboxylic acid 、 C₇H₇N₂PolS 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (2S,4R)-N-benzyl-4-[(4-bromo-2-fluorophenyl)methoxy]-1-[(2R)-2-(methanesulfonamido)-4-piperidin-4-ylbutanoyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS

  摘要：

  该发明提供了化合物及其药物组合物，用于调节通道激活蛋白酶，并使用这些化合物治疗、改善或预防与通道激活蛋白酶相关的疾病的方法，包括但不限于前列腺素酶、PRSS22、TMPRSS11（例如TMPRSS11B、TMPRSS11E）、TMPRSS2、TMPRSS3、TMPRSS4（MTSP-2）、酶蛋白酶（MTSP-1）、CAP2、CAP3、胰蛋白酶、卡特普西蛋白A或中性粒细胞弹性蛋白酶。

  公开号：

  US20080176901A1
• 作为产物：
  描述：

  Boc-L-羟脯氨酸 在 氢氧化钾 、 三氟乙酸 作用下， 以 二甲基亚砜 为溶剂， 生成 (2S,4R)-4-[(4-chlorophenyl)methoxy]-1-[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Properties and structure–activity studies of cyclic β-hairpin peptidomimetics based on the cationic antimicrobial peptide protegrin I

  摘要：

  The properties and structure-activity relationships (SAR) of a macrocyclic analogue of porcine protegrin I (PG-I) have been investigated. The lead compound, having the sequence cyclo-(-Leu-Arg-Leu-Lys-Lys-Arg-Arg-Trp-Lys-Tyr-Arg-Val-D-Pro-Pro-), shows antimicrobial activity against Gram-positive and -negative bacteria, but a much lower haemolytic activity and a much reduced ability to induce dye release from phosphatidylcholine/phosphatidylglycerol liposomes, when compared to PG-I. The enantiomeric form of the lead peptide shows comparable antimicrobial activity, a property shared with other cationic antimicrobial peptides acting on cell membranes. SAR studies involving the synthesis and biological profiling of over 100 single site substituted analogues, showed that the antimicrobial activity was tolerant to a large number of the substitutions tested. Some analogues showed slightly improved antimicrobial activities (2-4-fold lowering of MICs), whereas other substitutions caused large increases in haemolytic activity on human red blood cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.009

文献信息

• Compounds and compositions as channel activating protease inhibitors
  申请人：IRM LLC

  公开号：EP2279777A2

  公开（公告）日：2011-02-02

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

  本发明提供了可用于调节通道活化蛋白酶的化合物及其药物组合物，以及使用此类化合物治疗、改善或预防与通道活化蛋白酶相关的病症的方法，通道活化蛋白酶包括但不限于前列腺素、PRSS22、TMPRSS11（如TMPRSS11B、TMPRSS11E）、TMPRSS2、TMPRSS3、TMPRSS4（MTSP-2）、matriptase（MTSP-1）、CAP2、CAP3、胰蛋白酶、凝血酶 A 或中性粒细胞弹性蛋白酶。
• [EN] COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS<br/>[FR] COMPOSÉS ET COMPOSITIONS EN TANT QU'INHIBITEURS DE PROTÉASES ACTIVATRICES DE CANAUX
  申请人：IRM LLC

  公开号：WO2008085608A1

  公开（公告）日：2008-07-17

  [EN] The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.
  [FR] L'invention concerne des composés et leurs compositions pharmaceutiques, qui sont utiles pour moduler des protéases activatrices de canaux et des procédés d'utilisation de tels composés pour traiter, améliorer ou prévenir une affection associée à une protéase activatrice de canaux y compris, mais sans limitation, la prostasine, la PRSS22, les TMPRSS11 (par exemple, la TMPRSS11B, la TMPRSS11E), la TMPRSS2, la TMPRSS3, la TMPRSS4 (MTSP-2), la matriptase (MTSP-1), la CAP2, la CAP3, la trypsine, la cathepsine A ou l'élastase neutrophile.
• COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS
  申请人：Tully David C.

  公开号：US20080176901A1

  公开（公告）日：2008-07-24

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.

  该发明提供了化合物及其药物组合物，用于调节通道激活蛋白酶，并使用这些化合物治疗、改善或预防与通道激活蛋白酶相关的疾病的方法，包括但不限于前列腺素酶、PRSS22、TMPRSS11（例如TMPRSS11B、TMPRSS11E）、TMPRSS2、TMPRSS3、TMPRSS4（MTSP-2）、酶蛋白酶（MTSP-1）、CAP2、CAP3、胰蛋白酶、卡特普西蛋白A或中性粒细胞弹性蛋白酶。
• Properties and structure–activity studies of cyclic β-hairpin peptidomimetics based on the cationic antimicrobial peptide protegrin I
  作者：John A. Robinson、Sasalu C. Shankaramma、Peter Jetter、Ursula Kienzl、Reto A. Schwendener、Jan W. Vrijbloed、Daniel Obrecht

  DOI：10.1016/j.bmc.2005.01.009

  日期：2005.3

  The properties and structure-activity relationships (SAR) of a macrocyclic analogue of porcine protegrin I (PG-I) have been investigated. The lead compound, having the sequence cyclo-(-Leu-Arg-Leu-Lys-Lys-Arg-Arg-Trp-Lys-Tyr-Arg-Val-D-Pro-Pro-), shows antimicrobial activity against Gram-positive and -negative bacteria, but a much lower haemolytic activity and a much reduced ability to induce dye release from phosphatidylcholine/phosphatidylglycerol liposomes, when compared to PG-I. The enantiomeric form of the lead peptide shows comparable antimicrobial activity, a property shared with other cationic antimicrobial peptides acting on cell membranes. SAR studies involving the synthesis and biological profiling of over 100 single site substituted analogues, showed that the antimicrobial activity was tolerant to a large number of the substitutions tested. Some analogues showed slightly improved antimicrobial activities (2-4-fold lowering of MICs), whereas other substitutions caused large increases in haemolytic activity on human red blood cells. (c) 2005 Elsevier Ltd. All rights reserved.