(S)-1-(2-tert-butoxycarbonyl-4-methoxybutyl)cyclopentanecarboxylic acid | 465529-17-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-1-(2-tert-butoxycarbonyl-4-methoxybutyl)cyclopentanecarboxylic acid
• 英文别名: 1-[(2S)-2-(tert-butoxycarbonyl)-4-methoxybutyl]cyclopentanecarboxylatic acid；1-[(2S)-2-(tert-butoxycarbonyl)-4-methoxybutyl]cyclopentanecarboxylic acid；1-[(2S)-4-methoxy-2-[(2-methylpropan-2-yl)oxycarbonyl]butyl]cyclopentane-1-carboxylic acid
• CAS: 465529-17-3
• 化学式: C₁₆H₂₈O₅
• 分子量: 300.395
• InChiKey: KYFKJKHRTNOCDM-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-1-(2-tert-butoxycarbonyl-4-methoxybutyl)cyclopentanecarboxylic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (S)-2-{[1-({[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]amino}carbonyl)-cyclopentyl]methyl}-4-methoxybutanoic acid
  参考文献：
  名称：

  Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder

  摘要：

  A series of substituted glutaramides were synthesised using Candoxatrilat 1 as a lead and evaluated for potency against neutral endopeptidase (NEP) as a potential treatment for female sexual arousal disorder (FSAD). In this paper, we describe studies in which we were able to increase NEP activity substantially over the levels reported for previous compounds from this programme by appropriate substitution in both the P'(1) and P'(2) regions. Optimisation led to the 4-chlorophenpropylamide S-30 which was selected as a candidate for further study. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.002
• 作为产物：
  描述：

  (1S,2S)-1-hydroxy-N-methyl-1-phenyl-2-propanaminium 1-[(2S)-2-(tert-butoxycarbonyl)-4-methoxybutyl]cyclopentane carboxylate 在 盐酸 作用下， 以 醋酸异丙酯 、 水 为溶剂， 生成 (S)-1-(2-tert-butoxycarbonyl-4-methoxybutyl)cyclopentanecarboxylic acid
  参考文献：
  名称：

  [EN] CYCLOPENTIL-SUBSTITUTED GLUTARAMIDE COMPOUNDS AS ENDOPEPTIDASEV INHIBITORS
  [FR] COMPOSES GLUTARAMIDE A SUBSTITUTION CYCLOPENTILE UTILISES COMME INHIBITEURS DE L'ENDOPEPTIDASE

  摘要：

  该发明涉及NEP抑制剂用于治疗心血管疾病。首选的NEP抑制剂是具有以下结构的化合物(I)：其中R1为C1-C6烷基，C1-C6烷氧基C1-C3烷基或C1-C6烷氧基C1-C6烷氧基C1-C3烷基；R2为氢或C1-C6烷基；L为从-CH2-X-CH2-和-CH2-CH2-X-中选择的三个原子连接，其中连接的右侧连接到R3，X为氧、硫或亚甲基；R3为苯基或芳香杂环基，两者中的任何一个都可以独立地被一个或多个来自以下群的基取代：C1-C6烷基，卤素，卤代C1-C6烷基，C1-C6烷氧基，卤代C1-C6烷氧基，C1-C6烷基硫基，卤代C1-C6烷基硫基和腈基；R4和R5要么都是氢，要么R4和R5中的一个是氢，另一个是在患者体内被氢替代的生物可解脂基。

  公开号：

  WO2004056750A1

文献信息

• N-phenpropylcuclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
  申请人：——

  公开号：US20030105132A1

  公开（公告）日：2003-06-05

  The invention relates to compounds of formula (I) for treating for example sexual dysfunction, wherein R 1 is optionally substituted C 1-6 alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, hydrogen, C 1-6 alkoxy, —NR 2 R 3 or —NR 4 SO 2 R 5 ; X is the linkage —(CH 2 ) n — or —(CH 2 ) q —O— (wherein Y is attached to the oxygen); wherein one or more hydrogen atoms in linkage X may be replaced independently by C 1-4 alkoxy; hydroxy; hydroxy(C 1-3 alkyl); C 3-7 cycloalkyl; carbocyclyl; heterocyclyl; or by C 1-4 alkyl optionally substituted by one or more fluoro or phenyl groups; n is 3, 4, 5, 6 or 7; and q is 2, 3, 4, 5 or 6; and Y is phenyl or pyridyl, each of which may be substituted; or two R 8 groups on adjacent carbon atoms together with the interconnecting carbon atoms may form a fused optionally substituted 5 - or 6 -membered carbocyclic or heterocyclyic ring. 1

  该发明涉及用于治疗性功能障碍的化合物(I)的公式，其中R1是可选择取代的C1-6烷基，可选择取代的碳环烷基，可选择取代的杂环烷基，氢，C1-6烷氧基，—NR2R3或—NR4SO2R5；X是连接基—(CH2)n—或—(CH2)q—O—（其中Y连接到氧原子）；其中连接基X中的一个或多个氢原子可以独立地被C1-4烷氧基，羟基，羟基(C1-3烷基)，C3-7环烷基，碳环烷基，杂环烷基或可选择取代的一个或多个氟或苯基的C1-4烷基替代；n为3、4、5、6或7；q为2、3、4、5或6；Y为苯基或吡啶基，每个基都可以被取代；或相邻碳原子上的两个R8基连同相互连接的碳原子可以形成一个可选择取代的5-或6-成员碳环或杂环环。
• [EN] CYCLOPENTYL GLUTARAMIDES AND THEIR USE AS NEUTRAL ENDOPEPTIDASE INHIBITORS<br/>[FR] GLUTARAMIDES CYCLOPENTYLE ET UTILISATION DE CES COMPOSES COMME INHIBITEURS D'ENDOPEPTIDASE NEUTRE (NEP)
  申请人：PFIZER LTD

  公开号：WO2004056787A1

  公开（公告）日：2004-07-08

  The invention relates to NEP inhibitors for treating cardiovascular disorders wherein R1 is C1-C6alkyl, C1-C6alkoxyC1-C3alkyl or C1-C6alkoxyC1-C6alkoxyC,-C3alkyl; R2 is hydrogen or C1-C6alkyl; L is an aromatic heterocyclic ring, optionally substituted with C,­ C6alkyl or halo; R3 is C1-C6alkyl optionally substituted by halo, alkoxy, haloalkoxy, alkylthio, haloalkylthio or nitrile group, or R3 is phenyl or aromatic heterocyclyl each of which may be independently substituted by one or more alkyl, halo, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio or nitrile group; R4 and R5 are either both hydrogen, or one of R4 and R5 is hydrogen and the other is a biolabile ester-forming group that in the body of a patient is replaced by hydrogen; p is 0, 1 or 2; and q is 1 or 2.

  该发明涉及NEP抑制剂，用于治疗心血管疾病，其中R1为C1-C6烷基，C1-C6烷氧基C1-C3烷基或C1-C6烷氧基C1-C6烷氧基，R2为氢或C1-C6烷基，L为芳香杂环环，可选择性地取代为C，C6烷基或卤素，R3为C1-C6烷基，可选择性地取代为卤素，烷氧基，卤代烷氧基，烷基硫醚，卤代烷基硫醚或腈基，或R3为苯基或芳香杂环基，每个基团可独立地取代为一个或多个烷基，卤素，卤代烷基，烷氧基，卤代烷氧基，烷基硫醚，卤代烷基硫醚或腈基；R4和R5要么都是氢，要么R4和R5中的一个是氢，另一个是在患者体内被氢取代的生物易降解酯基团；p为0、1或2；q为1或2。
• Design, synthesis and antihypertensive evaluation of novel codrugs with combined angiotensin type 1 receptor antagonism and neprilysin inhibition
  作者：Alessandra Mascarello、Hatylas Azevedo、Marcos Antonio Ferreira Junior、Eloisa Eriko Ishikawa、Cristiano Ruch Werneck Guimarães

  DOI：10.1016/j.ejps.2021.105731

  日期：2021.4

  Specifically, the codrugs combine the AT1 antagonists losartan or its carboxylic acid active metabolite (E-3174) with selected monocarboxylic acid NEP inhibitors through a cleavable linker. The resulting codrugs exhibited high rates of in vitro conversion into the active molecules upon incubation with human/rat liver S9 fractions and in vivo conversion after oral administration in rodents. Moreover, the acute

  高血压的多因素病因促进了具有多靶点作用的降压药的研究，以取得更好的临床效果。我们在这里描述了结合药效基团与1型血管紧张素（AT1）受体拮抗作用和中性溶酶（NEP）抑制作用的新型双效降压药的发现。具体而言，这些药物的前药通过可裂解的接头将AT1拮抗剂洛沙坦或其羧酸活性代谢产物（E-3174）与选定的单羧酸NEP抑制剂结合在一起。在与人/大鼠肝脏S9组分温育和体内孵育后，所产生的共同药物表现出较高的体外转化为活性分子的速率在啮齿动物中口服后转化。此外，在自发性高血压大鼠（SHR）模型中，以10、30和60 mg / kg po的剂量证实了其中一种设计的药物前药（3b）的急性作用，在24小时内显示出比给予sd更好的降压反应。 15 mg / kg氯沙坦和14 mg / kg相同的NEP抑制剂的等效固定剂量组合，用于3b。结果表明，共药方法是开发具有AT1和NEP活性相结合的单一分子实体的可行策略
• 5-HT receptor ligands and uses thereof
  申请人：——

  公开号：US20030105106A1

  公开（公告）日：2003-06-05

  Compounds of Formula (IA) that act as 5-HT receptor ligands and their uses in the treatment of diseases linked to the activation of 5-HT 2 receptors in animals are described herein. 1

  本文描述了作为5-HT受体配体的化合物（IA）及其在治疗与动物5-HT2受体激活相关的疾病中的用途。
• [EN] NEUTRAL ENDOPEPTIDASE INHIBITOR POLYMORPH<br/>[FR] POLYMORPHE INHIBITEUR D'ENDOPEPTIDASE NEUTRE
  申请人：PFIZER LTD

  公开号：WO2005123702A1

  公开（公告）日：2005-12-29

  Disclosed are (2S)-2-1-[(1S)-1-Isobutoxycarbonyl-2-(5-phenyl-oxazol-2-yl)-ethylcarbamoyl]-cyclopentylmethyl}-4-methoxy-butyric, Potassium-(2S)-2-1-[(1S)-1-Isobutoxycarbonyl-2-(5-phenyl-oxazol-2-yl)-ethylcarbamoyl]-cyclopentylmethyl}-4-methoxy-butyrate, monohydrate and its Form I polymorph. Also disclosed are compositions of the described forms, kits including the described forms, and methods of using the described forms for the treatment diseases or disorders where the use of a neutral endopeptidase inhibitor is indicated, including cardiovascular diseases and conditions.

  披露了(2S)-2-1-[(1S)-1-异丁氧羰基-2-(5-苯基-噁唑-2-基)-乙基氨基]-环戊甲基}-4-甲氧基丁酸钾盐、(2S)-2-1-[(1S)-1-异丁氧羰基-2-(5-苯基-噁唑-2-基)-乙基氨基]-环戊甲基}-4-甲氧基丁酸盐、单水合物及其I型多形体。还披露了所述形式的组合物、包含所述形式的试剂盒，以及使用所述形式治疗心血管疾病和症状等需要使用中性内肽酶抑制剂的疾病或疾病的方法。