(1R,2S)-2-carbomethoxycyclopentyl amine hydrochloride | 362489-54-1

• 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: (1R,2S)-2-carbomethoxycyclopentyl amine hydrochloride
• 英文别名: (1S,2R)-2-amino-cyclopentanecarboxylic acid methyl ester hydrochloride；methyl (+/-)-cis-2-aminocyclopentanecarboxylate hydrochloride；methyl (1S,2R)-2-aminocyclopentane-1-carboxylate hydrochloride；methyl (1S,2R)-2-aminocyclopentanecarboxylate hydrochloride；(1S,2R)-Methyl 2-aminocyclopentanecarboxylate hydrochloride；methyl (1S,2R)-2-aminocyclopentane-1-carboxylate;hydrochloride
• CAS: 362489-54-1
• 化学式: C₇H₁₃NO₂*ClH
• 分子量: 179.647
• InChiKey: KXQFCNYQRWIKML-RIHPBJNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.71
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-carbomethoxycyclopentyl amine hydrochloride 在 钯 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， -30.0~25.0 ℃ 、101.33 kPa 条件下， 反应 27.0h， 生成 (1R,2S)-L-aspartyl-cis-2-aminocyclopentanecarboxylic acid methyl ester
  参考文献：
  名称：

  Probing a molecular model of taste utilizing peptidomimetic stereoisomers of 2-aminocyclopentanecarboxylic acid methyl ester

  摘要：

  On the basis of the preferred conformations of L-aspartyl dipeptide derivatives containing alpha-amino acids at the second position and their retro-inverso analogues deduced by a combination of X-ray crystallography, H-1 NMR spectroscopy, and molecular mechanics calculations, we have proposed a model describing the molecular array required for the sweet taste. The conformation of a sweet molecule is described as possessing an "L shape", with the AH (proton donor) and B (proton acceptor) zwitterionic ring of the aspartyl moiety forming the stem, and the hydrophobic group X forming the base of the "L". Planarity of the molecule in the x and y dimensions is critical for sweet taste. Substantial deviation from this plane into negative z dimension is correlated with bitter taste while other deviations lead to tasteless molecules. To examine the model, the preferred conformations for a series of L-aspartyl dipeptides containing a 2-aminocyclopentanecarboxylic acid (2-Ac5c) residue at the second position were calculated using molecular mechanics. The peptidomimetic 2-Ac5c residue is a beta-amino acid with two chiral centers, resulting in four isomers [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c, cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c]. Two stereoisomers, L-aspartyl-trans-(1R,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1R,2R)-2-Ac5c-OMe] and L-aspartyl-cis-(1S,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1S,2R)-2-Ac5c-OMe], prefer the L-shape conformations and are thus predicted to be sweet. For L-aspartyl-trans-(1S,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1S,2S)-2-Ac5c-OMe], the methyl ester group projects behind the stem of the L shape, producing a large negative z component and is predicted to exhibit a bitter taste. The calculations predict that L-aspartyl-cis-(1R,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1R,2S)-2-Ac5c-OMe] will be tasteless. In this investigation, in addition to the calculations, we report the synthesis and experimental conformational analysis of the four stereoisomers of Asp-2-Ac5c-OMe. The absolute configurations of the 2-Ac5c residues were assigned by X-ray diffraction studies and by correlating optical rotation and enantiomeric excess values. These studies fully confirm our configurational assignments of the stereoisomers of Asp-2-Ac5c-OMe. Thus, the structure-taste relationships observed for the new class of L-aspartyl taste ligands containing the 2-Ac5c beta-amino acid methyl esters in the second position agree with and strengthen our model for the sweet and bitter taste responses.

  DOI：

  10.1021/jo00023a033
• 作为产物：
  描述：

  cis-(1S,2R)-2-tert-butoxycarbonylaminocyclopentanecarboxylic acid methyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 (1R,2S)-2-carbomethoxycyclopentyl amine hydrochloride
  参考文献：
  名称：

  ORNITHINE DERIVATIVE

  摘要：

  提供了一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。目前的发明人对具有对EP4受体拮抗作用的鸟氨酸衍生物进行了广泛研究，结果发现通过在目前发明的化合物的鸟氨酸部分的C末端引入环烷基，可以改善物理化学性质，如溶解性等，从而赋予其作为药物的更优越性质。因此，他们完成了这项发明。目前发明的化合物对EP4受体表现出良好的拮抗作用，因此，它可用作慢性肾功能不全和糖尿病肾病的治疗剂。

  公开号：

  EP2141147A1

文献信息

• Cyclic hydroxamic acids as inhibitors of matrix metalloproteinases and/or TNF-alpha converting enzyme (TACE)
  申请人：——

  公开号：US20030139388A1

  公开（公告）日：2003-07-24

  The present application describes novel cyclic hydroxamic acids of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring B is a 5-7 membered cyclic system containing from 0-2 heteroatoms selected from O, N, NR 1 , and S(O) p , and 0-1 carbonyl groups and the other variables are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-&agr; converting enzyme (TACE), aggrecanase or a combination thereof, pharmaceutical compositions containing the same, and methods of using the same.

  本申请描述了新型的公式I:1的环式羟羧酸，或其药用盐形式，其中环B是一个包含0-2个来自O、N、NR1和S(O)p的杂原子以及0-1个羰基的5-7元环系统，其他变量在本说明书中有定义，这些化合物可作为基质金属蛋白酶（MMP）、TNF-α转化酶（TACE）、聚集素酶或其组合的抑制剂，包含这些化合物的药物组合物，以及使用这些化合物的方法。
• Cyclic beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha
  申请人：——

  公开号：US20020016336A1

  公开（公告）日：2002-02-07

  The present application describes novel cyclic &bgr;-amino acid derivatives of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring B is a 5-7 membered cyclic system containing from 0-2 heteroatoms selected from O, N, NR a , and S(O) p , and 0-1 carbonyl groups and the other variables are defined in the present specification, which are useful as metalloprotease and/or as TNF-&agr; inhibitors.

  本发明申请描述了新颖的环状β-氨基酸衍生物，其通式为I：1或其药学上可接受的盐形式，其中环B是含有0-2个选自O、N、NRa和S(O)p的杂原子以及0-1个羰基的5-7元环状系统，其他变量在本文中有定义，这些化合物可作为金属蛋白酶和/或TNF-α抑制剂使用。
• [EN] INHIBITORS OF DIACYLGLYCEROL ACYL TRANSFERASE<br/>[FR] INHIBITEUR DE DIACYLGLYCÉROL ACYLTRANSFÉRASE
  申请人：PIRAMAL LIFE SCIENCES LTD

  公开号：WO2011080718A1

  公开（公告）日：2011-07-07

  The present invention relates to heterocyclic compounds in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutically acceptable polymorphs. The invention also relates to processes for the manufacture of the heterocyclic compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1. The present invention further provides a method of treatment of such diseases or disorders by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof.

  本发明涉及杂环化合物及其所有立体异构体和互变异构体形式；以及它们的药学上可接受的盐、药学上可接受的溶剂合物和药学上可接受的多晶形态。该发明还涉及制备这些杂环化合物的方法以及含有它们的药物组合物。所述化合物及其药物组合物在预防和治疗由二酰基甘油酰基转移酶（DGAT）介导的疾病或紊乱方面具有用途，特别是DGAT1。本发明进一步提供了一种治疗这些疾病或紊乱的方法，通过向有需要的哺乳动物施用所述化合物或其药物组合物的治疗有效量。
• Synthesis and Antimalarial Evaluation of Cyclic β-Amino Acid-Containing Dipeptides
  作者：Manisha Sathe、D. Thavaselvam、A. Srivastava、M. Kaushik

  DOI：10.3390/molecules13020432

  日期：——

  This paper describes an efficient synthesis and the antiparasitic evaluation ofcyclic β-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. The antimalarial propertiesof all these dipeptides have been evaluated in vitro against Plasmodium falciparum and invivo against Plasmodium berghai. Compounds 4.4 and 4.5 have been found to be veryeffective in this respect, with IC50 values of 3.87 and 3.64 μg/mL in the in vitro test, while4.5 has also been found to be active in the in vivo evaluation.

  本文描述了一种有效的合成方法以及含有环β-氨基酸的二肽3.1-3.6和4.1-4.5的抗寄生虫评估。所有这些二肽的抗疟疾特性在体外针对恶性疟原虫（Plasmodium falciparum）和在体内针对伯氏疟原虫（Plasmodium berghai）进行了评估。化合物4.4和4.5在这方面被发现非常有效，体外测试的IC50值分别为3.87和3.64 μg/mL，而4.5在体内评估中也表现出活性。
• Diacylglycerol Acyltransferase Inhibitors
  申请人：Bolin David Robert

  公开号：US20090093497A1

  公开（公告）日：2009-04-09

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

  本文提供的是公式(I)的化合物，以及其药物可接受的盐，其中取代基如规范中所述。这些化合物和含有它们的药物组合物对于治疗疾病，例如肥胖症、2型糖尿病和代谢综合征是有用的。