cis/trans-2-<<(4-methoxyphenyl)methyl>thio>-cyclopentanecarboxylic acid | 104190-32-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: cis/trans-2-<<(4-methoxyphenyl)methyl>thio>-cyclopentanecarboxylic acid
• 英文别名: 2-[[(4-methoxyphenyl)methyl]thio]cyclopentanecarboxylic acid；2-[(4-methoxyphenyl)methylsulfanyl]cyclopentane-1-carboxylic acid
• CAS: 104190-32-1
• 化学式: C₁₄H₁₈O₃S
• 分子量: 266.361
• InChiKey: ASYDMHSLNFHOHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cis/trans-2-<<(4-methoxyphenyl)methyl>thio>-cyclopentanecarboxylic acid 在 对甲酚 、 氰基磷酸二乙酯 、 氢氟酸 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (2S)-N-[(2S)-1-amino-1-oxopropan-2-yl]-1-(2-sulfanylcyclopentanecarbonyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Apstatin Analogue Inhibitors of Aminopeptidase P, a Bradykinin-Degrading Enzyme

  摘要：

  Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-alaninamide); IC50,human = 2.9 mu M In the rat, apstatin can potentiate the vasodilatory effect of bradykinin, reduce blood pressure in an aortic-coarctation model of hypertension, and reduce cardiac damage and arrhythmias induced by ischemia/reperfusion. In this study, we have determined structure-activity relationships for apstatin analogues as well as for other chemical classes of inhibitors using AP-P isozymes from different sources. The most potent inhibitor was one in which the N-terminal residue of apstatin was replaced with a (2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl residue (6, IC50,human = 0.2.9 mu M). The (2R,3S)-analogue of 6 was equipotent with 6 while the (2S,3S)- and (2R,3R)-analogues were considerably less potent. Apstatin analogues lacking the L-alanine or having hydroxyproline in place of the proline in the second position had reduced affinity. Certain thiol,carboxylalkyl-, and hydroxamate-containing compounds were inhibitory in the low micromolar range. Human cytosolic AP-P isozymes and Escherichia coli AP-P exhibited different inhibitor profiles than mammalian membrane-bound AP-P isozymes. The effects of the compounds on X-Pro dipeptidase (prolidase) and leucyl aminopeptidase are also presented.

  DOI：

  10.1021/jm9805642
• 作为产物：
  描述：

  1-环戊烯羧酸 、 4-甲氧基苄硫醇 以 哌啶 、 正己烷 、 环己烷 为溶剂， 生成 cis/trans-2-<<(4-methoxyphenyl)methyl>thio>-cyclopentanecarboxylic acid
  参考文献：
  名称：

  Mercaptocycloalkylcarbonyl and mercaptoarylcarbonyl dipeptides

  摘要：

  本发明揭示了化学式##STR1##的化合物，其中A是环烷基环，取代环烷基环，苯环或取代苯环，而##STR2##是各种二肽基团。这些化合物具有血管紧张素转换酶抑制活性，并且根据末端氨基酸的不同，可能还具有脑啡肽酶抑制活性。

  公开号：

  US04560506A1

文献信息

• US4560506A
  申请人：——

  公开号：US4560506A

  公开（公告）日：1985-12-24
• Apstatin Analogue Inhibitors of Aminopeptidase P, a Bradykinin-Degrading Enzyme
  作者：Linda L. Maggiora、Arthur T. Orawski、William H. Simmons

  DOI：10.1021/jm9805642

  日期：1999.7.1

  Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-alaninamide); IC50,human = 2.9 mu M In the rat, apstatin can potentiate the vasodilatory effect of bradykinin, reduce blood pressure in an aortic-coarctation model of hypertension, and reduce cardiac damage and arrhythmias induced by ischemia/reperfusion. In this study, we have determined structure-activity relationships for apstatin analogues as well as for other chemical classes of inhibitors using AP-P isozymes from different sources. The most potent inhibitor was one in which the N-terminal residue of apstatin was replaced with a (2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl residue (6, IC50,human = 0.2.9 mu M). The (2R,3S)-analogue of 6 was equipotent with 6 while the (2S,3S)- and (2R,3R)-analogues were considerably less potent. Apstatin analogues lacking the L-alanine or having hydroxyproline in place of the proline in the second position had reduced affinity. Certain thiol,carboxylalkyl-, and hydroxamate-containing compounds were inhibitory in the low micromolar range. Human cytosolic AP-P isozymes and Escherichia coli AP-P exhibited different inhibitor profiles than mammalian membrane-bound AP-P isozymes. The effects of the compounds on X-Pro dipeptidase (prolidase) and leucyl aminopeptidase are also presented.
• Mercaptocycloalkylcarbonyl and mercaptoarylcarbonyl dipeptides
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04560506A1

  公开（公告）日：1985-12-24

  Compounds of the formula ##STR1## wherein A is a cycloalkyl ring, a substituted cycloalkyl ring, a phenyl ring, or a substituted phenyl ring and ##STR2## are various dipeptide groups are disclosed. The compounds possess angiotensin converting enzyme inhibition activity and depending upon the terminal amino acid may also possess enkephalinase inhibition activity.

  本发明揭示了化学式##STR1##的化合物，其中A是环烷基环，取代环烷基环，苯环或取代苯环，而##STR2##是各种二肽基团。这些化合物具有血管紧张素转换酶抑制活性，并且根据末端氨基酸的不同，可能还具有脑啡肽酶抑制活性。