(2S)-2-<<(2S)-2-<(2-hydroxy-2-methylpropyl)amino>-3-phenylpropionyl>amino>-4-methylpentanoic acid methyl ester | 137282-21-4

• 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)-2-<<(2S)-2-<(2-hydroxy-2-methylpropyl)amino>-3-phenylpropionyl>amino>-4-methylpentanoic acid methyl ester
• 英文别名: N-(2-hydroxy-2-methylpropyl)-L-phenylalanyl-L-leucine methyl ester；(2S)-2-({(2S)-2-[(2-hydroxy-2-methylpropyl)amino]-3-phenylpropionyl}amino)-4-methylpentanoic acid methyl ester；methyl (2S)-2-[[(2S)-2-[(2-hydroxy-2-methylpropyl)amino]-3-phenylpropanoyl]amino]-4-methylpentanoate
• CAS: 137282-21-4
• 化学式: C₂₀H₃₂N₂O₄
• 分子量: 364.485
• InChiKey: WBSJWQNXMXQAGQ-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-<<(2S)-2-<(2-hydroxy-2-methylpropyl)amino>-3-phenylpropionyl>amino>-4-methylpentanoic acid methyl ester 在 吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 (2S)-<<(2S)-2-(5,5-dimethyl-2-oxooxazolidin-3-yl)-3-phenylpropionyl>amino>-4-methylpentanoic acid
  参考文献：
  名称：

  New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin

  摘要：

  Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.

  DOI：

  10.1021/jm00083a005
• 作为产物：
  描述：

  甲基环氧丙烷 、 L-phenylalanyl-L-leucine methyl ester 以 乙醇 、 二氯甲烷 为溶剂， 以95%的产率得到(2S)-2-<<(2S)-2-<(2-hydroxy-2-methylpropyl)amino>-3-phenylpropionyl>amino>-4-methylpentanoic acid methyl ester
  参考文献：
  名称：

  New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin

  摘要：

  Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.

  DOI：

  10.1021/jm00083a005

文献信息

• Renin inhibitors
  申请人：American Home Products Corporation

  公开号：US05023338A1

  公开（公告）日：1991-06-11

  A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alky, phenyl, benzyl or phenethyl; Y is --CH.sub.2 --, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.

  公式为：##STR1## 的化合物，其中A为##STR2##，其中X为.dbd.CH--或.dbd.N--; R.sup.2为氢、烷基、苯基、苄基或苯乙基；Y为--CH.sub.2 --、--NH--或--O--; Z为--H.sub.2或.dbd.O；B为His、Leu、Ile、Nva、Nle、Ala或Val；而R.sup.1为氢、烷基、苯基或苯基烷基；或其药学上可接受的盐是肾素抑制剂。
• Pyrrolimidazolones useful as renin inhibitors
  申请人：American Home Products Corporation

  公开号：US05075451A1

  公开（公告）日：1991-12-24

  A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alkyl, phenyl, benzyl or phenethyl; Y is --CH.sub.2 --, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.

  化合物的公式为：##STR1## 其中A是##STR2##，其中X是.dbd.CH-或.dbd.N-; R.sup.2是氢、烷基、苯基、苄基或苯乙基; Y是--CH.sub.2--、--NH--或--O--; Z是--H.sub.2或.dbd.O; B是His、Leu、Ile、Nva、Nle、Ala或Val; R.sup.1是氢、烷基、苯基或苯基烷基; 或其药学上可接受的盐是肾素抑制剂。
• US5023338A
  申请人：——

  公开号：US5023338A

  公开（公告）日：1991-06-11
• US5095119A
  申请人：——

  公开号：US5095119A

  公开（公告）日：1992-03-10
• US5064965A
  申请人：——

  公开号：US5064965A

  公开（公告）日：1991-11-12