1-哌啶羧酸,4-[[(1,1-二甲基乙氧基)羰基]氨基]-,1-羧基-2-苯基乙基酯,(S)- | 135632-33-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: 1-哌啶羧酸,4-[[(1,1-二甲基乙氧基)羰基]氨基]-,1-羧基-2-苯基乙基酯,(S)-
• 英文名称: (2S)-2-<<<4-<(tert-butyloxycarbonyl)amino>-1-piperidyl>carbonyl>oxy>-3-phenylpropionic acid
• 英文别名: 2-<<<(4-Boc-amino)piperidino>carbonyl>oxy>-3-phenylpropanoic acid；2(S)-[4-(tert.-Butyloxycarbonyl)amino-1-piperidinylcarbonyloxy]-3-phenyl-propionic acid；(2S)-2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carbonyl]oxy-3-phenylpropanoic acid
• CAS: 135632-33-6
• 化学式: C₂₀H₂₈N₂O₆
• 分子量: 392.452
• InChiKey: DXQQQWZYYRNXHJ-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-哌啶羧酸,4-[[(1,1-二甲基乙氧基)羰基]氨基]-,1-羧基-2-苯基乙基酯,(S)- 、 在 N-甲基吗啉 、 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 N,N-二甲基甲酰胺 为溶剂， 生成 [(2S)-1-[[(2S)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-pyridin-2-ylsulfanylpentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl] 4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate
  参考文献：
  名称：

  Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'

  摘要：

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00097a010

文献信息

• Renin inhibitors containing a pyridyl amino diol derived C-terminus
  作者：Holger Heitsch、Rainer Henning、Heinz Werner Kleemann、Wolfgang Linz、Wolf Ulrich Nickel、Dieter Ruppert、Hansjoerg Urbach、Adalbert Wagner

  DOI：10.1021/jm00071a009

  日期：1993.9

  the concept of transition-state analogs, a series of nonpeptide renin inhibitors with the new (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-(2-pyridyl)hexane moiety at the C-terminal functionality were synthesized and evaluated for inhibition of renin both in vitro and in vivo. All compounds exhibited potencies in the nanomolar or even subnanomolar range when tested versus human renin in vitro. Selected

  基于过渡态类似物的概念，一系列具有新的（2S，3R，4S）-2-氨基-1-环己基-3,4-二羟基-6-（2-吡啶基）己烷部分的非肽肾素抑制剂合成了在C-末端的C末端功能，并在体外和体内评估了对肾素的抑制。当与人肾素进行体外测试时，所有化合物均显示出纳摩尔或什至亚纳摩尔范围的效力。在麻醉的，钠缺乏的恒河猴中评估选定的抑制剂，并在十二指肠内给予2 mg / kg的剂量后，平均动脉血压（MAP）明显降低。含有氨基哌啶基琥珀酸衍生的N端的化合物38（S 2864）是该系列中最有希望的成员。38种抑制人肾素的IC50为0.38 nM，不影响其他人天冬氨酸蛋白酶，
• Renin-hemmende Aminooligohydroxy-Derivate
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0410278A1

  公开（公告）日：1991-01-30

  Die vorliegende Erfindung betrifft Verbindungen der Formel I in welcher A, R², R³, R⁴ und n wie in der Beschreibung angegeben definiert sind, Verfahren zu ihrer Herstellung, ihre Verwendung als Heilmittel und diese enthaltende pharmazeutische Mittel.

  本发明涉及式 I 的化合物 其中 A、R²、R³、R⁴ 和 n 如描述中所定义、 其制备工艺、作为治疗剂的用途以及含有它们的药物组合物。
• Aminosäurederivate mit reninhemmenden Eigenschaften, Verfahren zu deren Herstellung, diese enthaltende Mittel und deren Verwendung
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0417698A2

  公开（公告）日：1991-03-20

  1. Aminosäurederivate mit reninhemmenden Eigenschaften, Verfahren zu deren Herstellung, diese enthaltende Mittel und deren Verwendung Die Erfindung betrifft reninhemmende Aminosäurederivate der Formel in welcher R¹ für einen Rest eines substituierten stickstoffhaltigen Heterocyclus wie Piperidin steht, X CO, CS, SO₂ oder SO, Y CH₂, O oder S bedeuten, B für den Rest einer Aminosäure der Formel H-B-OH steht und R³, R⁴ und R⁵ wie in der Beschreibung definiert sind, Verfahren zu deren Herstellung, diese enthaltenden Mittel und deren Verwendung.

  1. 具有肾素抑制特性的氨基酸衍生物、其制备工艺、含有这些衍生物的制剂及其用途 本发明涉及式如下的具有肾素抑制作用的氨基酸衍生物 其中 R¹ 是取代的含氮杂环如哌啶的基团，X 是 CO、CS、SO₂ 或 SO，Y 是 CH₂、O 或 S，B 是式 H-B-OH 的氨基酸的基团，R³、R⁴ 和 R⁵ 如描述中所定义，还涉及其制备工艺、含有它们的制剂及其用途。
• US5374731A
  申请人：——

  公开号：US5374731A

  公开（公告）日：1994-12-20
• Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'
  作者：Peter Raddatz、Alfred Jonczyk、Klaus Otto Minck、Friedrich Rippmann、Christine Schittenhelm、Claus Jochen Schmitges

  DOI：10.1021/jm00097a010

  日期：1992.9

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.