(3R)-3-hydroxy-(4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentanoic acid ethyl ester | 98105-44-3

• 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: (3R)-3-hydroxy-(4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentanoic acid ethyl ester
• 英文别名: ethyl (3R,4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexyl-3-hydroxypentanoate；N-Boc-(3R,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid ethyl ester；ethyl (3R,4S)-4-[(tert-butyloxycarbonyl)amino]-5-cyclohexyl-3-hydroxypentanoate；ethyl (3R,4S)-5-cyclohexyl-3-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 98105-44-3
• 化学式: C₁₈H₃₃NO₅
• 分子量: 343.464
• InChiKey: WDSXRCWSAYWNFK-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.16
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  L-环己基丙氨酸 在 sodium hydroxide 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 59.5h， 生成 (3R)-3-hydroxy-(4S)-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentanoic acid ethyl ester
  参考文献：
  名称：

  A short and efficient synthesis of (3S,4S)-4-[(tert-Butyloxycarbonyl)amino]-5-cyclohexyl-3-hydroxypentanoic acid ethyl ester

  摘要：

  DOI：

  10.1021/jo00239a036

文献信息

• Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analog inhibitors containing a novel analog of statine
  作者：Joshua Boger、Linda S. Payne、Debra S. Perlow、Nancy S. Lohr、Martin Poe、Edward H. Blaine、Edgar H. Ulm、Terry W. Schorn、Bruce I. LaMont

  DOI：10.1021/jm00150a007

  日期：1985.12

  Analogues of the renin octapeptide substrate were synthesized in which replacement of the scissile dipeptide with (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta) transformed the substrate sequence into potent, transition-state analogue, competitive inhibitors of renin. Synthesis and incorporation of the cyclohexylalanyl analogue of Sta, (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic

  合成了肾素八肽底物的类似物，其中用（3S，4S）-4-氨基-3-羟基-6-甲基庚酸（statine，Sta）取代易裂二肽将底物序列转变为有效的过渡态类似物，肾素的竞争性抑制剂。Sta的环己基丙氨酰基类似物（3S，4S）-4-氨基-5-环己基-3-羟基戊酸（ACHPA）的合成和掺入提供了迄今为止报道的最有效的肾素抑制剂，包括N-异戊基-L-组氨酸-L-脯氨酰基-L-苯丙氨酰基-L-组氨酸-ACHPA-L-亮氨酰-L-苯丙氨酰胺[Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2,3]，肾素抑制Ki = 1.6 X 10（-10）M（人肾素），IC50 = 1.7 X 10（-10）M（人血浆肾素），IC50 = 1.9 X 10（-9）M（犬血浆肾素）和IC50 = 2.1 X 10（-8）M（大鼠血浆肾素）。含有ACHPA的这种抑制剂3，与人肾素的效价比含Sta的抑
• 1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives
  作者：David A. Roberts、Robert H. Bradbury、David Brown、Alan Faull、David Griffiths、John S. Major、Alec A. Oldham、Robert J. Pearce、Arnold H. Ratcliffe

  DOI：10.1021/jm00171a005

  日期：1990.9

  A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.
• ROBERTS, DAVID A.;BRADBURY, ROBERT H.;BROWN, DAVID;FAULL, ALAN;GRIFFITHS,+, J. MED. CHEM., 33,(1990) N, C. 2326-2334
  作者：ROBERTS, DAVID A.、BRADBURY, ROBERT H.、BROWN, DAVID、FAULL, ALAN、GRIFFITHS,+

  DOI：——

  日期：——
• BREIPOHL, GERHARD;KNOLLE, JOCHEN;WEGMANN, HELMUT;RUPPERT, DIETER
  作者：BREIPOHL, GERHARD、KNOLLE, JOCHEN、WEGMANN, HELMUT、RUPPERT, DIETER

  DOI：——

  日期：——
• SCHUDA, PAUL FRANCIS;GREENLEE, WILLIAM J.;CHAKRAVARTY, P. K.;ESKOLA, PHIL+, J. ORG. CHEM., 53,(1988) N 4, 873-875
  作者：SCHUDA, PAUL FRANCIS、GREENLEE, WILLIAM J.、CHAKRAVARTY, P. K.、ESKOLA, PHIL+

  DOI：——

  日期：——