(3S,5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one | 124032-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3S,5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one
• 英文别名: (3S, 5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one；tert-butyl N-[(1S)-2-cyclohexyl-1-[(2S,4S)-5-oxo-4-propan-2-yloxolan-2-yl]ethyl]carbamate
• CAS: 124032-36-6
• 化学式: C₂₀H₃₅NO₄
• 分子量: 353.502
• InChiKey: ZDTJEMWDTSAFQU-ULQDDVLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one 在 Rh on carbon 氢气 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 80.0 ℃ 、405.3 kPa 条件下， 反应 48.0h， 生成
  参考文献：
  名称：

  Nonpeptide Renin Inhibitors with Good Intraduodenal Bioavailability and Efficacy in Dog

  摘要：

  The aim of this study was the discovery of nonpeptide renin inhibitors with much improved oral absorption, bioavailability, and efficacy, for use as antihypertensive agents. Our prior efforts led to the identification of A-74273 [1, R = 3-(4-morpholino)propyl], with a bioavailability of 26 +/- 10% [10 mg/kg intraduodenally (id), dog]. In vivo metabolism studies of A-74273 showed that the morpholino moiety underwent metabolic degradation. Computer modeling of A-74273 bound to renin indicated that the C-terminus was involved in a hydrogen-bonding network. New C-terminal groups were examined in two series of nonpeptides for effects on renin binding potency, lipophilicity (log P), and aqueous solubility. Those groups which possessed multiple hydrogen-bonding ability (3,5-diaminotriazole, cyanoguanidines, morpholino) provided particularly potent renin binding. Intraduodenal bioavailabilities of selected compounds, evaluated in rats, ferrets, and dogs, were higher for inhibitors with moderate solubility as well as moderate lipophilicity, in general. Although the absolute values varied substantially among species, the relative ordering of the inhibitors in terms of absorption and bioavailablity was reasonably consistent. Such well absorbed inhibitors (e.g. 41, 44, and 51) were demonstrated as highly efficacious hypotensive agents in the salt-depleted dog. We report here the discovery of a series of efficacious nonpeptide renin inhibitors based on the 3-azaglutaramide P-2-P-4 replacement, the best of which showed id bioavailabilities > 50% in dog.

  DOI：

  10.1021/jm00045a003
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-1-环己基-3-氧代-2-丙基]氨基甲酸酯 在 Rh/Al₂O₃ 盐酸 、 ruthenium trichloride 、 sodium periodate 、 lithium aluminium tetrahydride 、 正丁基锂 、 氢气 、 4-甲基苯磺酸吡啶 、 双(三甲基硅烷基)氨基钾 、 溶剂黄146 、 三乙胺 、 N,N'-羰基二咪唑 、 zinc dibromide 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醚 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (3S,5S)-5-[(1S)-1-(t-butoxycarbonyl)amino-2-cyclohexylethyl]-3-isopropyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  （2S，4S，5S）-5-氨基-6-环己基-4-羟基-2-异丙基己酸正丁基酰胺的羟乙烯二肽异戊烯的合成

  摘要：

  描述了由Boc-L-苯丙氨酸立体选择性地合成（2S，4S，5S）-5-氨基-6-环己基-4-羟基-2-异丙基己酸正丁基酰胺的羟基亚乙基二肽等排体。

  DOI：

  10.1016/s0040-4039(00)91634-4

文献信息

• Dipeptide isosteres. 2. Synthesis of hydroxyethylene dipeptide isostere diastereomers from a common γ-lactone intermediate. Preparation of renin and HIV-1 protease inhibitor transition state mimics.
  作者：William R. Baker、John K. Pratt

  DOI：10.1016/s0040-4020(01)81896-2

  日期：1993.1

  A general strategy for the synthesis of the hydroxyethylene dipeptide isostere diastereomers C or D has been developed. The syntheses proceeded through a common γ-lactone intermediate A or B. The C(3α) γ-lactone diastereomer A was prepared from the N-Cbz protected α-amino aldehyde and 2-(2-isopropylpropen-2-yl)trimethylsilane in five steps. The C(3β) γ-lactone diastereomer B was obtained by kinetic

  已经开发了合成羟乙烯二肽等排非对映异构体C或D的一般策略。合成过程通过常见的γ-内酯中间体A或B进行。由N-Cbz保护的α-氨基醛和2-（2-异丙基丙烯-2-基）三甲基硅烷分五个步骤制备C（3α）γ-内酯非对映异构体A。C（3β）γ-内酯非对映异构体B是通过使用丙二酸酯衍生物对内酯烯醇酯进行动态质子化而获得的。
• The synthesis of (2S,4S,5S) -5-(N-BOC)-amino-6-cyclohexyl-4-hydroxy-2-isopropyl-hexanoic acid lactone, an hydroxyethylene dipeptide isostere precusor
  作者：Prasun K. Chakravarty、Stephen E. de Laszlo、Carol S. Sarnella、James P. Sprinnger、Paul F. Schuda

  DOI：10.1016/s0040-4039(00)95215-8

  日期：1989.1

  A synthetic approach to the butyrolactones of (2SR,4SR)-5(S)-(N-Boc)-amino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanoic acid from (L)-phenylalanine and the preparation of the n-butyl amide of the 2(S),4(S),5(S) acid is presented.

  由（L）-苯丙氨酸合成（2SR，4SR）-5（S）-（N-Boc）-氨基-6-环己基-4-羟基-2-异丙基己酸的丁内酯的方法提出了2（S），4（S），5（S）酸的正丁基酰胺。
• Peptides having renin inhibitory activity, their preparation and use
  申请人：Sankyo Company, Limited

  公开号：US05378689A1

  公开（公告）日：1995-01-03

  Compounds of formula (I): ##STR1## [in which: R.sup.1 is heterocyclic group having 5 or 6 ring atoms, or --NR.sup.7 R.sup.8, where R.sup.7 is alkyl and R.sup.8 is optionally substituted phenyl, optionally substituted phenylalkyl or cycloalkyl; R.sup.2 is optionally substituted phenyl or naphthyl; R.sup.3 is thiazolyl; R.sup.4 is cyclohexyl or isopropyl; R.sup.5 is alkyl; and R.sup.6 is alkyl] and salts thereof have renin-inhibitory and, hence, hypotensive activities and are of value in the diagnosis and treatment of hypertension induced by failures in the renin-angiotensin system. They may be prepared by reacting together appropriate amino acids or derivatives thereof.

  化合物的化学式（I）：##STR1## [其中：R.sup.1是具有5个或6个环原子的杂环基团，或--NR.sup.7 R.sup.8，其中R.sup.7是烷基，R.sup.8是可选择取代的苯基，可选择取代的苯基烷基或环烷基；R.sup.2是可选择取代的苯基或萘基；R.sup.3是噻唑基；R.sup.4是环己基或异丙基；R.sup.5是烷基；R.sup.6是烷基]及其盐具有抑制肾素和因此降压活性，并且对于诊断和治疗由肾素-血管紧张素系统失调引起的高血压具有价值。它们可以通过将适当的氨基酸或其衍生物反应在一起制备。
• Nishi, Takahide; Kataoka, Mitsuru; Morisawa, Yasuhiro, Chemistry Letters, 1989, p. 1993 - 1996
  作者：Nishi, Takahide、Kataoka, Mitsuru、Morisawa, Yasuhiro

  DOI：——

  日期：——
• NISHI, TAKAHIDE;KATAOKA, MITSURU;MORISAWA, YASUHIRO, CHEM. LETT.,(1989) N1, C. 1993-1996
  作者：NISHI, TAKAHIDE、KATAOKA, MITSURU、MORISAWA, YASUHIRO

  DOI：——

  日期：——