(2S,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol | 104882-44-2

• 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,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol
• 英文别名: 2(S)-t-Butyloxycarbonylamino-l-cyclohexyl-3(S)-hydroxyhex-5-ene；tert-butyl N-[(2S,3S)-1-cyclohexyl-3-hydroxyhex-5-en-2-yl]carbamate
• CAS: 104882-44-2
• 化学式: C₁₇H₃₁NO₃
• 分子量: 297.438
• InChiKey: BOSZWHSOZHZBFM-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol 在 sodium tetrahydroborate 、 二甲基硫 、 potassium tert-butylate 、 对甲苯磺酸 、 臭氧 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 23.5h， 生成 (4S,5S)-3-tert-butoxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5-vinyloxazolidine
  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
• 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 、 3-溴丙烯 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以38%的产率得到(2S,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol
  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

• Peptidylaminodiols
  申请人：Abbott Laboratories

  公开号：US05214129A1

  公开（公告）日：1993-05-25

  A renin inhibiting compound of the formula: ##STR1## wherein A is a substituent; W is C.dbd.O or CHOH; U is CH.sub.2 or NR.sub.2, provided that when W is CHOH then U is CH.sub.2 ; R.sub.1 is loweralkyl, cycloalkylmethyl, benzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)methyl, .alpha.,.alpha.-dimethylbenzyl, 1-benzyloxyethyl, phenethyl, phenoxy, thiophenoxy or anilino; R.sub.2 is hydrogen or loweralkyl; R.sub.3 is loweralkyl, [(alkoxy)alkoxy]alkyl, (thioalkoxy)alkyl, loweralkenyl, benzyl or heterocyclic ring substituted methyl; R.sub.4 is loweralkyl, cycloalkylmethyl or benzyl; R.sub.5 is vinyl, formyl, hydroxymethyl or hydrogen; R.sub.7 is hydrogen or loweralkyl; R.sub.8 and R.sub.9 are independently selected from OH and NH.sub.2 ; and R.sub.6 is hydrogen, loweralkyl, vinyl or arylalkyl; provided that when R.sub.5 and R.sub.7 are both hydrogen and R.sub.8 and R.sub.9 are OH, the carbon bearing R.sub.5 is of the "R" configuration and the carbon bearing R.sub.6 is of the "S" configuration; or pharmaceutically acceptable salts or esters thereof. Also disclosed are renin inhibiting compositions, a method of treating hypertension, methods of making the renin inhibiting compounds and intermediates useful in making the renin inhibiting compounds.

  一种公式为：##STR1## 的抑制肾素化合物，其中A是取代基；W是C.dbd.O或CHOH；U是CH.sub.2或NR.sub.2，但当W是CHOH时，则U是CH.sub.2；R.sub.1是低碳基、环烷基甲基、苄基、4-甲氧基苄基、卤代苄基、(1-萘基)甲基、(2-萘基)甲基、(4-咪唑基)甲基、α，α-二甲基苄基、1-苄氧基乙基、苯乙基、苯氧基、噻吩氧基或苯胺基；R.sub.2是氢或低碳基；R.sub.3是低碳基、[(烷氧基)烷氧基]烷基、(硫代烷氧基)烷基、低碳烯基、苄基或杂环环上取代的甲基；R.sub.4是低碳基、环烷基甲基或苄基；R.sub.5是乙烯基、甲酰基、羟甲基或氢；R.sub.7是氢或低碳基；R.sub.8和R.sub.9分别选自OH和NH.sub.2；R.sub.6是氢、低碳基、乙烯基或芳基烷基；但当R.sub.5和R.sub.7均为氢且R.sub.8和R.sub.9为OH时，承载R.sub.5的碳处于“R”构型，承载R.sub.6的碳处于“S”构型；或其药学上可接受的盐或酯。还公开了抑制肾素的组合物、治疗高血压的方法、制备抑制肾素化合物和制备抑制肾素化合物有用的中间体的方法。
• PEPTIDYLAMINODIOLS
  申请人：ABBOTT LABORATORIES

  公开号：EP0295294A1

  公开（公告）日：1988-12-21
• EP0295294A4
  申请人：——

  公开号：EP0295294A4

  公开（公告）日：1990-04-10
• US4845079A
  申请人：——

  公开号：US4845079A

  公开（公告）日：1989-07-04
• US5032577A
  申请人：——

  公开号：US5032577A

  公开（公告）日：1991-07-16