ethyl 3-butyl-4,5-dihydro-5-oxo-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-1H-1,2,4-triazole-1-acetate | 139476-25-8

• 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: ethyl 3-butyl-4,5-dihydro-5-oxo-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-1H-1,2,4-triazole-1-acetate
• 英文别名: ethyl 2-[3-butyl-5-oxo-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,2,4-triazol-1-yl]acetate
• CAS: 139476-25-8
• 化学式: C₂₄H₂₇N₇O₃
• 分子量: 461.523
• InChiKey: OAFUQLPTEOVNTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-butyl-4,5-dihydro-5-oxo-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-1H-1,2,4-triazole-1-acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以94%的产率得到3-butyl-4,5-dihydro-5-oxo-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-1H-1,2,4-triazole-1-acetic acid
  参考文献：
  名称：

  Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists

  摘要：

  2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4'-yl]methyl] -3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.

  DOI：

  10.1021/jm00067a015
• 作为产物：
  描述：

  厄贝沙坦杂质19 在 palladium on activated charcoal 吡啶 、 trimethyltin azide 、 potassium tert-butylate 、 氢气 、 sodium methylate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 212.0h， 生成 ethyl 3-butyl-4,5-dihydro-5-oxo-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-1H-1,2,4-triazole-1-acetate
  参考文献：
  名称：

  Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists

  摘要：

  2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4'-yl]methyl] -3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.

  DOI：

  10.1021/jm00067a015

文献信息

• [EN] N-SUBSTITUTED-1,2,4-TRIAZOLONE COMPOUNDS FOR TREATMENT OF CARDIOVASCULAR DISORDERS
  申请人：G.D. SEARLE & CO.

  公开号：WO1991018888A1

  公开（公告）日：1991-12-12

  (EN) A class of N-substituted-1,2,4-triazolone compounds is described for use in treatment of cardiovascular disorders. Compounds of particular interest are angiotensin II antagonists of formula (I), wherein R1 is selected from 2-oxo-2-(tricyclo[3.3.1.1.3.7]dec-2-yl)ethyl, 3-phenylpropyl, 2-oxo-2-phenylethyl, 2-hyroxy-2-phenylethyl, 1,1-dimethylethyloxycarbonylmethyl, hexyl, ethoxycarbonylmethyl, carboxymethyl, 1-naphthalenylmethyl, 2-cyclohexylethyl, pentyl, ethoxycarbonylmethoxyethyl substituted with phenyl, carboxymethoxyethyl substituted with phenyl, 3,5,5-trimethylhexyl, (2-phenylmethoxy)-1-(phenylmethyl)-E-ethenyl, 1-benzoyl-2-phenylethyl, 1-oxobutyl, 2-(2,5-dimethyoxyphenyl)-2-oxoethyl, 2-phenyl-2-(phenylmethoxyethyl, 2-(2,5-dimethioxy-phenyl)-2-hydroxyethyl, 2-naphthalenylmethyl, methoxycarbonyl-butyl, ethoxycarbonylethyl substituted with benzoyl, 1-benzyoyl-1-methylethyl, 1-pentanoic acid, cyclopropylmethyl, 3-phenyl-2E-propenyl and 3-acetonitrile; wherein R2 is selected from ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, 4-methylbutyl, tert-butyl, n-pentyl, neopentyl, 1-cyanobutyl, propylthio and butylthio; wherein each of R3 through R11 is hydrido with the proviso that at least one of R5 and R9 must be selected from COOH, SH, PO3H2, SO3H, CONHNH2, CONHNHSO2CF3, OH, (a), (b) and (c), wherein each of R42 and R43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.(FR) L'invention concerne une classe de composés de 1,2,4-triazolones à substitution N utilisés dans le traitement de troubles cardiovasculaires. Les composés présentant un intérêt particulier sont des antagonistes d'angiotensine II de la formule (I), dans laquelle R1 est choisi parmi 2-oxo-2-(tricyclo[3.3.1.1.3.7]dec-2-yl)ethyl, 3-phénylpropyle, 2-oxo-2-phényléthyle, 2-hydroxy-2-phényléthyle, 1,1-diméthyléthyloxycarbonylméthyle, hexyle, éthoxycarbonylméthyle, carboxyméthyle, 1-naphtalènylméthyle, 2-cyclohexyléthyle, pentyl, éthoxycarbonyleméthoxyéthyle remplacés par phényle, carboxyméthoxyéthyle remplacés par phényle, 3,5,5-triméthylhexyle, (2-phénylméthoxy)-1-(phénylméthyle)-E-éthènyle, 1-benzoyl-2-phényléthyle, 1-oxobutyl, 2-(2,5-diméthyoxyphényle)-2-oxoéthyle, 2-phényle-2-(phénylméthoxy)éthyle, 2-(2,5-diméthyoxy-phényle)-2-hydroxyéthyle, 2-naphtalènylméthyle, méthoxycarbonyle-butyl, éthoxycarbonyléthyle remplacés par benzoyle, 1-benzyoyle-1-méthyléthyle, acide-1-pentanoïque, cyclopropylméthyle, 3-phényle-2E-propényle et 3-acétonitryle; dans laquelle R2 est choisi entre éthyle, n-propyle, isopropyle, n-butyle, sec-butyle, isobutyle, 4-méthylbutyle, tert-butyle, n-pentyle, néopentyle, 1-cyanobutyle, propylthio et butylthio; dans laquelle R3 à R11 représentent chacun hydrido à condition qu'au moins un des éléments R5 et R9 soient choisis parmi COOH, SH, PO3H2, SO3H, CONHNH2, CONHNHSO2CF3, OH, (a), (b) et (c), dans lesquels R42 et R43 sont choisis indépendamment entre chloro, cyano, nitro, trifluorométhyle, méthoxycarbonyle et trifluorométhylsulfonyle. Ces composés sont particulièrement utiles dans le traitement ou la régulation de l'hypertension et de l'insuffisance cardiaque.

  以下是一段英文文本的中文翻译： 有一类N-取代的1,2,4-三嗪化合物被描述用于治疗心血管疾病。其中特别感兴趣的化合物是抗angiotensin II型的，其分子式为(I)，其中R1选自以下物质： - 2-oxo-2-(tricyclo[3.3.1.1.3.7]dec-2-yl)ethyl， - 3-phenylpropyl， - 2-oxo-2-phenylethyl， - 2-hydroxy-2-phenylethyl， - 1,1-dimethylethyloxycarbonylmethyl， - hexyl， - ethoxycarbonylmethyl， - carboxymethyl， - 1-naphthalenylmethyl， - 2-cyclohexylethyl， - pentyl， - ethoxycarbonylmethoxyethyl（其中被取代为含苯基）， - 2-phenyl，替换成phényle， - 2-(2,5-dimethoxyphenyl)-2-oxoethyl， - 2-phenyl-2-(phenylmethoxy)， - 2-phenyl-2-hydroxyethyl， - 2-naphthalenylmethyl， - methoxycarbonyl-butyl， - ethoxycarbonylide，其中被取代为带有苯基的， - 1-benzoyl-1-methylethyl， - 1-pentanoic acid， - cyclopropylmethyl， - 3-phenyl-2E-propenyl， - 3-acetanilide。 在其中，R2选自： - ethyl， - n-propyl， - isopropyl， - n-butyl， - sec-butyl， - isobutyl， - 4-methylbutyl， - tert-butyl， - n-pentyl， - neopentyl， - 1-cyanobutyl， - propylthio， - butylthio。 在R3至R11中，每个基团被称作hydrido。在括号中给出的条件下，至少一个R5和R9必须选自COOH，SH，PO3H2，SO3H，CONHNH2，CONHNHSO2CF3，OH，(a)，(b)，(c)。 在R42和R43在独立选自： - chloro， - cyano， - nitro， - trifluoromethyl， - methoxycarbonyl， - trifluoromethylsulfonyl。 这些化合物在治疗或控制高血压和心力衰竭方面特别有用。
• N-SUBSTITUTED-1,2,4-TRIAZOLONE COMPOUNDS FOR TREATMENT OF CARDIOVASCULAR DISORDERS
  申请人：G.D. SEARLE & CO.

  公开号：EP0531382A1

  公开（公告）日：1993-03-17
• Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists
  作者：Horng Chih Huang、David B. Reitz、Timothy S. Chamberlain、Gillian M. Olins、Valerie M. Corpus、Ellen G. McMahon、Maria A. Palomo、John P. Koepke、Glenn J. Smits

  DOI：10.1021/jm00067a015

  日期：1993.7

  2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4'-yl]methyl] -3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.