2-Butyl-5-chloro-3-{4-[2-(2H-tetrazol-5-yl)-cyclohex-1-enyl]-benzyl}-3H-imidazole-4-carboxylic acid | 141754-26-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-Butyl-5-chloro-3-{4-[2-(2H-tetrazol-5-yl)-cyclohex-1-enyl]-benzyl}-3H-imidazole-4-carboxylic acid
• 英文别名: 2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)cyclohexen-1-yl]phenyl]methyl]imidazole-4-carboxylic acid
• CAS: 141754-26-9
• 化学式: C₂₂H₂₅ClN₆O₂
• 分子量: 440.933
• InChiKey: PAINEOUGVXNDCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  trifluoromethanesulfonic acid 2-cyano-1-cyclohexen-1-yl ester 在 盐酸 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 sodium dihydrogenphosphate 、 四(三苯基膦)钯 、 三正丁基叠氮化锡 、 四溴化碳 、 sodium perchlorate 、 四丁基氟化铵 、 sodium hydride 、 三苯基膦 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 乙腈 、 叔丁醇 为溶剂， 反应 65.17h， 生成 2-Butyl-5-chloro-3-{4-[2-(2H-tetrazol-5-yl)-cyclohex-1-enyl]-benzyl}-3H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Nonpeptide angiotensin II receptor antagonists: synthetic and computational chemistry of N-[[4-[2-(2H-tetrazol-5-yl)-1-cycloalken-1-yl]phenyl]methyl]imidazole derivatives and their in vitro activity

  摘要：

  A series of nonpeptide angiotensin II receptor antagonists was synthesized and tested in vitro to investigate requirements for recognition by and binding to AT1 receptors. Compared to a known series of N-(biphenylylmethyl)imidazoles, including losartan (DuP 753), which has a more rigid conformation in the 2-tetrazolylbiphenyl moiety, the new series replaces the terminal phenyl with cycloalkenyls. Compounds were made with five- to seven-membered rings and with either a hydroxymethyl (3) or carboxyl (4) group at the 5 position on the imidazole ring. The effects of the lipophilicity and steric bulk of the terminal ring system, the amount of pi-electron density in the terminal ring, and the relative spatial proximity of the tetrazolyl and the middle phenyl are explored in terms of binding affinity to AT1 receptors in rat adrenal glomerulosa and rabbit aorta. The physicochemical variables of the new compounds were quantitated by computational chemistry and compared to those of losartan and its carboxyl metabolite. Potency at the AT1 receptors is maximized when the terminal ring is six-membered; an aromatic ring binds better than a cycloalkenyl ring. The 5-carboxyimidazole compounds show higher affinity than the 5-hydroxymethyl series.

  DOI：

  10.1021/jm00092a017

文献信息

• Nonpeptide angiotensin II receptor antagonists: synthetic and computational chemistry of N-[[4-[2-(2H-tetrazol-5-yl)-1-cycloalken-1-yl]phenyl]methyl]imidazole derivatives and their in vitro activity
  作者：Ho Shen Lin、Ashraff A. Rampersaud、Karen Zimmerman、Mitchell I. Steinberg、Donald B. Boyd

  DOI：10.1021/jm00092a017

  日期：1992.7

  A series of nonpeptide angiotensin II receptor antagonists was synthesized and tested in vitro to investigate requirements for recognition by and binding to AT1 receptors. Compared to a known series of N-(biphenylylmethyl)imidazoles, including losartan (DuP 753), which has a more rigid conformation in the 2-tetrazolylbiphenyl moiety, the new series replaces the terminal phenyl with cycloalkenyls. Compounds were made with five- to seven-membered rings and with either a hydroxymethyl (3) or carboxyl (4) group at the 5 position on the imidazole ring. The effects of the lipophilicity and steric bulk of the terminal ring system, the amount of pi-electron density in the terminal ring, and the relative spatial proximity of the tetrazolyl and the middle phenyl are explored in terms of binding affinity to AT1 receptors in rat adrenal glomerulosa and rabbit aorta. The physicochemical variables of the new compounds were quantitated by computational chemistry and compared to those of losartan and its carboxyl metabolite. Potency at the AT1 receptors is maximized when the terminal ring is six-membered; an aromatic ring binds better than a cycloalkenyl ring. The 5-carboxyimidazole compounds show higher affinity than the 5-hydroxymethyl series.