2-butyl-4-chloro-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-1H-imidazole | 137582-52-6

• 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-4-chloro-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-1H-imidazole
• 英文别名: 2-butyl-4-chloro-5-[(t-butyldimethylsilyloxy)methyl]imidazole；2-butyl-5-t-butyldimethylsilyloxymethyl-4-chloroimidazole；2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazole；tert-butyl-[(2-butyl-4-chloro-1H-imidazol-5-yl)methoxy]-dimethylsilane
• CAS: 137582-52-6
• 化学式: C₁₄H₂₇ClN₂OSi
• 分子量: 302.92
• InChiKey: BDQGJUHISXBCPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-butyl-4-chloro-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-1H-imidazole 在 盐酸 、 manganese(IV) oxide 、 sodium dihydrogenphosphate 、 三正丁基叠氮化锡 、 sodium perchlorate 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 叔丁醇 为溶剂， 反应 26.67h， 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
• 作为产物：
  描述：

  2-丁基-4-氯-5-(羟甲基)咪唑 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以80%的产率得到2-butyl-4-chloro-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>-1H-imidazole
  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

• Imidazole angiotensin II antagonists incorporating a substituted benzyl
  申请人：Merck & Co., Inc.

  公开号：US05183810A1

  公开（公告）日：1993-02-02

  Substituted imidazoles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. ##STR1##

  通过甲基桥连接到新的取代苯基衍生物的咪唑醇，可用作血管紧张素II拮抗剂。
• Biphenyl oxadiazoles and thiadiazoles as angiothesin II antagonists
  申请人：Warner-Lambert Company

  公开号：US05210204A1

  公开（公告）日：1993-05-11

  Heterocyclic methyl derivatives of biphenyl oxadiazoles and thiadiazoles are described, as well as methods for the preparation of said derivatives and pharmaceutical compositions of the same, which are useful as antagonists of the angiotensin II enzyme and thus useful in treating hypertension, hyperaldosteronism, congestive heart failure, and glaucoma.

  本文描述了二苯并噁唑和噻唑的杂环甲基衍生物，以及制备这些衍生物的方法和药物组合物。这些衍生物可用作血管紧张素II酶拮抗剂，因此可用于治疗高血压、高醛固酮症、充血性心力衰竭和青光眼。
• Biphenyl oxadiazoles and thiadiazoles as angiotensin II antagonists
  申请人：Warner-Lambert Company

  公开号：US05338737A1

  公开（公告）日：1994-08-16

  Novel heterocyclic methyl derivatives of biphenyl oxadiazoles and thiadiazoles are described, as well as methods for the preparation of said derivatives and pharmaceutical compositions of the same, which are useful as antagonists of the angiotensin II enzyme and thus useful in treating hypertension, hyperaldosteronism, congestive heart failure, and glaucoma.

  本文介绍了新型的双苯氧噻二唑和噻二唑杂环甲基衍生物，以及制备这些衍生物的方法和制备药物组合物的方法。这些衍生物可用作血管紧张素II酶拮抗剂，因此可用于治疗高血压、高醛固酮症、充血性心力衰竭和青光眼。
• 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.