2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one | 165951-91-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one
• 英文别名: 2-propyl-4,5,6,7-tetrahydro-8-oxo-cycloheptimidazole；2-Propyl-4,5,6,7-tetrahydrocycloheptimidazole-8-one；2-propyl-5,6,7,8-tetrahydro-1H-cyclohepta[d]imidazol-4-one
• CAS: 165951-91-7
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: DCHAIIGOSFZNGS-UHFFFAOYSA-N

物化性质

• 熔点：
  76-77 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  421.9±14.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3,4-Dimethyl-5-isoxazolyl)-4'-[(1,4,5,6,7,8-hexahydro-8-oxo-2-propyl-1-cycloheptimidazolyl)methyl]-2'-(hydroxymethyl)[1,1'-biphenyl]-2-sulfonamide
  参考文献：
  名称：

  Discovery of 4′-[(Imidazol-1-yl)methyl]biphenyl-2-sulfonamides as dual endothelin/Angiotensin II receptor antagonists

  摘要：

  A series of 4'-[(imidazol-1-yl)methyl]biphenylsulfonamides has potent antagonist activity against both angiotensin II AT(1) and endothelin ETA receptors. Such dual-acting antagonists could have utility in the treatment of hypertension, heart failure, and other cardiovascular diseases in a broad patient population. Certain compounds in the present series are orally active in a rat model of angiotensin II-mediated hypertension. (C) 2603 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00018-0
• 作为产物：
  描述：

  2-propyl-3H-cycloheptimidazol-4-one 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 55.0 ℃ 、101.32 kPa 条件下， 反应 24.0h， 以99%的产率得到2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one
  参考文献：
  名称：

  Effective Preparation of Cycloheptimidazol-4-one Compounds

  摘要：

  开发了环庚基咪唑-4-酮的有效制备方法。在简单的条件下，如 35 °C 下甲苯中的 NaOH 溶液，将 2-tosyloxytropone（5）与酰胺（6）反应，可得到相应的环庚基咪唑-4-酮（3），但收率较低。然而，在该反应体系中加入四正丁基溴化铵（n-Bu4NBr）后，收率显著提高。对反应条件进行了详细的筛选。

  DOI：

  10.1248/cpb.54.703
• 作为试剂：
  描述：

  2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one 、 2-氰基-4'-溴甲基联苯 在 2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one 作用下， 以70.0的产率得到4'-((8-oxo-2-propyl-5,6,7,8-tetrahydrocyclohepta[d]imidazol-1(4H)-yl)methyl)-[1,1'-biphenyl]-2-carbonitrile
  参考文献：
  名称：

  J. Label. Compd. Radiopharm. 1995, 36, 915-919

  摘要：

  DOI：

文献信息

• Regioselective Alkylation of 2-Alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-ones and 2-Alkyl-3H-cycloheptimidazol-4-ones
  作者：Motoharu Sonegawa、Masayuki Yokota、Hiroshi Tomiyama、Tsuyoshi Tomiyama

  DOI：10.1248/cpb.54.706

  日期：——

  Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2′-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2′-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu4NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.

  研究了2-烷基-5,6,7,8-四氢-3H-环庚咪唑-4-酮（1）和2-烷基-3H-环庚咪唑-4-酮（2）的区域选择性烷基化反应。在DMF或THF中使用NaH的条件下，优先得到3-[2′-(1-叔丁基-1H-四唑-5-基)联苯-4-基甲基]-2-丙基-5,6,7,8-四氢-1H-环庚咪唑-4-酮（6）。另一方面，在甲苯中使用水合氢氧化钠作为碱和n-Bu4NBr存在下，选择性得到3-[2′-(1-叔丁基-1H-四唑-5-基)联苯-4-基甲基]-2-丙基-5,6,7,8-四氢-3H-环庚咪唑-4-酮（5），即普拉托沙坦的合成中间体化合物。在这项反应中，发现碱性溶液的浓度影响其区域选择性。这种选择性甚至在醛和酯衍生物中也观察到。
• Synthesis of [14C]KT3-671, 2-Propyl-8-oxo-1-[ (2′-(1H-[14C] tetrazole-5-yl) biphenyl-4-yl) methyl]-4,5,6, 7-tetrahydro-cycloheptimidazole, a novel potent nonpeptide angiotensin II receptor antagonist
  作者：Naoto Ueyama、Takashi Yanagisawa、Tsuyoshi Tomiyama

  DOI：10.1002/jlcr.2580361002

  日期：1995.10

  2-Propyl-8-oxo-1-[(2′-(1H-tetrazole-5-yl) biphenyl-4-yl)methyl]-4, 5, 6, 7-tetrahydrocyclohept imidazole (KT3-671), which has been found to be a potent and selective angiotesin II receptor antagonist, was synthesized in 14C-labelled form by using potassium[14C]-cyanide. [14C](KT3-671) 9 with a specific activity of 1.74GBq/mmol was prepared in four steps in 29.8% overall radio-chemical yield from potassium[14C]-cyanide.

  2-丙基-8-氧-1-[(2′-(1H-四氮唑-5-基)联苯-4-基)甲基]-4, 5, 6, 7-四氢环庚咪唑（KT3-671），已被发现是一种强效且选择性的血管紧张素II受体拮抗剂，通过使用氰化钾[14C]合成了14C标记形式。特异活度为1.74GBq/mmol的[14C](KT3-671)在四个步骤中制备而成，总放射化学收率为29.8%，来源于氰化钾[14C]。
• Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists
  申请人：——

  公开号：US20020143024A1

  公开（公告）日：2002-10-03

  Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

  声称结合了血管紧张素和内皮素受体拮抗剂的新型联苯磺酰胺化合物，以及使用这种化合物治疗高血压和其他疾病的方法，以及含有这种化合物的药物组合物。
• [EN] BIPHENYL SULFONAMIDES AS DUAL ANGIOTENSIN ENDOTHELIN RECEPTOR ANTAGONISTS<br/>[FR] BIPHENYL SULFONAMIDES EN TANT QUE DOUBLES ANTAGONISTES DE RECEPTEURS D'ANGIOTENSINE ET D'ENDOTHELINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2000001389A1

  公开（公告）日：2000-01-13

  Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

  本发明涉及一种新型的联合血管紧张素和内皮素受体拮抗剂的双苯基磺酰胺类化合物，以及使用这些化合物治疗高血压和其他疾病的方法，以及含有这些化合物的制药组合物。
• [EN] BIPHENYL SULFONAMIDES AS DUAL ANGIOTENSIN ENDOTHELIN RECEPTOR ANTAGONISTS<br/>[FR] BIPHENYL SULFONAMIDES UTILISES COMME DOUBLES ANTAGONISTES DES RECEPTEURS DE L'ANGIOTENSINE ET DE L'ENDOTHELINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2001044239A2

  公开（公告）日：2001-06-21

  Novel biphenyl sulfonamide compounds which are combined angiotensin and endothelin receptor antagonists are claimed along with methods of using such compounds in the treatment of conditions such as hypertension and other diseases, as well as pharmaceutical compositions containing such compounds.

  本专利申请涉及一种新型的联合血管紧张素和内皮素受体拮抗剂的新型二苯基磺酰胺化合物，以及使用这些化合物治疗高血压和其他疾病的方法，同时还包括含有这些化合物的制药组合物。