5-n-Butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one | 133690-83-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-n-Butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one
• 英文别名: 5-butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one；2-(2-chlorophenyl)-5-Butyl-2,4-dihydro-3H-1,2,4-triazol-3-one；3H-1,2,4-Triazol-3-one, 5-butyl-2-(2-chlorophenyl)-2,4-dihydro-；5-butyl-2-(2-chlorophenyl)-4H-1,2,4-triazol-3-one
• CAS: 133690-83-2
• 化学式: C₁₂H₁₄ClN₃O
• 分子量: 251.716
• InChiKey: YHWXVDRLPUJGNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-n-Butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one 在 盐酸 、 sodium hydride 、 tin(ll) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 5-n-butyl-4-<4-<(2-carboxybenzoyl)amino>benzyl>-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Triazolinones as nonpeptide angiotensin II antagonists. 1. Synthesis and evaluation of potent 2,4,5-trisubstituted triazolinones

  摘要：

  A series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones was prepared via several synthetic routes and evaluated as AII receptor antagonists in vitro and in vivo. The preferred compounds contained a [2'-(5-tetrazolyl)biphenyl-4-yl]methyl side chain at N4 and an n-butyl group at C5. A number of these bearing an alkyl or aralkyl substituent at N2 showed in vitro potency in the nanomolar range (rabbit aorta membrane receptor), and several of these, e.g., the 2,2-dimethyl-1-propyl analogue (54, IC50 = 2.1 nM), effectively blocked the AII pressor response in conscious rats with significant duration (2.5 h at 1 mg/kg orally for 54). Among analogues possessing aryl substituents at N2, ortho substitution on the phenyl moiety resulted in several derivatives with in vitro potency in the low nanomolar range. One of these, featuring a 2-(trifluoromethyl)phenyl substituent at N2 (25, IC50 = 1.2 nM), was effective at 1 mg/kg orally in the rat model, with a duration of >6 h. Implications for hydrophobic and hydrogen-bonding interactions with the AT1 receptor are discussed.

  DOI：

  10.1021/jm00069a015
• 作为产物：
  描述：

  ethyl valerimidate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 5-n-Butyl-2-(2-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Triazolinones as nonpeptide angiotensin II antagonists. 1. Synthesis and evaluation of potent 2,4,5-trisubstituted triazolinones

  摘要：

  A series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones was prepared via several synthetic routes and evaluated as AII receptor antagonists in vitro and in vivo. The preferred compounds contained a [2'-(5-tetrazolyl)biphenyl-4-yl]methyl side chain at N4 and an n-butyl group at C5. A number of these bearing an alkyl or aralkyl substituent at N2 showed in vitro potency in the nanomolar range (rabbit aorta membrane receptor), and several of these, e.g., the 2,2-dimethyl-1-propyl analogue (54, IC50 = 2.1 nM), effectively blocked the AII pressor response in conscious rats with significant duration (2.5 h at 1 mg/kg orally for 54). Among analogues possessing aryl substituents at N2, ortho substitution on the phenyl moiety resulted in several derivatives with in vitro potency in the low nanomolar range. One of these, featuring a 2-(trifluoromethyl)phenyl substituent at N2 (25, IC50 = 1.2 nM), was effective at 1 mg/kg orally in the rat model, with a duration of >6 h. Implications for hydrophobic and hydrogen-bonding interactions with the AT1 receptor are discussed.

  DOI：

  10.1021/jm00069a015

文献信息

• Quinazolinone, triazolinone and pyrimidinone angiotensin II antagonists
  申请人：Merck & Co., Inc.

  公开号：US05264439A1

  公开（公告）日：1993-11-23

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

  通过一个亚甲基桥连接到新的取代苯基衍生物的取代杂环对式I的化合物可作为血管紧张素II拮抗剂。
• Substituted triazolinones, triazolinethiones, and triazolinimines as
  申请人：Merck & Co., Inc.

  公开号：US05411980A1

  公开（公告）日：1995-05-02

  There are disclosed new substituted triazolinone, triazolinethione, and triazolinimine compounds which are useful as angiotensin II antagonists. These compounds have the general formula: ##STR1## wherein G is R.sup.1 or ##STR2##

  已披露了新的取代三唑酮，三唑硫酮和三唑亚胺化合物，这些化合物可用作血管紧张素II拮抗剂。这些化合物具有一般式：##STR1## 其中G为R.sup.1或##STR2##
• Angiotensin II antagonists incorporating a substituted thiophene or furan
  申请人：Merck & Co., Inc.

  公开号：US05252574A1

  公开（公告）日：1993-10-12

  Substituted heterocycles attached through a methylene bridge to novel substituted phenyl thiophene or phenyl furan derivative of the Formula I are useful as angiotensin II antagonists. ##STR1##

  取代的杂环通过亚甲基桥与新颖的取代苯基噻吩或苯基呋喃衍生物的公式I连接，可用作血管紧张素II拮抗剂。
• Angiotensin II antagonists incorporating a substituted benzyl element
  申请人：Merck & Co., Inc.

  公开号：US05162325A1

  公开（公告）日：1992-11-10

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

  通过亚甲基桥连接到新的取代苯基衍生物的取代杂环对式I的化合物可用作血管紧张素II拮抗剂。
• Angiotensin II antagonists incorporating a substituted indole or
  申请人：Merck & Co., Inc.

  公开号：US05175164A1

  公开（公告）日：1992-12-29

  Substituted heterocycles attached through a methylene bridge to novel substituted indole or dihydroindole derivative of the Formula I are useful as angiotensin II antagonists. ##STR1##

  通过一个亚甲基桥连接到新的取代吲哚或二氢吲哚衍生物的取代杂环对抗剂，对抗II型血管紧张素有用。