2-(5-amino-2-chlorophenyl)-4-<<2'-biphenyl-4-yl>methyl>-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one | 159544-66-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(5-amino-2-chlorophenyl)-4-<<2'-biphenyl-4-yl>methyl>-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one
• 英文别名: 2-(5-amino-2-chlorophenyl)-4-[[2'-[N-(t-butoxycarbonyl)sulfamoyl]biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one；2-(5-amino-2-chlorophenyl)-4-({2'-[N-(tert-butoxycarbonyl)sulfamoyl]biphenyl-4-yl}methyl)-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one；tert-butyl N-[2-[4-[[1-(5-amino-2-chlorophenyl)-3-butyl-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]phenyl]sulfonylcarbamate
• CAS: 159544-66-8
• 化学式: C₃₀H₃₄ClN₅O₅S
• 分子量: 612.149
• InChiKey: KTGISUNIGVRPCB-UHFFFAOYSA-N

物化性质

• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  戊酰氯 、 2-(5-amino-2-chlorophenyl)-4-<<2'-biphenyl-4-yl>methyl>-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one 在 4-二甲氨基吡啶 水 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 silica gel 作用下， 以 吡啶 为溶剂， 反应 16.0h， 以to provide 41 mg (46%) of the title compound as a white solid, mp 177°-179° C.的产率得到4-<<2'-<(N-tert-butoxycarbonyl)sulfamoyl>biphenyl-4-yl>methyl>-5-n-butyl-2-<2-chloro-5-(valerylamino)phenyl>-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Substituted 1,2,4-triazoles bearing acidic functional groups as

  摘要：

  化合物I的代替新型三唑酮，三唑硫酮和三唑亚胺化合物作为血管紧张素II拮抗剂是有用的。

  公开号：

  US05281614A1
• 作为产物：
  描述：

  ethyl N-carbethoxy-valerimidate 在 PtO₂/C potassium fluoride 、 copper(l) iodide 、 氢气 、 sodium hydride 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 133.5h， 生成 2-(5-amino-2-chlorophenyl)-4-<<2'-biphenyl-4-yl>methyl>-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Triazolinone Biphenylsulfonamides as Angiotensin II Receptor Antagonists with High Affinity for Both the AT1 and AT2 Subtypes

  摘要：

  Angiotensin II (AII), the endogenous peptide Ligand of the AII receptor, has equivalent high affinity for both the AT(1) and AT(2) receptor subtypes while most of the reported nonpeptide AII antagonists are AT(1)-selective. In an effort to identify dual AT(1)/AT(2) nonpeptide AII antagonists, we have pursued modifications of previously prepared trisubstituted 1,2,4-triazolinone biphenylsulfonamides which exhibited subnanomolar in vitro AT(1) (rabbit aorta) AII antagonism and AT(2) (rat midbrain) IC50 values of <40 nM. Present results show that a suitable amide (or reversed amide) side chain appropriately positioned on the N-2-aryl group of these compounds gave >15-fold enhancement in AT(2) binding affinity without sacrificing nanomolar AT(1) potency (IC50). This added amide, combined with an appropriate choice of the N-substituent on the sulfonamide and the ortho substituent on the N-2-aryl group, led to an analogue (46, L-163,- 007) which exhibited subnanomolar AT(1) binding affinity and an AT(2)/AT(1) IC50 ratio of 3. This compound showed excellent iv activity at 1 mg/kg and oral efficacy at 3 mg/kg with >6 h duration in a conscious rat model. Available data suggest that the newly introduced amide side chain, mandatory for low nanomolar binding affinity at the AT(2) receptor, is well-tolerated by the AT(1) receptor and has minimal effect on the in vivo properties of these molecules.

  DOI：

  10.1021/jm00052a006

文献信息

• Substituted 1,2,4-triazoles bearing acidic functional groups as
  申请人：Merck & Co., Inc.

  公开号：US05281614A1

  公开（公告）日：1994-01-25

  Novel substituted triazolinone, triazolinethione, and triazolinimine compounds of the formula I are useful as angiotensin II antagonists. ##STR1##

  这些公式I中的新型替代三唑酮，三唑硫酮和三唑亚胺化合物可用作抗血管紧张素II拮抗剂。
• US5281614A
  申请人：——

  公开号：US5281614A

  公开（公告）日：1994-01-25
• [EN] ACIDIC ARALKYL TRIAZOLE DERIVATIVES ACTIVE AS ANGIOTENSIN II ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：WO1992020662A1

  公开（公告）日：1992-11-26

  (EN) Novel substituted triazolinone, triazolinethione, and triazolinimine compounds of formula (I) are useful as angiotensin II antagonists.(FR) Nouveaux composés de triazolinone, de triazolinethione et de triazolinimine substitués, de la formule (I), utiles en tant qu'antagonistes de l'angiotensine II.
• Triazolinone Biphenylsulfonamides as Angiotensin II Receptor Antagonists with High Affinity for Both the AT1 and AT2 Subtypes
  作者：Linda L. Chang、Wallace T. Ashton、Kelly L. Flanagan、Tsing-Bau Chen、Stacey S. O'Malley、Gloria J. Zingaro、Peter K. S. Siegl、Salah D. Kivlighn、Victor J. Lotti

  DOI：10.1021/jm00052a006

  日期：1994.12

  Angiotensin II (AII), the endogenous peptide Ligand of the AII receptor, has equivalent high affinity for both the AT(1) and AT(2) receptor subtypes while most of the reported nonpeptide AII antagonists are AT(1)-selective. In an effort to identify dual AT(1)/AT(2) nonpeptide AII antagonists, we have pursued modifications of previously prepared trisubstituted 1,2,4-triazolinone biphenylsulfonamides which exhibited subnanomolar in vitro AT(1) (rabbit aorta) AII antagonism and AT(2) (rat midbrain) IC50 values of <40 nM. Present results show that a suitable amide (or reversed amide) side chain appropriately positioned on the N-2-aryl group of these compounds gave >15-fold enhancement in AT(2) binding affinity without sacrificing nanomolar AT(1) potency (IC50). This added amide, combined with an appropriate choice of the N-substituent on the sulfonamide and the ortho substituent on the N-2-aryl group, led to an analogue (46, L-163,- 007) which exhibited subnanomolar AT(1) binding affinity and an AT(2)/AT(1) IC50 ratio of 3. This compound showed excellent iv activity at 1 mg/kg and oral efficacy at 3 mg/kg with >6 h duration in a conscious rat model. Available data suggest that the newly introduced amide side chain, mandatory for low nanomolar binding affinity at the AT(2) receptor, is well-tolerated by the AT(1) receptor and has minimal effect on the in vivo properties of these molecules.