5-n-butyl-4-<<2'-(N-tert-butylsulfamoyl)biphenyl-4-yl>methyl>-2,4-dihydro-2-<4-nitro-2-(trifluoromethyl)phenyl>-3H-1,2,4-triazol-3-one | 146949-01-1

• 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: 5-n-butyl-4-<<2'-(N-tert-butylsulfamoyl)biphenyl-4-yl>methyl>-2,4-dihydro-2-<4-nitro-2-(trifluoromethyl)phenyl>-3H-1,2,4-triazol-3-one
• 英文别名: 5-n-butyl-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-2,4-dihydro-2-[4-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one；N-tert-butyl-2-[4-[[3-butyl-1-[4-nitro-2-(trifluoromethyl)phenyl]-5-oxo-1,2,4-triazol-4-yl]methyl]phenyl]benzenesulfonamide
• CAS: 146949-01-1
• 化学式: C₃₀H₃₂F₃N₅O₅S
• 分子量: 631.676
• InChiKey: GOAXWSGKSZJJJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-n-butyl-4-<<2'-(N-tert-butylsulfamoyl)biphenyl-4-yl>methyl>-2,4-dihydro-2-<4-nitro-2-(trifluoromethyl)phenyl>-3H-1,2,4-triazol-3-one 在 盐酸 、 苯甲醚 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氟乙酸 、 tin(ll) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 2-<4-amino-2-(trifluoromethyl)phenyl>-5-n-butyl-4-<<2'-biphenyl-4-yl>methyl>-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
• 作为产物：
  描述：

  ethyl N-carbethoxy-valerimidate 在 sodium hydride 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 17.5h， 生成 5-n-butyl-4-<<2'-(N-tert-butylsulfamoyl)biphenyl-4-yl>methyl>-2,4-dihydro-2-<4-nitro-2-(trifluoromethyl)phenyl>-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 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##
• 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。
• Substituted triazolinones
  申请人：MERCK & CO. INC.

  公开号：EP0526001A1

  公开（公告）日：1993-02-03

  Substituted triazolinone compounds are angiotensin II antagonists and therefore useful in the treatment of hypertension, and related cardiovascular disorders and ocular hypertension. These compounds have the general formula:

  取代的三唑啉酮化合物是血管紧张素 II 拮抗剂，因此可用于治疗高血压、相关心血管疾病和眼压过高。这些化合物的通式如下
• ACIDIC ARALKYL TRIAZOLE DERIVATIVES ACTIVE AS ANGIOTENSIN II ANTAGONISTS
  申请人：MERCK & CO. INC.

  公开号：EP0586513A1

  公开（公告）日：1994-03-16
• US5281614A
  申请人：——

  公开号：US5281614A

  公开（公告）日：1994-01-25