2,4-dimethyl-5-hydroxy-8-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one

• 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: 2,4-dimethyl-5-hydroxy-8-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 5-hydroxy-2,4-dimethyl-8-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one
• 化学式: C₂₃H₂₁N₇O₂
• 分子量: 427.465
• InChiKey: WNDWLZHSOQLSBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

Enoltasosartan 是 Tasosartan 的已知人体代谢物。

Enoltasosartan is a known human metabolite of Tasosartan.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  他索沙坦 在 sodium hydroxide 、 potassium permanganate 、 magnesium sulfate 作用下， 反应 24.0h， 以8%的产率得到2,4-dimethyl-5-hydroxy-8-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group

  摘要：

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.

  DOI：

  10.1021/jm970690q

文献信息

• Intermediates useful in the production of pyridopyrimidone angiotensin AII antagonists
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0863143A1

  公开（公告）日：1998-09-09

  This invention relates to intermediates useful in the production of substituted pyridopyrimidinones of general formula (I): wherein n is 0 to 3; R1 and R2 are, independently, H, C1-C6alkyl, hydroxy(C1-C6alkyl), formyl, carbonyl(C1-C6alkyl), carboxy, or carboxy(C1-C6alkyl); R3 and R4 are, independently, H, C1-C6alkyl, or hydroxy; R3a and R4a are H, or one of -CR3R3a and -CR4R4a is a carbonyl group; with the proviso that at least one of the groups R1 and R2 must be hydroxy(C1-C6alkyl), formyl, carbonyl(C1-C6alkyl), carboxy, or carboxy(C1-C6alkyl); or one of R3 and R4 must be hydroxy; or one of -CR3R3a and -CR4R4a must be a carbonyl group; ; Ar1 is    wherein W is H, C1-C6alkyl, halogen, hydroxy, or C1-C6alkoxy; Ar2 is    wherein X is    wherein R5 is H, CH3, tert-butyl, tri-n-butylstannyl, or triphenylmethyl; or a tautomer of said compound, or a pharmaceutically acceptable salt of said compound or tautomer. The compounds of Formula I are useful for treating hypertension and congestive heart failure. Also disclosed are pharmaceutical compositions containing compounds of Formula I and a pharmaceutically acceptable carrier and methods for production of the compounds of Formula I. Intermediates for making the pharmaceutical useful compounds are also enclosed.

  本发明涉及用于生产通式(I)的取代吡啶嘧啶酮的中间体： 其中 n 为 0 至 3； R1和R2独立地为H、C1-C6烷基、羟基（C1-C6烷基）、甲酰基、羰基（C1-C6烷基）、羧基或羧基（C1-C6烷基）； R3 和 R4 独立地为 H、C1-C6 烷基或羟基； R3a 和 R4a 是 H，或 -CR3R3a 和 -CR4R4a 中的一个是羰基； 但 R1 和 R2 中至少有一个基团必须是羟基（C1-C6 烷基）、甲酰基、羰基（C1-C6 烷基）、羧基或羧基（C1-C6 烷基）；或 R3 和 R4 中必须有一个是羟基；或 -CR3R3a 和 -CR4R4a 中必须有一个是羰基；； Ar1 是 其中 W 是 H、C1-C6 烷基、卤素、羟基或 C1-C6 烷氧基； Ar2 是 其中 X 是 其中 R5 是 H、CH3、叔丁基、三正丁基锡基或三苯甲基；或所述化合物的同分异构体、 或所述化合物或同系物的药学上可接受的盐。 式 I 的化合物可用于治疗高血压和充血性心力衰竭。还公开了含有式 I 化合物和药学上可接受的载体的药物组合物，以及生产式 I 化合物的方法。
• Substituted pyridopyrimidines as antihypertensives
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0618207B1

  公开（公告）日：1999-01-07
• US5466692A
  申请人：——

  公开号：US5466692A

  公开（公告）日：1995-11-14
• Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group
  作者：John W. Ellingboe、Michael D. Collini、Dominick Quagliato、James Chen、Madelene Antane、Jean Schmid、Dale Hartupee、Valerie White、C. Hyung Park、Tarak Tanikella、Jehan F. Bagli

  DOI：10.1021/jm970690q

  日期：1998.10.1

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.