2-methyl-7-oxo-8-<(2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl)methyl>-5,6,7,8-tetrahydropyrido<2,3-d>pyrimidine-4-carbaldehyde | 153042-14-9

• 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-methyl-7-oxo-8-<(2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl)methyl>-5,6,7,8-tetrahydropyrido<2,3-d>pyrimidine-4-carbaldehyde
• 英文别名: 2-methyl-7-oxo-8-{[2'-(2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl}-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-4-carboxaldehyde；2-methyl-7-oxo-8-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-4-carbaldehyde；2-methyl-7-oxo-8-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidine-4-carbaldehyde
• CAS: 153042-14-9
• 化学式: C₂₃H₁₉N₇O₂
• 分子量: 425.45
• InChiKey: DKMLYADVVLIQTK-UHFFFAOYSA-N

物化性质

• 沸点：
  803.6±75.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-methyl-7-oxo-8-<(2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl)methyl>-5,6,7,8-tetrahydropyrido<2,3-d>pyrimidine-4-carbaldehyde 在 苯亚硒酸 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 生成 2-methyl-7-oxo-8-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects

  摘要：

  Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45 nM. The in vivo effects of these compounds in attenuating the pressor response to angiotensin-II challenge in anesthetized rats were also investigated. An unsaturated diol metabolite exhibited in vivo efficacy at intravenous doses of 1 and 3 mg/kg, while the other metabolites, both carboxylic acids, had no significant effect at the same doses. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00303-7
• 作为产物：
  描述：

  他索沙坦 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 以102 mg (12%)的产率得到2-methyl-7-oxo-8-<(2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl)methyl>-5,6,7,8-tetrahydropyrido<2,3-d>pyrimidine-4-carbaldehyde
  参考文献：
  名称：

  Substituted pyridopyrimidines and antihypertensives

  摘要：

  这项发明涉及通式（I）的取代吡啶吡嘧啶酮：其中R.sup.1和R.sup.2分别是H、含有1至6个碳原子的较低烷基、含有1至6个碳原子的羟基烷基、甲酰基、含有1至6个碳原子的羰基烷基、羧基或含有1至6个碳原子的羧基烷基；R.sup.3和R.sup.4分别是H、含有1至6个碳原子的较低烷基、羟基；R.sup.3a和R.sup.4a是H，且与R.sup.3和R.sup.4分别结合时包括一个羰基；但必须至少有R1和R.sup.2中的一个是羟基烷基、甲酰基、含有1至6个碳原子的羰基烷基、羧基或含有1至6个碳原子的羧基烷基；或R.sup.3和R.sup.4必须是羟基，或者与R.sup.3a和R.sup.4a分别结合时必须包括一个羰基；n为0至3；Ar.sup.1为其中W为H、含有1至6个碳原子的较低烷基、卤素、羟基或含有1至6个碳原子的较低烷氧基；Ar.sup.2为其中X为CO.sub.2 H、CN或其中R.sup.5为H、CH.sub.3、叔丁基、三正丁基锡基或三苯基甲基；及其药用盐，用于治疗高血压和充血性心力衰竭，制药组合物以及其生产方法。

  公开号：

  US05466692A1

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。
• Pyrido[2,3-d]pyrimidine Angiotensin II Antagonists
  作者：John W. Ellingboe、Madelene Antane、Thomas T. Nguyen、Michael D. Collini、Schuyler Antane、Reinhold Bender、Dale Hartupee、Valerie White、John McCallum

  DOI：10.1021/jm00030a013

  日期：1994.2

  A series of pyrido[2,3-d]pyrimidine angiotensin II (A II) antagonists was synthesized and tested for antagonism of A II. Compounds with a biphenylyltetrazole pharmacophore and small alkyl groups at the 2- and ii-positions Of the pyridopyrimidine ring were found to be the most potent in an AT(1) receptor binding assay and in blocking the A II presser response in anesthetized, ganglion-blocked A II-infused rats. 5,8-Dihydro-2,4-dimethyl-8-[(2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl)methyl] pyrido[2,3-d]pyrimidin-7(6H)-one (4a) was one of the more potent compounds in the binding assay and was the most efficacious compound in the A II-infused rat model. Further study of 4a;in Goldblatt (2K-1C) rats showed the compound to have oral bioavailability and to be an efficacious and potent compound in a high renin form of hypertension.
• Ellingboe John W., Antane Madelene, Nguyen Thomas T., Collini Michael D.,+, J. Med. Chem, 37 (1994) N 4, S 542-550
  作者：Ellingboe John W., Antane Madelene, Nguyen Thomas T., Collini Michael D.,+

  DOI：——

  日期：——
• Substituted pyridopyrimidines as antihypertensives
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0618207B1

  公开（公告）日：1999-01-07
• JPH06321945A
  申请人：——

  公开号：JPH06321945A

  公开（公告）日：1994-11-22