5,8-dihydro-2,4-dimethyl-8-<<5-(2-(1H-tetrazol-5-yl)phenyl)-2-pyridinyl>methyl>pyrido<2,3-d>pyrimidin-7(6H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5,8-dihydro-2,4-dimethyl-8-<<5-(2-(1H-tetrazol-5-yl)phenyl)-2-pyridinyl>methyl>pyrido<2,3-d>pyrimidin-7(6H)-one
• 英文别名: 2,4-dimethyl-5,6,8-trihydro-8-[[5-[2-(1H-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-7H-pyrido[2,3-d]pyrimidin-7-one；2,4-dimethyl-8-[[5-[2-(2H-tetrazol-5-yl)phenyl]pyridin-2-yl]methyl]-5,6-dihydropyrido[2,3-d]pyrimidin-7-one
• 化学式: C₂₂H₂₀N₈O
• 分子量: 412.454
• InChiKey: HPKMJTIQUSGVRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 吡啶 、 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium fluoride 、 copper(l) iodide 、 四溴化碳 、 sodium hydride 、 间氯过氧苯甲酸 、 三苯基膦 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 76.5h， 生成 5,8-dihydro-2,4-dimethyl-8-<<5-(2-(1H-tetrazol-5-yl)phenyl)-2-pyridinyl>methyl>pyrido<2,3-d>pyrimidin-7(6H)-one
  参考文献：
  名称：

  Pyrido[2,3-d]pyrimidine Angiotensin II Antagonists

  摘要：

  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.

  DOI：

  10.1021/jm00030a013

文献信息

• Substituted pyridopyrimidines useful as antgiotensin II antagonists
  申请人：American Home Products Corporation

  公开号：US05149699A1

  公开（公告）日：1992-09-22

  This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I ##STR1## useful for treating hypertension and congestive heart failure, to pharmaceutical compositions, and to methods for production thereof.

  本发明涉及一般式I的吡咯基、吡啶基、氮杂七元环和氮杂环丙嘧啶类化合物，对治疗高血压和充血性心力衰竭有用，还涉及制药组合物及其生产方法。
• Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines
  申请人：American Home Products Corporation

  公开号：US05256654A1

  公开（公告）日：1993-10-26

  This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently H, lower alkyl containing 1 to 6 carbon atoms, or perfluoroalkyl containing 1 to 6 carbon atoms; R.sup.5 is H or when n is 1 R.sup.5 taken together with R.sup.3 comprises a double bond; n is 0 to 1; p is 0 to 2; m is 0 to 3; Ar.sup.1 is ##STR2## wherein W is H, lower alkyl containing 1 to 6 carbon atoms, halogen, hydroxy, or lower alkoxy containing 1 to 6 carbon atoms; Ar.sup.2 is ##STR3## wherein X is ##STR4## wherein R.sup.6 is H, tert-butyl, tri-n-butylstannyl, or triphenylmethyl; and the pharmaceutically acceptable salts thereof which by virtue of their ability to antagonize angiotensin II are useful for the treatment of hypertension, congestive heart failure, and restenosis. The compounds are also useful for reducing lipid levels in the blood plasma and are thus useful for treating hyperlipidemia and hypercholesterolemia. Also disclosed are processes for the production of said compounds and pharmaceutical compositions containing said compounds.

  这项发明涉及一般式I的吡咯烯、吡啶烯、氮杂七元环和氮杂七元杂环嘧啶类化合物，其中R.sup.1、R.sup.2、R.sup.3和R.sup.4分别独立地为H、含有1至6个碳原子的较低烷基，或含有1至6个碳原子的全氟烷基；R.sup.5为H，当n为1时，R.sup.5与R.sup.3一起构成双键；n为0至1；p为0至2；m为0至3；Ar.sup.1为##STR2##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##STR3##其中X为##STR4##其中R.sup.6为H、叔丁基、三正丁基锡基或三苯甲基；以及它们的药用可接受盐，由于它们具有拮抗血管紧张素II的能力，因此可用于治疗高血压、充血性心力衰竭和再狭窄。这些化合物还可用于降低血浆中的脂质水平，因此可用于治疗高脂血症和高胆固醇血症。还公开了生产这些化合物的方法和含有这些化合物的药物组合物。
• Condensed pyrimidine derivatives and their use as angiotensine II antagonists
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0539086A2

  公开（公告）日：1993-04-28

  This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I useful for treating hypertension or congestive heart failure and for preventing or treating restenosis following angioplasty, to pharmaceutical compositions, and to methods for production thereof.

  本发明涉及通式 I 的吡咯并嘧啶、吡啶并嘧啶、氮杂环庚并嘧啶和氮杂环辛并嘧啶。 用于治疗高血压或充血性心力衰竭以及预防或治疗血管成形术后的再狭窄、药物组合物及其生产方法。
• 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：——
• US5149699A
  申请人：——

  公开号：US5149699A

  公开（公告）日：1992-09-22