methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketone | 159237-74-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketone
• 英文别名: 1-[4-[(4-bromophenyl)methylamino]-2,6-dimethylpyrimidin-5-yl]ethanone
• CAS: 159237-74-8
• 化学式: C₁₅H₁₆BrN₃O
• 分子量: 334.216
• InChiKey: SSOKMQLENDBUHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketone 在 四(三苯基膦)钯 、 三氟甲磺酸 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 6.0h， 生成 2,4-dimethyl-5-hydroxy-8-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-8H-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
• 作为产物：
  描述：

  4-(4-bromobenzylamino)-2,6-dimethyl-5-(1-ethoxyvinyl)pyrimidine 在 盐酸 作用下， 以 丙酮 为溶剂， 以2.24 g (89%)的产率得到methyl(4-(4-bromobenzylamino)-2,6-dimethylpyrimidin-5-yl)ketone
  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

• Substituted pyridopyrimidines and antihypertensives
  申请人：American Home Products Corporation

  公开号：US05466692A1

  公开（公告）日：1995-11-14

  This invention relates to substituted pyridopyrimidinones of general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are independently H, lower alkyl containing 1 to 6 carbon atoms, hydroxyalkyl containing 1 to 6 carbon atoms, formyl, carbonylalkyl containing 1 to 6 carbon atoms, carboxy, or carboxyalkyl containing 1 to 6 carbon atoms; R.sup.3 and R.sup.4 are independently H, lower alkyl containing 1 to 6 carbon atoms, hydroxy; R.sup.3a and R.sup.4a are H, and when taken together with R.sup.3 and R.sup.4 respectively comprise a carbonyl; with the proviso that at least one of the groups R1 and R.sup.2 must be hydroxyalkyl, formyl, carbonylalkyl containing 1 to 6 carbon atoms, carboxy, or carboxyalkyl containing 1 to 6 carbon atoms; or R.sup.3 and R.sup.4 must be hydroxy or taken together with R.sup.3a and R.sup.4a respectively must comprise a carbonyl; n 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 CO.sub.2 H, CN, or ##STR4## wherein R.sup.5 is H, CH.sub.3, tert-butyl, tri-n-butylstannyl, or triphenylmethyl; and the pharmaceutically acceptable salts thereofuseful for treating hypertension and congestive heart failure, to pharmaceutical compositions, and to methods for production thereof.

  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。
• 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.