(4S)-1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid 1-methylethyl ester | 128162-87-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (4S)-1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid 1-methylethyl ester
• 英文别名: propan-2-yl (4S)-2-methoxy-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate
• CAS: 128162-87-8
• 化学式: C₁₆H₁₉N₃O₅
• 分子量: 333.344
• InChiKey: GMGQEGDLCYGDNS-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  103.06
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (4S)-1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid 1-methylethyl ester 、 4-甲氧基苄硫醇 在 柠檬酸 作用下， 反应 16.0h， 生成 (4S)-1,4-dihydro-2-<<(4-methoxyphenyl)methyl>thio>-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid 1-methylethyl ester
  参考文献：
  名称：

  Dihydropyrimidine calcium channel blockers. II. 3-Substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines

  摘要：

  To enhance the intrinsic potency of dihydropyrimidine calcium channel blockers, we have modified the structure of previously described 2-heteroalkyl-1,4-dihydropyrimidines 2 to 3-substituted 1,4-dihydropyrimidines 3. Structure-activity studies using potassium-depolarized rabbit aorta show that ortho, meta-disubstituted aryl derivatives are more potent than either ortho- or meta-monosubstituted compounds. While vasorelaxant activity was critically dependent on the size of the C5 ester group, isopropyl ester being the best, a variety of substituents (carbamate, acyl, sulfonyl, alkyl) were tolerated at N3. Our results show dihydropyrimidines 3 are significantly more potent than corresponding 2-heteroalkyl-1,4-dihydropyrimidines 2 and only slightly less potent than similarly substituted 2-heteroalkyl-1,4-dihydropyridines 4 and 5. Whereas dihydropyridine enantiomers usually show 10-15-fold difference in activity, the enantiomers of dihydropyrimidine 3j show more than a 1000-fold difference in activity. These results strengthen the requirement of an enamino ester for binding to the dihydropyridine receptor and indicate a nonspecific role for the N3-substituent.

  DOI：

  10.1021/jm00171a044
• 作为产物：
  描述：

  <1(R)>-1,6-dihydro-2-methoxy-4-methyl-6(S)-(4-nitrophenyl)-1-<<(1-phenylethyl)amino>carbonyl>-5-pyrimidine carboxylic acid 1-methylethyl ester 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以56%的产率得到(4S)-1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid 1-methylethyl ester
  参考文献：
  名称：

  Dihydropyrimidine calcium channel blockers. II. 3-Substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines

  摘要：

  To enhance the intrinsic potency of dihydropyrimidine calcium channel blockers, we have modified the structure of previously described 2-heteroalkyl-1,4-dihydropyrimidines 2 to 3-substituted 1,4-dihydropyrimidines 3. Structure-activity studies using potassium-depolarized rabbit aorta show that ortho, meta-disubstituted aryl derivatives are more potent than either ortho- or meta-monosubstituted compounds. While vasorelaxant activity was critically dependent on the size of the C5 ester group, isopropyl ester being the best, a variety of substituents (carbamate, acyl, sulfonyl, alkyl) were tolerated at N3. Our results show dihydropyrimidines 3 are significantly more potent than corresponding 2-heteroalkyl-1,4-dihydropyrimidines 2 and only slightly less potent than similarly substituted 2-heteroalkyl-1,4-dihydropyridines 4 and 5. Whereas dihydropyridine enantiomers usually show 10-15-fold difference in activity, the enantiomers of dihydropyrimidine 3j show more than a 1000-fold difference in activity. These results strengthen the requirement of an enamino ester for binding to the dihydropyridine receptor and indicate a nonspecific role for the N3-substituent.

  DOI：

  10.1021/jm00171a044

文献信息

• ATWAL, KARNAIL S.;ROVNYAK, GEORGE C.;KIMBALL, S. DAVID;FLOYD, DAVID M.;MO+, J. MED. CHEM., 33,(1990) N, C. 2629-2635
  作者：ATWAL, KARNAIL S.、ROVNYAK, GEORGE C.、KIMBALL, S. DAVID、FLOYD, DAVID M.、MO+

  DOI：——

  日期：——