2,6-Dimethyl-5-methoxycarbonyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid-N-(1,2-benzisothiazolyl-3(2H)one-1,1-dioxide)-methylester | 136941-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2,6-Dimethyl-5-methoxycarbonyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid-N-(1,2-benzisothiazolyl-3(2H)one-1,1-dioxide)-methylester
• 英文别名: 3-O-methyl 5-O-[(1,1,3-trioxo-1,2-benzothiazol-2-yl)methyl] 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 136941-46-3
• 化学式: C₂₄H₂₁N₃O₉S
• 分子量: 527.511
• InChiKey: CIXPQMOOTZCPME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  173
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (1,1,3-trioxo-2,3-dihydro-1,2-benzisothiazol-2-yl)methyl acetylacetate 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 29.0h， 生成 2,6-Dimethyl-5-methoxycarbonyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid-N-(1,2-benzisothiazolyl-3(2H)one-1,1-dioxide)-methylester
  参考文献：
  名称：

  Synthesis of 3-[(2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazol-2-yl)alkyl] 1,4-dihydropyridine-3,5-dicarboxylate derivatives as calcium channel modulators

  摘要：

  1,4-Dihydropyridine (DHP) derivatives with a 1,2-benzisothiazol-3-one 1,1-dioxide group, linked through an alkylene bridge to the C-3 carboxylate of the DHP ring, with both vasconstricting and vasorelaxant properties were obtained. In blocking Ca2+-evoked contractions of K+-depolarized rabbit aortic strips, compounds 12 and 41 were 10-fold more potent than nifedipine; 27 other compounds were 1-4-fold more potent. Their vascular versus cardiac selectivity was very pronounced; for instance, the selectivity index for compound 41 was 70-fold higher than that of nifedipine. This was also true for the vasoconstricting compound 22, which was as potent as Bay K 8644 in enhancing the Ca2+-evoked contractions of rabbit aorta strips, yet it had poor inotropic activity in rabbit left atria. Oral adminstration of compounds 38, 40, 43, and 53 (20 mg/kg) caused a 35-37% decrease in systolic blood pressure in spontaneously hypertensive rats (SHR); these effects were similar to those of nifedipine. However, iv administration of these compounds to anesthetized SHR caused a decrease in blood pressure which was more pronounced and long-lasting than that of nifedipine. When administered iv at 100-mu-g/kg, the vasoconstricting compound 22 caused a 40% increase in systolic and diastolic blood pressure. Compound 22 exhibited an unusually interesting feature over the other five Ca2+ DHP agonists: it had diester substitutions at the C-3 and C-5 positions of the DHP ring. Overall, compounds processing these properties might be useful in treating clinical cardiovascular conditions in which DHP Ca2+ antagonists or agonists are indicated.

  DOI：

  10.1021/jm00091a008

文献信息

• New 1,4-dihydropyridine derivatives, a process for their preparation and their use for influencing the blood flow
  申请人：ALTER, S.A.

  公开号：EP0441736A3

  公开（公告）日：1992-04-22

  The invention relates to new 1,4-dihydropyridine derivatives of the general formula I in which R¹, R², R³ and n have the meaning stated in the patent claims.The compounds of the invention have a vasodilatory effect and are therefore suitable for the treatment of hypertension. Some of the compounds have a vasoconstrictory effect and can therefore be used for the treatment of hypotension.

  本发明涉及通式I的新型1,4-二氢吡啶衍生物，其中R¹、R²、R³和n的含义如专利权利要求中所述。本发明的化合物具有血管舒张作用，因此适用于治疗高血压。其中一些化合物具有血管收缩作用，因此可用于治疗低血压。