N-methylnitrendipine | 50698-12-9

• 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: N-methylnitrendipine
• 英文别名: MRS 1844；1,2,6-trimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl-ester-5-ethyl-ester；Ethyl methyl 1,2,6-trimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；5-O-ethyl 3-O-methyl 1,2,6-trimethyl-4-(3-nitrophenyl)-4H-pyridine-3,5-dicarboxylate
• CAS: 50698-12-9
• 化学式: C₁₉H₂₂N₂O₆
• 分子量: 374.393
• InChiKey: HHWSTZALTBWGPQ-UHFFFAOYSA-N

物化性质

• 沸点：
  483.5±45.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  尼群地平 、 碘甲烷 以95%的产率得到N-methylnitrendipine
  参考文献：
  名称：

  Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

  摘要：

  A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or in-trifluoromethyl (IC50 values: 3-6 muM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 muM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 muM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. Published by Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(02)01488-0

文献信息

• Unsymmetrical esters of N-substituted 1,4-dihydropyridine
  申请人：Bayer Aktiengesellschaft

  公开号：US03933834A1

  公开（公告）日：1976-01-20

  Unsymmetrical esters of N-substituted 4-substituted-1,4-dihydropyridine 3,5-dicarboxylic acid substituted in the 4-position by pyridyl, thienyl, furyl and pyrryl and optionally substituted in the 2- and 6-positions by lower alkyl. The products can be prepared (A) through condensation of an ylidene-.beta.-ketocarboxylic acid ester, with a .beta.-ketocarboxylic acid ester and an amine or salt thereof, or with an enamino carboxylic acid ester or (B) through condensation of an aldehyde, an enamino carboxylic acid ester and a .beta.-ketocarboxylic acid ester. The said products have utility as cardiovascular agents.

  N-取代的4-取代-1,4-二氢吡啶-3,5-二羧酸不对称酯，其在4位被吡啶基，噻吩基，呋喃基和吡咯基取代，并在2和6位可选地被低碳基取代。该产品可以通过以下方法制备：（A）将一个伊利丹-β-酮羧酸酯与一个β-酮羧酸酯和胺或其盐，或与烯氨基羧酸酯缩合，或（B）将一个醛，一个烯氨基羧酸酯和一个β-酮羧酸酯缩合。该产品可用作心血管药物。
• US3883540A
  申请人：——

  公开号：US3883540A

  公开（公告）日：1975-05-13
• US3933834A
  申请人：——

  公开号：US3933834A

  公开（公告）日：1976-01-20
• US4703119A
  申请人：——

  公开号：US4703119A

  公开（公告）日：1987-10-27
• Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells
  作者：Jacquie L Harper、Carol S Camerini-Otero、An-Hu Li、Soon-Ai Kim、Kenneth A Jacobson、John W Daly

  DOI：10.1016/s0006-2952(02)01488-0

  日期：2003.2

  A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or in-trifluoromethyl (IC50 values: 3-6 muM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 muM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 muM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. Published by Elsevier Science Inc.