3-ethyl 5-(2-hydroxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

• 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: 3-ethyl 5-(2-hydroxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 3-O-ethyl 5-O-(2-hydroxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 化学式: C₁₉H₂₂N₂O₇
• 分子量: 390.393
• InChiKey: BWVUMXCLRFRMFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  达唑氧苯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 3-ethyl 5-(2-hydroxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 在 ammonium chloride 、 N,N'-羰基二咪唑 作用下， 以96.2%的产率得到3-ethyl 5-[2-[4-[2-(1-imidazolyl)-ethoxy]-benzoyloxy]-ethyl]2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Anti-arteriosclerotic pyridyl or imidazolyl derivatives of

  摘要：

  这项发明涉及一种由以下一般式（I）表示的1,4-二氢吡啶-3,5-二羧酸盐衍生物：其中R表示咪唑基或吡啶基，R.sub.1表示氢原子或卤素原子或硝基或三氟甲基基团，R.sub.2是较低的烷基基团，X是CH或N，A表示较低的烷基基团，B是较低的烷基或O-较低的烷基基团，R.sub.4是氢原子或较低的烷基基团，或m表示1-3的数字，n代表1或2。该衍生物具有扩张血管作用、高动力作用、抑制血小板聚集作用、抑制血栓素A.sub.2形成作用等作用，因此可用作药物产品，如血管扩张剂、降压剂、抗血栓剂、抗动脉硬化剂等。

  公开号：

  US04737506A1
• 作为产物：
  描述：

  2-hydroxyethyl acetoacetate 、 间硝基苯甲醛 、 3-氨基巴豆酸乙酯 以 乙醇 为溶剂， 以41%的产率得到3-ethyl 5-(2-hydroxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  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

• NOVEL 1,4-DIHIDROPYRIDINE-3,5-DICARBOXYLATE DERIVATIVES
  申请人：KOWA CO. LTD.

  公开号：EP0190364A1

  公开（公告）日：1986-08-13

  1,4-Dihydropyridine-3,5-dicarboxylate derivatives represented by general formula (I) (wherein R represents an imidazolyl group or a pyridyl group, R1 represents a hydrogen atom, a halogen atom, a nitro group or a trifluoromethyl group, R2 represents a lower alkyl group, X represents CH or N, A represents a lower alkylene group, a compound of formula (II) (wherein B represents a lower alkylene group or an 0-lower alkylene group), a compound of formula (III) (wherein R4 represents a hydrogen atom or a lower alkyl group) or a compound of formula (IV), m represents a number of 1 to 3, and n represents a number of 1 or 2. They have effects of vasodilation, increasing blood stream, inhibition of platelet coagulation, and inhibition of production of thromboxan A2, and are useful as drugs such as vasodilators, hypotensives, anti-thrombotic drugs, arterial sclerosis-preventing agents, etc.

  通式(I)代表的 1,4-二氢吡啶-3,5-二甲酸酯衍生物（其中 R 代表咪唑基团或吡啶基团，R1 代表氢原子、卤素原子、硝基或三氟甲基，R2 代表低级烷基，X 代表 CH 或 N，A 代表低级亚烷基、式（II）化合物（其中 B 代表低级亚烷基或 0-低级亚烷基）、式（III）化合物（其中 R4 代表氢原子或低级亚烷基）或式（IV）化合物，m 代表 1 至 3 的数字，n 代表 1 或 2 的数字。它们具有扩张血管、增加血流量、抑制血小板凝结和抑制血栓素 A2 生成的作用，可用作血管扩张剂、降血压药、抗血栓药、动脉硬化预防剂等药物。
• US4737506A
  申请人：——

  公开号：US4737506A

  公开（公告）日：1988-04-12
• Anti-arteriosclerotic pyridyl or imidazolyl derivatives of
  申请人：Kowa Co., Ltd.

  公开号：US04737506A1

  公开（公告）日：1988-04-12

  This invention relates to a 1,4-dihydropyridine-3,5-dicarboxylate derivative represented by the following general formula (I): ##STR1## wherein R means an imidazolyl or pyridyl group, R.sub.1 denotes a hydrogen or halogen atom or a nitro or trifluoromethyl group, R.sub.2 is a lower alkyl group, X is CH or N, A means a lower alkylene group, ##STR2## B being a lower alkylene or O-lower alkylene group, ##STR3## R.sub.4 being a hydrogen atom or lower alkyl group, or ##STR4## m denotes a number of 1-3, and n stands for 1 or 2. The derivative has vasodilative effects, hyperkinemic effects, platelet aggregation inhibitory effects, thromboxane A.sub.2 formation inhibitory effects and so on, and are hence useful as a pharmaceutical product such as vasodilator, antihypertensive, antithrombotic agent, antiarteriosclerotic agent or the like.

  这项发明涉及一种由以下一般式（I）表示的1,4-二氢吡啶-3,5-二羧酸盐衍生物：其中R表示咪唑基或吡啶基，R.sub.1表示氢原子或卤素原子或硝基或三氟甲基基团，R.sub.2是较低的烷基基团，X是CH或N，A表示较低的烷基基团，B是较低的烷基或O-较低的烷基基团，R.sub.4是氢原子或较低的烷基基团，或m表示1-3的数字，n代表1或2。该衍生物具有扩张血管作用、高动力作用、抑制血小板聚集作用、抑制血栓素A.sub.2形成作用等作用，因此可用作药物产品，如血管扩张剂、降压剂、抗血栓剂、抗动脉硬化剂等。
• 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.