diethyl 1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-(trifluoromethyl)-pyridine-3,5-dicarboxylate | 95400-30-9

• 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: diethyl 1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-(trifluoromethyl)-pyridine-3,5-dicarboxylate
• 英文别名: 1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-trifluoromethylpyridine-3,5-dicarboxylic acid diethyl ester；4-(3-Nitrophenyl)-2-methyl-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester；diethyl 2-methyl-4-(3-nitrophenyl)-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 95400-30-9
• 化学式: C₁₉H₁₉F₃N₂O₆
• 分子量: 428.365
• InChiKey: ZAULKMCTNNVKAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  咪唑 、 苯基三甲基溴化铵 、 diethyl 1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-(trifluoromethyl)-pyridine-3,5-dicarboxylate 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 2-Trifluoromethyl-1,4-dihydro-6-(imidazol-1-ylmethyl)-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  1,4-dihydropyridines

  摘要：

  本发明涉及以下式子的化合物或其盐：##STR1## 其中：.alpha.和.beta.一起代表一个键，此外，当B是一个电子提取基团时，.alpha.也可以代表OH，.beta.可以代表氢；Ar是一个可选的取代芳基或杂环芳基基团；R代表氢或一个可选的取代烷基或芳基烷基基团；R.sup.1和R.sup.2相同或不同，选择自氢和饱和或不饱和的、环状或非环状的脂肪烃残基，其可以被一个或多个从卤素、OH、羧基、CN、烷氧基、烷基硫基、芳基氧基、烷氧羰基、氨基、取代氨基和可选取代的芳基或杂环芳基中选择的基团所取代；A代表一个公式--XR.sup.3的基团，其中X代表一个公式--(CHR.sup.6).sub.p --Y--(CHR.sup.7).sub.q --，在该公式中：Y代表--O--、--S--、NR.sup.8或直接键，p和q分别代表0、1或2，R.sup.6、R.sup.7和R.sup.8独立地代表氢或低烷基，R.sup.3是一个可选的取代氮环杂芳基，其可以选自氧、氮或硫的其他环杂原子；B代表卤代烷基、可选取代的苯基、--CN、--CHO、--CH(O低烷基).sub.2或--CH.sub.2 OH。

  公开号：

  US05064842A1
• 作为产物：
  描述：

  (E)-3-氨基巴豆酸乙酯 在 三氯氧磷 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 diethyl 1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-(trifluoromethyl)-pyridine-3,5-dicarboxylate
  参考文献：
  名称：

  1,4-二氢-6-三氟甲基吡啶的高效合成：利用硅胶吸附磷酰氯/吡啶对α-三氟甲醇进行脱水的简便有效方法

  摘要：

  用 β-氨基巴豆酸酯 (2) 处理 α-烷氧基羰基-α,β-不饱和三氟甲基酮 (1) 得到 2-羟基-6-甲基-2-三氟甲基-1,2,3,4-四氢吡啶 (3)，通过使用吸附在硅胶上的三氯氧化磷/吡啶进行容易的脱水，产生良好至高产率的 1,4-二氢-2-甲基-6-三氟甲基吡啶 (4)。

  DOI：

  10.3987/com-06-10827

文献信息

• Pharmaceutically active dihydropyridines
  申请人：FISONS plc

  公开号：EP0125803A2

  公开（公告）日：1984-11-21

  There are described compounds of formula I, in which R1 represents benzofurazanyl, pyridyl or phenyl, the pyridyl or phenyl being substituted, -COOR2 and -COOR3 are various ester groups, Yand Ztogetherform a bond, and additionally, when R. is an electron withdrawing group Y may be hydrogen and Z may be hydroxy, one of R7 and R. represents alkyl Cl to 6 and the other represents -CONR10R11; -CSNH2; -C(=NN)SR9; -S(O)mR9; phenyl optionally substituted by one or more of alkyl Cl to 6, halogen, alkoxy CI to 6 or nitro; alkyl Cl to 6 substituted by halogen; or furanyl, or R7 and R. may be the same or different and each represents phenyl optionally substituted by one or more of alkyl CI to 6, halogen, alkoxy Cl to 6 or nitro; amino; alkyl CI to 6 substituted by halogen; -CN; -CH2OH; -CHO or-CH(OR9)2, m is 0 or 1 R9 is alkyl CI to 6, and R10 and R11 each independently represent hydrogen or alkyl Cl to 6, or together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring. There are also described processes for making the compounds, and pharmaceutical, eg calcium antagonist, formulations containing them.

  所述化合物为式 I、 其中 R1 代表苯并呋喃基、吡啶基或苯基，吡啶基或苯基被取代、 -COOR2和-COOR3是各种酯基、 Y和Z共同构成键，此外，当R.是取电子基团时，Y可以是氢，Z可以是羟基、 R7 和 R. 中的一个代表 Cl 至 6 烷基，另一个代表-CONR10R11；-CSNH2；-C(=NN)SR9；-S(O)mR9；任选被 Cl 至 6 烷基、卤素、CI 至 6 烷氧基或硝基中的一个或多个取代的苯基；被卤素取代的 Cl 至 6 烷基；或呋喃基、 或 R7 和 R.可以相同或不同，且各自代表被以下一种或多种任选取代的苯基：CI 至 6 号烷基、卤素、CI 至 6 号烷氧基或硝基；氨基；被卤素取代的 CI 至 6 号烷基；-CN；-CH2OH；-CHO 或-CH(OR9)2、 m为0或1 R9 是 CI-6 烷基，和 R10和R11各自独立地代表氢或Cl至6的烷基，或与它们所连接的氮原子一起形成5或6个成员的杂环。 此外，还介绍了制造这些化合物的工艺，以及含有这些化合物的药物制剂（如钙拮抗剂）。
• 1,4-Dihydropyridines
  申请人：JOHN WYETH & BROTHER LIMITED

  公开号：EP0233015A2

  公开（公告）日：1987-08-19

  The invention concerns compounds of formula or salts thereof; wherein: α and β together represent a bond and additionally when B is an electron withdrawing group α can also represent OH and β can represent hydrogen; Ar is an optionally substituted aryl radical; R represents hydrogen or an optionally substituted alkyl or aralkyl group; R¹ and R² are the same or different and are selected from hydrogen and saturated or unsaturated, cyclic or acyclic aliphatic hydrocarbon residues optionally substituted by one or more groups selected from halogen, OH, carboxy, CN, alkoxy, alkylthio, aryloxy, alkoxycarbonyl, amino, substituted amino, and optionally substituted aryl; A represents a group of formula -XR³ wherein X is a group of formula -(CHR⁶)p-Y-(CHR⁷)q- ­in which formula : Y represents -O-, -S-, NR⁸ or a direct bond, p and q each represent 0, 1 or 2 R⁶, R⁷ and R⁸ independently represent hydrogen or lower alkyl and R³ is an optionally substituted nitrogen ring heteroaryl radical optionally containing other ring heteroatoms selected from oxygen, nitrogen or sulphur; B represents haloalkyl, optionally substituted phenyl, -CN, -CHO, -CH(Olower­alkyl)₂ or -CH²OH.

  本发明涉及式 或其盐类； 其中：α 和 β 共同代表一个键，此外，当 B 是一个取电子基团时，α 还可以代表 OH，β 可以代表氢； Ar 是任选取代的芳基； R 代表氢或任选取代的烷基或芳烷基； R¹ 和 R² 可以相同或不同，并且选自氢 和饱和或不饱和、环状或非环状脂族烃残基，可任选被一个或多个选自卤素、 OH、羧基、CN、烷氧基、烷硫基、芳氧基、烷氧基羰基、氨基、取代氨基和任选取代芳基的基团取代； A 代表式 -XR³ 的基团，其中 X 是式-(CHR⁶)p-Y-(CHR⁷)q-的基团，其中式：Y 代表-O-、-S-、NR⁸ 或直接键，p 和 q 各自代表 0、1 或 2 个 R⁶，R⁷ 和 R⁸ 独立地代表氢或低级烷基，R³ 是任选取代的氮环杂芳基，任选含有选自氧、氮或硫的其他环杂原子；B 代表卤代烷基、任选取代的苯基、-CN、-CHO、-CH(低级烷基)₂ 或 -CH²OH。
• 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.
• US4686217A
  申请人：——

  公开号：US4686217A

  公开（公告）日：1987-08-11
• US5064842A
  申请人：——

  公开号：US5064842A

  公开（公告）日：1991-11-12