dimethyl 1,2,6-trimethyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate | 137888-00-7

• 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: dimethyl 1,2,6-trimethyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: dimethyl 4-(4-chlorophenyl)-1,2,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate；Dimethyl 4-(4-chlorophenyl)-1,2,6-trimethyl-1,4-dihydro-3,5-pyridinedicarboxylate；dimethyl 4-(4-chlorophenyl)-1,2,6-trimethyl-4H-pyridine-3,5-dicarboxylate
• CAS: 137888-00-7
• 化学式: C₁₈H₂₀ClNO₄
• mdl: MFCD02105315
• 分子量: 349.814
• InChiKey: UQUVPLMRFOKXJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  443.8±45.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl 1,2,6-trimethyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 、 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium 以 乙腈 为溶剂， 生成 4-(4-chlorophenyl)-3,5-bis(methoxycarbonyl)-1,2,6-trimethylpyridin-1-ium 、 N-(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)acetamide
  参考文献：
  名称：

  氢化物转移反应的经典但新的动力学方程式†

  摘要：

  根据过渡态理论，使用氢化物​​供体的莫尔斯型自由能曲线释放氢化物阴离子和氢化物受体以捕获氢化物阴离子，开发了一种经典但新颖的动力学方程式，用于估算各种氢化物转移反应的活化能。 187个典型的氢化物自交换反应和超过3万个氢化物交叉转移反应的活化能 乙腈被安全地估计在这项工作中。由于动力学方程式的发展仅基于氢化物转移反应物的相关化学键变化，因此该动力学方程式也应适用于质子转移反应，氢原子转移反应以及所有其他涉及断裂和化学反应的化学反应。化学键的形成。这项工作最重要的贡献之一是实现了氢化物转移反应动力学方程和热力学方程的完美统一。

  DOI：

  10.1039/c3ob40831k
• 作为产物：
  描述：

  4-氯苯甲醛 、 甲胺 、 2-丁炔酸甲酯 在 三苯基膦氯金 、 silver trifluoromethanesulfonate 、 potassium hydrogencarbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以86%的产率得到dimethyl 1,2,6-trimethyl-4-(4-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  金催化多组分反应：使用活化炔、醛和甲胺合成 N-取代 1,4-二氢吡啶的简便策略

  摘要：

  开发了一种方便有效的金催化多组分反应，用于合成各种 N-取代的 1,4-二氢吡啶，这些化合物存在于各种生物活性化合物中。该过程在温和条件下使用市售底物顺利进行，并以良好到极好的产率提供所需的产品。该方法为从活化炔烃、醛和甲胺制备 N-取代 1,4-二氢吡啶提供了一种高效的合成路线，催化方法稀缺。

  DOI：

  10.1002/ejoc.201301203

文献信息

• [EN] 1,4- DIHYDROPYRIDINE DERIVATIVES WITH HSP MODULATING ACTIVITY<br/>[FR] DÉRIVÉS DE 1,4-DIHYDROPYRIDINE AYANT UNE ACTIVITÉ MODULANT HSP
  申请人：LIPIDART KUTATO FEJLESZTO ES TANACSADO KFT

  公开号：WO2013076516A1

  公开（公告）日：2013-05-30

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R1 is optionally substituted C6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R2 and R3 are independently hydrogen or C1-6alkyl group; R4 and R5 are independently hydrogen, C1-6alkyl group optionally substituted with amino, mono-or di(C1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C1-6alkyl group or C1-6 alkoxy group; R6 is C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl or arylC1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  该发明提供了式（I）的1,4-二氢吡啶衍生物，其中R1是可选择取代的C6-24芳基或含有1至3个氮原子或其他杂原子（如氧和硫）的5至6成员杂芳基，以及它们的组合；R2和R3分别是氢或C1-6烷基基团；R4和R5分别是氢、C1-6烷基基团，可选择地取代为氨基、单或双（C1-6烷基）氨基，或通过氮原子连接的5至24成员可选择融合的杂环基团，可选择地包含额外的1至3个N、O、S杂原子，并可选择地取代为C1-6烷基基团或C1-6烷氧基基团；R6是C1-6烷基、C3-7环烷基、C3-7环烷基C1-6烷基或芳基C1-6烷基基团；以及包括对映异构体、二对映异构体、外消旋混合物、对映异构体混合物和它们的组合，以及多型体、药用可接受盐、溶剂合物、酯类和它们的前药，用于治疗或预防由热休克蛋白介导的疾病。
• 1,4- DIHYDROPYRIDINE DERIVATIVES WITH HSP MODULATING ACTIVITY
  申请人：LIPIDART KUTATÓ FEJLESZTÖ ÉS TANÁCSADÓ KFT.

  公开号：US20140315893A1

  公开（公告）日：2014-10-23

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R 1 is optionally substituted C 6-24 aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R 2 and R 3 are independently hydrogen or C 1-6 alkyl group; R 4 and R 5 are independently hydrogen, C 1-6 alkyl group optionally substituted with amino, mono- or di(C 1-6 alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C 1-6 alkyl group or C 1-6 alkoxy group; R 6 is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl or arylC 1-6 alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  本发明提供了式（I）的1,4-二氢吡啶衍生物，其中R1是可选择取代的C6-24芳基或含有1至3个氮原子或其他杂原子（如氧和硫）的5至6成员杂芳基，以及它们的组合；R2和R3分别是氢或C1-6烷基；R4和R5分别是氢，C1-6烷基（可选择取代氨基，单-或双（C1-6烷基）氨基）或带有氮原子的5至24成员可选择融合的杂环，该杂环可选择包含附加的1至3个N、O、S杂原子并可选择取代C1-6烷基或C1-6烷氧基；R6是C1-6烷基，C3-7环烷基，C3-7环烷基C1-6烷基或芳基C1-6烷基；以及立体异构体，包括对映异构体，顺反异构体，混合对映体和它们的组合，以及其药物学上可接受的盐，溶剂化合物，酯和前药，用于治疗或预防由热休克蛋白介导的疾病。
• 1,4-dihydropyridine derivatives with Hsp modulating activity
  申请人：RICHTER GEDEON NYRT.

  公开号：US10258498B2

  公开（公告）日：2019-04-16

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R1 is optionally substituted C6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R2 and R3 are independently hydrogen or C1-6alkyl group; R4 and R5 are independently hydrogen, C1-6alkyl group optionally substituted with amino, mono- or di(C1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C1-6alkyl group or C1-6 alkoxy group; R6 is C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl or arylC1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  本发明提供了式(I)的1,4-二氢吡啶衍生物，其中R1是任选取代的C6-24芳基或包含1-3个氮原子或其他杂原子（如氧和硫）的5-6成员杂芳基及其组合；R2和R3独立地为氢或C1-6烷基；R4 和 R5 独立地为氢、任选被氨基、一或二（C1-6-烷基）氨基取代的 C1-6 烷基、或由氮连接的 5 至 24 个成员的任选融合杂环，并任选包含 1 至 3 个 N、O、S 杂原子和任选被 C1-6 烷基或 C1-6 烷氧基取代；R6是C1-6烷基、C3-7环烷基、C3-7环烷基C1-6烷基或芳基C1-6烷基；以及立体异构体，包括对映体、非对映体、外消旋混合物、对映体混合物及其组合，以及其多晶型、药学上可接受的盐、溶液剂、酯和原药，用于治疗或预防由热休克蛋白介导的疾病。
• 1,4-dihydropyridine derivatives with HSP modulating activity
  申请人：Richter Gedeon NYRT.

  公开号：US10660789B2

  公开（公告）日：2020-05-26

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R1 is optionally substituted C6-24aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R2 and R3 are independently hydrogen or C1-6alkyl group; R4 and R5 are independently hydrogen, C1-6alkyl group optionally substituted with amino, mono- or di(C1-6alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C1-6alkyl group or C1-6 alkoxy group; R6 is C1-6alkyl, C3-7cycloalkyl, C3-7cycloalkylC1-6alkyl or arylC1-6alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.

  本发明提供了式(I)的1,4-二氢吡啶衍生物，其中R1是任选取代的C6-24芳基或包含1-3个氮原子或其他杂原子（如氧和硫）的5-6成员杂芳基及其组合；R2和R3独立地为氢或C1-6烷基；R4 和 R5 独立地为氢、任选被氨基、一或二（C1-6-烷基）氨基取代的 C1-6 烷基、或由氮连接的 5 至 24 个成员的任选融合杂环，并任选包含 1 至 3 个 N、O、S 杂原子和任选被 C1-6 烷基或 C1-6 烷氧基取代；R6是C1-6烷基、C3-7环烷基、C3-7环烷基C1-6烷基或芳基C1-6烷基；以及立体异构体，包括对映体、非对映体、外消旋混合物、对映体混合物及其组合，以及其多晶型、药学上可接受的盐、溶液剂、酯和原药，用于治疗或预防由热休克蛋白介导的疾病。
• 1,4-Dihydropyridine Derivatives With HSP Modulating Activity
  申请人：Richter Gedeon NYRT.

  公开号：US20190192336A1

  公开（公告）日：2019-06-27

  The invention provides 1,4-dihydropyridine derivatives of formula (I) wherein R 1 is optionally substituted C 6-24 aryl group or 5 to 6 membered heteroaryl group comprising 1 to 3 nitrogen atoms or other heteroatoms like oxygen and sulphur, and combinations thereof; R 2 and R 3 are independently hydrogen or C 1-6 alkyl group; R 4 and R 5 are independently hydrogen, C 1-6 alkyl group optionally substituted with amino, mono- or di(C 1-6 alkyl)amino, or with 5 to 24 membered optionally fused heterocyclic ring attached by nitrogen and optionally comprising additional 1 to 3 N, O, S heteroatoms and optionally substituted with C 1-6 alkyl group or C 1-6 alkoxy group; R 6 is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl or arylC 1-6 alkyl group; and stereoisomers including enantiomers, diastereomers, racemic mixtures, mixture of enantiomers and combination thereof, as well as polymorphs, pharmaceutically acceptable salts, solvates, esters and prodrugs thereof for use in the therapeutic or prophylactic treatment of a disorder mediated by heat shock proteins.