1,5-dimethylpyrazole-4-carboxylic acid methyl ester | 78703-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,5-dimethylpyrazole-4-carboxylic acid methyl ester
• 英文别名: methyl 1,5-dimethyl-1H-pyrazole-4-carboxylate；methyl 1,5-dimethylpyrazole-4-carboxylate
• CAS: 78703-54-5
• 化学式: C₇H₁₀N₂O₂
• 分子量: 154.169
• InChiKey: IFTFDQGCTIBBPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,5-dimethylpyrazole-4-carboxylic acid methyl ester 在 sodium hydroxide 、 硫酸 、 碘 、 碘酸 作用下， 以 吡啶 、 甲醇 、 溶剂黄146 为溶剂， 反应 32.0h， 生成 2,3-Dimethyl-6-phenyl-2H-pyrano[4,3-c]pyrazol-4-one
  参考文献：
  名称：

  Condensation of iodo-N-methylpyrazole-4-carboxylic acids with copper acetylides

  摘要：

  DOI：

  10.1007/bf00949744
• 作为产物：
  描述：

  1-甲基-5-甲基吡唑-4-甲醛 在 盐酸 、 potassium permanganate 作用下， 以 水 为溶剂， 反应 10.0h， 生成 1,5-dimethylpyrazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Condensation of iodo-N-methylpyrazole-4-carboxylic acids with copper acetylides

  摘要：

  DOI：

  10.1007/bf00949744

文献信息

• [EN] PYRAZOLE N-LINKED CARBAMOYL CYCLOHEXYL ACIDS AS LPA ANTAGONISTS<br/>[FR] ACIDES CARBAMOYLE CYCLOHEXYLIQUES À LIAISON N PYRAZOLE UTILISÉS EN TANT QU'ANTAGONISTES DE LPA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019126085A1

  公开（公告）日：2019-06-27

  The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N; Q2 is N or NR5a; one of Q1 and Q3 is CR5, and the other is N or NR5a; and the dashed circle denotes optional bonds forming an aromatic ring; Y1 is O or NR3; Y2 is -CO-, -SO2-, or -S(O(NH)-; Y3 is O or NR4a; provided that (1) Y1 and Y3 are not both O, and (2) when Y2 is C(O), Y1 is not O; L is a covalent bond or C1-4 alkylene substituted with 0 to 4 R7; R1 is (-CH2)aR9; a is an integer of 0 or 1; R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 and R4a are independently hydrogen, C1-6 alkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R4 is C1-10 alkyl, C1-10 haloalkyi, C1-10 deuterated alkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(Ci-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R; or alternatively, R3 and R4, taken together with the N and 0 atoms which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R8; or alternatively, (R3 and R5a) or (R3 and R5), taken together with the atoms to which they are attached to, form a 5 to 8-membered heterocyclic ring moiety which is substituted with 0 to 3 R8; R5a is hydrogen, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atom(s) to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12; R9 is selected from -CN, -C(O)OR10, -C(O)NR11aR11b, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re,-SO2-OH, -SO2-NH-CO-Re, -P(O)(OH)2, tetrazol-5-yl, -CH2-CO-NH-CO-Re, -CH2-CO-NH-SO2-Re, -CH2-CO-NH-SO-Re, -CH2-SO2-OH, -CH2-SO2-NH-CO-Re, -CH2-P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyi, aminoalkyi, alkoxyalkyi, or haloalkoxyalkyi; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.

  本发明提供了式（I）的化合物或其立体异构体、互变异构体、或药学上可接受的盐或溶剂，其中X1、X2、X3和X4分别独立地为CR6或N；但X1、X2、X3或X4中不超过两个为N；Q2为N或NR5a；Q1和Q3中的一个为CR5，另一个为N或NR5a；虚线圆圈表示形成芳香环的可选键；Y1为O或NR3；Y2为-CO-、-SO2-或-S(O(NH)-；Y3为O或NR4a；但要求（1）Y1和Y3不同时为O，（2）当Y2为C(O)时，Y1不为O；L为共价键或C1-4烷基烯，取代为0至4个R7；R1为（-CH2）aR9；a为0或1的整数；R2分别为卤素、氰基、羟基、氨基、C1-6烷基、C3-6环烷基、C4-6杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基、烷氧基烷基、卤代烷氧基烷基或卤代烷氧基；n为0、1或2的整数；R3和R4a独立地为氢、C1-6烷基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R4为C1-10烷基、C1-10卤代烷基、C1-10氘代烷基、C1-10烯基、C3-8环烷基、6至10成员芳基、3至8成员杂环烷基、-(C1-6烷基)-(C3-8环烷基)、-(C1-6烷基)-(6至10成员芳基)、-(C1-6烷基)-(3至8成员杂环烷基)或-(C1-6烷基)-(5至6成员杂芳基)；其中烷基、烷基烯、烷基烷、环烷基、芳基、杂环烷基和杂芳基中的每一个，单独或作为其他基团的一部分，独立地取代为0至3个R；或者，R3和R4连同它们连接的N和O原子，形成取代为0至3个R8的4至9成员杂环环基；或者，(R3和R5a)或(R3和R5)，连同它们连接的原子，形成取代为0至3个R8的5至8成员杂环环基；R5a为氢、C1-6烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R5和R6分别独立地为氢、卤素、氰基、羟基、氨基、烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R7为卤素、氧、氰基、羟基、氨基、C1-6烷基、C3-6环烷基、C4-6杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R8分别独立地为氘、卤素、羟基、氨基、氰基、C1-6烷基、C1-6氘代烷基、C2-6烯基、C2-6炔基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基、卤代烷氧基、苯基或5至6成员杂芳基；或者，两个R8连同它们连接的原子，形成取代为0至3个R12的3至6成员碳环或3至6成员杂环，每个独立地取代为0至3个R12；R9从-CN、-C(O)OR10、-C(O)NR11aR11b、-CO-NH-CO-Re、-CO-NH-SO2-Re、-CO-NH-SO-Re、-SO2-OH、-SO2-NH-CO-Re、-P(O)(OH)2、四唑-5-基、-CH2-CO-NH-CO-Re、-CH2-CO-NH-SO2-Re、-CH2-CO-NH-SO-Re、-CH2-SO2-OH、-CH2-SO2-NH-CO-Re、-CH2-P(O)(OH)2、四唑-5-基甲基中选择；Re为C1-6烷基、C3-6环烷基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基或卤代烷氧基烷基；R10为氢或C1-10烷基；R11a和R11b分别独立地为氢、C1-6烷基、C3-6环烷基、C4-6杂环烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基或卤代烷氧基；R12为卤素、氰基、羟基、氨基、C1-6烷基、烷基氨基、卤代烷基、羟基烷基、氨基烷基、烷氧基烷基、卤代烷氧基烷基、烷氧基、卤代烷氧基、苯基或5至6成员杂芳基。这些化合物是选择性的LPA受体抑制剂。
• [EN] HETEROARYL COMPOUNDS USEFUL AS RAF KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROARYLES UTILES EN TANT QU'INHIBITEURS DE KINASE RAF
  申请人：BIOGEN IDEC INC

  公开号：WO2010078408A1

  公开（公告）日：2010-07-08

  The present invention provides compounds of formula (I) useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf -mediated diseases.

  本发明提供了一种化合物，其化学式为（I），可用作Raf蛋白激酶的抑制剂。本发明还提供了这些化合物的组合物，以及治疗Raf介导疾病的方法。
• [EN] CYCLOHEXYL ACID PYRAZOLE AZINES AS LPA ANTAGONISTS<br/>[FR] AZINES PYRAZOLES D'ACIDE CYCLOHEXYLE UTILISÉS EN TANT QU'ANTAGONISTES DE LPA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019126089A1

  公开（公告）日：2019-06-27

  The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.

  本发明提供了式（I）的化合物：或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是选择性LPA受体抑制剂。
• [EN] PYRAZOLE O-LINKED CARBAMOYL CYCLOHEXYL ACIDS AS LPA ANTAGONISTS<br/>[FR] ACIDES CARBAMOYLE CYCLOHEXYLIQUES À LIAISON O PYRAZOLE UTILISÉS EN TANT QU'ANTAGONISTES DE LPA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019126098A1

  公开（公告）日：2019-06-27

  The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.

  本发明提供了式（I）的化合物或其立体异构体、互变异构体、或其药用可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是选择性LPA受体抑制剂。
• [EN] CYCLOHEXYL ACID PYRAZOLE AZOLES AS LPA ANTAGONISTS<br/>[FR] ACIDES PYRAZOLES AZOLES CYCLOHEXYLIQUES UTILISÉS EN TANT QU'ANTAGONISTES DE LPA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019126103A1

  公开（公告）日：2019-06-27

  The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.

  本发明提供了式（I）的化合物或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是选择性LPA受体抑制剂。