1-(2,5-Difluorobenzyl)-4-methylpiperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2,5-Difluorobenzyl)-4-methylpiperazine
• 英文别名: 1-[(2,5-difluorophenyl)methyl]-4-methylpiperazine
• 化学式: C₁₂H₁₆F₂N₂
• 分子量: 226.27
• InChiKey: SOAGAGYAVVCTMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  4

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-A]PYRIDINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS SUBSTITUÉS DE PYRAZOLO[1,5-A]PYRIDINES COMME INHIBITEURS DE LA KINASE RET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2017011776A1

  公开（公告）日：2017-01-19

  Provided herein are compounds of the General Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了一般式I的化合物及其立体异构体和药用可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4的含义如规范中所述，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：MEDICAL RES COUNCIL TECHNOLOGY

  公开号：WO2010106333A1

  公开（公告）日：2010-09-23

  A compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein R1 is selected from: aryl; heteroaryl; -NHR3; fused aryl-C4-7-heterocycloalkyI; -CONR4R5; -NHCOR6; -C3-7-cycloalkyl; -O-C3-7-cycloalkyl; -NR3R6; and optionally substituted -C1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C4-7-heterocycloalkyl and C4-7-heterocycloalkyl are each optionally substituted; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl, heteroaryl, C4-7 heterocycloalkyl and halogen, wherein said C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl and C4-7-heterocycloalkyl are each optionally substituted. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).

  一种具有式（I）的化合物，或其药学上可接受的盐或酯，其中R1选自：芳基；杂环芳基；-NHR3；融合芳基-C4-7-杂环烷基；-CONR4R5；-NHCOR6；-C3-7-环烷基；-O-C3-7-环烷基；-NR3R6；和可选择地取代的-C1-6烷基；其中所述的芳基、杂环芳基、融合芳基-C4-7-杂环烷基和C4-7-杂环烷基均可选择地取代；R2选自氢、芳基、C1-6-烷基、C2-6-烯基、C3-7-环烷基、杂环芳基、C4-7-杂环烷基和卤素，其中所述的C1-6-烷基、C2-6-烯基、芳基、杂环芳基和C4-7-杂环烷基均可选择地取代。进一步涉及制备具有式（I）的化合物的药物组合物、治疗用途和制备方法的其他方面。
• [EN] SUBSTITUTED PYRAZOLO[1,5-a]PYRAZINE COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRAZOLO[1,5-A]PYRAZINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE RET
  申请人：ANDREWS STEVEN W

  公开号：WO2018136661A1

  公开（公告）日：2018-07-26

  Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供了Formula I的化合物及其立体异构体和药学上可接受的盐或溶剂，其中A、B、D、E、X1、X2、X3和X4在规范中给出的含义，这些化合物是RET激酶的抑制剂，可用于治疗和预防可以用RET激酶抑制剂治疗的疾病，包括由RET激酶介导的疾病或紊乱。
• COMPOUNDS
  申请人：Mciver Edward Giles

  公开号：US20100317646A1

  公开（公告）日：2010-12-16

  A compound of formula I, or a pharmaceutically acceptable salt or ester thereof, wherein R 1 is selected from: aryl; heteroaryl; —NHR 3 ; fused aryl-C 4-7 -heterocycloalkyl; —CONR 4 R 5 ; —NHCOR 6 ; —C 3-7 -cycloalkyl; —O—C 3-7 -cycloalkyl; —NR 3 R 6 ; and optionally substituted —C 1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C 4-7 -heterocycloalkyl and C 4-7 -heterocycloalkyl are each optionally substituted; R 2 is selected from hydrogen, aryl, C 1-6 -alkyl, C 2-6 -alkenyl, C 3-7 -cycloalkyl, heteroaryl, C 4-7 heterocycloalkyl and halogen, wherein said C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl and C 4-7 -heterocycloalkyl are each optionally substituted; R 3 is selected from aryl, heteroaryl, C 4-7 -heterocycloalkyl, C 3-7 -cycloalkyl, fused aryl-C 4-7 -heterocycloalkyl and C 1-6 -alkyl, each of which is optionally substituted; R 4 and R 5 are each independently hydrogen, or optionally substituted C 3-7 -cycloalkyl, aryl, heteroaryl, C 1-6 -alkyl or C 3-6 -heterocycloalkyl; or R 4 and R 5 together with the N to which they are attached form a C 3-6 -heterocycloalkyl ring; each R 6 is independently selected from C 1-6 -alkyl, C 3-7 cycloalkyl, C 4-7 -heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted each R 7 is selected from hydrogen, optionally substituted C 1-6 -alkyl and C 3-7 -cycloalkyl; each of R 8 and R 9 is independently hydrogen or optionally substituted C 1-6 -alkyl; or R 8 and R 9 together with the N to which they are attached form a C 4-6 -heterocycloalkyl; each R 10 is selected from C 3-7 -cycloalkyl and optionally substituted C 1-6 -alkyl; each R 11 is independently selected from C 1-6 -alkyl, C 3-7 -cycloalkyl, C 1-6 alkyl-C 3-7 -cycloalkyl, C 4-7 -heterocycloalkyl, aryl and heteroaryl, each of which is optionally substituted; A is selected from halogen, —NR 4 SO 2 R 5 , —CN, —OR 6 , —NR 4 R 5 , —NR 7 R 11 , hydroxyl, —CF 3 , —CONR 4 R 5 , —NR 4 COR 5 , —NR 7 (CO)NR 4 R 5 , —NO 2 , —CO 2 H, —CO 2 R 6 , —SO 2 R 6 , —SO 2 NR 4 R 5 , —NR 4 COR 5 , —NR 4 COOR 5 , C 1-6 -alkyl and —COR 6 . Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula I.

  化合物I的公式，或其药学上可接受的盐或酯，其中R1选自：芳基；杂环芳基；—NHR3；融合的芳基-C4-7-杂环烷基；—CONR4R5；—NHCOR6；—C3-7-环烷基；—O—C3-7-环烷基；—NR3R6；和可选择取代的—C1-6烷基；其中所述的芳基，杂环芳基，融合的芳基-C4-7-杂环烷基和C4-7-杂环烷基均可选择取代；R2选自氢，芳基，C1-6-烷基，C2-6-烯基，C3-7-环烷基，杂环芳基，C4-7-杂环烷基和卤素，其中所述的C1-6-烷基，C2-6-烯基，芳基，杂环芳基和C4-7-杂环烷基均可选择取代；R3选自芳基，杂环芳基，C4-7-杂环烷基，C3-7-环烷基，融合的芳基-C4-7-杂环烷基和C1-6-烷基，每种均可选择取代；R4和R5各自独立地选自氢，或可选择取代的C3-7-环烷基，芳基，杂环芳基，C1-6-烷基或C3-6-杂环烷基；或R4和R5与它们连接的N一起形成C3-6-杂环烷基环；每个R6各自独立地选自C1-6-烷基，C3-7-环烷基，C4-7-杂环烷基，芳基和杂环芳基，每种均可选择取代；每个R7选自氢，可选择取代的C1-6-烷基和C3-7-环烷基；每个R8和R9各自独立地选自氢或可选择取代的C1-6-烷基；或R8和R9与它们连接的N一起形成C4-6-杂环烷基；每个R10选自C3-7-环烷基和可选择取代的C1-6-烷基；每个R11各自独立地选自C1-6-烷基，C3-7-环烷基，C1-6-烷基-C3-7-环烷基，C4-7-杂环烷基，芳基和杂环芳基，每种均可选择取代；A选自卤素，—NR4SO2R5，—CN，—OR6，—NR4R5，—NR7R11，羟基，—CF3，—CONR4R5，—NR4COR5，—NR7（CO）NR4R5，—NO2，—CO2H，—CO2R6，—SO2R6，—SO2NR4R5，—NR4COR5，—NR4COOR5，C1-6-烷基和—COR6。进一步方面涉及公式I化合物的制药组合物，治疗用途和制备过程。
• Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US11168090B2

  公开（公告）日：2021-11-09

  Provided herein are compounds of the Formula I: and stereoisomers and pharmaceutically acceptable salts or solvates thereof, in which A, B, D, E, X1, X2, X3 and X4 have the meanings given in the specification, which are inhibitors of RET kinase and are useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including diseases or disorders mediated by a RET kinase.

  本文提供的是式 I 的化合物： 及其立体异构体和药学上可接受的盐或溶液，其中 A、B、D、E、X1、X2、X3 和 X4 具有说明书中给出的含义，它们是 RET 激酶的抑制剂，可用于治疗和预防可以用 RET 激酶抑制剂治疗的疾病，包括由 RET 激酶介导的疾病或紊乱。