1-(4-Fluoro-benzyl)-trans-2,5-dimethyl-piperazine

• 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-(4-Fluoro-benzyl)-trans-2,5-dimethyl-piperazine
• 英文别名: 1-(4-fluorobenzyl)-2,5-dimethylpiperazine；1-(4-fluoro-benzyl)-2R,5S-dimethyl-piperazine；N-4-Fluorobenzyl-trans-2,5-dimethylpiperazine；E-1-(4-Fluorobenzyl)-2,5-dimethylpiperazine；Piperazine, 1-[(4-fluorophenyl)methyl]-2,5-dimethyl-, (2S,5R)-；1-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine
• 化学式: C₁₃H₁₉FN₂
• 分子量: 222.306
• InChiKey: VWFLVEICKAOIRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-Fluoro-benzyl)-trans-2,5-dimethyl-piperazine 、 4-溴肉桂酸 在 1-羟基苯并三唑 、 TBD-methyl polystyrene 作用下， 以 氯仿 为溶剂， 反应 0.08h， 以97%的产率得到(E)-(trans)-3-(4-bromo-phenyl)-1-[4-(4-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-prop-2-en-1-one
  参考文献：
  名称：

  Novel cinnamic amides

  摘要：

  根据公式（I），X为氯或氟，R1为芳香或杂芳基的哌嗪衍生物的E-肉桂酰胺，其药学上可接受的盐或溶剂。该发明还涉及含有公式（I）化合物的药物组合物，以及制备公式（I）化合物的方法，以及通过向哺乳动物施用具有公式（I）的化合物来治疗患有炎症、自身免疫、增殖性或过度增殖性疾病的方法。

  公开号：

  US20050192289A1
• 作为产物：
  描述：

  cis-2,5-dimethylpiperazine dihydrobromide 、 4-氟溴苄 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以4%的产率得到1-(4-Fluoro-benzyl)-trans-2,5-dimethyl-piperazine
  参考文献：
  名称：

  Novel cinnamic amides

  摘要：

  根据公式（I），X为氯或氟，R1为芳香或杂芳基的哌嗪衍生物的E-肉桂酰胺，其药学上可接受的盐或溶剂。该发明还涉及含有公式（I）化合物的药物组合物，以及制备公式（I）化合物的方法，以及通过向哺乳动物施用具有公式（I）的化合物来治疗患有炎症、自身免疫、增殖性或过度增殖性疾病的方法。

  公开号：

  US20050192289A1

文献信息

• Inhibitors of p38 kinase
  申请人：——

  公开号：US20030092717A1

  公开（公告）日：2003-05-15

  The invention is directed to methods to inhibit p38-&agr; kinase using compounds of the formula 1 and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein represents a single or double bond; B is —W i —COX j Y wherein Y is COR 2 or an isostere thereof and R 2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; each R 3 is independently a noninterfering substituent, where n is 0-3; Z 3 is NR 7 or O; wherein R 7 is H or a noninterfering substituent; one Z 2 is CA or CR 8 A and the other is CR 1 , CR 1 2 , NR 6 or N wherein each R 1 , R 6 and R 8 is independently hydrogen or noninterfering substituent; wherein A is: 2 such that Z 1 is CR 5 or N wherein R 5 is hydrogen or a noninterfering substituent; each of 1 and k is an integer from 0-2 wherein the sum of 1 and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; each R 4 is independently a noninterfering substituent where m is 0-4; each of L 1 and L 2 is a linker; and the distance between the atom of Ar linked to L 2 and the center of the &bgr; ring is 4.5-24 Å.

  该发明涉及使用式1化合物及其药用盐来抑制p38-α激酶的方法，或者其药物组合物，其中表示单键或双键；B为—Wi—COXjY，其中Y为COR2或其同分异构体，R2为氢或非干扰基，W和X各自为2-6埃的间隔物，i和j各自独立为0或1；每个R3各自为非干扰基，其中n为0-3；Z3为NR7或O；其中R7为H或非干扰基；一个Z2为CA或CR8A，另一个为CR1、CR12、NR6或N，其中每个R1、R6和R8各自独立为氢或非干扰基；其中A为:2，使得Z1为CR5或N，其中R5为氢或非干扰基；每个1和k为0-2的整数，其中1和k的和为0-3；Ar为带有0-5个非干扰基的芳基，其中两个非干扰基可形成融合环；每个R4各自为非干扰基，其中m为0-4；每个L1和L2为连接物；以及与L2连接的Ar原子与β环中心之间的距离为4.5-24埃。
• Novel benzofurans and indols
  申请人：Wellner Eric

  公开号：US20050192288A1

  公开（公告）日：2005-09-01

  Compounds of formula (I) wherein X is a fluorine or a chlorine atom; the methyl groups located at the 2- and 5-position of the piperazine ring are in trans-configuration to each other; Y is NH or O; R 1 is selected front hydrogen, chloro, bromo, nitro, methyl or trifluoromethyl; R 2 is selected from hydrogen, halo, methyl, trifluoromethyl, methoxy or trifluoromethoxy; or a pharmaceutically acceptable salt or solvate thereof, The invention also relates to pharmaceutical compositions containing a compound of formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of compounds of formula (I), as well as methods for treating mammals suffering from inflammatory, autoimmune, proliferative or hyperproliferative diseases by administering a compound having the formula (I) to said mammal.

  式(I)的化合物，其中X是氟或氯原子；位于哌嗪环的2-和5-位置的甲基基团相对于彼此处于反式构型；Y是NH或O；R1从氢、氯、溴、硝基、甲基或三氟甲基中选择；R2从氢、卤、甲基、三氟甲基、甲氧基或三氟甲氧基中选择；或其药学上可接受的盐或溶剂，本发明还涉及含有式(I)的化合物的药物组合物，连同药学上可接受的载体。还包括制备式(I)化合物的方法，以及通过向哺乳动物投与具有式(I)的化合物来治疗患有炎症、自身免疫、增殖或过度增殖疾病的哺乳动物的方法。
• Piperidine/piperazine-type inhibitors of p38 kinase
  申请人：——

  公开号：US20020198214A1

  公开（公告）日：2002-12-26

  The invention is directed to inhibition of p38-&agr; kinase using compounds of the formula 1 and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein: Ar 1 is an aryl group substituted with 0-5 non-interfering substituents, wherein two adjacent noninterfering substituents can form a fused aromatic or nonaromatic ring; L 1 and L 2 are linkers; each R 1 is independently a noninterfering substituent; Z 1 is CR 2 or N wherein R 2 is hydrogen or a noninterfering substituent; m is 0-4; each of n and p is an integer from 0-2 wherein the sum of n and p is 0-3; Ar 2 is a substantially planar, monocyclic or polycyclic aromatic moiety having one or more optional ring heteroatoms, said moiety being optionally substituted with one or more non-interfering substituents, two or more of which may form a fused ring; Z is —W i —COX j Y wherein Y is COR 3 or an isostere thereof; R 3 is a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; wherein the smallest number of covalent bonds in the compound separating the atom of Ar 1 bonded to L 2 to the atom of Ar 2 bonded to L 1 is at least 6, where each of said bonds has a bond length of 1.2 to 2.0 angstroms; and/or wherein the distance in space between the atom of Ar 1 bonded to L 2 and the atom of Ar 2 bonded to L 1 is 4.5-24 angstroms; with the proviso that the portion of the compound represented by Ar 2 —Z is not 2 wherein represents a single or double bond; n is 0-3; one Z 2 is CA or CRA and the other is CR, CR 2 , NR or N; A is —W i —COX j Y wherein Y is COR or an isostere thereof, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; Z 3 is NR or O; and each R is independently hydrogen or a noninterfering substituent.

  本发明涉及使用公式1及其药学上可接受的盐或药物组合物来抑制p38-α激酶，其中： Ar1是芳基基团，取代有0-5个不干扰的取代基，其中两个相邻的不干扰的取代基可以形成融合的芳香或非芳香环； L1和L2是连接基； 每个R1独立地是一个不干扰的取代基； Z1是CR2或N，其中R2是氢或不干扰的取代基； m为0-4； n和p各自是0-2的整数，其中n和p的总和为0-3； Ar2是一个具有一个或多个可选环杂原子的基本平面、单环或多环芳香基团，该基团可以选择性地取代有一个或多个不干扰的取代基，其中两个或更多个可以形成融合环； Z是—Wi—COXjY，其中Y是COR3或其同分异构体；R3是不干扰的取代基，W和X各自是2-6Å的间隔基，i和j各自独立地为0或1； 其中，在化合物中分离与L2结合的Ar1原子到与L1结合的Ar2原子之间的共价键的最小数量至少为6，其中每个键的键长为1.2到2.0 Å；和/或在空间中，在与L2结合的Ar1原子和与L1结合的Ar2原子之间的距离为4.5-24 Å； 但化合物中由Ar2—Z所代表的部分不是2，其中： 表示单键或双键； n为0-3； 一个Z2是CA或CRA，另一个是CR、CR2、NR或N； A是—Wi—COXjY，其中Y是COR或其同分异构体，W和X各自是2-6Å的间隔基，i和j各自独立地为0或1； Z3是NR或O； 每个R独立地是氢或不干扰的取代基。
• Azaindole derivatives as inhibitors of p38 kinase
  申请人：Mavunkel J. Babu

  公开号：US20050288299A1

  公开（公告）日：2005-12-29

  The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through a piperidine or piperazine type linker to another cyclic moiety.

  本发明涉及抑制p38激酶的方法，优选抑制p38-α，使用的化合物是氮杂吲哚，其中氮杂吲哚通过哌啶或哌嗪型连接剂与另一个环状基团耦合。
• [EN] INDOLE-TYPE DERIVATIVES AS INHIBITORS OF p38 KINASE<br/>[FR] DERIVES DE TYPE INDOLE EN TANT QU'INHIBITEURS DE p38 KINASE
  申请人：SCIOS INC

  公开号：WO2000071535A1

  公开（公告）日：2000-11-30

  The invention is directed to methods to inhibit p38-α kinase using compounds of formula (1), and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein (a) represents a single or double bond; one Z2 is CA or CR8A and the other is CR1, CR12, NR6 or N wherein each R?1, R6 and R8¿ is independently hydrogen or noninterfering substituent; A is -W¿i?-COXjY wherein Y is COR?2¿ or an isostere thereof and R2 is hydrogen or a noninterfering substituent, each of W and X is a spacer of 2-6Å, and each of i and j is independently 0 or 1; Z?3 is NR7¿ or O; each R3 is independently a noninterfering substituent; n is 0-3; each of L?1 and L2¿ is a linker; each R4 is independently a noninterfering substituent; m is 0-4; Z?1 is CR5¿ or N wherein R5 is hydrogen or a noninterfering substituent; each of l and k is an integer from 0-2 wherein the sum of l and k is 0-3; Ar is an aryl group substituted with 0-5 noninterfering substituents, wherein two noninterfering substituents can form a fused ring; and the distance between the atom of Ar linked to L2 and the center of the α ring is 4.5-24Å.

  该发明涉及使用式（1）的化合物及其药学上可接受的盐或药物组合物来抑制p38-α激酶的方法，其中（a）表示单个或双键；Z2中的一个为CA或CR8A，另一个为CR1、CR12、NR6或N，其中每个R?1、R6和R8¿都独立地表示氢或非干扰取代基；A为-W¿i?-COXjY，其中Y为COR?2¿或其同分异构体，R2为氢或非干扰取代基，W和X各自为2-6Å的间隔，i和j各自独立地为0或1；Z?3为NR7¿或O；每个R3都独立地表示非干扰取代基；n为0-3；每个L?1和L2¿都是一个连接基；每个R4都独立地表示非干扰取代基；m为0-4；Z?1为CR5¿或N，其中R5为氢或非干扰取代基；每个l和k都是0-2的整数，其中l和k的和为0-3；Ar是一个芳基基团，其被0-5个非干扰取代基取代，其中两个非干扰取代基可以形成融合环；并且与L2连接的Ar原子与α环中心的距离为4.5-24Å。