(2S,5R)-1-苄基-2,5-二甲基哌嗪 | 260254-80-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2S,5R)-1-苄基-2,5-二甲基哌嗪
• 中文别名: (2S,5R)-1-苄基-2,5-二甲基哌嗪二盐酸盐
• 英文名称: trans-2R,5S-dimethyl-4-benzyl-piperazine
• 英文别名: N-benzyl-2S,5R-dimethylpiperazine；1-benzyl-2(S)-methyl-5(R)-methylpiperazine；(2S,5R)-1-benzyl-2,5-dimethylpiperazine；1-benzyl-2R,5S-dimethyl-piperazine；1-Benzyl-trans-2,5-dimethyl-piperazin
• CAS: 260254-80-6
• 化学式: C₁₃H₂₀N₂
• 分子量: 204.315
• InChiKey: WJTCHBVEUFDSIK-NEPJUHHUSA-N

物化性质

• 沸点：
  291.5±20.0 °C(Predicted)
• 密度：
  0.964±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 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：
  2

反应信息

• 作为反应物：
  描述：

  (2S,5R)-1-苄基-2,5-二甲基哌嗪 在 palladium on activated charcoal sodium hydroxide 、 硫酸 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 60.0~80.0 ℃ 、150.0 kPa 条件下， 反应 52.0h， 生成 {(2S,5R)-4-[2-(4-Methoxy-phenylsulfanyl)-phenyl]-2,5-dimethyl-piperazin-1-yl}-acetic acid
  参考文献：
  名称：

  The synthesis and SAR of 2-arylsulfanyl-phenyl piperazinyl acetic acids as glyT-1 inhibitors

  摘要：

  Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing,the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)- phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC50 = 150 nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2-4.6 mg/kg s.c. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.043
• 作为产物：
  描述：

  N-[叔丁氧羰基]-N-(苯基甲基)-L-丙氨酸 在 盐酸 、 lithium aluminium tetrahydride 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 49.17h， 生成 (2S,5R)-1-苄基-2,5-二甲基哌嗪
  参考文献：
  名称：

  WO2008/125945

  摘要：

  公开号：

文献信息

• Secondary Amides of (<i>R</i>)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionic Acid as Inhibitors of Pyruvate Dehydrogenase Kinase
  作者：Thomas D. Aicher、Robert C. Anderson、Jiaping Gao、Suraj S. Shetty、Gary M. Coppola、James L. Stanton、Douglas C. Knorr、Donald M. Sperbeck、Leonard J. Brand、Christine C. Vinluan、Emma L. Kaplan、Carol J. Dragland、Hollis C. Tomaselli、Amin Islam、Robert J. Lozito、Xilin Liu、Wieslawa M. Maniara、William S. Fillers、Dominick DelGrande、R. Eric Walter、William R. Mann

  DOI：10.1021/jm990358+

  日期：2000.1.1

  6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is

  N'-甲基-N-（4-叔丁基-1,2,5,6-四氢吡啶）硫脲SDZ048-619（1）是丙酮酸脱氢酶激酶的适度抑制剂（IC（50）= 180 microM） （PDHK）。在最优化1的N-甲基碳硫酰胺部分时，发现具有小的酰基的酰胺，特别是（R）-3,3,3-三氟-2-羟基-2-甲基-2-丙酸的适当取代的酰胺，是PDHK的抑制剂。本文报道了利用该酰基部分的原理，其导致一系列酰化哌嗪衍生物的优化。哌嗪在2和5位上的甲基取代（具有S和R绝对立体化学）显着提高了前导化合物的效价（> 1,000倍）。当哌嗪的4位被电子贫乏的苯甲酰基部分取代时，该系列化合物的口服生物利用度良好且最佳（通过AUC测定）。（+）-1-N- [2,5-（S，R）-二甲基-4-N-（4-氰基苯甲酰基）哌嗪]-（R）-3,3，3-三氟-2-羟基-2 -甲基丙酰胺（14e）抑制PDHK在主要酶促测定中的IC（50）为16 +/-
• CARBINOL DERIVATIVES HAVING HETEROCYCLIC LINKER
  申请人：Koura Minoru

  公开号：US20100280013A1

  公开（公告）日：2010-11-04

  [Object] It is to provide a novel LXRβ agonist useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. [Solving Means] A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate: (wherein, each V and W independently show N or C—R 7 ; each X and Y independently show CH 2 , C═O, SO 2 , etc; Z shows CH or N; each R 1 , R 2 and R 7 independently show a hydrogen atom, C 1-8 alkyl group, etc.; R 3 shows C 1-8 alkyl group; R 4 shows an optionally substituted C 6-10 aryl group or an optionally substituted 5- to 11-membered heterocyclic group; R 5 and R 6 show a hydrogen atom, etc.; L shows a C 1-8 alkyl chain optionally substituted with an oxo group, etc.; and n shows any integer of 0 to 2.)

  它是提供一种新型的LXRβ激动剂，可用作预防和/或治疗动脉粥样硬化；动脉硬化，如由糖尿病引起的动脉硬化；血脂异常；高胆固醇血症；与脂质相关的疾病；由炎性细胞因子引起的炎症性疾病；过敏性皮肤病；糖尿病；或阿尔茨海默病的预防和/或治疗剂。【解决手段】由以下一般式（I）表示的羟甲基化合物或其盐，或它们的溶剂化合物： （其中，每个V和W独立地表示N或C—R 7 ；每个X和Y独立地表示CH 2 ，C═O，SO 2 等；Z表示CH或N；每个R 1 ，R 2 和R 7 独立地表示氢原子，C 1-8 烷基基团等；R 3 表示C 1-8 烷基基团；R 4 表示可选择地取代的C 6-10 芳基基团或可选择地取代的5-至11-成员杂环基团；R 5 和R 6 表示氢原子等；L表示可选择地取代有氧基团等的C 1-8 烷基链；n表示0至2的任意整数。】
• Indole-type derivatives as inhibitors of p38 kinase
  申请人：——

  公开号：US20040142940A1

  公开（公告）日：2004-07-22

  The invention is directed to methods to inhibit p38-&agr; kinase using compounds comprising a phenyl or thienyl coupled through a piperidine or piperazine nucleus to an indole residue wherein the indole residue mandatorily has a substituent on the ring nitrogen which is an amino or substituted amino group.

  该发明涉及使用含有苯基或噻吩基通过哌啶或哌嗪核与吲哚残基相连的化合物来抑制p38-α激酶的方法，其中吲哚残基上强制地具有环氮上的氨基或取代氨基基团。
• [EN] BICYCLIC DERIVATIVES FOR USE IN THE TREATMENT OF ANDROGEN RECEPTOR ASSOCIATED CONDITIONS<br/>[FR] DÉRIVÉS BICYCLIQUES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT D'AFFECTIONS ASSOCIÉES AU RÉCEPTEUR DES ANDROGÈNES
  申请人：ASTRAZENECA AB

  公开号：WO2009081197A1

  公开（公告）日：2009-07-02

  The invention concerns bicyclic compounds of Formula (I), wherein the integers X1, X2, X3, Ring A, R4, R5 and m are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of androgen-receptor associated conditions.

  该发明涉及式(I)的双环化合物，其中整数X1、X2、X3、环A、R4、R5和m的定义如描述中所示。本发明还涉及制备这些化合物的方法、含有它们的药物组合物以及它们在制备用于预防或治疗雄激素受体相关疾病的药物中的应用。
• 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。