(R)-2-苄基哌嗪 | 131288-11-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: (R)-2-苄基哌嗪
• 中文别名: (R)-2-苄基哌嗪盐酸盐
• 英文名称: 2-(R)-benzylpiperazine
• 英文别名: (R)-2-benzylpiperazine；(2R)-2-benzylpiperazine
• CAS: 131288-11-4
• 化学式: C₁₁H₁₆N₂
• 分子量: 176.261
• InChiKey: RITMXTLCKYLIKW-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  11-氯-二苯并[b,f][1,4]硫氮杂卓 、 (R)-2-苄基哌嗪 在 二氯甲烷 、 甲醇 作用下， 以 甲苯 为溶剂， 反应 19.0h， 以gradient of methanol 3-10%) to give the title compound as a white solid (734 mg, 74%)的产率得到11-(3-(R)-benzylpiperazin-1-yl)dibenzo[b,f][1,4]thiazepine
  参考文献：
  名称：

  Substituted piperazines of azepines, oxazepines and thiazepines

  摘要：

  本文描述了式(I)的抗精神病化合物，其中： - 是一个可选的苯并五元或六元芳香环，其具有0-3个杂原子，独立地选自N，O和S； - R1是氢，(C1-6)氟烷基，(C3-6)环烷基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了羟基，甲氧基，乙氧基，OCH2CH2OH，—CN，咪唑啉-2-酮，苯基或四唑，其中四唑未取代或取代了(C1-4)烷基； - R2是H，卤素，(C1-6)氟烷基，(C3-6)环烷基，OR6，SR6，NO2，CN，COR6，C(O)OR6，C(OH)R6，CONR7R8，苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代了羟基； - R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了苯基； - R4和R5独立地选自氢，卤素，(C1-6)烷基，(C1-6)氟烷基，OR9，SR9，NO2，CN或COR9； - R6是氢，(C1-6)氟烷基或(C1-6)烷基； - R7和R8独立地是氢或(C1-6)烷基； - R9是氢，(C1-6)氟烷基或(C1-6)烷基； - Alk是(C1-4)烷基，未取代或取代了羟基； - Y是氧，硫，SO2或键； - X是CH2，C═O，S，O或SO2； - Z是氢，卤素，(C1-6)烷基，(C1-6)氟烷基，—OH，(C1-6)烷氧基，(C1-6)氟烷氧基，(C1-6)烷硫基，(C1-6)酰基，(C1-4)烷基磺酰基，—OCF3，—NO2，—CN，羧酰胺，其氮上可能通过一个或两个(C1-4)烷基取代，以及—NH2，在其中一个氢可能被(C1-4)烷基取代，另一个氢可能被(C1-4)烷基，(C1-6)酰基或(C1-4)烷基磺酰基取代； - R1，R2或R3的苯基独立地未取代或取代了1-3个Z取代基； - R3的单环杂芳基未取代或取代了1-3个Z取代基； - R3的双环杂芳基未取代或取代了1-3个Z取代基； - 还描述了该化合物的盐，溶剂化合物和晶体形式。 还描述了将式(I)化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及式(I)化合物的制剂。

  公开号：

  US20060270656A1

文献信息

• [EN] SUBSTITUTED PIPERAZINES OF AZEPINES, OXAZEPINES, AND THIAZEPINES<br/>[FR] PIPERAZINES SUBSTITUTEES D'AZEPINES, D'OXAZEPINES, ET DE THIAZEPINES
  申请人：LILLY CO ELI

  公开号：WO2005026177A1

  公开（公告）日：2005-03-24

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C1-4) alkyl; R2 is H, halogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, OR6, SR6, NO2, CN, COR6, C(O)OR6, C(OH)R6, CONR7R8, phenyl or (C1-6) alkyl, wherein the (C1-6) alkyl is unsubstituted or substituted with a hydroxy; R3 is hydrogen, (C 1-6)fluoroalkyl , (C3-6) cycloalkyl, (C 2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C1-4)alkyl wherein (C1-4) alkyl is unsubstituted or substituted with a phenyl; R4 and R5 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR9, SR9, NO2, CN, or COR9; R6 is hydrogen, (C1-6) fluoroalkyl, or (C1-6) alkyl; R7 and R8 are independently hydrogen, or (C1-6) alkyl; R9 is hydrogen, (C1-6) fluoroalkyl, (C1-6) alkyl; Alk is (C1-4) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO2, or a bond; X is CH2, C=O, S, O, or SO2; Z is hydrogen, halogen, (C1-6) alkyl, (C1-6)fluoroalkyl, -OH, (C1-6) alkoxy, (C1-6) fluoroalkoxy, (C1-6) alkylthio, (C1-6) acyl, (C1-4)alkylsulfonyl, -OCF3, -NO2, - CN, carboxamido which may be substituted on the nitrogen by one or two (C1-4) alkyl groups, and -NH2 in which one of the hydrogens may be replaced by a (C1-4) alkyl group and the other hydrogen may be replaced by either a (C1-4) alkyl group, a (C1-6) acyl group, or a (C1-4) alkylsulfonyl group; the phenyl of R1, R2 or R3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中：是一个可选的苯并五元或六元芳香环，其中含有零至三个异原子，独立选择自N、O和S；R1是氢，(C1-6)氟烷基，(C3-6)环烷基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为羟基、甲氧基、乙氧基、OCH2CH2OH、-CN、咪唑烷-2-酮、苯基或四氮唑，其中四氮唑未取代或取代为(C1-4)烷基；R2是H、卤素、(C1-6)氟烷基、(C3-6)环烷基、OR6、SR6、NO2、CN、COR6、C(O)OR6、C(OH)R6、CONR7R8、苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代为羟基；R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为苯基；R4和R5独立选择自氢、卤素、(C1-6)烷基、(C1-6)氟烷基、OR9、SR9、NO2、CN或COR9；R6是氢、(C1-6)氟烷基或(C1-6)烷基；R7和R8独立选择自氢或(C1-6)烷基；R9是氢、(C1-6)氟烷基或(C1-6)烷基；Alk是未取代或取代为羟基的(C1-4)烷基；Y是氧、硫、SO2或键；X是CH2、C=O、S、O或SO2；Z是氢、卤素、(C1-6)烷基、(C1-6)氟烷基、-OH、(C1-6)烷氧基、(C1-6)氟烷氧基、(C1-6)烷硫基、(C1-6)酰基、(C1-4)烷基磺酰基、-OCF3、-NO2、-CN、羧酰胺基，该羧酰胺基可在氮上被一个或两个(C1-4)烷基取代，以及-NH2，其中一个氢原子可被(C1-4)烷基取代，另一个氢原子可被(C1-4)烷基、(C1-6)酰基或(C1-4)烷基磺酰基取代；R1、R2或R3的苯基独立地未取代或取代为从Z中独立选择的一个至三个取代基；R3的单环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；R3的双环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；以及其盐、溶剂化合物和晶型形式。还描述了将式(I)的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相情感障碍的药物，以及式(I)的药物配方。
• Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist
  作者：Seon-Mi Kim、Minhee Lee、So Young Lee、Euisun Park、Soo-Min Lee、Eun Jeong Kim、Min Young Han、Taekyung Yoo、Jihyae Ann、Suyoung Yoon、Jiyoun Lee、Jeewoo Lee

  DOI：10.1021/acs.jmedchem.6b01071

  日期：2016.10.13

  We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this

  我们开发了基于尿嘧啶支架的口服促性腺激素释放激素（GnRH）受体拮抗剂的化合物库。根据体外活性和CYP抑制谱，我们选择18a（SKI2496）进行进一步的体内研究。与猴子和大鼠中的GnRHR相比，化合物18a对人GnRH受体具有更高的选择性拮抗活性，并且该化合物还对GnRH介导的信号传导途径具有抑制作用。与临床上最先进的化合物Elagolix相比，对18a的药代动力学和药效学评估显示出更高的生物利用度和优异的促性腺激素抑制活性。考虑到18a表现出对h GnRHRs的强效和选择性拮抗活性以及良好的药代动力学特征，我们认为18a可能代表口服激素治疗的有希望的候选者。
• Renin inhibitors
  申请人：Jones Benjamin

  公开号：US20090105251A1

  公开（公告）日：2009-04-23

  Compounds, pharmaceutical compositions, kits and methods are provided for use with renin that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.

  提供了与肾素一起使用的化合物、药物组合物、试剂盒和方法，其中包括从以下组中选择的化合物：其中变量如本文所定义。
• [EN] HETEROCYCLIC THIOSEMICARBAZONE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE THIOSEMICARBAZONE HÉTÉROCYCLIQUES ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：NANT HOLDINGS IP LLC

  公开号：WO2017024315A1

  公开（公告）日：2017-02-09

  Pharmaceutical compounds, compositions, and methods are presented in which various heterocyclic thiosemicarbazone derivatives are prepared. Contemplated compounds will be suitable to inhibit or reduce cellular growth or proliferation and are thus beneficial in the manufacture of drugs to treat neoplastic diseases.

  本文介绍了制备各种杂环硫脲类衍生物的药物化合物、组合物和方法。考虑到这些化合物适用于抑制或减少细胞生长或增殖，因此在制造用于治疗肿瘤性疾病的药物方面具有益处。
• Cyclic Amine Compound and Use Thereof for the Prophylaxis or Treatment of Hypertension
  申请人：Kuroita Takanobu

  公开号：US20100121048A1

  公开（公告）日：2010-05-13

  The present invention relates to a compound represented by the formula: (I) wherein ring A is a 5- or 6-membered aromatic heterocycle optionally having substituent (s); U, V and W are each independently C or N, provided that when any one of U, V and W is N, then the others should be C; Ra and Rb are each independently a cyclic group optionally having substituent(s), a C 1-10 alkyl group optionally having substituent(s), a C 2-10 alkenyl group optionally having substituent(s), or a C 2-10 alkynyl group optionally having substituent(s); X is a bond, or a spacer having 1 to 6 atoms in the main chain; Y is a spacer having 1 to 6 atoms in the main chain; Rc is a hydrocarbon group optionally containing heteroatom(s) as the constituting atom(s), which optionally has substituent(s); m and n are each independently 1 or 2; and ring B optionally further has substituent(s), or a salt thereof. The compound of the present invention has excellent renin inhibitory activity, and thus is useful as an agent for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension, and the like.

  本发明涉及一种由式(I)表示的化合物：其中，环A是一种5或6成员的芳香杂环，可选地具有取代基；U、V和W分别独立地为C或N，但当U、V和W中的任何一个为N时，其他的应为C；Ra和Rb分别独立地为一个环状基团，可选地具有取代基；一个C1-10烷基，可选地具有取代基；一个C2-10烯基，可选地具有取代基；或一个C2-10炔基，可选地具有取代基；X是一条键或具有1到6个原子的主链间隔；Y是具有1到6个原子的主链间隔；Rc是一个含有杂原子作为构成原子的碳氢基团，可选地具有取代基；m和n分别独立地为1或2；环B可选地具有取代基，或其盐。本发明的化合物具有优异的肾素抑制活性，因此可用作预防或治疗高血压、高血压引起的各种器官损伤等的药物。