(3R)-(+)-[1-(3-nitrobenzyl)-3-pyrrolidyl]carbamic acid tert-butyl ester | 876162-07-1

• 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: (3R)-(+)-[1-(3-nitrobenzyl)-3-pyrrolidyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl [(3R)-1-(3-nitrobenzyl)-3-pyrrolidinyl]carbamate；tert-butyl N-[(3R)-1-[(3-nitrophenyl)methyl]pyrrolidin-3-yl]carbamate
• CAS: 876162-07-1
• 化学式: C₁₆H₂₃N₃O₄
• 分子量: 321.376
• InChiKey: IJECJQJCADLRQM-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  87.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R)-(+)-[1-(3-nitrobenzyl)-3-pyrrolidyl]carbamic acid tert-butyl ester 在 palladium diacetate caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 21.0h， 生成 (3R)-N-[1-(3-nitrobenzyl)-3-pyrrolidyl]-N-(5-isoquinolyl)amine
  参考文献：
  名称：

  Design and synthesis of rho kinase inhibitors (III)

  摘要：

  The structure-activity relationship of Rho kinase inhibitors bearing an isoquinoline scaffold was studied. N-(1-Benzyl-3-pyrrolidyl)-N-(5-isoquinolyl)amine analogues were optimized with respect to their inhibitory potencies for the enzyme and for chemotaxis. The potent analogues were further evaluated by an ex vivo test in which the selected compounds were orally administered to rats, and the Rho kinase inhibitory potency observed in the rat serum was evaluated 3 h after the administration. Compound 23g showed a high level of Rho kinase inhibitory activity in the rat serum and was stable in an in vitro metabolic test using a microsomal cytochrome preparation. The (R)-isomer of 23g displayed a higher level of inhibitory potency than the (S)-isomer in a cell-free kinase assay and in the cell migration assay (IC50ENZ = 25 nM and IC50MCP = 1 mu M). The (R)-isomer successfully inhibited the phosphorylation of MBS (myosin-binding subunit) in cells. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2006.10.028
• 作为产物：
  描述：

  (R)-3-叔丁氧羰基氨基吡咯烷 、 间硝基氯化苄 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 (3R)-(+)-[1-(3-nitrobenzyl)-3-pyrrolidyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  ISOQUINOLINE DERIVATIVES HAVING KINASAE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME

  摘要：

  本发明的一个目标是提供具有Rho激酶抑制活性并用于治疗由Rho激酶介导的疾病的化合物。根据本发明的化合物是由以下式（I）表示的，或者其药学上可接受的盐或溶剂：其中Q代表苯基、吡啶基、吡咯基、噻吩基或呋喃基；这些基团可以选择地被一个或两个卤素或烷基、硝基或氨基取代；而p为2或3。

  公开号：

  EP1550660A1

文献信息

• ISOQUINOLINE DERIVATIVES HAVING KINASAE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1550660A1

  公开（公告）日：2005-07-06

  An objective of the present invention is to provide compounds having Rho kinase inhibitory activity and useful for the treatment of diseases mediated by Rho kinase. The compounds according to the present invention are those represented by formula (I) or pharmaceutically acceptable salts or solvates thereof: wherein Q represents phenyl, pyridyl, pyrrolyl, thienyl, or furyl; these groups are optionally substituted by one or two halogens or alkyl, nitro, or amino groups; and p is 2 or 3.

  本发明的一个目标是提供具有Rho激酶抑制活性并用于治疗由Rho激酶介导的疾病的化合物。根据本发明的化合物是由以下式（I）表示的，或者其药学上可接受的盐或溶剂：其中Q代表苯基、吡啶基、吡咯基、噻吩基或呋喃基；这些基团可以选择地被一个或两个卤素或烷基、硝基或氨基取代；而p为2或3。
• HDAC inhibitor
  申请人：Ishibashi Naoki

  公开号：US20060052599A1

  公开（公告）日：2006-03-09

  A compound having the following formula (I): wherein R 1 is hydrogen, lower alkyl, lower alkenyl, lower or higher alkynyl, cyclo(lower)alkyl, cyclo(higher)alkyl, cyclo(lower)alkyl(lower)alkyl, cyclo(higher)alkyl(lower)alkyl, cyclo(lower)alkenyl(lower)alkyl, aryl-fused cyclo(lower)alkyl, lower alkoxy, acyl, aryl, ar(lower)alkoxy, ar(lower)alkyl, heteroar(lower) alkyl, amino, heteroaryl, heterocyclyl or heterocyclyl(lower)alkyl, which may be substituted with one or more suitable substituent(s), R 2 is hydrogen or lower alkyl, X is arylene, heteroarylene, cycloalkylene, heterocycloalkylene or aryl-fused cycloalkylene, Y is arylene or heteroarylene, which may be substituted with one or more suitable substituent(s), Z is lower alkenylene, which may be substituted with lower alkyl or halogen, or a salt thereof. The compound is useful as a histone deacetylase inhibitor.

  以下化合物具有以下式子(I)： 其中， R1为氢、低烷基、低烯基、低或高炔基、环(低)烷基、环(高)烷基、环(低)烷基(低)烷基、环(高)烷基(低)烷基、环(低)烯基(低)烷基、芳基-融合环(低)烷基、低烷氧基、酰基、芳基、芳基(低)烷氧基、芳基(低)烷基、杂芳基(低)烷基、氨基、杂芳基、杂环基或杂环基(低)烷基，可以用一个或多个适当的取代基取代， R2为氢或低烷基， X为芳基亚烷基、杂芳基亚烷基、环烷基、杂环烷基或芳基-融合环烷基， Y为芳基或杂芳基，可以用一个或多个适当的取代基取代， Z为低烯基，可以用低烷基或卤素取代，或其盐。 该化合物可用作组蛋白去乙酰化酶抑制剂。
• HDAC INHIBITOR
  申请人：ISHIBASHI Naoki

  公开号：US20090054464A1

  公开（公告）日：2009-02-26

  Compounds having the formula (I): wherein R 1 is hydrogen, lower alkyl, lower alkenyl, lower or higher alkynyl, cyclo(lower)alkyl, cyclo(higher)alkyl, cyclo(lower)alkyl(lower)alkyl, cyclo(higher)alkyl(lower)alkyl, cyclo(lower)alkenyl(lower)alkyl, aryl-fused cyclo(lower)alkyl, lower alkoxy, acyl, aryl, ar(lower)alkoxy, ar(lower)alkyl, heteroar(lower)alkyl, amino, heteroaryl, heterocyclyl or heterocyclyl(lower)alkyl, which may be substituted with one or more suitable substituent(s), R 2 is hydrogen or lower alkyl, X is pyrrolidinylene or piperidinylene, Y is pyridylene, which may be substituted with one or more suitable substituent(s), Z is lower alkenylene, which may be substituted with lower alkyl or halogen, and salts thereof are useful as a histone deacetylase inhibitors.

  具有以下式（I）的化合物： 其中，R1是氢，低烷基，低烯基，低或高炔基，环低（）烷基，环高（）烷基，环低（）烷基（）烷基，环高（）烷基（）烷基，环低烯基（）烷基，芳基-融合环低（）烷基，低烷氧基，酰基，芳基，芳基（低）烷氧基，芳基（低）烷基，杂芳基（低）烷基，氨基，杂芳基，杂环基或杂环基（低）烷基，可以用一个或多个适当的取代基替代，R2是氢或低烷基，X是吡咯烷基或哌嗪烷基，Y是吡啶烷基，可以用一个或多个适当的取代基替代，Z是低烯基，可以用低烷基或卤素替代，并且它们的盐可用作组蛋白去乙酰化酶抑制剂。
• Design and synthesis of rho kinase inhibitors (III)
  作者：Masayuki Iwakubo、Atsuya Takami、Yuji Okada、Takehisa Kawata、Yoshimichi Tagami、Motoko Sato、Terumi Sugiyama、Kayoko Fukushima、Shinichiro Taya、Mutsuki Amano、Kozo Kaibuchi、Hiroshi Iijima

  DOI：10.1016/j.bmc.2006.10.028

  日期：2007.1

  The structure-activity relationship of Rho kinase inhibitors bearing an isoquinoline scaffold was studied. N-(1-Benzyl-3-pyrrolidyl)-N-(5-isoquinolyl)amine analogues were optimized with respect to their inhibitory potencies for the enzyme and for chemotaxis. The potent analogues were further evaluated by an ex vivo test in which the selected compounds were orally administered to rats, and the Rho kinase inhibitory potency observed in the rat serum was evaluated 3 h after the administration. Compound 23g showed a high level of Rho kinase inhibitory activity in the rat serum and was stable in an in vitro metabolic test using a microsomal cytochrome preparation. The (R)-isomer of 23g displayed a higher level of inhibitory potency than the (S)-isomer in a cell-free kinase assay and in the cell migration assay (IC50ENZ = 25 nM and IC50MCP = 1 mu M). The (R)-isomer successfully inhibited the phosphorylation of MBS (myosin-binding subunit) in cells. (c) 2006 Published by Elsevier Ltd.