3-(2'-(螺-5-氯金刚烷))-4-甲氧基-4-(3'-磷氧基)苯基-1,2-二噁丁环 | 171567-85-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-(2'-(螺-5-氯金刚烷))-4-甲氧基-4-(3'-磷氧基)苯基-1,2-二噁丁环
• 英文名称: N-methoxycarbonyl-D-phenylalanine
• 英文别名: N-methoxycarbonyl-(R)-alanine；(R)-2-(methoxycarbonylamino)-propanoic acid；(2R)-2-(methoxycarbonylamino)propanoic Acid
• CAS: 171567-85-4
• 化学式: C₅H₉NO₄
• 分子量: 147.131
• InChiKey: JAFZODJINWJNPZ-GSVOUGTGSA-N

物化性质

• 沸点：
  304.9±25.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2'-(螺-5-氯金刚烷))-4-甲氧基-4-(3'-磷氧基)苯基-1,2-二噁丁环 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 methyl N-[(2R)-1-chloro-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Synthesis and antidepressant activity of optical isomers of 2-(4-benzylpiperazin-1-yl)-1-(5-chloro-6-methoxynaphthalen-2-yl) propan-1-ol (SIPI5056)

  摘要：

  Four optical isomers of SIPI5056 were synthesized and evaluated for their antidepressant activities and acute toxicities as novel multiple reuptake inhibitors of monoamine transmitters. Chiral alanines were used as educts to prepare their respective target compounds in nine steps. Pharmacological results showed that the (1R,2S)-SIPI5056 isomer has higher inhibitory activity and lower toxicity than other three isomers and is worthy of further development. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.108
• 作为产物：
  描述：

  p-nitrophenyl N-methoxycarbonyl-D-phenylalaninate 在 N-decanoyl-L-histidine methyl ester 十六烷基三甲基溴化铵 作用下， 以 水 为溶剂， 生成 3-(2'-(螺-5-氯金刚烷))-4-甲氧基-4-(3'-磷氧基)苯基-1,2-二噁丁环
  参考文献：
  名称：

  Ihara, Yasuji; Hosako, Reiko; Nango, Mamoru, Journal of the Chemical Society. Perkin transactions II, 1983, p. 5 - 10

  摘要：

  DOI：

文献信息

• An investigation of antibody acyl hydrolysis catalysis using a large set of related haptens
  作者：Amy L. Odenbaugh、Eric D. Helms、Brent L. Iverson

  DOI：10.1016/s0968-0896(99)00302-8

  日期：2000.2

  observed in the catalytic activities of polyclonal antibodies elicited by the different haptens. A phosphate hapten with a phenyl ring on the side of the hapten opposite the linker elicited reproducibly high levels of polyclonal antibody catalytic activity. The other 11 haptens, most with benzyl groups on the side of the hapten opposite the linker, elicited immune responses in which catalytic activity was

  催化抗体研究的一个方面在文献中很少受到关注，涉及半抗原系统，尽管该系统具有高亲和力免疫反应，但仍无法引发抗体催化剂，并且半抗原设计类似于已知可引发催化剂的那些。我们在总共三个动物系统中研究了一系列12种磷酸盐和膦酸半抗原。在不同的半抗原引起的多克隆抗体的催化活性中观察到了巨大的和可重复的差异。在与连接子相对的半抗原侧上具有苯环的磷酸半抗原引起可再现地高水平的多克隆抗体催化活性。其他11个半抗原，大部分在与连接子相对的半抗原侧带有苄基，在所观察到的催化活性的水平以及所引发的催化剂的频率方面，产生了其中催化活性明显较弱的免疫应答。我们的结果表明，过渡态类似物半抗原结构的细微特征可以对相关半抗原中引发的抗体的催化活性产生戏剧性和可复制的影响。无论作出何种解释，由于离去基团的能力/位置或半抗原整体柔性的改变而引起的机械特性的细微变化，此处提供的综合数据表明，与半抗原连接体相对的苯基或4-硝基苯基离
• Peptidomimetic protease inhibitors
  申请人：Babine Edward Robert

  公开号：US20050197299A1

  公开（公告）日：2005-09-08

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，可用作蛋白酶抑制剂，特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎NS3蛋白酶抑制剂；其中间体；它们的制备，包括新的立体选择性过程到中间体。本发明还涉及制药组合物和使用该化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了制药组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，以及使用该组合物治疗或预防患有HCV感染的患者的方法。本发明还涉及用于治疗或预防患有HCV感染的患者的工具包或药物包装。
• PEPTIDOMIMETIC PROTEASE INHIBITORS
  申请人：BABINE ROBERT EDWARD

  公开号：US20120282219A1

  公开（公告）日：2012-11-08

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel stereoselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，作为蛋白酶抑制剂，特别是作为丝氨酸蛋白酶抑制剂，更特别是作为丙型肝炎NS3蛋白酶抑制剂；以及其中间体；它们的制备，包括新的对中间体的立体选择性过程。本发明还涉及制药组合物，以及使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物来治疗或预防患者的HCV感染。本发明还涉及用于治疗或预防患者HCV感染的工具包或药物包。
• Hepatitis C Virus NS5A Replication Complex Inhibitors: The Discovery of Daclatasvir
  作者：Makonen Belema、Van N. Nguyen、Carol Bachand、Dan H. Deon、Jason T. Goodrich、Clint A. James、Rico Lavoie、Omar D. Lopez、Alain Martel、Jeffrey L. Romine、Edward H. Ruediger、Lawrence B. Snyder、Denis R. St. Laurent、Fukang Yang、Juliang Zhu、Henry S. Wong、David R. Langley、Stephen P. Adams、Glenn H. Cantor、Anjaneya Chimalakonda、Aberra Fura、Benjamin M. Johnson、Jay O. Knipe、Dawn D. Parker、Kenneth S. Santone、Robert A. Fridell、Julie A. Lemm、Donald R. O’Boyle、Richard J. Colonno、Min Gao、Nicholas A. Meanwell、Lawrence G. Hamann

  DOI：10.1021/jm401836p

  日期：2014.3.13

  The biphenyl derivatives 2 and 3 are prototypes of a novel class of NS5A replication complex inhibitors that demonstrate high inhibitory potency toward a panel of clinically relevant HCV strains encompassing genotypes 1-6. However, these compounds exhibit poor systemic exposure in rat pharmacokinetic studies after oral dosing. The structure- activity relationship investigations that improved the exposure properties of the parent bis-phenylimidazole chemotype, culminating in the identification of the highly potent NS5A replication complex inhibitor daclatasvir (33) are described. An element critical to success was the realization that the arylglycine cap of 2 could be replaced with an alkylglycine derivative and still maintain the high inhibitory potency of the series if accompanied with a stereoinversion, a finding that enabled a rapid optimization of exposure properties. Compound 33 had EC50 values of 50 and 9 pM toward genotype-1a and -1b replicons, respectively, and oral bioavailabilities of 38-108% in preclinical species. Compound 33 provided clinical proof-of-concept for the NS5A replication complex inhibitor class, and regulatory approval to market it with the NS3/4A protease inhibitor asunaprevir for the treatment of HCV genotype-1b infection has recently been sought in Japan.
• MCCLURE, D. E.;LUMMA, P. K.;ARISON, B. H.;JONES, J. H.;BALDWIN, J. J., J. ORG. CHEM., 1983, 48, N 16, 2675-2679
  作者：MCCLURE, D. E.、LUMMA, P. K.、ARISON, B. H.、JONES, J. H.、BALDWIN, J. J.

  DOI：——

  日期：——