(4R)-cyclohexylmethoxypyrrolidine-1,(2S)-dicarboxylic acid 1-tert-butyl ester | 147267-14-9

• 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
• 英文名称: (4R)-cyclohexylmethoxypyrrolidine-1,(2S)-dicarboxylic acid 1-tert-butyl ester
• 英文别名: (2S,4R)-4-(cyclohexylmethoxy)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 147267-14-9
• 化学式: C₁₇H₂₉NO₅
• 分子量: 327.421
• InChiKey: KHOIOJHEBUTMMD-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-cyclohexylmethoxypyrrolidine-1,(2S)-dicarboxylic acid 1-tert-butyl ester 在 吡啶 、 盐酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  O-benzyl hydroxyproline as a bioisostere for Phe-Pro: Novel dipeptide thrombin inhibitors

  摘要：

  A series of analogs were prepared based on the known thrombin inhibitor PPACK, in which the D-Phe-ho dipeptide has been replaced by trans-4-O-benzyl hydroxyproline. One of these analogs is a more potent inhibitor of thrombin, and is more selective, than PPACK itself. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00404-0
• 作为产物：
  描述：

  N-叔丁氧羰基-O-苄基-反式-4-羟基-L-脯氨酸 在 Rh/Al₂O₃ 、 氢气 作用下， 以 异丙醇 为溶剂， 反应 24.0h， 以100%的产率得到(4R)-cyclohexylmethoxypyrrolidine-1,(2S)-dicarboxylic acid 1-tert-butyl ester
  参考文献：
  名称：

  Potent and Fully Noncompetitive Peptidomimetic Inhibitor of Multidrug Resistance P-Glycoprotein

  摘要：

  N-alpha-Boc-L-Asp(OBn)-L-Lys(Z)-OtBu (reversin 121, I), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-L-proline (4(R)Hyp) gave compounds 11 and 15 characterized by half-maximal inhibitory concentrations (1050) of 0.6 and 0.2 mu M, which are 2- and 7-fold lower than that of the parent molecule. The difference in IC50 between 11 and 15 rests on the carbonyl group of the peptidyl bond, reduced in 15. Those compounds are rather specific of P-gp, having no or limited activity on MRP1 and BCRP. 15 displayed no marked cytotoxicity up to 10-fold its IC50. Importantly, 15 equally inhibited the Hoechst 33342 and daunorubicin effluxes through a typical noncompetitive inhibition mechanism, suggesting its binding to a site different from the and R drug-transport sites.

  DOI：

  10.1021/jm100839w

文献信息

• Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design
  作者：David C. Tully、Agnès Vidal、Arnab K. Chatterjee、Jennifer A. Williams、Michael J. Roberts、H. Michael Petrassi、Glen Spraggon、Badry Bursulaya、Reynand Pacoma、Aaron Shipway、Andrew M. Schumacher、Henry Danahay、Jennifer L. Harris

  DOI：10.1016/j.bmcl.2008.08.029

  日期：2008.11

  Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.
• BRADYKININ ANTAGONIST PEPTIDES
  申请人：SCIOS NOVA INC.

  公开号：EP0618810A1

  公开（公告）日：1994-10-12
• BRADYKININ TYPE PEPTIDES
  申请人：SCIOS NOVA INC.

  公开号：EP0618809B1

  公开（公告）日：1998-08-19
• EP0618810A4
  申请人：——

  公开号：EP0618810A4

  公开（公告）日：1994-12-07
• US5385889A
  申请人：——

  公开号：US5385889A

  公开（公告）日：1995-01-31