(S)-1-(4-cyanobenzyl)-5-oxopyrrolidine-2-carboxylic acid | 132311-92-3

• 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: (S)-1-(4-cyanobenzyl)-5-oxopyrrolidine-2-carboxylic acid
• 英文别名: (S)-N-(4-cyanobenzoic)-5-oxoproline；N-(4-Cyanobenzyl)-L-pyroglutamic acid；(2S)-1-[(4-cyanophenyl)methyl]-5-oxopyrrolidine-2-carboxylic acid
• CAS: 132311-92-3
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: GAHUPZWGZJUTMW-NSHDSACASA-N

物化性质

• 沸点：
  552.0±50.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-1-(4-cyanobenzyl)-5-oxopyrrolidine-2-carboxylic acid 在 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.67h， 生成 4-(((S)-2-((R)-3-((4-fluorophenyl)sulfonyl)-3-(4-(perfluoropropan-2-yl)phenyl)pyrrolidine-1-carbonyl)-5-oxopyrrolidin-1-yl)methyl)benzamide
  参考文献：
  名称：

  使用虚拟筛选方法鉴定作为有效 RORγt 反向激动剂的新型三环焦谷酰胺衍生物

  摘要：

  采用虚拟筛选方法，我们将焦谷酰胺部分鉴定为环己烷羧酸基团的非酸替代物，当与我们之前报道的构象锁定三环核心结合时，提供有效和选择性的 RORγt 反向激动剂。焦谷酰胺部分的构效关系优化导致化合物18被鉴定为有效且选择性的 RORγt 反向激动剂，尽管水溶性较差。我们利用18中的叔甲醇基团合成了一种磷酸盐前药，该前药具有良好的溶解性，在小鼠 PK 研究中具有出色的暴露性，并且在银屑病小鼠模型中具有显着疗效。

  DOI：

  10.1021/acsmedchemlett.0c00496
• 作为产物：
  描述：

  L-焦谷氨酸 在 硫酸 sodium hydroxide 、 sodium hydride 作用下， 以 苯 为溶剂， 反应 70.0h， 生成 (S)-1-(4-cyanobenzyl)-5-oxopyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Beani; Bianchi; Baraldi, Arzneimittel-Forschung/Drug Research, 1990, vol. 40, # 11, p. 1187 - 1191

  摘要：

  DOI：

文献信息

• Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids
  作者：Ankita Misra、K.S. Anil Kumar、Manish Jain、Kirti Bajaj、Shyamali Shandilya、Smriti Srivastava、Pankaj Shukla、Manoj K. Barthwal、Madhu Dikshit、Dinesh K. Dikshit

  DOI：10.1016/j.ejmech.2016.01.019

  日期：2016.3

  N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular

  制备了取代的联吡啶的N-芳烷基焦谷氨酰胺，并在体内和体外评估其抑制胶原诱导的血小板聚集的能力。一些化合物显示出很高的抗血小板功效（体外），其中有六种化合物通过双重机制抑制胶原蛋白以及U46619诱导的血小板凝集，并具有浓度依赖性的抗血小板功效。特别地，该化合物4 Ĵ提供针对显著保护胶原诱导肾上腺素肺血栓栓塞症，以及氯化铁诱导的动脉血栓形成，而不影响在小鼠出血倾向。因此，本研究表明化合物4 j 显示出显着的抗血栓形成功效，比阿司匹林和氯吡格雷好得多。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05624936A1

  公开（公告）日：1997-04-29

  The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compounds of the instant invention also incorporate a cyclic amine moiety in the A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

  本发明涉及蛋白质Ras的CA.sup.1 A.sup.2 X基序列的类似物，该序列在体内通过法尼酰化进行修饰。这些CA.sup.1 A.sup.2 X类似物抑制法尼酰蛋白转移酶和某些蛋白质的法尼酰化。此外，这些CA.sup.1 A.sup.2 X类似物与先前描述的抑制法尼酰蛋白转移酶的类似物不同，因为它们不含有巯基。缺乏巯基在改善动物体内药代动力学行为、预防依赖巯基的化学反应（如快速自氧化和与内源巯基形成二硫键）以及降低全身毒性方面具有独特优势。该即时发明的化合物还在基序列的A.sup.2位置包含一个环状胺基团。本发明还包括含有这些法尼酰转移酶抑制剂的化疗组合物以及其生产方法。
• 3,7-DIAZABICYCLO[3.3.1]NONANE CARBOXAMIDES AS ANTITHROMBOTIC AGENTS
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US20160214983A1

  公开（公告）日：2016-07-28

  The present invention relates to the 3,7-diazabicyclo[3.3.1]nonane carboxamides and process for preparation thereof. The present invention further relates to the compounds of general formula 1 possessing anti-thrombotic (anti-platelet) activities. The invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors both in vitro and in vivo. Further, invention also relates these class of compounds exhibiting anti-platelet efficacy through dual mechanism inhibited both collagen as well as U46619 (thromboxane receptor agonist) induced platelet aggregation. wherein, R′ is; wherein R is selected from alkyl, acyl, tosyl, tert-butyloxycarbonyl, araalkyl or substituted araalkyl groups; R″ is selected preferably from halogen, cyano, lower alkyl, aryl, substituted aryl, and tosyl groups; R1 is selected from hydrogen and lower alkyl groups; R2 is selected from lower alkyl and aryl groups; R3 is selected from tert-butyloxycarbonyl and bezyloxycarbonyl groups; n=0,1.

  本发明涉及3,7-二氮杂双环[3.3.1]壬烷羧酰胺及其制备方法。本发明进一步涉及一般式1的化合物，具有抗血栓（抗血小板）活性。发明还涉及使用这些分子作为体外和体内抑制胶原诱导的血小板粘附和聚集介导的胶原受体的抑制剂。此外，发明还涉及这类化合物通过双重机制抑制胶原和U46619（血栓素A2受体激动剂）诱导的血小板聚集，表现出抗血小板功效。其中，R'为；其中，R选择自烷基，酰基，对甲苯磺酰基，叔丁氧羰基，芳基烷基或取代芳基基团；R″优选选择自卤素，氰基，低烷基，芳基，取代芳基和对甲苯磺酰基基团；R1选择自氢和低烷基基团；R2选择自低烷基和芳基基团；R3选择自叔丁氧羰基和苄氧羰基基团；n=0,1。
• Tricyclic sulfones as RORγ modulators
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10273259B2

  公开（公告）日：2019-04-30

  There are described RORγ modulators of the formula (I), and formula (II) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

  描述了式 (I) 的 RORγ 调节剂、 和式(II) 或其立体异构体、同系物、药学上可接受的盐、溶液或原药，其中所有取代基均在本文中定义。还提供了包含上述化合物的药物组合物。此类化合物和组合物可用于调节细胞中RORγ活性的方法和治疗患有疾病或失调的受试者的方法，其中受试者将从调节RORγ活性中获得治疗益处，例如自身免疫和/或炎症性失调。
• Antiviral compounds
  申请人：HAPLOGEN GMBH

  公开号：US11091428B2

  公开（公告）日：2021-08-17

  The present invention relates to novel compounds of general formula (I) wherein the groups X, and R1 to R4 have the meanings given in the description and claims, process for preparing these compounds and their use as for treating, preventing or ameliorating viral infections and their use for treating, preventing or ameliorating diseases which are associated with PLA2G16.

  本发明涉及通式(I)的新型化合物（其中基团X和R1至R4的含义见说明书和权利要求书）、制备这些化合物的工艺及其用于治疗、预防或改善病毒感染的用途，以及用于治疗、预防或改善与PLA2G16有关的疾病的用途。