(2S,5R)-N-叔丁氧羰基-5-苯基吡咯烷-2-甲酸 | 221352-49-4

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 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: (2S,5R)-N-叔丁氧羰基-5-苯基吡咯烷-2-甲酸
• 中文别名: (2S,5R)-5-苯基-1,2-吡咯烷二羧酸-1-(1,1-二甲基乙基)酯
• 英文名称: (2S,5R)-(tert-butyloxycarbonyl)-5-phenylpyrrolidine-2-carboxylic acid
• 英文别名: (2S,5R)-N-butoxycarbonyl-5-phenyl-pyrrolidine-2-carboxylic acid；(2S,5R)-1-(tertbutoxycarbonyl)-5-phenylpyrrolidine-2-carboxylic acid；(2S,5R)-Boc-5-phenylpyrrolidine-2-carboxylic acid；N-Boc-5-(R)-phenyl-(S)-proline；(2S,5R)-5-phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester；(2S,5R)-1-[(2-methylpropan-2-yl)oxycarbonyl]-5-phenylpyrrolidine-2-carboxylic acid
• CAS: 221352-49-4
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: ADTXMICUZGOWDF-OLZOCXBDSA-N

物化性质

• 沸点：
  441.5±45.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (2S,5R)-N-叔丁氧羰基-5-苯基吡咯烷-2-甲酸 在 盐酸 、 lithium aluminium tetrahydride 、 10 wt% Pd(OH)2 on carbon 、 水 、 氢气 、 戴斯-马丁氧化剂 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸酐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 生成 tert-butyl (R)-5-oxo-2-phenylpiperidine-1-carboxylate
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055
• 作为产物：
  描述：

  1-tert-butyl 2-methyl (2S,5R)-5-phenylpyrrolidine-1,2-dicarboxylate 在 lithium hydroxide monohydrate 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 生成 (2S,5R)-N-叔丁氧羰基-5-苯基吡咯烷-2-甲酸
  参考文献：
  名称：

  Flexible and Modular Syntheses of Enantiopure 5-cis-Substituted Prolinamines from l-Pyroglutamic Acid

  摘要：

  A wide range (25 examples) of 5-cis-substituted prolinamines is prepared in five to ten steps starting from cheap L-pyroglutamic acid. Three routes, differing mainly in the order of introduction of the substituents at the 5-cis position, the pyrrolidine nitrogen atom, and the exocyclic amino function, are successfully developed.

  DOI：

  10.1055/s-0034-1379457

文献信息

• Discovery, Structure−Activity Relationship, and Pharmacological Evaluation of (5-Substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as Potent Dipeptidyl Peptidase IV Inhibitors
  作者：Zhonghua Pei、Xiaofeng Li、Kenton Longenecker、Thomas W. von Geldern、Paul E. Wiedeman、Thomas H. Lubben、Bradley A. Zinker、Kent Stewart、Stephen J. Ballaron、Michael A. Stashko、Amanda K. Mika、David W. A. Beno、Michelle Long、Heidi Wells、Anita J. Kempf-Grote、David J. Madar、Todd S. McDermott、Lakshmi Bhagavatula、Michael G. Fickes、Daisy Pireh、Larry R. Solomon、Marc R. Lake、Rohinton Edalji、Elizabeth H. Fry、Hing L. Sham、James M. Trevillyan

  DOI：10.1021/jm051283e

  日期：2006.6.1

  A series of (5-substituted pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidine (C5-Pro-Pro) analogues was discovered as dipeptidyl peptidase IV (DPPIV) inhibitors as a potential treatment of diabetes and obesity. X-ray crystallography data show that these inhibitors bind to the catalytic site of DPPIV with the cyano group forming a covalent bond with the serine residue of DPPIV. The C5-substituents make various

  发现了一系列（5-取代的吡咯烷基-2-羰基）-2-氰基吡咯烷（C5-Pro-Pro）类似物作为二肽基肽酶IV（DPPIV）抑制剂，可用于治疗糖尿病和肥胖症。X射线晶体学数据表明，这些抑制剂与DPPIV的催化位点结合，其中氰基与DPPIV的丝氨酸残基形成共价键。C5取代基与酶发生各种相互作用，并影响抑制剂的效能，化学稳定性，选择性和PK特性。优化的类似物对亚纳摩尔的K（i）具有极强的效力，化学性质稳定，在血浆存在下几乎没有效力降低，并且对相关肽酶的选择性超过1,000倍。
• [EN] HIV INTEGRASE INHIBITORS<br/>[FR] INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：MERCK & CO INC

  公开号：WO2005092099A1

  公开（公告）日：2005-10-06

  Bicyclic uracils and related compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the compounds are of Formula (I) wherein a, b, Y, R1, R2, R3 and R4 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  双环尿嘧啶及相关化合物是HIV整合酶的抑制剂，也是HIV复制的抑制剂。在一个实施例中，这些化合物符合以下式（I）的定义，其中a、b、Y、R1、R2、R3和R4在此处被定义。这些化合物对预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病具有用处。这些化合物可作为化合物本身或作为药学上可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合物中的成分，可选择性地与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。
• VLA-4 inhibitor compounds
  申请人：Daiichi Pharmaceutical Co., LTD.

  公开号：US20030078249A1

  公开（公告）日：2003-04-24

  Compounds that selectively inhibit the binding of ligands to &agr;4&bgr;1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: 1 As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.

  本发明公开了选择性抑制配体与α4β1整合素（VLA-4）结合的化合物及其制备方法。在一个实施例中，本发明的化合物由式I表示： 1 作为VLA-4介导的细胞粘附的选择性抑制剂，本发明的化合物可用于治疗与该粘附相关的疾病，包括但不限于炎症和自身免疫反应、糖尿病、哮喘、银屑病、炎症性肠病、移植排斥和肿瘤转移。还公开了包含式I化合物的药物组合物、抑制VLA-4介导的细胞粘附的方法以及治疗与VLA-4介导的细胞粘附相关疾病的方法。
• Vanilloid receptor ligands and their use in treatments
  申请人：Bo Y. Yunxin

  公开号：US20060183745A1

  公开（公告）日：2006-08-17

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  具有一般结构的化合物及其组合物，用于治疗急性、炎症性和神经性疼痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合征、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎性肠道疾病、炎性眼部疾病、炎性或不稳定膀胱疾病、牛皮癣、伴有炎症成分的皮肤疾病、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经性疼痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧伤性神经痛、交感神经维持性疼痛、去神经综合征、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、消化或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• [EN] COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ET UTILISATIONS DE CES DERNIERS
  申请人：YUMANITY THERAPEUTICS

  公开号：WO2018081167A1

  公开（公告）日：2018-05-03

  The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

  本发明涉及对神经系统疾病治疗中有用的化合物。本发明的化合物，单独或与其他药用活性剂结合，可用于治疗或预防神经系统疾病。