3-[(R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid | 1137882-37-1

• 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: 3-[(R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid
• 英文别名: (R)-3-(2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl)benzoic acid；3-[(2R)-2-(4-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid
• CAS: 1137882-37-1
• 化学式: C₁₆H₁₆N₂O₃S
• 分子量: 316.381
• InChiKey: GBHKUDXOSPJFJH-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 (R)-3-((2-(4-methylthiazol-2-yl)pyrrolidin-1-yl)methyl)benzaldehyde
  参考文献：
  名称：

  Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

  摘要：

  Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K-i of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 angstrom resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 angstrom resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.005
• 作为产物：
  描述：

  间苯二甲酸单甲酯 在 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 3-[(R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl]benzoic acid
  参考文献：
  名称：

  Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

  摘要：

  Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K-i of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 angstrom resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 angstrom resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.04.005

文献信息

• [EN] OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS OXADIAZOLE QUI INHIBENT L'ACTIVITÉ DE LA BÊTA-SECRÉTASE, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：COMENTIS INC

  公开号：WO2012054510A1

  公开（公告）日：2012-04-26

  The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.

  这项发明提供了新型β-分泌酶抑制剂以及它们的方法，包括治疗阿尔茨海默病的方法。
• [EN] (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS BETA-SECRETASE INHIBITORS FOR TREATING<br/>[FR] DÉRIVÉS DE (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE ET COMPOSÉS ASSOCIÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA BÊTA-SÉCRÉTASE POUR LE TRAITEMENT
  申请人：COMENTIS INC

  公开号：WO2009042694A1

  公开（公告）日：2009-04-02

  The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease. (Formula)

  本发明提供了新颖的β-分泌酶抑制剂及其使用方法，包括用于治疗阿尔茨海默病的方法。
• [EN] COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS CONTENANT DES CYCLES FUSIONNÉS QUI INHIBENT L'ACTIVITÉ BÊTA SECRÉTASE ET LEURS MÉTHODES D'UTILISATION
  申请人：COMENTIS INC

  公开号：WO2011130383A1

  公开（公告）日：2011-10-20

  The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.

  这项发明提供了新型β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默病的方法。
• BACE 2 INHIBITORS
  申请人：Mauser Harald

  公开号：US20120053200A1

  公开（公告）日：2012-03-01

  The present invention relates to N-1-Benzyl-2-hydroxy-3-(hetero)arylamino-propyl)-isophthalamides of formula I having BACE2 inhibitory activity and their use as therapeutically active substances, their manufacture and pharmaceutical compositions. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. type 2 diabetes.

  本发明涉及具有BACE2抑制活性的N-1-苄基-2-羟基-3-((杂)芳基)氨基丙基)-异苯二酰胺的公式I，以及它们作为治疗活性物质的用途、它们的制备和制药组合物。本发明的活性化合物在治疗和/或预防治疗例如2型糖尿病方面是有用的。
• [EN] BACE INHIBITORS FOR USE IN THE TREATMENT OF DIABETES<br/>[FR] INHIBITEURS DE LA BACE POUR UNE UTILISATION DANS LE TRAITEMENT DU DIABÈTE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012028563A1

  公开（公告）日：2012-03-08

  The present invention relates to N-1-Benzyl-2-hydroxy-3-(hetero)arylamino-propyl)-isophthalamides of formula (I) having BACE2 inhibitory activity and their use as therapeutically active substances, their manufacture and pharmaceutical compositions. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. type 2 diabetes.

  本发明涉及具有BACE2抑制活性的式(I)的N-1-苄基-2-羟基-3-(杂)芳基氨基丙基异苯二酰胺，以及它们作为治疗活性物质的用途，它们的制造和药物组合物。本发明的活性化合物在治疗和/或预防治疗例如2型糖尿病方面是有用的。