2’-(tert-butyl)-1-(2-methoxyquinoline-7-carbonyl)-4’,6’-dihydrospiro[piperidine-4,5’-pyrazolo[3,4-c]pyridin]-7’(2’H)-one | 1374257-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2’-(tert-butyl)-1-(2-methoxyquinoline-7-carbonyl)-4’,6’-dihydrospiro[piperidine-4,5’-pyrazolo[3,4-c]pyridin]-7’(2’H)-one
• 英文别名: 2'-(tert-butyl)-1-(2-methoxyquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one；2-tert-butyl-1'-(2-methoxyquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4'-piperidine]-7-one
• CAS: 1374257-25-6
• 化学式: C₂₅H₂₉N₅O₃
• 分子量: 447.537
• InChiKey: ZXUGLISADYYLBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  喹啉-7-羧酸甲酯 在 过氧乙酸 、 溶剂黄146 、 1-丙基磷酸酐 、 三乙胺 、 sodium hydroxide 、 甲基磺酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.25h， 生成 2’-(tert-butyl)-1-(2-methoxyquinoline-7-carbonyl)-4’,6’-dihydrospiro[piperidine-4,5’-pyrazolo[3,4-c]pyridin]-7’(2’H)-one
  参考文献：
  名称：

  Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

  摘要：

  Acetyl-CoA carboxylase (ACC) catalyzes the rate-determining step in de novo lipogenesis and plays a crucial role in the regulation of fatty acid oxidation. Alterations in lipid metabolism are believed to contribute to insulin resistance; thus inhibition of ACC offers a promising option for intervention in type 2 diabetes mellitus. Herein we disclose a series of ACC inhibitors based on a spirocyclic pyrazololactam core. The lactam series has improved chemical and metabolic stability relative to our previously reported pyrazoloketone series, while retaining potent inhibition of ACC1 and ACC2. Optimization of the pyrazole and amide substituents led to quinoline amide 21, which was advanced to preclinical development.

  DOI：

  10.1021/jm401033t

文献信息

• [EN] USE OF ACETYL-COA CARBOXYLASE INHIBITORS FOR TREATING ACNE VULGARIS<br/>[FR] UTILISATION D'INHIBITEURS DE L'ACÉTYL-COA CARBOXYLASE POUR TRAITER L'ACNÉ VULGAIRE
  申请人：PFIZER

  公开号：WO2015036892A1

  公开（公告）日：2015-03-19

  The present invention relates to methods of treating and/or preventing acne in patients comprising the step of administering to patients in need of such treatment a therapeutically effective amount of an ACC inhibitor or a pharmaceutically acceptable salt thereof.

  本发明涉及治疗和/或预防痤疮的方法，包括向需要此类治疗的患者施用治疗有效量的ACC抑制剂或其药用盐。
• N1/N2-LACTAM ACETYL-COA CARBOXYLASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20150152109A1

  公开（公告）日：2015-06-04

  The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R 1 , R 2 and R 3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

  本发明提供了一种公式(I)的化合物或其药学上可接受的盐；其中G是R1，R2和R3如此处所述；以及其药物组合物；以及在治疗动物中通过抑制乙酰辅酶A羧化酶酶的作用调节的疾病，病况或障碍中的使用。
• USE OF ACETYL-COA CARBOXYLASE INHIBITORS FOR TREATING ACNE VULGARIS
  申请人：PFIZER INC.

  公开号：US20160220557A1

  公开（公告）日：2016-08-04

  The present invention relates to methods of treating and/or preventing acne in patients comprising the step of administering to patients in need of such treatment a therapeutically effective amount of an ACC inhibitor or a pharmaceutically acceptable salt thereof.

  本发明涉及一种治疗和/或预防痤疮的方法，包括向需要此类治疗的患者施用治疗有效量的ACC抑制剂或其药学上可接受的盐。
• METHODS OF IDENTIFYING MYC-DRIVEN AND LIPOGENESIS-DEPENDENT NEOPLASMS AND METHODS OF TREATING THE SAME
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20210137934A1

  公开（公告）日：2021-05-13

  Provided are methods of identifying MYC-Driven and/or lipogenesis-dependent neoplasms. Also provided are methods of treating the MYC-Driven neoplasms and methods of treating lipogenesis-dependent neoplasms. Methods of identifying therapeutic agents that are effective against MYC-driven neoplasms are also provided.
• US9181252B2
  申请人：——

  公开号：US9181252B2

  公开（公告）日：2015-11-10