(E)-N,N-dimethyl-N'-(1H-pyrrolo[3,2-b]pyridin-5-yl)formimidamide | 1135437-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (E)-N,N-dimethyl-N'-(1H-pyrrolo[3,2-b]pyridin-5-yl)formimidamide
• 英文别名: (E)-N,N-dimethyl-N′-(1H-pyrrolo[3,2-b]pyridin-5-yl)formimidamide
• CAS: 1135437-93-2
• 化学式: C₁₀H₁₂N₄
• 分子量: 188.232
• InChiKey: PBLCIAUNEZBCPV-KPKJPENVSA-N

物化性质

• 沸点：
  364.8±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

文献信息

• Discovery of 3-Cyano-<i>N</i>-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist
  作者：Mark E. Schnute、Mattias Wennerstål、Jennifer Alley、Martin Bengtsson、James R. Blinn、Charles W. Bolten、Timothy Braden、Tomas Bonn、Bo Carlsson、Nicole Caspers、Ming Chen、Chulho Choi、Leon P. Collis、Kimberly Crouse、Mathias Färnegårdh、Kimberly F. Fennell、Susan Fish、Andrew C. Flick、Annika Goos-Nilsson、Hjalmar Gullberg、Peter K. Harris、Steven E. Heasley、Martin Hegen、Alexander E. Hromockyj、Xiao Hu、Bolette Husman、Tomasz Janosik、Peter Jones、Neelu Kaila、Elisabet Kallin、Björn Kauppi、James R. Kiefer、John Knafels、Konrad Koehler、Lars Kruger、Ravi G. Kurumbail、Robert E. Kyne、Wei Li、Joakim Löfstedt、Scott A. Long、Carol A. Menard、Scot Mente、Dean Messing、Marvin J. Meyers、Lee Napierata、Daniel Nöteberg、Philippe Nuhant、Matthew J. Pelc、Michael J. Prinsen、Patrik Rhönnstad、Eva Backström-Rydin、Johnny Sandberg、Maria Sandström、Falgun Shah、Maria Sjöberg、Aron Sundell、Alexandria P. Taylor、Atli Thorarensen、John I. Trujillo、John D. Trzupek、Ray Unwalla、Felix F. Vajdos、Robin A. Weinberg、David C. Wood、Li Xing、Edouard Zamaratski、Christoph W. Zapf、Yajuan Zhao、Anna Wilhelmsson、Gabriel Berstein

  DOI：10.1021/acs.jmedchem.8b00392

  日期：2018.12.13

  The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for

  核激素受体视黄酸受体相关的孤儿C2（RORC2，也称为RORγt）是治疗自身免疫性疾病的有希望的靶标。预期该受体的小分子反向激动剂会减少关键的促炎细胞因子IL-17的产生。通过高通量筛选方法，我们鉴定了一种分子，该分子显示出对RORC2的有希望的结合亲和力，抑制Th17细胞中IL-17的产生以及对相关RORA和RORB受体同工型的选择性。铅优化以提高这种命中的效力和代谢稳定性为重点，主要集中在两个关键设计策略上，即，通过提高亲脂性效率和结构指导的构象限制驱动的迭代优化，以实现最佳的基态能量学和最大化受体停留时间。N-（3-（1-异丁酰基哌啶-4-基）-1-甲基-4-（三氟甲基）-1 H-吡咯并[2,3 - b ]吡啶-5-基）苯甲酰胺为强效且选择性的RORC2逆激动剂，在临床前体内动物模型中，口服给药后表现出良好的代谢稳定性，口服生物利用度以及降低IL-17水平和皮肤炎症的能力。
• [EN] ISOINDOLINE COMPOUNDS FOR THE TREATMENT OF SPINAL MUSCULAR ATROPHY AND OTHER USES<br/>[FR] COMPOSÉS D'ISOINDOLINE POUR LE TRAITEMENT D'UNE AMYOTROPHIE SPINALE ET AUTRES UTILISATIONS
  申请人：US HEALTH

  公开号：WO2009042907A1

  公开（公告）日：2009-04-02

  Disclosed is a compound of Formula (I) in which W and R1-R6 are defined herein. Also disclosed is a method of treating spinal muscular atrophy, as well as methods of using such compounds to increase SMN expression, increase EAAT2 expression, or increase the expression of a nucleic acid that encodes a translational stop codon introduced directly or indirectly by mutation or frameshift.

  公开的是一种化合物，其化学式为（I），其中W和R1-R6在此处被定义。还公开了一种治疗脊髓性肌萎缩症的方法，以及使用这种化合物增加SMN表达、增加EAAT2表达，或增加通过突变或移码直接或间接引入的编码翻译终止密码子的核酸表达的方法。
• RORC2 INHIBITORS AND METHODS OF USE THEREOF
  申请人：PFIZER INC.

  公开号：US20160046597A1

  公开（公告）日：2016-02-18

  The present invention provides compounds, pharmaceutical compositions, methods of inhibiting RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such compounds and pharmaceutical compositions.

  本发明提供化合物、药物组合物、抑制RORγ活性和/或减少受试者体内IL-17含量的方法，以及利用这些化合物和药物组合物治疗各种医学疾病的方法。
• Quinazoline derivatives for use against cancer
  申请人：Ple Patrick

  公开号：US20090036474A1

  公开（公告）日：2009-02-05

  The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of p, R 1 , q, R 2 , R 3 , R 4 , R 5 , Ring A, X 1 , R 6 , r and R 7 has any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.

  该发明涉及式（I）的喹唑啉衍生物或其药学上可接受的盐、溶剂或前药，其中p、R1、q、R2、R3、R4、R5、环A、X1、R6、r和R7中的每一个具有描述中定义的任何含义；它们的制备过程、含有它们的制药组合物以及它们在制造用于治疗细胞增殖性疾病或与血管生成和/或血管通透性相关的疾病状态的药物中的使用。
• Quinazoline derivatives
  申请人：Ple Patrick

  公开号：US20090233924A1

  公开（公告）日：2009-09-17

  The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X 1 , p, R 1 , q, R 2 , R 3 , R 4 , R 5 , Ring A, r and R 6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.

  本发明涉及公式（I）的喹唑啉衍生物或其药学上可接受的盐、溶剂或前药，其中X1、p、R1、q、R2、R3、R4、R5、环A、r和R6中的每一个都具有在本说明书中定义的任何含义；制备它们的过程，含有它们的制药组合物以及它们用于制造用于治疗细胞增殖性疾病或与血管生成和/或血管通透性相关的疾病状态的药物的用途。