2-(4-fluoroindolin-1-yl)ethanamine | 552866-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(4-fluoroindolin-1-yl)ethanamine
• 英文别名: 2-(4-Fluoro-2,3-dihydroindol-1-yl)ethanamine
• CAS: 552866-99-6
• 化学式: C₁₀H₁₃FN₂
• 分子量: 180.225
• InChiKey: LGLUWIPVFAYANY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-fluoroindolin-1-yl)ethanamine 、 异氰酸2-溴苯酯 以 二氯甲烷 为溶剂， 生成 1-(2-bromophenyl)-3-[2-(4-fluoro-2,3-dihydro-1H-indol-1-yl)ethyl]urea
  参考文献：
  名称：

  Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development

  摘要：

  Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.030
• 作为产物：
  描述：

  4-氟吲哚 在 sodium cyanoborohydride 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 反应 36.0h， 生成 2-(4-fluoroindolin-1-yl)ethanamine
  参考文献：
  名称：

  Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development

  摘要：

  Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.030

文献信息

• Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays
  作者：Albert Ren、Xiuwen Zhu、Konrad Feichtinger、Juerg Lehman、Michelle Kasem、Thomas O. Schrader、Amy Wong、Huong Dang、Minh Le、John Frazer、David J. Unett、Andrew J. Grottick、Kevin T. Whelan、Michael E. Morgan、Carleton R. Sage、Graeme Semple

  DOI：10.1016/j.bmcl.2019.126929

  日期：2020.3

  potential new 5-HT2 receptor scaffolds based on a simplification of the clinically studied, 5-HT2CR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT2C receptor that were highly

  根据简化的临床研究，设计了一系列潜在的新型5-HT2受体支架5-HT2CR激动剂vabicaserin。在筛选过程的早期，体内喂养试验在铅识别过程中发挥了重要作用，使我们专注于6,5,7-三环支架。随后的早期SAR研究提供了有效的5-HT2C受体激动剂，该激动剂在功能和结合测定中具有高度选择性，具有良好的大鼠PK特性，并显着降低了大鼠的急性食物摄入量。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DU RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2015066344A1

  公开（公告）日：2015-05-07

  Provided are 5-HT2C receptor agonists. Also provided are methods for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea. Also provided are compositions comprising a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent, and methods for reducing the frequency of smoking tobacco in an individual attempting to reduce frequency of smoking tobacco; aiding in the cessation or lessening of use of a tobacco product in an individual attempting to cease or lessen use of a tobacco product; aiding in smoking cessation and preventing associated weight gain; controlling weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; reducing weight gain associated with smoking cessation by an individual attempting to cease smoking tobacco; treating nicotine dependency, addiction and/or withdrawal in an individual attempting to treat nicotine dependency, addiction and/or withdrawal; or reducing the likelihood of relapse use of nicotine by an individual attempting to cease nicotine use comprising administering a selective 5-HT2C receptor agonist, optionally in combination with a supplemental agent.

  提供了5-HT2C受体激动剂。还提供了用于体重管理、诱导饱腹感、减少食物摄入量、预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病态赌博、奖赏缺乏综合征和性成瘾）、强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲）、睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱）、尿失禁、精神障碍（包括精神分裂症、厌食症和暴食症）、阿尔茨海默病、性功能障碍、勃起功能障碍、癫痫、运动障碍（包括帕金森病和抗精神病药物引起的运动障碍）、高血压、血脂异常、非酒精性脂肪肝病、肥胖相关肾脏疾病和睡眠呼吸暂停。还提供了包含选择性5-HT2C受体激动剂的组合物，可选地与辅助剂结合，以及用于减少个体尝试减少吸烟频率的吸烟频率；帮助个体戒除或减少使用烟草制品的个体戒除或减少使用烟草制品；帮助戒烟并预防相关体重增加；通过个体尝试戒烟来控制与戒烟相关的体重增加；通过个体尝试戒烟来减少与戒烟相关的体重增加；治疗尼古丁依赖、成瘾和/或戒断的个体尝试治疗尼古丁依赖、成瘾和/或戒断；或减少个体尝试戒除尼古丁使用的复发可能性，包括给予选择性5-HT2C受体激动剂，可选地与辅助剂结合。
• Novel compounds
  申请人：Rami Kantilal Harshad

  公开号：US20060100202A1

  公开（公告）日：2006-05-11

  Compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein, R 1 , R 2 , P, p and n are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition containing such compounds and the use of such compounds in medicine.

  式(I)的化合物或其药学上可接受的盐或溶剂，其中，R1，R2，P，p和n如规范中所定义，制备这种化合物的过程，包含这种化合物的药物组成物，以及这种化合物在医学上的用途。
• UREA DERIVATIVES AND THEIR USE AS VANILLOID RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1474403A2

  公开（公告）日：2004-11-10
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2003053945A2

  公开（公告）日：2003-07-03

  Compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof: (I) wherein, R1, R2, P, p and n are as defined in the specification, a process for preparing such compounds, a pharmaceutical composition containing such compounds and the use of such compounds in medicine.