tert-butyl 7-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate | 1443129-67-6

• 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: tert-butyl 7-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
• 英文别名: tert-butyl 7-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate；Tert-butyl 7-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate
• CAS: 1443129-67-6
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: ONJGLPSFBCEDQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl 7-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate 在 盐酸 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 ethyl 2-(2-benzoyl-7-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetate
  参考文献：
  名称：

  Identification of 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968), a Potent, Selective, and Orally Bioavailable Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) Antagonist

  摘要：

  Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist.

  DOI：

  10.1021/jm400122f
• 作为产物：
  描述：

  2-溴-5-甲基苯胺 、 N-叔丁氧羰基-4-哌啶酮 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 palladium diacetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.17h， 以1.07 g的产率得到tert-butyl 7-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
  参考文献：
  名称：

  Identification of 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968), a Potent, Selective, and Orally Bioavailable Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) Antagonist

  摘要：

  Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist.

  DOI：

  10.1021/jm400122f

文献信息

• [EN] CARBOLINE ANTIPARASITICS<br/>[FR] ANTIPARASITAIRES À BASE DE CARBOLINE
  申请人：ZOETIS SERVICES LLC

  公开号：WO2016209635A1

  公开（公告）日：2016-12-29

  The present invention provides Formula (1 ) compounds that are gamma-carbolines, Formula (1) wherein R1 a, R1 b, R1 c, R1d, R2, R3, and "— " are as defined herein; veterinary acceptable salts thereof, and stereoisomers thereof, which act as parasiticides, in particular, endoparasiticides.

  本发明提供了一种γ-咔啉化合物的化学式（1），其中R1a，R1b，R1c，R1d，R2，R3和“—”如本文所定义；其兽用可接受盐，以及对映异构体，可作为寄生虫药物，特别是内寄生虫药物。
• ANTIBACTERIAL COMPOUNDS AND METHODS FOR USE
  申请人：PTC THERAPEUTICS, INC.

  公开号：US20150038437A1

  公开（公告）日：2015-02-05

  The present description relates to compounds and forms and pharmaceutical compositions thereof and methods for use thereof to treat or ameliorate bacterial infections caused by wild-type and multi-drug resistant Gram-negative and Gram-positive pathogens.

  本说明涉及化合物和形式以及其制药组合物，以及使用它们治疗或改善由野生型和多重耐药革兰氏阴性和革兰氏阳性病原体引起的细菌感染的方法。
• Carboline antiparasitics
  申请人：Zoetis Services LLC

  公开号：US10570129B2

  公开（公告）日：2020-02-25

  The present invention provides Formula (1) compounds that are gamma-carbolines, Formula (1) wherein R1a, R1b, R1c, R1d, R2, R3, and “-” are as defined herein; veterinary acceptable salts thereof, and stereoisomers thereof, which act as parasiticides, in particular, endoparasiticides.

  本发明提供了属于γ-羰基化合物的式(1)化合物，式(1)中的R1a、R1b、R1c、R1d、R2、R3和"-"如本文所定义；其兽药可接受盐及其立体异构体，可作为杀寄生虫剂，特别是内吸性杀寄生虫剂。
• CARBOLINE ANTIPARASITICS
  申请人：Zoetis Services LLC

  公开号：EP3313837A1

  公开（公告）日：2018-05-02
• US9409905B2
  申请人：——

  公开号：US9409905B2

  公开（公告）日：2016-08-09