8-氯-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯 | 1443129-65-4

• 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
• 中文名称: 8-氯-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯
• 英文名称: tert-butyl 8-chloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate
• 英文别名: tert-Butyl 8-chloro-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate；tert-butyl 8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylate
• CAS: 1443129-65-4
• 化学式: C₁₆H₁₉ClN₂O₂
• mdl: MFCD31231417
• 分子量: 306.792
• InChiKey: KUVFEPZNXAXIQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  8-氯-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯 在 盐酸 、 caesium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.5h， 生成 2-(2-(1-naphthoyl)-8-chloro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid
  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：

  对氯苯胺 在 ferrous(II) sulfate heptahydrate 、 sodium nitrite 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 23.0h， 生成 8-氯-3,4-二氢-1H-吡啶并[4,3-B]吲哚-2(5H)-羧酸叔丁酯
  参考文献：
  名称：

  使用芳基重氮盐和烷基碘化物的基于卤素原子转移 (XAT) 的吲哚合成方法

  摘要：

  吲哚是药物中最重要的N-杂环化合物之一。在这里，我们提出了一种基于芳基重氮和烷基碘之间的自由基偶联的经典 Fischer 吲哚合成的替代方法。这种铁介导的策略具有芳基重氮盐的双重作用，芳基重氮盐通过卤素原子转移依次激活烷基碘，然后充当自由基受体。该过程在温和的条件下运行，可以制备致密功能化的吲哚。

  DOI：

  10.1021/acs.orglett.2c02840

文献信息

• 三环类化合物及其用途
  申请人：上海辉启生物医药科技有限公司

  公开号：CN113121527A

  公开（公告）日：2021-07-16

  本发明公开了一种三环类化合物及其用途。本发明具体公开了一种如式I所示化合物或其药学上可接受的盐。本发明的三环类化合物对HDAC尤其是HDAC6具有很好的抑制作用，并具有较好的选择性，还能够抑制多种肿瘤细胞的增殖；
• [EN] 1, 3, 4, 5-TETRAHYDRO-2H-PYRIDO[4,3-B]INDOLE DERIVATIVES FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES LIKE ALZHEIMER'S DISEASE<br/>[FR] DÉRIVÉS DE 1,3,4,5-TÉTRAHYDRO-2H-PYRIDO[4,3-B]INDOLE POUR LE TRAITEMENT, LE SOULAGEMENT OU LA PRÉVENTION DE TROUBLES ASSOCIÉS À DES AGRÉGATS DE TAU COMME LA MALADIE D'ALZHEIMER
  申请人：AC IMMUNE SA

  公开号：WO2019134978A1

  公开（公告）日：2019-07-11

  The present invention relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

  本发明涉及一类新化合物，可用于治疗、缓解或预防与Tau蛋白聚集相关的一组疾病和异常，包括但不限于神经原纤维缠结（NFTs），如阿尔茨海默病（AD）。
• Compounds for the treatment, alleviation or prevention of disorders associated with Tau aggregates
  申请人：AC Immune SA

  公开号：US10633383B2

  公开（公告）日：2020-04-28

  The present invention relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

  本发明涉及新型化合物，可用于治疗、缓解或预防与 Tau（微管蛋白相关单位）蛋白聚集有关的一组疾病和异常，包括但不限于神经纤维缠结（NFT），如阿尔茨海默病（AD）。
• Selective Thermal Deprotection of <i>N</i>-Boc Protected Amines in Continuous Flow
  作者：Michelle-Rose Ryan、Denis Lynch、Stuart G. Collins、Anita R. Maguire

  DOI：10.1021/acs.oprd.3c00498

  日期：——

  Sequential selective deprotection of N-Boc groups has been demonstrated through temperature control, as exemplified by effective removal of an aryl N-Boc group in the presence of an alkyl N-Boc group. As a proof of principle, a telescoped sequence involving selective deprotection of an aryl N-Boc group from 9h followed by benzoylation and deprotection of the remaining alkyl N-Boc group to form amide

  在不存在酸催化剂的情况下，一系列胺的热N -Boc 脱保护很容易在连续流中进行。虽然在甲醇或三氟乙醇中获得了最佳结果，但脱保护可以在一系列不同极性的溶剂中进行。已经通过温度控制证明了N -Boc基团的顺序选择性脱保护，如在烷基N -Boc基团存在下有效去除芳基N -Boc基团所例证的。作为原理证明，涉及从9h开始选择性脱保护芳基N -Boc 基团，然后苯甲酰化并脱除剩余烷基N -Boc 基团以形成酰胺13的伸缩序列被证明是成功的。
• 1, 3, 4, 5-TETRAHYDRO-2H-PYRIDO[4,3-B]INDOLE DERIVATIVES FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES LIKE ALZHEIMER'S DISEASE
  申请人：AC Immune SA

  公开号：EP3735411A1

  公开（公告）日：2020-11-11