(+/-)-cis-[3-(5-amino-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-cis-[3-(5-amino-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(1S,3R)-3-[[5-amino-1-(benzenesulfonyl)pyrrolo[2,3-b]pyridin-4-yl]amino]cyclopentyl]carbamate
• 化学式: C₂₃H₂₉N₅O₄S
• 分子量: 471.58
• InChiKey: BNLXWEMFSAGSTO-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(+/)-cis-[3-(5-nitro-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ESTER	1315495-90-9	C23H27N5O6S	501.563
  1-(苯磺酰基)-4-氯-5-硝基吡咯并[2,3-b]吡啶	4-chloro-5-nitro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine	1245649-52-8	C13H8ClN3O4S	337.743
  4-氯-1-苯磺酰基-1H-吡咯并[2,3-b]吡啶	4-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine	744209-63-0	C13H9ClN2O2S	292.746

反应信息

• 作为反应物：
  描述：

  (+/-)-cis-[3-(5-amino-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester 在 对甲苯磺酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 2.5h， 生成 (+/-)-cis-3-[(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)-cyclopentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors

  摘要：

  A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor I led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAP. through a series of cycloamino and cycloalkylamino analogues demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of subnanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogues to enhance affinity and selectivity.

  DOI：

  10.1021/jm300438j
• 作为产物：
  描述：

  4-氯-7-氮杂吲哚 在 4-二甲氨基吡啶 、 四丁基硝酸铵 、 铁粉 、 氯化铵 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸酐 作用下， 以 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 24.5h， 生成 (+/-)-cis-[3-(5-amino-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors

  摘要：

  A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor I led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAP. through a series of cycloamino and cycloalkylamino analogues demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of subnanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogues to enhance affinity and selectivity.

  DOI：

  10.1021/jm300438j

文献信息

• TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：Babu Srinivasan

  公开号：US20110201593A1

  公开（公告）日：2011-08-18

  The invention provides novel compounds of formula I having the general formula: wherein R 1 , R 2 , R 3 , X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  本发明提供了具有以下一般式的新化合物I： 其中R1、R2、R3、X和Y如本文所述。因此，这些化合物可以在药学上可接受的组合物中提供，并用于治疗免疫或过度增生性疾病。
• US8461328B2
  申请人：——

  公开号：US8461328B2

  公开（公告）日：2013-06-11