3-[[5-amino-1-(phenylsulfony)l-1H-pyrrolo[2,3-b]pyridin-4-yl]amino]-azetidine-1-carboxylic acid tert-butyl ester | 1315494-65-5

• 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: 3-[[5-amino-1-(phenylsulfony)l-1H-pyrrolo[2,3-b]pyridin-4-yl]amino]-azetidine-1-carboxylic acid tert-butyl ester
• 英文别名: 3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-azetidine-1-carboxylic acid tert-butyl ester；tert-butyl 3-[[5-amino-1-(benzenesulfonyl)pyrrolo[2,3-b]pyridin-4-yl]amino]azetidine-1-carboxylate
• CAS: 1315494-65-5
• 化学式: C₂₁H₂₅N₅O₄S
• 分子量: 443.527
• InChiKey: FVDKFMPJZVOWHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[[5-amino-1-(phenylsulfony)l-1H-pyrrolo[2,3-b]pyridin-4-yl]amino]-azetidine-1-carboxylic acid tert-butyl ester 在 对甲苯磺酸 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 93.0h， 生成 1-(azetidin-3-yl)-1,6-dihydro-imidazo[4,5-d]pyrrolo[2,3-b]pyridine
  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 、 10% Pd(OH)₂ on C 、 氢气 、 四丁基硝酸铵 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 47.7h， 生成 3-[[5-amino-1-(phenylsulfony)l-1H-pyrrolo[2,3-b]pyridin-4-yl]amino]-azetidine-1-carboxylic 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

• [EN] FUSED TRICYCLIC COMPOUNDS FOR USE AS INHIBITORS OF JANUS KINASES<br/>[FR] COMPOSÉS TRICYCLIQUES FUSIONNÉS UTILISÉS EN TANT QU'INHIBITEURS DES JANUS KINASES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013007765A1

  公开（公告）日：2013-01-17

  The invention provides novel compounds of formula (I) having the general formula (I) wherein R1, V, W, X, Y and Z are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.

  这项发明提供了具有通式（I）的新化合物，其通式为（I），其中R1、V、W、X、Y和Z如本文所述。因此，这些化合物可以制备成药用合适的组合物，并用于治疗免疫性或过度增殖性疾病。
• [EN] TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES TRICYCLIQUES, LEURS COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011086053A1

  公开（公告）日：2011-07-21

  The invention provides novel compounds of formula (I) having the general formula, wherein R1, R2, R3, 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.

  该发明提供了具有通式（I）的新化合物，通式如下，其中R1、R2、R3、X和Y如本文所述。因此，这些化合物可以用于制备药学上可接受的组合物，并用于治疗免疫或过度增殖性疾病。
• 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。
• Tricyclic heterocyclic compounds, compositions and methods of use thereof
  申请人：Babu Srinivasan

  公开号：US08461328B2

  公开（公告）日：2013-06-11

  The invention provides novel compounds of formula I having the general formula: wherein R1, R2, R3, 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.

  该发明提供了一种具有公式I的新化合物，其一般公式为：其中R1，R2，R3，X和Y如本文所述。因此，这些化合物可以以药学上可接受的成分形式提供，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