2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-cyanoazetidine-1-carbonyl)-2,2-dimethylpropyl]amide | 1334673-53-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-cyanoazetidine-1-carbonyl)-2,2-dimethylpropyl]amide
• 英文别名: Jak-IN-1；N-[(2R)-1-(3-cyanoazetidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl]-2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide
• CAS: 1334673-53-8
• 化学式: C₂₀H₂₄N₆O₂
• 分子量: 380.45
• InChiKey: SIEMFXMJGAMFQR-INIZCTEOSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2-溴-5H-吡咯并[2,3-B]吡嗪-7-基)甲醇 在 sodium chlorite 、 potassium phosphate 、 potassium dihydrogenphosphate 、 Jones reagent 、 氨基磺酸 、 palladium diacetate 、 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 三环己基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 59.5h， 生成 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-cyanoazetidine-1-carbonyl)-2,2-dimethylpropyl]amide
  参考文献：
  名称：

  3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models

  摘要：

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

  DOI：

  10.1021/jm301646k

文献信息

• Pyrrolopyrazine Kinase Inhibitors
  申请人：Hendricks Robert Than

  公开号：US20110230462A1

  公开（公告）日：2011-09-22

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables n, p, q, Q, X, X′ and Y are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

  本发明涉及使用新型吡咯吡嗪衍生物的公式I，其中变量n、p、q、Q、X、X'和Y如本文所述定义，这些衍生物抑制JAK和SYK，并且适用于治疗自身免疫和炎症性疾病。
• LIPID PRODRUGS OF JAK INHIBITORS AND USES THEREOF
  申请人：PureTech LYT, Inc.

  公开号：US20220125933A1

  公开（公告）日：2022-04-28

  The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
• US8518945B2
  申请人：——

  公开号：US8518945B2

  公开（公告）日：2013-08-27
• 3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models
  作者：Michael Soth、Johannes C. Hermann、Calvin Yee、Muzaffar Alam、Jim W. Barnett、Pamela Berry、Michelle F. Browner、Karl Frank、Sandra Frauchiger、Seth Harris、Yang He、Mohammad Hekmat-Nejad、Than Hendricks、Robert Henningsen、Ramona Hilgenkamp、Hoangdung Ho、Ann Hoffman、Pei-Yuan Hsu、Dong-Qing Hu、Andrea Itano、Saul Jaime-Figueroa、Alam Jahangir、Sue Jin、Andreas Kuglstatter、Alan K. Kutach、Cheng Liao、Stephen Lynch、John Menke、Linghao Niu、Vaishali Patel、Aruna Railkar、Douglas Roy、Ada Shao、David Shaw、Sandra Steiner、Yongliang Sun、Seng-Lai Tan、Sandra Wang、Minh Diem Vu

  DOI：10.1021/jm301646k

  日期：2013.1.10

  The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.