N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide | 1160756-76-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 亚磺酸及其衍生物
• 英文名称: N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide
• 英文别名: (S)-N-((R)-1-cyclopropyl-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide；(S)-N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-2-methylpropane-2-sulfinamide
• CAS: 1160756-76-2
• 化学式: C₉H₁₆F₃NOS
• 分子量: 243.293
• InChiKey: WXRNWDHBHUQISH-MLXNANBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 双氧水 、 potassium acetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 、 三环己基膦 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 水 、 二甲基亚砜 为溶剂， 反应 36.5h， 生成 1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-pyrido[4,3-b]indole-4-carboxamide
  参考文献：
  名称：

  Discovery of 1-Amino-5H-pyrido[4,3-b]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders

  摘要：

  The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK.2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. The genetic, biological, and physiological evidence suggests that JAK2 inhibitors could be effective in treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H-pyrido [4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent optimization of cell potency, metabolic stability, and off-target activities of the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent selectivity, PK profile, and in vivo efficacy in animal models.

  DOI：

  10.1021/jm200909u
• 作为产物：
  描述：

  (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfinamide 、 四甲基氟化铵 、 (三氟甲基)三甲基硅烷 在 氮气 、 水 、 乙酸乙酯 、 crude product 、 silica gel 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以to give compound 2 (1.9 g, 30%) as a white solid的产率得到N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-(S)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE

  摘要：

  提供具有如下式（IX）的结构，或其立体异构体、互变异构体或药学上可接受的盐，其中R1、R2a、R2b、R3a、R3b、R4a、R4b、Q1- - - -Q2、R6、R7、A、B、W、x和y在此处定义并给出。还提供包括这些化合物的制药组合物和通过给予这些化合物的治疗各种HAT相关疾病或疾病，包括癌症的方法。

  公开号：

  US20160235716A1

文献信息

• [EN] SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE<br/>[FR] INHIBITEURS DE HAT SPIROCYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ABBVIE INC

  公开号：WO2016044770A1

  公开（公告）日：2016-03-24

  Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.

  具有式（IX）的结构或其立体异构体、互变异构体或药学上可接受的盐的化合物，其中R1、R2a、R2b、R3a、R3b、R4a、R4b、Q1----Q2、R6、R7、A、B、W、x和y如本文所定义，并提供。还提供了包括这些化合物的药物组合物和通过给予这些化合物治疗各种HAT相关疾病或疾病，包括癌症的方法。
• INHIBITORS OF JANUS KINASES
  申请人：Young Jonathan R.

  公开号：US20100267709A1

  公开（公告）日：2010-10-21

  The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

  本发明提供了抑制四种已知哺乳动物JAK激酶（JAK1、JAK2、JAK3和TYK2）和PDK1的化合物。本发明还提供了包含这种抑制剂化合物的组合物和通过将该化合物用于需要治疗骨髓增生性疾病或癌症的患者中，抑制JAK1、JAK2、JAK3、TYK2和PDK1活性的方法。
• US8431569B2
  申请人：——

  公开号：US8431569B2

  公开（公告）日：2013-04-30
• Discovery of 1-Amino-5<i>H</i>-pyrido[4,3-<i>b</i>]indol-4-carboxamide Inhibitors of Janus Kinase 2 (JAK2) for the Treatment of Myeloproliferative Disorders
  作者：Jongwon Lim、Brandon Taoka、Ryan D. Otte、Kerrie Spencer、Christopher J. Dinsmore、Michael D. Altman、Grace Chan、Craig Rosenstein、Sujata Sharma、Hua-Poo Su、Alexander A. Szewczak、Lin Xu、Hong Yin、Joan Zugay-Murphy、C. Gary Marshall、Jonathan R. Young

  DOI：10.1021/jm200909u

  日期：2011.10.27

  The JAK-STAT pathway mediates signaling by cytokines, which control survival, proliferation, and differentiation of a variety of cells. In recent years, a single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present with a high incidence in myeloproliferative disorders (MPDs). This mutation led to hyperactivation of JAK.2, cytokine-independent signaling, and subsequent activation of downstream signaling networks. The genetic, biological, and physiological evidence suggests that JAK2 inhibitors could be effective in treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H-pyrido [4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent optimization of cell potency, metabolic stability, and off-target activities of the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent selectivity, PK profile, and in vivo efficacy in animal models.
• SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
  申请人：ABBVIE INC.

  公开号：US20160235716A1

  公开（公告）日：2016-08-18

  Compounds having a structure of Formula (IX): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 4a , R 4b , Q 1 - - - -Q 2 , R 6 , R 7 , A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.

  提供具有如下式（IX）的结构，或其立体异构体、互变异构体或药学上可接受的盐，其中R1、R2a、R2b、R3a、R3b、R4a、R4b、Q1- - - -Q2、R6、R7、A、B、W、x和y在此处定义并给出。还提供包括这些化合物的制药组合物和通过给予这些化合物的治疗各种HAT相关疾病或疾病，包括癌症的方法。