cyclobutanecarboxylic acid {3-[5-bromo-2-(3-fluoro-phenylamino)-pyrimidin-4-ylamino]-propyl}-amide | 1347570-76-6

• 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: cyclobutanecarboxylic acid {3-[5-bromo-2-(3-fluoro-phenylamino)-pyrimidin-4-ylamino]-propyl}-amide
• 英文别名: N-[3-[[5-bromo-2-(3-fluoroanilino)pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide
• CAS: 1347570-76-6
• 化学式: C₁₈H₂₁BrFN₅O
• 分子量: 422.3
• InChiKey: JUSSXPRFOJRUEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  78.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3-((5-bromo-2-chloropyrimidin-4-yl)amino)propyl)carbamic acid tert-butyl ester 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 cyclobutanecarboxylic acid {3-[5-bromo-2-(3-fluoro-phenylamino)-pyrimidin-4-ylamino]-propyl}-amide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases

  摘要：

  The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKK epsilon pathway in inflammatory diseases. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.063

文献信息

• Compound
  申请人：Mciver Edward Giles

  公开号：US20100056524A1

  公开（公告）日：2010-03-04

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein: R 1 is C 3-8 -cycloalkyl; X is O, NR 7 or C 3-6 -heterocycloalkyl; R 2 is aryl, heteroaryl, fused or unfused aryl-C 3-6 -heterocycloalkyl or fused or unfused heteroaryl-C 3-6 -heterocycloalkyl, each of which is optionally substituted by one or more substitutents selected from aryl, heteroaryl, C 1-6 -alkyl, C 3-7 -cycloalkyl and a group A, wherein said C 1-6 -alkyl group is optionally substituted by one or more substituents selected from aryl, heteroaryl, R 10 and a group A, said heteroaryl group is optionally substituted by one or more R 10 groups; and wherein said C 3-6 -heterocycloalkyl group optionally contains one or more groups selected from oxygen, sulfur, nitrogen and CO; R 3 is C 1-6 -alkyl optionally substituted by one or more substituents selected from aryl, heteroaryl, —NR 4 R 5 , —OR 6 , —NR 7 (CO)R 6 , —NR 7 (CO)NR 4 R 5 , —NR 7 SO 2 R 6 , —NR 7 COOR 7 , —CONR 4 R 5 , C 3-6 -heterocycloalkyl and wherein R 4-7 and A are as defined in the claims. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of one or more kinases.

  本发明的第一方面涉及化合物(I)的公式，或其药学上可接受的盐或酯，其中： R1是C3-8环烷基；X是O，NR7或C3-6杂环烷基；R2是芳基、杂芳基、融合或未融合的芳基-C3-6杂环烷基或融合或未融合的杂芳基-C3-6杂环烷基，其中每个基团可选地由一个或多个取代基选自芳基、杂芳基、C1-6烷基、C3-7环烷基和A组成，其中所述的C1-6烷基可选地由一个或多个取代基选自芳基、杂芳基、R10和A组成，所述的杂芳基可选地由一个或多个R10基团取代；其中所述的C3-6杂环烷基可选地包含一个或多个选自氧、硫、氮和CO的基团；R3是C1-6烷基，可选地被一个或多个取代基选自芳基、杂芳基、-NR4R5、-OR6、-NR7(CO)R6、-NR7(CO)NR4R5、-NR7SO2R6、-NR7COOR7、-CONR4R5、C3-6杂环烷基和其中R4-7和A如权利要求所定义。 进一步的方面涉及所述化合物在治疗各种治疗性疾病中的应用，特别是作为一个或多个激酶的抑制剂。
• Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases
  作者：Edward G. McIver、Justin Bryans、Kristian Birchall、Jasveen Chugh、Thomas Drake、Stephen J. Lewis、Joanne Osborne、Ela Smiljanic-Hurley、William Tsang、Ahmad Kamal、Alison Levy、Michelle Newman、Debra Taylor、J. Simon C. Arthur、Kristopher Clark、Philip Cohen

  DOI：10.1016/j.bmcl.2012.09.063

  日期：2012.12

  The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKK epsilon pathway in inflammatory diseases. (C) 2012 Elsevier Ltd. All rights reserved.