Ethyl 2-(4-bromophenyl)-5-[2-(2,2-dimethylpropanoylamino)-4-methyl-1,3-thiazol-5-yl]pyrazole-3-carboxylate | 1236278-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Ethyl 2-(4-bromophenyl)-5-[2-(2,2-dimethylpropanoylamino)-4-methyl-1,3-thiazol-5-yl]pyrazole-3-carboxylate
• CAS: 1236278-94-6
• 化学式: C₂₁H₂₃BrN₄O₃S
• 分子量: 491.409
• InChiKey: RFGPNAXFUOFNIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Ethyl 4-[2-(2,2-dimethylpropanoylamino)-4-methyl-1,3-thiazol-5-yl]-2,4-dioxobutanoate 、 对溴苯肼 以 乙醇 为溶剂， 反应 18.0h， 以87%的产率得到ethyl 1-(4-bromophenyl)-5-(4-methyl-2-pivalamidothiazol-5-yl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Pyrazolylthiazole as ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator Correctors with Improved Hydrophilicity Compared to Bithiazoles

  摘要：

  Deletion of phenylalanine residue 508 (Delta F508) in the cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR) is a major cause of CF. Small molecule "correctors" of defective A Delta 508-CFTR cellular processing hold promise for CF therapy. We previously identified and characterized bithiazole CF corrector 1 and s-cis-locked bithiazole 2. Herein, we report the regiodivergent synthesis of N gamma and N beta isomers of thiazole-tethered pyrazoles with improved hydrophilicity compared to bithiazoles. We synthesized a focused library of 54 pyrazolylthiazoles 3, which included examples of both regioisomers 4 and 5. The thiazole-tethered pyrazoles allowed incorporation of property-modulating functionality on the pyrazole ring (ester, acid, and amide) while retaining Delta F508-CFTR corrector activity (EC50) of under 1 mu M. The most active pyrazolylthiazole (14h) has an experimentally determined log P of 4.1, which is 1.2 log units lower than bithiazole CF corrector 1.

  DOI：

  10.1021/jm100235h

文献信息

• HETEROARYLS AND USES THEREOF
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20130165483A1

  公开（公告）日：2013-06-27

  This invention provides compounds of formula IB: wherein HY, R 1 , R 2 , R 3 , R 15 , G 5 , G 6 , G 7 , G 8 , and G 9 are as described in the specification. The compounds are inhibitors of VPS34 and/or PI3K and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

  本发明提供了式IB的化合物：其中HY，R1，R2，R3，R15，G5，G6，G7，G8和G9如规范中所述。这些化合物是VPS34和/或PI3K的抑制剂，因此对于治疗增殖性，炎症性或心血管疾病有用。