N-[(4S)-1-(4-amino-2-methyl-pyrazol-3-yl)azepan-4-yl]-2,2,2-trifluoro-acetamide | 1447922-32-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[(4S)-1-(4-amino-2-methyl-pyrazol-3-yl)azepan-4-yl]-2,2,2-trifluoro-acetamide
• 英文别名: (S)-N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)azepan-4-yl)-2,2,2-trifluoroacetamide；N-[(4S)-1-(4-amino-2-methylpyrazol-3-yl)azepan-4-yl]-2,2,2-trifluoroacetamide
• CAS: 1447922-32-8
• 化学式: C₁₂H₁₈F₃N₅O
• 分子量: 305.303
• InChiKey: DLJILTHOGZKXNQ-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[(4S)-1-(4-amino-2-methyl-pyrazol-3-yl)azepan-4-yl]-2,2,2-trifluoro-acetamide 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 水 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 90.0h， 生成 (S)-tert-butyl (4-((5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)carbamoyl)-2-(2,6-difluorophenyl)thiazol-5-yl)carbamate
  参考文献：
  名称：

  Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

  摘要：

  Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

  DOI：

  10.1021/acs.jmedchem.8b01857
• 作为产物：
  描述：

  2,2,2-trifluoro-N-[(4S)-1-(2-methyl-4-nitropyrazol-3-yl)azepan-4-yl]acetamide 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 80.0 ℃ 、5.0 MPa 条件下， 以84%的产率得到N-[(4S)-1-(4-amino-2-methyl-pyrazol-3-yl)azepan-4-yl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

  摘要：

  Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

  DOI：

  10.1021/acs.jmedchem.8b01857

文献信息

• PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE
  申请人：GENENTECH, INC.

  公开号：US20130079321A1

  公开（公告）日：2013-03-28

  Pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula I, including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein X is thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Formula I中的吡唑-4-基杂环基-羧酰胺化合物，包括其立体异构体、几何异构体、互变异构体和药学上可接受的盐，其中X为噻唑基、吡啶基、吡啶基或嘧啶基，用于抑制Pim激酶，并用于治疗由Pim激酶介导的癌症等疾病。公开了使用Formula I化合物进行体外、原位和体内诊断、预防或治疗哺乳动物细胞中的这类疾病或相关病理条件的方法。
• US8614206B2
  申请人：——

  公开号：US8614206B2

  公开（公告）日：2013-12-24
• US9505746B2
  申请人：——

  公开号：US9505746B2

  公开（公告）日：2016-11-29
• [EN] PYRAZOL-4-YL-HETEROCYCLYL-CARBOXAMIDE COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS DE TYPE PYRAZOL-4-YL-HÉTÉROCYCLYL-CARBOXAMIDE ET LEURS MÉTHODES D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013045461A1

  公开（公告）日：2013-04-04

  Pyrazol-4-yl-heterocyclyl-carboxamide compounds of Formula (I), including stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, wherein X is a thiazolyl, pyrazinyl, pyridinyl, or pyrimidinyl, are useful for inhibiting Pim kinase, and for treating disorders such as cancer mediated by Pim kinase. Methods of using compounds of Formula (I), for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
• Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma
  作者：Xiaojing Wang、Wesley Blackaby、Vivienne Allen、Grace Ka Yan Chan、Jae H. Chang、Po-Chang Chiang、Coura Diène、Jason Drummond、Steven Do、Eric Fan、Eric B. Harstad、Alastair Hodges、Huiyong Hu、Wei Jia、William Kofie、Aleksandr Kolesnikov、Joseph P. Lyssikatos、Justin Ly、Mizio Matteucci、John G. Moffat、Veerendra Munugalavadla、Jeremy Murray、David Nash、Cameron L. Noland、Geoff Del Rosario、Leanne Ross、Craig Rouse、Andrew Sharpe、Dionysos Slaga、Minghua Sun、Vickie Tsui、Heidi Wallweber、Shang-Fan Yu、Allen J. Ebens

  DOI：10.1021/acs.jmedchem.8b01857

  日期：2019.2.28

  Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.