N-(3-氨基-4-甲基苯基)-3-甲基苯甲酰胺 | 1016670-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(3-氨基-4-甲基苯基)-3-甲基苯甲酰胺
• 英文名称: N-(3-amino-4-methylphenyl)-3-methylbenzamide
• CAS: 1016670-99-7
• 化学式: C₁₅H₁₆N₂O
• mdl: MFCD09931774
• 分子量: 240.305
• InChiKey: TWTCQTZPPRRFQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-氨基-4-甲基苯基)-3-甲基苯甲酰胺 在 溶剂黄146 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 72.5h， 生成 3-methyl-N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)benzamide
  参考文献：
  名称：

  Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia

  摘要：

  Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream Mediators such as STATS, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI(50) = 14 nM), KU812 (GI(50) = 25 nM), and MEG-01 (GI(50) = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.

  DOI：

  10.1021/acs.jmedchem.5b01618
• 作为产物：
  描述：

  4-甲基-3-硝基苯胺 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 N-(3-氨基-4-甲基苯基)-3-甲基苯甲酰胺
  参考文献：
  名称：

  Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia

  摘要：

  Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream Mediators such as STATS, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI(50) = 14 nM), KU812 (GI(50) = 25 nM), and MEG-01 (GI(50) = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.

  DOI：

  10.1021/acs.jmedchem.5b01618

文献信息

• Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38α MAP kinase inhibitors
  作者：Stephen T. Wrobleski、Shuqun Lin、John Hynes、Hong Wu、Sidney Pitt、Ding Ren Shen、Rosemary Zhang、Kathleen M. Gillooly、David J. Shuster、Kim W. McIntyre、Arthur M. Doweyko、Kevin F. Kish、Jeffrey A. Tredup、Gerald J. Duke、John S. Sack、Murray McKinnon、John Dodd、Joel C. Barrish、Gary L. Schieven、Katerina Leftheris

  DOI：10.1016/j.bmcl.2008.02.067

  日期：2008.4

  A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38 alpha MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series

  基于吡咯并[2,1-f] [1,2,4]三嗪环系统的一系列新化合物已被鉴定为有效的p38αMAP激酶抑制剂。报道了从这类抑制剂中选择的类似物的合成，结构-活性关系（SAR）和体内活性。基于X射线共晶体的其他研究表明，该系列的有效抑制剂之一与p38α酶的DFG-out构象结合。
• HEPATITIS B ANTIVIRAL AGENTS
  申请人：Novira Therapeutics Inc.

  公开号：EP2794565B1

  公开（公告）日：2017-07-26
• [EN] BENZOTHIAZOLE DERIVATIVES AND THEIR USE AS PROTEIN KINASE INHIBITORS<br/>[FR] DERIVES DE BENZOTHIAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DES PROTEINES KINASES
  申请人：IRM LLC

  公开号：WO2008124393A1

  公开（公告）日：2008-10-16

  [EN] The invention provides compounds of formula (1 ) and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, and methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of AIk, AbI, Aurora-A, B-Raf, Bcr-Abl, BRK, BIk, Bmx, c-Kit, c-RAF, cSRC. CSK, FLTl, Fms, Fyn, JAK2, KDR, Lck, Lyn, PDGFRa, PDGFRß, PKCa. p38 (p38 MAP kinase, SAPK2a), Src, SIK, Syk, Tie2 and TrkB kinases. FORMULE (I)
  [FR] L'invention concerne des composés de formule (1) et des compositions pharmaceutiques associées, utiles en tant qu'inhibiteurs des protéines kinases, ainsi que des méthodes d'utilisation de ces composés dans le traitement, l'atténuation ou la prévention d'une affection associée à une activité kinase anormale ou déréglée. Dans certains modes de réalisation, l'invention concerne des méthodes d'utilisation de ces composés dans le traitement, l'atténuation ou la prévention de maladies ou troubles impliquant une activation anormale des kinases AIk, AbI, Aurora-A, B-Raf, Bcr-Abl, BRK, BIk, Bmx, c-Kit, c-RAF, cSRC. CSK, FLTl, Fms, Fyn, JAK2, KDR, Lck, Lyn, PDGFRa, PDGFRß, PKCa. p38 (kinase p38 MAP, SAPK2a), Src, SIK, Syk, Tie2 et TrkB. FORMULE (I)
• Discovery of 2-((3-Amino-4-methylphenyl)amino)-<i>N</i>-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia
  作者：Xiaofei Liang、Xiaochuan Liu、Beilei Wang、Fengming Zou、Aoli Wang、Shuang Qi、Cheng Chen、Zheng Zhao、Wenchao Wang、Ziping Qi、Fengchao Lv、Zhenquan Hu、Li Wang、Shanchun Zhang、Qingsong Liu、Jing Liu

  DOI：10.1021/acs.jmedchem.5b01618

  日期：2016.3.10

  Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream Mediators such as STATS, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI(50) = 14 nM), KU812 (GI(50) = 25 nM), and MEG-01 (GI(50) = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.