2-氨基-3-氯-N-甲基苯甲酰胺 | 18343-42-5

• 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: 2-氨基-3-氯-N-甲基苯甲酰胺
• 英文名称: 2-amino-3-chloro-N-methyl-benzamide
• 英文别名: 2-Amino-3-chloro-N-methylbenzamide
• CAS: 18343-42-5
• 化学式: C₈H₉ClN₂O
• 分子量: 184.625
• InChiKey: GHOLSLMSOLPAQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335

反应信息

• 作为反应物：
  描述：

  2-氨基-3-氯-N-甲基苯甲酰胺 在 camphor-10-sulfonic acid 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 仲丁醇 为溶剂， 生成 3-chloro-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidine-4-ylamino}-N-methyl-benzamide
  参考文献：
  名称：

  2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines

  摘要：

  Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.013
• 作为产物：
  描述：

  2-氨基-3-氯苯甲酸 、 甲胺 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-氨基-3-氯-N-甲基苯甲酰胺
  参考文献：
  名称：

  新型2- [4-（氨基烷氧基）苯基] -4（3H）-喹唑啉酮衍生物的开发作为有效和选择性的组胺H3受体反向激动剂。

  摘要：

  新型2- [4-（氨基烷氧基）苯基] -4（3H）-喹唑啉酮衍生物被确定为有效的人H（3）受体反向激动剂。在对铅5a进行系统修饰后，鉴定出了有效且选择性的类似物5r。消除hERG K（+）通道和人类alpha（1A）-肾上腺素受体活性是本研究的主要重点。

  DOI：

  10.1016/j.bmcl.2008.10.034

文献信息

• FUSED BICYCLIC DERIVATIVES OF 2,4-DIAMINOPYRIMIDINE AS ALK AND c-MET INHIBITORS
  申请人：Ahmed Gulzar

  公开号：US20090221555A1

  公开（公告）日：2009-09-03

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供公式I或II化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。公式I或II化合物具有ALK和/或c-Met抑制活性，可用于治疗增殖性疾病。
• Fused Bicyclic Derivatives of 2,4-Diaminopyrimidine as ALK and c-MET Inhibitors
  申请人：Ahmed Gulzar

  公开号：US20120165519A1

  公开（公告）日：2012-06-28

  The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , A 2 , A 3 , A 4 , and A 5 , are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

  本发明提供了式I或II的化合物或其药学上可接受的盐形式，其中R1、R2、R3、R4、R5、A1、A2、A3、A4和A5如本文所定义。式I或II的化合物具有ALK和/或c-Met抑制活性，并可用于治疗增生性疾病。
• Optimization of 2,3-Dihydroquinazolinone-3-carboxamides as Antimalarials Targeting PfATP4
  作者：Trent D. Ashton、Madeline G. Dans、Paola Favuzza、Anna Ngo、Adele M. Lehane、Xinxin Zhang、Deyun Qiu、Bikash Chandra Maity、Nirupam De、Kyra A. Schindler、Tomas Yeo、Heekuk Park、Anne-Catrin Uhlemann、Alisje Churchyard、Jake Baum、David A. Fidock、Kate E. Jarman、Kym N. Lowes、Delphine Baud、Stephen Brand、Paul F. Jackson、Alan F. Cowman、Brad E. Sleebs

  DOI：10.1021/acs.jmedchem.2c02092

  日期：2023.3.9

  analogues with potent activity against asexual parasites equivalent to clinically used antimalarials. Resistance selection and profiling against drug-resistant parasite strains revealed that this antimalarial chemotype targets PfATP4. Dihydroquinazolinone analogues were shown to disrupt parasite Na+ homeostasis and affect parasite pH, exhibited a fast-to-moderate rate of asexual kill, and blocked gametogenesis

  由于对一线抗疟药的耐药性，迫切需要用新的候选药物填充抗疟临床产品组合。为了发现新的抗疟化学型，我们针对恶性疟原虫无性血期寄生虫对Janssen Jumpstarter 文库进行了高通量筛选，并鉴定了 2,3-二氢喹唑啉酮-3-甲酰胺支架。我们定义了 SAR，发现三环系统上的 8-取代和环外芳烃的 3-取代产生的类似物对无性寄生虫具有相当于临床使用的抗疟药的有效活性。针对耐药寄生虫菌株的耐药性选择和分析表明，这种抗疟化学型以 PfATP4 为目标。二氢喹唑啉酮类似物显示可破坏寄生虫 Na+稳态并影响寄生虫 pH 值，表现出快速到中等的无性杀灭率，并阻断配子发生，与临床使用的 PfATP4 抑制剂的表型一致。最后，我们观察到优化的领跑者类似物 WJM-921 在疟疾小鼠模型中显示出口服疗效。
• Fused bicyclic derivatives of 2,4-diaminopyrimidine as c-Met inhibitors
  作者：Linda R. Weinberg、Mark S. Albom、Thelma S. Angeles、Jean Husten、Joseph G. Lisko、Robert J. McHugh、Karen L. Milkiewicz、Seetha Murthy、Gregory R. Ott、Jay P. Theroff、Rabindranath Tripathy、Ted L. Underiner、Craig A. Zificsak、Bruce D. Dorsey

  DOI：10.1016/j.bmcl.2010.11.045

  日期：2011.1

  The HGF-c-Met signaling axis is an important paracrine mediator of epithelial-mesenchymal cell interactions involving the regulation of multiple cellular activities including cell motility, mitogenesis, morphogenesis, and angiogenesis. Dysregulation of c-Met signaling (e. g., overexpression or increased activation) is associated with the development of a wide range of tumor types; thus, inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of a 2-arylaminopyrimidine scaffold led to a series of potent c-Met inhibitors bearing a C4-2-amino-N-methylbenzamide group. Specifically, a series of C2-benzazepinone analogs demonstrated potent inhibition of c-Met in enzymatic and cellular assays. Kinase selectivity could be tuned by varying the nature of the alkyl group on the benzazepinone nitrogen. (C) 2010 Elsevier Ltd. All rights reserved.
• FUSED BICYCLIC DERIVATIVES OF 2,4-DIAMINOPYRIMIDINE AS ALK AND C-MET INHIBITORS
  申请人：Cephalon, Inc.

  公开号：EP2222647A1

  公开（公告）日：2010-09-01