4-Brom-N-(3-dimethylamino-propyl)-anilin | 91214-47-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-Brom-N-(3-dimethylamino-propyl)-anilin
• 英文别名: N-(4-bromophenyl)-N',N'-dimethylpropane-1,3-diamine
• CAS: 91214-47-0
• 化学式: C₁₁H₁₇BrN₂
• 分子量: 257.173
• InChiKey: QJFVKIFZYXNEBC-UHFFFAOYSA-N

物化性质

• 沸点：
  332.7±27.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Brom-N-(3-dimethylamino-propyl)-anilin 、 3-甲氧苄基异氰酸酯 以 二氯甲烷 为溶剂， 生成 1-(4-Bromophenyl)-1-[3-(dimethylamino)propyl]-3-[(3-methoxyphenyl)methyl]urea
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r
• 作为产物：
  描述：

  对溴碘苯 、 N,N-二甲基-1,3-二氨基丙烷 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 为溶剂， 以46%的产率得到4-Brom-N-(3-dimethylamino-propyl)-anilin
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r

文献信息

• SUBSTITUTED FUSED HETEROARYL COMPOUND SERVING AS A KINASE INHIBITOR, AND APPLICATIONS THEREOF
  申请人：Impact Therapeutics (Shanghai), Inc

  公开号：EP3567041A9

  公开（公告）日：2022-04-20

  The disclosure relates to substituted fused heteroaromatic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A1-A4, B1-B3, D1-D4 and R1-R3 are defined herein. Compounds having Formula I are kinalse inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

  本公开涉及取代的融合杂芳香化合物及其用途。具体而言，本公开提供了以下式I的化合物： 或其药用可接受的盐或前药，其中A1-A4、B1-B3、D1-D4和R1-R3如本文所述定义。具有式I的化合物是激酶抑制剂。因此，本公开的化合物可用于治疗由DDR功能缺陷引起的临床状况，如癌症。
• Substituted fused heteroaromatic compounds as kinase inhibitors and the use thereof
  申请人：IMPACT THERAPEUTICS, INC.

  公开号：US10874670B2

  公开（公告）日：2020-12-29

  The disclosure relates to substituted fused heteroaromatic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A1-A4, B1-B3, D1-D4 and R1-R3 are defined herein. Compounds having Formula I are kinalse inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

  本公开涉及取代的融合杂芳香族化合物及其用途。具体地说，本公开提供了如下式 I 的化合物： 或其药学上可接受的盐或原药，其中 A1-A4、B1-B3、D1-D4 和 R1-R3 在本文中定义。具有式 I 的化合物是 Kinalse 抑制剂。因此，本公开的化合物可用于治疗由 DDR 功能缺陷引起的临床病症，如癌症。
• Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors
  作者：Yan Yin、Li Lin、Claudia Ruiz、Susan Khan、Michael D. Cameron、Wayne Grant、Jennifer Pocas、Nibal Eid、HaJeung Park、Thomas Schröter、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm400062r

  日期：2013.5.9

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.