tert-butyl [(3'-amino-5-{[(3-fluoropyridin-4-yl)amino]carbonyl}biphenyl-2-yl)methyl]carbamate | 1333401-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl [(3'-amino-5-{[(3-fluoropyridin-4-yl)amino]carbonyl}biphenyl-2-yl)methyl]carbamate
• 英文别名: [3'-amino-5-(3-fluoro-pyridin-4-ylcarbamoyl)-biphenyl-2-ylmethyl]-carbamic acid tert-butyl ester；tert-butyl N-[[2-(3-aminophenyl)-4-[(3-fluoropyridin-4-yl)carbamoyl]phenyl]methyl]carbamate
• CAS: 1333401-02-7
• 化学式: C₂₄H₂₅FN₄O₃
• 分子量: 436.486
• InChiKey: HPTQEUJULIVCGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl [(3'-amino-5-{[(3-fluoropyridin-4-yl)amino]carbonyl}biphenyl-2-yl)methyl]carbamate 在 盐酸 、 sodium chlorite 、 氨基磺酸 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 2-methoxyethyl 3-{[(2'-(aminomethyl)-5'-{[(3-fluoropyridin-4-yl)amino]carbonyl}biphenyl-3-yl)amino]carbonyl}-4-fluorobenzoate hydrochloric acid salt
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel, Highly Active Soft ROCK Inhibitors

  摘要：

  ROCK1 and ROCK2 play important roles in numerous cellular functions, including smooth muscle cell contraction, cell proliferation, adhesion, and migration. Consequently, ROCK inhibitors are of interest for treating multiple indications including cardiovascular diseases, inflammatory and autoimmune diseases, lung diseases, and eye diseases. However; systemic inhibition of ROCK is expected to result in significant side effects. Strategies allowing reduced systemic exposure are therefore of interest. In a continuing effort toward identification of ROCK inhibitors, we here report the design, synthesis, and evaluation of novel soft ROCK inhibitors displaying an ester function allowing their rapid inactivation in the systemic circulation. Those compounds display subnanomolar activity against ROCK and strong differences of functional activity between parent compounds and expected metabolites. The binding mode of a representative compound was determined experimentally in a single-Crystal X-ray diffraction study. Enzymes responsible for inactivation of these compounds once they enter systemic circulation are also discussed.

  DOI：

  10.1021/acs.jmedchem.5b00308
• 作为产物：
  描述：

  [2-bromo-4-{3-fluoro-pyridin-4-ylcarbamoyl}-benzyl]-carbamic acid tert butyl ester 、 3-氨基苯硼酸 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 tert-butyl [(3'-amino-5-{[(3-fluoropyridin-4-yl)amino]carbonyl}biphenyl-2-yl)methyl]carbamate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel, Highly Active Soft ROCK Inhibitors

  摘要：

  ROCK1 and ROCK2 play important roles in numerous cellular functions, including smooth muscle cell contraction, cell proliferation, adhesion, and migration. Consequently, ROCK inhibitors are of interest for treating multiple indications including cardiovascular diseases, inflammatory and autoimmune diseases, lung diseases, and eye diseases. However; systemic inhibition of ROCK is expected to result in significant side effects. Strategies allowing reduced systemic exposure are therefore of interest. In a continuing effort toward identification of ROCK inhibitors, we here report the design, synthesis, and evaluation of novel soft ROCK inhibitors displaying an ester function allowing their rapid inactivation in the systemic circulation. Those compounds display subnanomolar activity against ROCK and strong differences of functional activity between parent compounds and expected metabolites. The binding mode of a representative compound was determined experimentally in a single-Crystal X-ray diffraction study. Enzymes responsible for inactivation of these compounds once they enter systemic circulation are also discussed.

  DOI：

  10.1021/acs.jmedchem.5b00308

文献信息

• HETEROCYCLIC AMIDES AS ROCK INHIBITORS
  申请人：Leysen Dirk

  公开号：US20120322801A1

  公开（公告）日：2012-12-20

  The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases.

  本发明涉及新的激酶抑制剂，更具体地说是ROCK抑制剂，包括这些抑制剂的组合物，特别是制药用途的组合物，并且涉及使用这些抑制剂在治疗和预防疾病方面的用途。特别是，本发明涉及新的ROCK抑制剂，包括这些抑制剂的组合物，特别是制药用途的组合物，并且涉及使用这些抑制剂在治疗和预防疾病方面的用途。此外，本发明还涉及治疗和使用所述化合物制造药物的方法，应用于多种治疗适应症，包括性功能障碍、炎症性疾病、眼科疾病和呼吸系统疾病。
• NOVEL ROCK INHIBITORS
  申请人：Amakem NV

  公开号：US20130252975A1

  公开（公告）日：2013-09-26

  The present invention relates to new kinase inhibitors, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including sexual dysfunction, inflammatory diseases, ophthalmic diseases and Respiratory diseases.

  本发明涉及新的激酶抑制剂，更具体地，是ROCK抑制剂，包括这种抑制剂的组合物，特别是制药组合物，并且涉及这种抑制剂在治疗和预防疾病方面的用途。特别地，本发明涉及新的ROCK抑制剂，包括这种抑制剂的组合物，特别是制药组合物，并且涉及这种抑制剂在治疗和预防疾病方面的用途。此外，本发明还涉及使用该化合物的治疗方法和制造药物的用途，适用于多种治疗适应症，包括性功能障碍、炎症性疾病、眼科疾病和呼吸系统疾病。
• Heterocyclic amides as rock inhibitors
  申请人：Amakem NV

  公开号：EP2626348A1

  公开（公告）日：2013-08-14

  The present invention relates to new kinase inhibitors of general formula IIaa, more specifically ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new ROCK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including ophthalmic diseases.

  本发明涉及通式IIaa的新激酶抑制剂，更具体地说，涉及ROCK抑制剂、包含此类抑制剂的组合物，特别是药物，以及此类抑制剂在治疗和预防疾病中的用途。特别是，本发明涉及新的 ROCK 抑制剂、包含这种抑制剂的组合物，尤其是药物，以及这种抑制剂在治疗和预防疾病中的用途。 此外，本发明还涉及上述化合物的治疗方法和在制造药物中的用途，以应用于包括眼科疾病在内的多种治疗适应症。
• US8815873B2
  申请人：——

  公开号：US8815873B2

  公开（公告）日：2014-08-26
• US8912209B2
  申请人：——

  公开号：US8912209B2

  公开（公告）日：2014-12-16