2-[3-(4-chlorophenyl)-ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide | 1246966-74-4

• 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: 2-[3-(4-chlorophenyl)-ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide
• 英文别名: 2-[3-(4-Chloro-phenyl)-ureido]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid amide；2-[(4-chlorophenyl)carbamoylamino]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
• CAS: 1246966-74-4
• 化学式: C₁₅H₁₅ClN₄O₂S
• 分子量: 350.829
• InChiKey: CAZQCXXQUIGTME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-(4-chlorophenyl)-ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.67h， 生成 2-{[(4-chlorophenyl)carbamoyl]amino}-6-{3-[3-(pyridin-3-yl)propanamido]propyl}-4H,5H,6H,7H-thieno[2,3-c]pyridine-3-carboxamide
  参考文献：
  名称：

  Phenotypic Optimization of Urea–Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss

  摘要：

  Hearing loss is a major public health concern with no pharmaceutical intervention for hearing protection or restoration. Using zebrafish neuromast hair cells, a robust model for mammalian auditory and vestibular hair cells, we identified a ureathiophene carboxamide, 1 (ORC-001), as protective against aminoglycoside antibiotic (AGA)-induced hair cell death. The 50% protection (HC50) concentration conferred by 1 is 3.2 mu M with protection against 200 mu M neomycin approaching 100%. Compound 1 was sufficiently safe and drug-like to validate otoprotection in an in vivo rat hearing loss model. We explored the structureactivity relationship (SAR) of this compound series to improve otoprotective potency, improve pharmacokinetic properties and eliminate off-target activity. We present the optimization of 1 to yield 90 (ORC-13661). Compound 90 protects mechanosensory hair cells with HC50 of 120 nM and demonstrates 100% protection in the zebrafish assay and superior physiochemical, pharmacokinetic, and toxicologic properties, as well as complete in vivo protection in rats.

  DOI：

  10.1021/acs.jmedchem.7b00932
• 作为产物：
  描述：

  tert-butyl 3-carbamoyl-2-[3-(4-chlorophenyl)ureido]-4,5-dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 以59%的产率得到2-[3-(4-chlorophenyl)-ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid amide
  参考文献：
  名称：

  [EN] AUTOTAXIN INHIBITORS
  [FR] INHIBITEURS DE L'AUTOTAXINE

  摘要：

  本发明涉及按照式(I)的化合物作为自体脂肪酶抑制剂，以及利用这种化合物治疗和/或预防由增加的溶酶磷脂酸水平和/或自体脂肪酶的激活引起、介导和/或传播的生理和/或病理条件，特别是不同癌症的治疗。

  公开号：

  WO2010112124A1

文献信息

• Autotaxin inhibitors
  申请人：Merck Patent GmbH

  公开号：US08329907B2

  公开（公告）日：2012-12-11

  The present invention relates to compounds according to formula (I) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by increased lysophosphatic acid levels and/or the activation of autotaxin, in particular of different cancers.

  本发明涉及公式（I）的化合物，作为自体税脂酶抑制剂，并且使用这种化合物治疗和/或预防由增加的溶解磷脂酸水平和/或自体税脂酶的激活引起、介导和/或传播的生理和/或病理生理状况，特别是不同类型的癌症。
• AUTOTAXIN INHIBITORS
  申请人：Schultz Melanie

  公开号：US20120015976A1

  公开（公告）日：2012-01-19

  The present invention relates to compounds according to formula (I) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by increased lysophosphatic acid levels and/or the activation of autotaxin, in particular of different cancers.

  本发明涉及公式（I）的化合物，作为自体税脂酰酰肽酶抑制剂，并且利用这种化合物治疗和/或预防由升高的溶解磷脂酸水平和/或自体税脂酰酰肽酶的激活引起、介导和/或传播的生理和/或病理生理状况，特别是不同癌症。
• COMPOUNDS AND METHODS FOR PREVENTING, TREATING AND/OR PROTECTING AGAINST SENSORY HAIR CELL DEATH
  申请人：UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

  公开号：US20150232476A1

  公开（公告）日：2015-08-20

  Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing, treating, and/or protecting against sensory hair cell death. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

  本文披露了一些化合物和包含这些化合物的药物组成物，用于预防、治疗和/或保护感觉毛细胞死亡。还披露了使用这些化合物的方法，单独或与其他治疗剂联合使用。
• US8329907B2
  申请人：——

  公开号：US8329907B2

  公开（公告）日：2012-12-11
• US8497283B2
  申请人：——

  公开号：US8497283B2

  公开（公告）日：2013-07-30