(4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide hydrochloride | 1979935-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide hydrochloride
• 英文别名: (+)-2-[3-(4-chlorophenyl)ureido]-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide hydrochloride；ORC-13661；KB5U8P38TV；(1R,8S)-4-[(4-chlorophenyl)carbamoylamino]-11-methyl-5-thia-11-azatricyclo[6.2.1.02,6]undeca-2(6),3-diene-3-carboxamide;hydrochloride
• CAS: 1979935-34-6
• 化学式: C₁₈H₁₉ClN₄O₂S*ClH
• 分子量: 427.354
• InChiKey: VFXQFPNKKZLQHQ-ZVWHLABXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ecgonidine 在 吗啉 、 盐酸 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 112.82h， 生成 (4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide hydrochloride
  参考文献：
  名称：

  COMPOUNDS AND METHODS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH

  摘要：

  本文揭示了一些化合物和包含这些化合物的药物组合物，用于预防或治疗听力损失。本文描述的化合物和药物组合物可以预防或治疗毛细胞死亡。此外，本文描述的化合物和药物组合物可以保护接受氨基糖苷类抗生素的个体免受肾脏损伤。还公开了使用这些化合物的方法，单独或与其他治疗剂联合使用。

  公开号：

  US20160229869A1

文献信息

• Compounds and methods for preventing or treating sensory hair cell death
  申请人：UNIVERSITY OF WASHINGTON

  公开号：US10399994B2

  公开（公告）日：2019-09-03

  Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

  本文公开了用于预防或治疗听力损失的化合物以及包含此类化合物的药物组合物。本文所述的化合物和药物组合物可预防或治疗毛细胞死亡。此外，本文所述的化合物和药物组合物还能防止接受氨基糖苷类抗生素治疗的人的肾脏受损。还公开了单独使用或与其他治疗剂结合使用这些化合物的方法。
• Phenotypic Optimization of Urea–Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss
  作者：Sarwat Chowdhury、Kelly N. Owens、R. Jason Herr、Qin Jiang、Xinchao Chen、Graham Johnson、Vincent E. Groppi、David W. Raible、Edwin W Rubel、Julian A. Simon

  DOI：10.1021/acs.jmedchem.7b00932

  日期：2018.1.11

  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.
• US9493482B2
  申请人：——

  公开号：US9493482B2

  公开（公告）日：2016-11-15
• [EN] COMPOUNDS AND METHODS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR PRÉVENIR OU TRAITER LA MORT DE CELLULES CAPILLAIRES SENSORIELLES
  申请人：UNIV WASHINGTON

  公开号：WO2016127123A2

  公开（公告）日：2016-08-11

  Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.