2-[3-(4-chlorophenyl)ureido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide | 312951-85-2

• 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]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
• 英文别名: 2-({[(4-chlorophenyl)amino]carbonyl}amino)-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide；Proto-1；2-[(4-chlorophenyl)carbamoylamino]-6-ethyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxamide
• CAS: 312951-85-2
• 化学式: C₁₇H₁₉ClN₄O₂S
• mdl: MFCD01923572
• 分子量: 378.882
• InChiKey: QBLKUVUKIZEWAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[3-(4-chlorophenyl)ureido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 2-[3-(4-chlorophenyl)ureido]-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide hydrochloride
  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：

  N-乙基-4-哌啶酮 在 吗啉 、 sulfur 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 2-[3-(4-chlorophenyl)ureido]-6-ethyl-4,5,6,7-tetrahydrothieno[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

文献信息

• 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。
• Assay for compounds that protect against sensory hair cell death and compounds identified by same
  申请人：Ou C. Henry

  公开号：US20060188445A1

  公开（公告）日：2006-08-24

  The present invention provides methods of identifying compounds that protect against ototoxicity induced by one or more noxious stimuli, and methods of treating an individual with compounds identified using the present screening methods. Also provided are compounds demonstrated to have otoprotective effects.

  本发明提供了鉴定可防止由一种或多种有害刺激诱发的耳毒性的化合物的方法，以及用本筛选方法鉴定的化合物治疗个体的方法。本发明还提供了经证实具有耳保护作用的化合物。
• OTIC FORMULATIONS FOR DRUG-INDUCED OTOTOXICITY
  申请人：Otonomy, Inc.

  公开号：EP3810146A1

  公开（公告）日：2021-04-28
• COMPOUNDS THAT PROTECT AGAINST SENSORY HAIR CELL DEATH
  申请人：Ou Henry C.

  公开号：US20090023751A1

  公开（公告）日：2009-01-22

  The present invention provides methods of identifying compounds that protect against ototoxicity induced by one or more noxious stimuli, and methods of treating an individual with compounds identified using the present screening methods. Also provided are compounds demonstrated to have otoprotective effects.
• Methods for Screening for Antibiotic Compounds
  申请人：Cheung Ambrose

  公开号：US20120115157A1

  公开（公告）日：2012-05-10

  The present invention is a method for screening drugs for antibiotic activity by screening a drug for activity to disrupt a toxin-antitoxin complex in a bacterial cell.