2-{[(4-chlorophenyl)carbamoyl]amino}-6-{3-[3-(1H-indol-3-yl)propanamido]propyl}-4H,5H,6H,7H-thieno[2,3-c]pyridine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-{[(4-chlorophenyl)carbamoyl]amino}-6-{3-[3-(1H-indol-3-yl)propanamido]propyl}-4H,5H,6H,7H-thieno[2,3-c]pyridine-3-carboxamide
• 英文别名: 2-[(4-chlorophenyl)carbamoylamino]-6-[3-[3-(1H-indol-3-yl)propanoylamino]propyl]-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxamide
• 化学式: C₂₉H₃₁ClN₆O₃S
• 分子量: 579.123
• InChiKey: JSGCPWMOHCOCSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  161
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  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-(1H-indol-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

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。
• 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：US09416141B2

  公开（公告）日：2016-08-16

  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.

  本文披露了用于预防、治疗和/或保护感觉毛细胞死亡的化合物和包括这些化合物的制药组合物。还披露了使用这些化合物，单独或与其他治疗药物联合使用的方法。
• OTIC FORMULATIONS FOR DRUG-INDUCED OTOTOXICITY
  申请人：OTONOMY, INC.

  公开号：US20210186943A1

  公开（公告）日：2021-06-24

  Provided herein are methods for preventing and/or reducing the severity of drug induced ototoxicity. Provided herein are methods for recovery from hearing loss due to drug-induced ototoxicity. In an aspect, the present disclosure provides a method for preventing drug-induced ototoxicity in an individual in need thereof comprising intratympanic administration of a pharmaceutical composition comprising a therapeutic agent selected from a JNK inhibitor, a TRPV modulator, an MET channel inhibitor, and an otoprotectant to the individual in need thereof, wherein the pharmaceutical composition is administered prior to onset of therapy with the drug, and wherein the composition provides sustained release of the therapeutic agent into the ear for a period of at least 5 days after a single administration.
• US9416141B2
  申请人：——

  公开号：US9416141B2

  公开（公告）日：2016-08-16
• US9902738B2
  申请人：——

  公开号：US9902738B2

  公开（公告）日：2018-02-27