(4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide | 1979935-33-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环七噻吩
• 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
• 英文别名: (+)-2-[3-(4-chlorophenyl)ureido]-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide；Orc-13661；(1R,8S)-4-[(4-chlorophenyl)carbamoylamino]-11-methyl-5-thia-11-azatricyclo[6.2.1.02,6]undeca-2(6),3-diene-3-carboxamide
• CAS: 1979935-33-5
• 化学式: C₁₈H₁₉ClN₄O₂S
• 分子量: 390.893
• InChiKey: DAHGONXBHYVOPI-NWDGAFQWSA-N

物化性质

• 沸点：
  438.0±45.0 °C(Predicted)
• 密度：
  1.478±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 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：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide 在 ice water 、 盐酸 、 水 、 甲醇 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以to give the title compound (9) (18.0 g) as an off-white solid的产率得到(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：

  本文介绍了一些化合物和包括这些化合物的药物组合物，用于预防或治疗听力损失。这些化合物和药物组合物可以预防或治疗毛细胞死亡。此外，这些化合物和药物组合物还可以保护接受氨基糖苷类抗生素的个体免受肾损伤。还介绍了使用这些化合物单独或与其他治疗药物组合使用的方法。

  公开号：

  US20160229869A1
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 4-二甲氨基吡啶 、 硫酸 、 叠氮磷酸二苯酯 、 sodium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 138.91h， 生成 (4R,7S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide
  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

• [EN] CRYSTALLINE FORMS OF COMPOUNDS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH<br/>[FR] FORMES CRISTALLINES DE COMPOSÉS POUR PRÉVENIR OU TRAITER LA MORT DE CELLULES CILIÉES SENSORIELLES
  申请人：UNIV WASHINGTON

  公开号：WO2019046731A1

  公开（公告）日：2019-03-07

  Described herein is (4R,7,S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[ƅ]thiophene-3-carboxamide mesylate, including crystalline forms and solvates thereof.

  本文描述的是（4R,7,S）-2-(3-(4-氯苯基)脲基)-9-甲基-5,6,7,8-四氢-4H-4,7-环庚[ƅ]噻吩-3-羧酰胺甲磺酸盐，包括其结晶形式和溶剂合物。
• 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.
• CRYSTALLINE FORMS OF COMPOUNDS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH
  申请人：University of Washington

  公开号：US20200345705A1

  公开（公告）日：2020-11-05

  Described herein is (4R,7,S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide mesylate, including crystalline forms and solvates thereof.
• 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.