5-methyl-5'-phenyl-3'H-spiro[dihydroindole-3,2'-[1,3,4]thiadiazol]-2-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-methyl-5'-phenyl-3'H-spiro[dihydroindole-3,2'-[1,3,4]thiadiazol]-2-one
• 英文别名: spiro 5'-(phenyl)-2',3'-dihydro-[1',3',4']thiadiazol-2',3-1,3-dihydro-5-methyl-indol-2-one；5-methyl-5'-phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one；Thiadiazole derivative, 10；5-methyl-5'-phenylspiro[1H-indole-3,2'-3H-1,3,4-thiadiazole]-2-one
• 化学式: C₁₆H₁₃N₃OS
• 分子量: 295.365
• InChiKey: FREUDXYIZICEHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  78.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯二硫代甲酸 在 hydrazine hydrate 、 sodium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 39.0h， 生成 5-methyl-5'-phenyl-3'H-spiro[dihydroindole-3,2'-[1,3,4]thiadiazol]-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 5′-phenyl-3′H-spiro-[indoline-3,2′-[1,3,4]oxadiazol]-2-one analogs

  摘要：

  A series of 5'-phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one analogs were synthesized and their Bcl-2 protein inhibitory activities were studied. The lead compound was originally identified using a fluorescence polarization-based competitive binding assay. Among the 10 compounds investigated, 1k showed good binding affinities to Bcl-xL and Mcl-1, with inhibition constants of 8.9 mu mol/L and 3.4 mu mol/L, respectively. While compound 1c achieved tight binding affinities to Bcl-xL (Ki = 0.16 mu mol/L), has the potential to be a new lead compound. (C) 2013 De-Cai Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2013.06.001

文献信息

• Thiadiazole compounds and methods of use thereof
  申请人：Bursavich Matthew G.

  公开号：US20080125469A1

  公开（公告）日：2008-05-29

  The present invention relates to Thiadiazole Compounds; compositions comprising an effective dose of a Thiadiazole Compound; and methods treating or preventing a metalloproteinase-related disorder, such as, an arthritic disorder, osteoarthritis, cancer, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, atherosclerosis, age-related macular degeneration, myocardial infarction, a corneal ulceration, an ocular surface disease, hepatitis, an aortic aneurysm, tendonitis, a central nervous system disorder, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritis, graft versus host disease, diabetes, an inflammatory bowel disease, shock, invertebral disc degeneration, stroke, osteopenia or a periodontal disease or comprising administering an effective dose of a Thiadiazole Compound to a mammal in need thereof.

  本发明涉及噻二唑化合物；包含有效剂量噻二唑化合物的组合物；以及治疗或预防金属蛋白酶相关疾病的方法，例如关节炎、骨关节炎、癌症、类风湿性关节炎、哮喘、慢性阻塞性肺病、动脉粥样硬化、老年性黄斑变性、心肌梗死、角膜溃疡、眼表疾病、肝炎、主动脉瘤、肌腱炎、中枢神经系统疾病、异常伤口愈合、血管生成、再狭窄、肝硬化、多发性硬化、肾小球肾炎、移植物抗宿主病、糖尿病、炎症性肠病、休克、椎间盘退行性变、中风、骨质疏松症或牙周疾病，或包括向需要的哺乳动物施用有效剂量噻二唑化合物。
• [EN] SMALL MOLECULE INHIBITORS OF GPCR GPR68 AND RELATED RECEPTORS<br/>[FR] INHIBITEURS À PETITES MOLÉCULES DE RCPG GPR68 ET RÉCEPTEURS ASSOCIÉS POUR LE TRAITEMENT DU CANCER, DU GLIOBLASTOME ET D'AUTRES INDICATIONS
  申请人：UNIV MARYLAND

  公开号：WO2020214896A1

  公开（公告）日：2020-10-22

  The invention relates to a class of small molecule inhibitors of GPR68/OGR1, a proton-sensing/stretch-sensing/sheer-stress-sending G-protein coupled receptor, and related receptors GPR4 and GPR65. These inhibitors are useful as a therapeutic for glioblastoma and other neoplasms, as a monotherapy or adjuvant, and also can be used as a treatment for other conditions, such as osteoporosis, inflammatory bowel disease, autoimmune and chronic inflammatory diseases such as multiple sclerosis and inflammatory pain syndromes, GERD, aspiration pneumonitis, bacterial and viral pneumonia, COPD, acute respiratory distress syndrome (ARDS), and COVID-19.

  该发明涉及一类GPR68/OGR1的小分子抑制剂，这是一种质子感应/拉伸感应/剪切应力发送的G蛋白偶联受体，以及相关的受体GPR4和GPR65。这些抑制剂可用作治疗胶质母细胞瘤和其他肿瘤的药物，作为单独治疗或辅助治疗，也可用作治疗其他疾病，如骨质疏松症、炎症性肠病、自身免疫和慢性炎症性疾病（如多发性硬化和炎症性疼痛综合征）、胃食管反流病、吸入性肺炎、细菌和病毒性肺炎、慢性阻塞性肺疾病、急性呼吸窘迫综合征（ARDS）和COVID-19的治疗。
• 5′-Phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2)
  作者：Matthew G. Bursavich、Adam M. Gilbert、Sabrina Lombardi、Katy E. Georgiadis、Erica Reifenberg、Carl R. Flannery、Elisabeth A. Morris

  DOI：10.1016/j.bmcl.2007.07.048

  日期：2007.10

  5'-Phenyl-3' H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug. (c) 2007 Elsevier Ltd. All rights reserved.
• THIADIAZOLE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Wyeth

  公开号：EP2032584A2

  公开（公告）日：2009-03-11
• SMALL MOLECULE INHIBITORS OF GPCR GPR68 AND RELATED RECEPTORS FOR TREATING CANCER, GLIOBLASTOMA, AND OTHER INDICATIONS
  申请人：UNIVERSITY OF MARYLAND, BALTIMORE

  公开号：US20220202785A1

  公开（公告）日：2022-06-30

  The invention relates to a class of small molecule inhibitors of GPR68/OGR1, a proton-sensing/stretch-sensing/sheer-stress-sending G-protein coupled receptor, and related receptors GPR4 and GPR65. These inhibitors are useful as a therapeutic for glioblastoma and other neoplasms, as a monotherapy or adjuvant, and also can be used as a treatment for other conditions, such as osteoporosis, inflammatory bowel disease, autoimmune and chronic inflammatory diseases such as multiple sclerosis and inflammatory pain syndromes, GERD, aspiration pneumonitis, bacterial and viral pneumonia, COPD, acute respiratory distress syndrome (ARDS), and COVID-19.