N-methyl-3-methylsulfinylaniline | 222734-71-6

• 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: N-methyl-3-methylsulfinylaniline
• 英文别名: 3-methylsulfinyl-N-methylaniline；3-methanesulfinyl-N-methylaniline
• CAS: 222734-71-6
• 化学式: C₈H₁₁NOS
• 分子量: 169.247
• InChiKey: GSGSSRVLLAXORZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methyl-3-methylsulfinylaniline 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 0.5h， 以100%的产率得到N-methyl-3-methylsulfinylaniline hydrochloride
  参考文献：
  名称：

  Pharmaceutically active compound and methods of use

  摘要：

  该发明涉及消旋体和光学活性N-(2-氯-5-甲基硫代苯基)-N′-(3-甲基亚磺基苯基)-N′-甲基胍啉、N-(2-氯-5-甲基亚磺基苯基)-1-(7-三氟甲基-1,2,3,4-四氢喹啉基)羧酰胍啉和N-(3-甲基亚磺基苯基)-N-甲基-N′-(2-氯-5-甲氧基苯基)胍啉及其药学上可接受的盐，以及包含这些化合物的药物组合物和治疗方法。该发明的化合物特别适用于治疗或预防神经损伤和神经退行性疾病。

  公开号：

  US06774263B1
• 作为产物：
  描述：

  3-氨基茴香硫醚 在 lithium aluminium tetrahydride 、 双氧水 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 20.0h， 生成 N-methyl-3-methylsulfinylaniline
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of N-(2,5-Disubstituted phenyl)-N‘-(3-substituted phenyl)-N‘-methylguanidines As N-Methyl-d-aspartate Receptor Ion-Channel Blockers

  摘要：

  In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both a receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (27b, R-2 = R-5 = Br, R-3 = C2H5) exhibited potency at both a receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R-2 and R-5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5-(methylthio)phenyl)-N'-(3-ethylphenyl)- N'-methylguanidine (34b, R-2 = Br, R-5 = SMe, R-3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R-3. Optimal activity in this series are afforded by 43b and 44b (R-2 = Cl or Br, R-5 = R-3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (K-i vs [H-3]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure-activity relationships for-these compounds at the NMDA receptor ion-channel site are discussed.

  DOI：

  10.1021/jm970459c

文献信息

• [EN] PHARMACEUTICALLY ACTIVE COMPOUND AND METHODS OF USE<br/>[FR] COMPOSE ACTIF DU POINT DE VUE PHARMACEUTIQUE ET SES METHODES D'UTILISATION
  申请人：CAMBRIDGE NEUROSCIENCE, INC.

  公开号：WO1999018962A1

  公开（公告）日：1999-04-22

  (EN) The present invention relates to racemic and optically active N-(2-chloro-5- methylthiophenyl) -N'-(3- methylsulfinylphenyl) -N'-methylguanidine, N-(2-chloro-5- methylsulfinylphenyl) -1-(7-trifluoromethyl -1,2,3,4- tetrahydroquinolinyl) carboximidamide, and N-(3-methylsulfinylphenyl) -N-methyl-N'- (2-chloro-5- methoxyphenyl) guanidine and pharmaceutically acceptable salts thereof, and pharmaceutical compositions and therapeutic methods of treatment that comprise such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.(FR) La présente invention concerne N-(2-chloro-5- méthylthiophényl) -N'-(3-méthylsulfinylphényl) -N'-méthylguanidine, N-(2-chloro-5- méthylsulfinylphényl) -1-(7-trifluorométhyl -1,2,3,4- tétrahydroquinolinyl) carboximidamide, et N-(3-méthylsulfinylphényl) -N-méthyl-N'- (2-chloro-5-méthoxyphényl) guanidine, ainsi que leurs sels acceptables du point de vue pharmaceutique, des compositions pharmaceutiques et des méthodes thérapeutiques de traitement comprenant ces composés. Les composés de l'invention sont particulièrement utiles pour le traitement ou la prophylaxie de lésions neurologiques et de troubles neurodégénératifs.

  本发明涉及光学活性和外消旋性N-（2-氯-5-甲基硫代苯基）-N'-(3-甲基磺酰基苯基)-N'-甲基胍、N-(2-氯-5-甲基磺酰基苯基)-1-(7-三氟甲基-1,2,3,4-四氢喹啉基)羧酰亚胺和N-(3-甲基磺酰基苯基)-N-甲基-N'-(2-氯-5-甲氧基苯基)胍及其药学上可接受的盐，以及包含这些化合物的药物组成物和治疗方法。本发明的化合物特别适用于治疗或预防神经损伤和神经退行性疾病。
• BENZENE, PYRIDINE, AND PYRIDAZINE DERIVATIVES
  申请人：Huang Kenneth He

  公开号：US20110183977A1

  公开（公告）日：2011-07-28

  Disclosed are compounds and pharmaceutically acceptable salts of Formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , n, Q 1 , Q 2 , Q 3 , Y, and X 1 -X 4 are as defined herein. Compounds of Formula I are useful in the treatment of diseases and/or conditions related to cell proliferation, such as cancer, inflammation, arthritis, angiogenesis, or the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.

  本发明揭示了公式I的化合物和药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、n、Q1、Q2、Q3、Y和X1-X4的定义如本文所述。公式I的化合物在治疗与细胞增殖相关的疾病和/或病况，例如癌症、炎症、关节炎、血管生成等方面非常有用。本发明还揭示了包含本发明化合物的药物组合物以及使用这些化合物治疗上述病况的方法。
• Identification and characterization of a potential ischemia-selective N-methyl-d-aspartate (NMDA) receptor ion-channel blocker, CNS 5788
  作者：Seetharamaiyer Padmanabhan、Michael E Perlman、Lu Zhang、Deke Moore、Dan Zhou、James B Fischer、Graham J Durant、Robert N McBurney

  DOI：10.1016/s0960-894x(00)00695-8

  日期：2001.2

  The identification and characterization of a potentially ischemia-selective and orally-active sulfoxide based NMDA ion-channel blocker showing good neuroprotective activity, (R)-(+)-N-(2-chloro-5-methylthiophenyl)-N'-(3-methylsulfinylphenyl)-N'-methylguanidine (CNS 5788), is described. (C) 2001 Elsevier Science Ltd. All rights reserved.
• THERAPEUTIC SUBSTITUTED GUANIDINES
  申请人：CAMBRIDGE NEUROSCIENCE, INC.

  公开号：EP0705100A1

  公开（公告）日：1996-04-10
• EP0705100A4
  申请人：——

  公开号：EP0705100A4

  公开（公告）日：1996-05-29