N-(2-chloro-5-(methylthio)phenyl)cyanamide | 222734-77-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-(2-chloro-5-(methylthio)phenyl)cyanamide
• 英文别名: 2-chloro-5-methylthiophenylcyanamide；(2-Chloro-5-methylsulfanylphenyl)cyanamide
• CAS: 222734-77-2
• 化学式: C₈H₇ClN₂S
• 分子量: 198.676
• InChiKey: QYCDDHANJRMISS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-chloro-5-(methylthio)phenyl)cyanamide 在 sodium periodate 作用下， 以 甲醇 、 水 、 xylene 为溶剂， 生成 2-(2-Chloro-5-methylsulfinylphenyl)-1-methyl-1-(3-methylsulfanylphenyl)guanidine;hydrochloride
  参考文献：
  名称：

  Identification and characterization of a potential ischemia-selective N-methyl-d-aspartate (NMDA) receptor ion-channel blocker, CNS 5788

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(00)00695-8
• 作为产物：
  描述：

  2-氯-5-(甲硫基)苯甲酸 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 水 、 叔丁醇 为溶剂， 反应 12.0h， 生成 N-(2-chloro-5-(methylthio)phenyl)cyanamide
  参考文献：
  名称：

  Identification and characterization of a potential ischemia-selective N-methyl-d-aspartate (NMDA) receptor ion-channel blocker, CNS 5788

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(00)00695-8

文献信息

• Pharmaceutically active compound and methods of use
  申请人：Cambridge Neuroscience, Inc.

  公开号：US06774263B1

  公开（公告）日：2004-08-10

  This 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.

  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。
• [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。
• <i>N</i>′-3-(Trifluoromethyl)phenyl Derivatives of <i>N</i>-Aryl-<i>N</i>′-methylguanidines as Prospective PET Radioligands for the Open Channel of the <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor: Synthesis and Structure–Affinity Relationships
  作者：Gregory R. Naumiec、Kimberley J. Jenko、Sami S. Zoghbi、Robert B. Innis、Lisheng Cai、Victor W. Pike

  DOI：10.1021/acs.jmedchem.5b01510

  日期：2015.12.24

  N-Methyl-D-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain. NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies,: To date, no radioligands have Shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure affinity relationships in N'-3-(trifluoromethyl)phenyl derivatives of N-aryl-N'-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N'-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [H-3](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development.
• Asymmetric synthesis of a neuroprotective and orally active N-methyl-d-aspartate receptor ion-channel blocker, CNS 5788
  作者：Seetharamaiyer Padmanabhan、Ruth C Lavin、Graham J Durant

  DOI：10.1016/s0957-4166(00)00328-1

  日期：2000.9

  Asymmetric synthesis of N-(2-chloro-5-methylthiophenyl)-N'-(3-methylsulfinylphenyl)-N'-methyl-guanidine (CNS 5788) was achieved in high enantiomeric excess through condensation of the cyanamide derivative, 6 and the sulfinylaniline hydrochloride, 5. The key step involved the asymmetric oxidation of N-methyl-3-methylthioaniline using a Davis reagent. (C) 2000 Elsevier Science Ltd. All rights reserved.
• PHARMACEUTICALLY ACTIVE COMPOUND AND METHODS OF USE
  申请人：CAMBRIDGE NEUROSCIENCE, INC.

  公开号：EP1041986A1

  公开（公告）日：2000-10-11