3'-((2-Cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)-6-methylbiphenyl-3-carboxylic acid | 1334317-77-9

• 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: 3'-((2-Cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)-6-methylbiphenyl-3-carboxylic acid
• 英文别名: 3-[3-[(2-cyclopentyl-3-oxo-1,2-benzothiazol-6-yl)oxymethyl]phenyl]-4-methylbenzoic acid
• CAS: 1334317-77-9
• 化学式: C₂₇H₂₅NO₄S
• 分子量: 459.566
• InChiKey: VUMIBIDABVTRIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-((2-cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)phenylboronic acid 、 3-碘-4-甲基苯甲酸 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 12.0h， 以23 mg的产率得到3'-((2-Cyclopentyl-3-oxo-2,3-dihydrobenzo[d]isothiazol-6-yloxy)methyl)-6-methylbiphenyl-3-carboxylic acid
  参考文献：
  名称：

  Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure–Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

  摘要：

  Compounds that modulate metabotropic glutamate subtype 2 (mGlu(2)) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu(2) receptor positive allosteric modulators (PAMs). The effects of N-substitution (R-1) and substitutions on the aryl ring (R-2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu(2) receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans.

  DOI：

  10.1021/jm3005306

文献信息

• POSITIVE ALLOSTERIC MODULATORS OF GROUP II MGLURS
  申请人：Cosford Nicholas D. P.

  公开号：US20120071503A1

  公开（公告）日：2012-03-22

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive allosteric modulators of the metabotropic glutamate subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.

  本公开提供化合物和组合物，以及使用这些化合物和组合物的方法，作为代谢型谷氨酸亚型2（mGlu2）受体的正向变构调节剂，并用于治疗与mGlu2受体相关的中枢神经系统疾病，包括精神分裂症、焦虑症、成瘾等，例如可卡因成瘾、尼古丁成瘾等。
• Positive allosteric modulators of group II mGluRs
  申请人：Cosford Nicholas D. P.

  公开号：US08748632B2

  公开（公告）日：2014-06-10

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive allosteric modulators of the metabotropic glutamate subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.

  该披露提供了化合物和组合物，以及使用这些化合物和组合物的方法，作为代谢型谷氨酸亚型2（mGlu2）受体的正向变构调节剂，并用于治疗与mGlu2受体相关的中枢神经系统疾病，包括精神分裂症、焦虑、成瘾，例如可卡因成瘾、尼古丁成瘾等。
• US8748632B2
  申请人：——

  公开号：US8748632B2

  公开（公告）日：2014-06-10
• [EN] POSITIVE ALLOSTERIC MODULATORS OF GROUP II MGLURS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DE MGLURS DE TYPE 2
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2011116356A2

  公开（公告）日：2011-09-22

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive ailosteric modulators of the melabotropic glutamatc subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.
• Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure–Activity Relationships and Assessment in a Rat Model of Nicotine Dependence
  作者：Shyama Sidique、Raveendra-Panickar Dhanya、Douglas J. Sheffler、Hilary Highfield Nickols、Li Yang、Russell Dahl、Arianna Mangravita-Novo、Layton H. Smith、Manoranjan S. D’Souza、Svetlana Semenova、P. Jeffrey Conn、Athina Markou、Nicholas D. P. Cosford

  DOI：10.1021/jm3005306

  日期：2012.11.26

  Compounds that modulate metabotropic glutamate subtype 2 (mGlu(2)) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu(2) receptor positive allosteric modulators (PAMs). The effects of N-substitution (R-1) and substitutions on the aryl ring (R-2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu(2) receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans.