首页> 外国专利> INDAZOLE DERIVATIVES AS ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD) INHIBITORS FOR USE IN DIABETES AND RELATED DISEASES OF METABOLIC SYNDROME

INDAZOLE DERIVATIVES AS ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD) INHIBITORS FOR USE IN DIABETES AND RELATED DISEASES OF METABOLIC SYNDROME

机译:吲哚衍生物作为腺嘌呤单磷酸腺苷脱氨酶(AMPD)抑制剂,用于糖尿病和代谢综合征的相关疾病

摘要

Herein, we describe a method for treatment of diabetes and other disorders classified as Metabolic Syndrome. The invention provides novel AMP Deaminase (AMPD) inhibitors comprising novel indazole and benzotriazole derivatives including a phosphorous containing derivative, a carboxylic acid, or an amino acid ester prodrug. The invention also provides support for a novel mechanism of action for the existing drug metformin: direct inhibition of the enzyme AMPD. The inhibition of AMPD in turn activates AMP Kinase, known to be linked to the action of metformin. The invention also makes novel use of a double inhibitor assay allowing identification of selective AMPD inhibitors over ADA inhibitors. The new inhibitors, structurally distinct from metformin, offer selectivity that may obviate side effects known for metformin itself, providing new benefits for diabetes and Metabolic Syndrome.
机译:在本文中,我们描述了一种用于治疗糖尿病和其他被分类为代谢综合征的疾病的方法。本发明提供了新颖的AMP脱氨酶(AMPD)抑制剂,其包含新颖的吲唑和苯并三唑衍生物,所述衍生物包括含磷衍生物,羧酸或氨基酸酯前药。本发明还为现有药物二甲双胍的新颖作用机理提供了支持:直接抑制酶AMPD。 AMPD的抑制又激活了已知与二甲双胍作用有关的AMP激酶。本发明还利用了双重抑制剂测定法的新颖用途,该测定法允许鉴定选择性的AMPD抑制剂而不是ADA抑制剂。新的抑制剂在结构上与二甲双胍不同,其选择性可消除二甲双胍本身已知的副作用,为糖尿病和代谢综合征提供新的益处。

著录项

  • 公开/公告号US2012130078A1

    专利类型

  • 公开/公告日2012-05-24

    原文格式PDF

  • 申请/专利权人 RAYMOND S. OCHS;TANAJI T. TALELE;

    申请/专利号US20100950071

  • 发明设计人 RAYMOND S. OCHS;TANAJI T. TALELE;

    申请日2010-11-19

  • 分类号C07D401/06;C07D249/18;C07D231/56;

  • 国家 US

  • 入库时间 2022-08-21 17:32:45

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