4-(chloromethyl)-2,6-diethoxy-4'-fluoro-1,1'-biphenyl | 1227405-84-6

• 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: 4-(chloromethyl)-2,6-diethoxy-4'-fluoro-1,1'-biphenyl
• 英文别名: 4-(chloromethyl)-2,6-diethoxy-4′-fluoro-1,1′-biphenyl；4-(Chloromethyl)-2,6-diethoxy-4'-fluorobiphenyl；5-(chloromethyl)-1,3-diethoxy-2-(4-fluorophenyl)benzene
• CAS: 1227405-84-6
• 化学式: C₁₇H₁₈ClFO₂
• 分子量: 308.78
• InChiKey: GGJXTUISLTYDEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-2,6-diethoxy-4'-fluoro-1,1'-biphenyl 在 Pd(OH)2/C (50% w/w) 、 氢气 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 正庚烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 methyl 2-(((3a,6a-cis)-1-((2,6-diethoxy-4'-fluoro-[1,1'-biphenyl]-4-yl)methyl)octahydrocyclopenta[b]pyrrol-4-yl)amino)benzo[d]oxazole-6-carboxylate
  参考文献：
  名称：

  Discovery and Pharmacology of a Novel Somatostatin Subtype 5 (SSTR5) Antagonist: Synergy with DPP-4 Inhibition

  摘要：

  We report new SSTR5 antagonists with enhanced potency, subtype selectivity, and minimal off-target activities as compared to previously reported compounds. Starting from the reported SSTR5 antagonist 1, we systematically surveyed changes in the central core and head piece while maintaining the diphenyl tail group constant. From this study the azaspirodecanone 10 emerged as a new highly potent and selective SSTR5 antagonist. Compound 10 lowered glucose excursion by 94% in an oral glucose tolerance test (OGTT) in mice following a 3 mg/kg oral dose. The compound increased both total and active circulating incretin hormone GLP-1 levels in mice at a dose of 10 mg/kg. A synergistic effect was also demonstrated when compound 10 was coadministered with a DPP-4 inhibitor, substantially increasing circulating active GLP-1[7-36] amide and insulin in response to a glucose challenge.

  DOI：

  10.1021/acsmedchemlett.8b00305
• 作为产物：
  描述：

  4-溴-3,5-二羟基苯甲酸 在 potassium phosphate 、 lithium aluminium tetrahydride 、 氯化亚砜 、 palladium diacetate 、 potassium carbonate 、 zinc(II) chloride 、 三环己基膦 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.0h， 生成 4-(chloromethyl)-2,6-diethoxy-4'-fluoro-1,1'-biphenyl
  参考文献：
  名称：

  [EN] SSTR5 ANTAGONISTS
  [FR] ANTAGONISTES DE SSTR5

  摘要：

  这项披露至少部分针对SSTR5拮抗剂，用于治疗涉及肠脑轴的疾病或疾病。在某些实施例中，SSTR5拮抗剂是肠限制性化合物。在某些实施例中，该疾病或疾病是代谢性疾病，如糖尿病、肥胖症、非酒精性脂肪肝炎（NASH）或营养紊乱，如短肠综合征。

  公开号：

  WO2021113368A1

文献信息

• [EN] SUBSTITUTED BICYCLIC AMINES FOR THE TREATMENT OF DIABETES<br/>[FR] AMINES BICYCLIQUES SUBSTITUÉES POUR LE TRAITEMENT DU DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2010056717A1

  公开（公告）日：2010-05-20

  Described herein are substituted bicyclic amines. In particular, described herein are substituted bicyclic amines that are effective as antagonists of SSTR5 and useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, metabolic syndrome, depression, and anxiety.

  本文描述了替代的双环胺。具体来说，本文描述了作为SSTR5拮抗剂有效的替代双环胺，用于治疗、控制或预防对SSTR5拮抗有响应的疾病，如2型糖尿病、胰岛素抵抗、脂质紊乱、肥胖、动脉粥样硬化、代谢综合征、抑郁症和焦虑症。
• [EN] SUBSTITUTED SPIROCYCLIC AMINES USEFUL AS ANTIDIABETIC COMPOUNDS<br/>[FR] AMINES SPIROCYCLIQUES SUBSTITUÉES UTILES EN TANT QUE COMPOSÉS ANTIDIABÉTIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010129729A1

  公开（公告）日：2010-11-11

  Substituted spirocyclic amines of structural formula I are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, metabolic syndrome, depression, and anxiety.

  结构式I的螺环胺是生长抑素亚型受体5（SSTR5）的选择性拮抗剂，可用于治疗、控制或预防对SSTR5拮抗敏感的疾病，如2型糖尿病、胰岛素抵抗、脂质紊乱、肥胖、动脉粥样硬化、代谢综合征、抑郁症和焦虑症。
• [EN] SSTR5 ANTAGONISTS<br/>[FR] ANTAGONISTES DE SSTR5
  申请人：KALLYOPE INC

  公开号：WO2021113368A1

  公开（公告）日：2021-06-10

  This disclosure is directed, at least in part, to SSTR5 antagonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the SSTR5 antagonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

  这项披露至少部分针对SSTR5拮抗剂，用于治疗涉及肠脑轴的疾病或疾病。在某些实施例中，SSTR5拮抗剂是肠限制性化合物。在某些实施例中，该疾病或疾病是代谢性疾病，如糖尿病、肥胖症、非酒精性脂肪肝炎（NASH）或营养紊乱，如短肠综合征。
• [EN] SPIRO ISOXAZOLINE COMPOUNDS AS SSTR5 ANTAGONISTS<br/>[FR] COMPOSÉS SPIROISOXAZOLINES EN TANT QU'ANTAGONISTES SSTR5
  申请人：MERCK SHARP & DOHME

  公开号：WO2011146324A1

  公开（公告）日：2011-11-24

  Substituted spirocyclic amines of structural formula (I) are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, Metabolic Syndrome, depression, and anxiety.

  结构式（I）的螺环胺是生长抑素亚型受体5（SSTR5）的选择性拮抗剂，对于对抗SSTR5有响应的疾病的治疗、控制或预防是有用的，如2型糖尿病、胰岛素抵抗、脂质紊乱、肥胖、动脉粥样硬化、代谢综合征、抑郁症和焦虑症。
• [EN] SPIROXAZOLIDINONE COMPOUNDS<br/>[FR] COMPOSÉS SPIROXAZOLIDINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012024183A1

  公开（公告）日：2012-02-23

  Substituted spirocyclic amines of structural formula (I) are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, Metabolic Syndrome, depression, and anxiety.

  结构式（I）的螺环胺是生长抑素亚型受体5（SSTR5）的选择性拮抗剂，可用于治疗、控制或预防对SSTR5拮抗敏感的疾病，如2型糖尿病、胰岛素抵抗、脂质紊乱、肥胖、动脉粥样硬化、代谢综合征、抑郁症和焦虑症。