isopropyl 4-((1R)-1-((5r,8R)-8-tert-butyl-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]decan-1-yl)-4,4-dimethylpentyl)benzoate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: isopropyl 4-((1R)-1-((5r,8R)-8-tert-butyl-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]decan-1-yl)-4,4-dimethylpentyl)benzoate
• 英文别名: propan-2-yl 4-[(1R)-1-[8-tert-butyl-2-(3,5-dichlorophenyl)-3-oxo-1,4-diazaspiro[4.5]decan-4-yl]-4,4-dimethylpentyl]benzoate
• 化学式: C₃₅H₄₈Cl₂N₂O₃
• 分子量: 615.684
• InChiKey: LGKILSHCOQRMIM-ZOAROYIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  isopropyl 4-((1R)-1-((5r,8R)-8-tert-butyl-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]decan-1-yl)-4,4-dimethylpentyl)benzoate 在 次氯酸叔丁酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以94.2%的产率得到isopropyl 4-((R)-1-((5r,8R)-8-tert-butyl-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzoate
  参考文献：
  名称：

  The Discovery of N-((2H-Tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822): A Potent and Selective Glucagon Receptor Antagonist

  摘要：

  A novel series of spiroimidazolone-based antagonists of the human glucagon receptor (hGCGR) has been developed. Our efforts have led to compound 1, N-((2H-tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822), a potent hGCGR antagonist with exceptional selectivity over the human glucagon-like peptide-1 receptor. Oral administration of 1 lowered 24 h nonfasting glucose levels in imprinting control region mice on a high fat diet with diet-induced obesity following single oral doses of 3 and 10 mg/kg. Furthermore, compound 1, when dosed orally, was found to decrease fasting blood glucose at 30 mg/kg in a streptozotocin-treated, diet-induced obesity mouse pharmacodynamic assay and blunt exogenous glucagon-stimulated glucose excursion in prediabetic mice.

  DOI：

  10.1021/jm401858f
• 作为产物：
  描述：

  2-(叔丁氧基羰基)-2-(3,5-二氯苯基)乙酸 在 对甲苯磺酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 16.0h， 生成 isopropyl 4-((1R)-1-((5r,8R)-8-tert-butyl-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]decan-1-yl)-4,4-dimethylpentyl)benzoate
  参考文献：
  名称：

  The Discovery of N-((2H-Tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822): A Potent and Selective Glucagon Receptor Antagonist

  摘要：

  A novel series of spiroimidazolone-based antagonists of the human glucagon receptor (hGCGR) has been developed. Our efforts have led to compound 1, N-((2H-tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822), a potent hGCGR antagonist with exceptional selectivity over the human glucagon-like peptide-1 receptor. Oral administration of 1 lowered 24 h nonfasting glucose levels in imprinting control region mice on a high fat diet with diet-induced obesity following single oral doses of 3 and 10 mg/kg. Furthermore, compound 1, when dosed orally, was found to decrease fasting blood glucose at 30 mg/kg in a streptozotocin-treated, diet-induced obesity mouse pharmacodynamic assay and blunt exogenous glucagon-stimulated glucose excursion in prediabetic mice.

  DOI：

  10.1021/jm401858f

文献信息

• NOVEL SPIRO IMIDAZOLONES AS GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE
  申请人：Wong Michael K.

  公开号：US20130012434A1

  公开（公告）日：2013-01-10

  The present invention relates to compounds of the general formula: wherein ring A, ring B, R1, R3, Z, L1, and L2 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and to methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

  本发明涉及通式化合物：其中环A、环B、R1、R3、Z、L1和L2是彼此独立选择并如下所定义的，以及包含该化合物的组合物，以及使用该化合物作为胰高血糖素受体拮抗剂以及治疗或预防2型糖尿病及相关疾病的方法。
• US8361959B2
  申请人：——

  公开号：US8361959B2

  公开（公告）日：2013-01-29
• The Discovery of <i>N</i>-((2<i>H</i>-Tetrazol-5-yl)methyl)-4-((<i>R</i>)-1-((5<i>r</i>,8<i>R</i>)-8-(<i>tert</i>-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822): A Potent and Selective Glucagon Receptor Antagonist
  作者：Duane DeMong、Xing Dai、Joyce Hwa、Michael Miller、Sue-Ing Lin、Ling Kang、Andrew Stamford、William Greenlee、Wensheng Yu、Michael Wong、Brian Lavey、Joseph Kozlowski、Guowei Zhou、De-Yi Yang、Bhuneshwari Patel、Aileen Soriano、Ying Zhai、Christopher Sondey、Hongtao Zhang、Jean Lachowicz、Diane Grotz、Kathleen Cox、Richard Morrison、Teresa Andreani、Yang Cao、Mark Liang、Tao Meng、Paul McNamara、Jesse Wong、Prudence Bradley、Kung-I Feng、Jitendra Belani、Ping Chen、Peng Dai、Jolicia Gauuan、Peishan Lin、He Zhao

  DOI：10.1021/jm401858f

  日期：2014.3.27

  A novel series of spiroimidazolone-based antagonists of the human glucagon receptor (hGCGR) has been developed. Our efforts have led to compound 1, N-((2H-tetrazol-5-yl)methyl)-4-((R)-1-((5r,8R)-8-(tert-butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro[4.5]dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822), a potent hGCGR antagonist with exceptional selectivity over the human glucagon-like peptide-1 receptor. Oral administration of 1 lowered 24 h nonfasting glucose levels in imprinting control region mice on a high fat diet with diet-induced obesity following single oral doses of 3 and 10 mg/kg. Furthermore, compound 1, when dosed orally, was found to decrease fasting blood glucose at 30 mg/kg in a streptozotocin-treated, diet-induced obesity mouse pharmacodynamic assay and blunt exogenous glucagon-stimulated glucose excursion in prediabetic mice.