(1R,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole | 1104599-57-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1R,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• 英文别名: (1R,3R)-3-[5-(4-fluorophenyl)-1H-imidazol-2-yl]-1-(1-methylpyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• CAS: 1104599-57-6
• 化学式: C₂₄H₂₁FN₆
• 分子量: 412.469
• InChiKey: UCGLIDADIQNGPX-IFMALSPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  BOC-D-色氨酸 在 盐酸 、 caesium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 3.5h， 生成 (1R,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 、 (1S,3R)-3-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  参考文献：
  名称：

  The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes

  摘要：

  A structure-activity relationship study of the imidazolyl-beta-tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice.

  DOI：

  10.1021/ml300063m

文献信息

• The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes
  作者：Shuwen He、Zhixiong Ye、Quang Truong、Shrenik Shah、Wu Du、Liangqin Guo、Peter H. Dobbelaar、Zhong Lai、Jian Liu、Tianying Jian、Hongbo Qi、Raman K. Bakshi、Qingmei Hong、James Dellureficio、Alexander Pasternak、Zhe Feng、Reynalda deJesus、Lihu Yang、Mikhail Reibarkh、Scott A. Bradley、Mark A. Holmes、Richard G. Ball、Rebecca T. Ruck、Mark A. Huffman、Frederick Wong、Koppara Samuel、Vijay B. Reddy、Stan Mitelman、Sharon X. Tong、Gary G. Chicchi、Kwei-Lan Tsao、Dorina Trusca、Margaret Wu、Qing Shao、Maria E. Trujillo、George J. Eiermann、Cai Li、Bei B. Zhang、Andrew D. Howard、Yun-Ping Zhou、Ravi P. Nargund、William K. Hagmann

  DOI：10.1021/ml300063m

  日期：2012.6.14

  A structure-activity relationship study of the imidazolyl-beta-tetrahydrocarboline series identified MK-4256 as a potent, selective SSTR3 antagonist, which demonstrated superior efficacy in a mouse oGTT model. MK-4256 reduced glucose excursion in a dose-dependent fashion with maximal efficacy achieved at doses as low as 0.03 mg/kg po. As compared with glipizide, MK-4256 showed a minimal hypoglycemia risk in mice.