3-氯-4-(6-氯-5-氟嘧啶-4-基氨基)苯甲腈 | 1147558-27-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氯-4-(6-氯-5-氟嘧啶-4-基氨基)苯甲腈
• 英文名称: 3-chloro-4-((6-chloro-5-fluoropyrimidin-4-yl)amino)benzonitrile
• 英文别名: 3-Chloro-4-(6-chloro-5-fluoropyrimidin-4-ylamino)benzonitrile；3-chloro-4-[(6-chloro-5-fluoropyrimidin-4-yl)amino]benzonitrile
• CAS: 1147558-27-7
• 化学式: C₁₁H₅Cl₂FN₄
• 分子量: 283.092
• InChiKey: WBCHJNBQJGWIPF-UHFFFAOYSA-N

物化性质

• 密度：
  1.56

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-Boc-3-�f-7-氮杂双环[3.3.1]-9-壬醇 、 3-氯-4-(6-氯-5-氟嘧啶-4-基氨基)苯甲腈 在 strong base 作用下， 以 四氢呋喃 为溶剂， 反应 4.17h， 以3.8 g的产率得到tert-butyl (1R,5S,9r)-9-((6-((2-chloro-4-cyanophenyl)amino)-5-fluoropyrimidin-4-yl)oxy)-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate
  参考文献：
  名称：

  Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes

  摘要：

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.

  DOI：

  10.1021/acsmedchemlett.8b00073
• 作为产物：
  描述：

  4,6-二氯-5-氟嘧啶 、 4-氨基-3-氯苯甲腈 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以0.3 g的产率得到3-氯-4-(6-氯-5-氟嘧啶-4-基氨基)苯甲腈
  参考文献：
  名称：

  Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes

  摘要：

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.

  DOI：

  10.1021/acsmedchemlett.8b00073

文献信息

• [EN] BRIDGED BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'HÉTÉROCYCLES BICYCLIQUES PONTÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2010114958A1

  公开（公告）日：2010-10-07

  The present invention relates to Bridged Bicyclic Heterocycle Derivatives, compositions comprising a Bridged Bicyclic Heterocycle Derivative, and methods of using the Bridged Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

  本发明涉及桥环双环杂环衍生物，包含桥环双环杂环衍生物的组合物，以及利用桥环双环杂环衍生物治疗或预防肥胖、糖尿病、代谢紊乱、心血管疾病或与患者GPCR活性有关的疾病的方法。
• BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS MODULATORS OF THE ACTIVITY OF GPR119
  申请人：Xia Yan

  公开号：US20110212938A1

  公开（公告）日：2011-09-01

  The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

  本发明涉及双环杂环衍生物、包含双环杂环衍生物的组合物以及使用双环杂环衍生物治疗或预防患者的肥胖症、糖尿病、代谢紊乱、心血管疾病或与GPR119活性相关的疾病的方法。
• BRIDGED BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Neelamkavil Santhosh Francis

  公开号：US20120040975A1

  公开（公告）日：2012-02-16

  The present invention relates to Bridged Bicyclic Heterocycle Derivatives, compositions comprising a Bridged Bicyclic Heterocycle Derivative, and methods of using the Bridged Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.
• US8907095B2
  申请人：——

  公开号：US8907095B2

  公开（公告）日：2014-12-09
• Discovery of MK-8282 as a Potent G-Protein-Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes
  作者：Santhosh F. Neelamkavil、Andrew W. Stamford、Timothy Kowalski、Dipshikha Biswas、Craig Boyle、Samuel Chackalamannil、Yan Xia、Charles Jayne、Bernard Neustadt、Jinsong Hao、Hong Liu、Xing Dai、Hana Baker、Brian Hawes、Kim O’Neill、Huadong Tang、William J. Greenlee

  DOI：10.1021/acsmedchemlett.8b00073

  日期：2018.5.10

  The ever-growing prevalence of type 2 diabetes in the world has necessitated an urgent need for multiple orally effective agents that can regulate glucose homeostasis with a concurrent reduction in body weight. G-Protein coupled receptor 119 (GPR119) is a GPCR target at which agonists have demonstrated glucose-dependent insulin secretion and shows beneficial effects on glycemic control. Herein, we describe our efforts leading to the identification of a potent, oral GPR-119 agonist, MK-8282, which shows improved glucose tolerance in multiple animal models and has excellent off-target profile. The key design elements in the compounds involved a combination of a fluoro-pyrimidine and a conformationally constrained bridged piperidine to impart good potency and efficacy.