Discovery of potent and stable conformationally constrained analogues of the MCH R1 antagonist SB-568849
详细信息 查看全文
- 作者：David R. Witty ; John Bateson ; Guillaume J. Hervieu ; Kamal Al-Barazanji ; Phillip Jeffrey ; Dieter Hamprecht ; Andrea Haynes ; Christopher N. Johnson ; Alison I. Muir ; Peter J. O’ ; Hanlon et al.
- 关键词：MCH ; MCH R1 ; Biphenylcarboxamide ; Antagonist ; Melanin-concentrating hormone ; Obesity ; Feeding ; Stress ; Anxiety ; Quinazolinone ; Benzotriazinone ; Thienopyrimidinone ; Cyclisation ; Bicyclic heterocycle
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：15 September 2006
- 年：2006
- 卷：16
- 期：18
- 页码：4872-4878
- 全文大小：161 K
文摘
A strategy of systematically targeting more rigid analogues of the known MCH R1 receptor antagonist, SB-568849, serendipitously uncovered a binding mode accessible to N-aryl-phthalimide ligands. Optimisation to improve the stability of this compound class led to the discovery of novel N-aryl-quinazolinones, benzotriazinones and thienopyrimidinones as selective ligands with good affinity for human melanin-concentrating hormone receptor 1.