Zhou Jinglan, Campbell-Conroy Erica L, Silina Alina, Uy Johnny, Pierre Fabrice, Hurley Dennis J, Hilgraf Nicole, Frieman Bryan A, DeNinno Michael P
Department of Chemistry, Vertex Pharmaceuticals, Inc., 11010 Torreyana Road, San Diego, California 92121, United States.
J Org Chem. 2015 Jan 2;80(1):70-9. doi: 10.1021/jo501967m. Epub 2014 Nov 26.
An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.
制备了一系列六个吡啶取代的稠合双环哌啶，作为药物化学的新型核心。为了实现最大程度的多样性，稠合环的大小从三个到六个原子不等，并且含有多达两个氧原子。引入吡啶环是为了改善物理化学性质，并检验化学方法的稳健性。吡啶的存在确实干扰了我们最初合成这些分子的方法，在几种情况下，不得不采用阻断策略。这些新的骨架具有较高的sp3杂化特征，可能在多种药物化学应用中证明是有用的。
