De Corte Bart L, Kinney William A, Liu Li, Ghosh Shyamali, Brunner Livia, Hoekstra William J, Santulli Rosemary J, Tuman Robert W, Baker Judith, Burns Candace, Proost Jef C, Tounge Brett A, Damiano Bruce P, Maryanoff Bruce E, Johnson Dana L, Galemmo Robert A
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477-0776, USA.
Bioorg Med Chem Lett. 2004 Oct 18;14(20):5227-32. doi: 10.1016/j.bmcl.2004.06.061.
The synthesis and SAR of a new class of piperidine-based alphavbeta3/alphavbeta5 integrin antagonists is described. Replacement of an amide bond in a prototype isonipecotamide by a C-C isostere, and adjustment of the spacer length between the carboxylic acid and basic moieties, led to low nanomolar antagonists of alphavbeta3 and/or alphavbeta5 integrins with excellent selectivity versus alpha(IIb)beta3.
本文描述了一类新型基于哌啶的αvβ3/αvβ5整合素拮抗剂的合成及其构效关系。用碳-碳电子等排体取代原型异烟酰胺中的酰胺键，并调整羧酸与碱性部分之间的间隔长度，得到了低纳摩尔浓度的αvβ3和/或αvβ5整合素拮抗剂，对α(IIb)β3具有优异的选择性。
