Gharbaoui Tawfik, Skinner Philip J, Shin Young-Jun, Averbuj Claudia, Jung Jae-Kyu, Johnson Benjamin R, Duong Tracy, Decaire Marc, Uy Jane, Cherrier Martin C, Webb Peter J, Tamura Susan Y, Zou Ning, Rodriguez Nathalie, Boatman P Douglas, Sage Carleton R, Lindstrom Andrew, Xu Jerry, Schrader Thomas O, Smith Brian M, Chen Ruoping, Richman Jeremy G, Connolly Daniel T, Colletti Steven L, Tata James R, Semple Graeme
Department of Medicinal Chemistry, Arena Pharmaceuticals, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2007 Sep 1;17(17):4914-9. doi: 10.1016/j.bmcl.2007.06.028. Epub 2007 Jun 10.
A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.
本文描述了一种从已知能激活GPR109a受体的化合物出发，鉴定该受体新激动剂的先导化合物的策略。早期的化合物筛选得出了一个结合假说，并最终使我们将重点放在了一系列吡唑酸衍生物上。对这些化合物的进一步优化得到了一系列5,5-稠合吡唑，用作先导化合物以进行进一步优化。
