Kercher Timothy, Rao Chang, Bencsik Josef R, Josey John A
Array BioPharma Inc., 3200 Walnut Street, Boulder, Colorado 80301, USA.
J Comb Chem. 2007 Nov-Dec;9(6):1177-87. doi: 10.1021/cc0700290. Epub 2007 Sep 8.
Due to their diverse range of biological activities, imidazoheterocycles are recognized as privileged structures making these structural motifs attractive targets for library preparation. We report herein the synthesis of a sizable collection of imidazo[1,2- a]heterocycle scaffolds well-suited for divergent library preparation by virtue of amine functional handles with diverse positioning and connectivities. Partial reduction of imidazo[1,2- a]pyrazines to the tetrahydroimidazo[1,2- a]pyrazines and regiospecific Mannich-type bond formation at the C-3 of imidazo[1,2- a]pyridine under mild conditions achieved additional topological and connective diversity within the scaffold collection. Subsequent parallel reaction of the functionalized imidazoheterocycles with polystyrene-tetrafluorophenol esters and sulfonates produced a 7500 compound library in high purity.
由于咪唑并杂环具有广泛多样的生物活性，它们被认为是优势结构，使得这些结构基序成为文库制备的有吸引力的目标。我们在此报告了大量咪唑并[1,2 - a]杂环支架的合成，这些支架由于具有不同定位和连接性的胺官能手柄，非常适合用于多样化的文库制备。在温和条件下，将咪唑并[1,2 - a]吡嗪部分还原为四氢咪唑并[1,2 - a]吡嗪，并在咪唑并[1,2 - a]吡啶的C - 3处进行区域特异性的曼尼希型键形成，实现了支架集合内额外的拓扑和连接多样性。随后，功能化的咪唑并杂环与聚苯乙烯 - 四氟苯酚酯和磺酸盐进行平行反应，产生了一个高纯度的7500化合物文库。
