Molecular modeling, synthesis, and activity studies of novel biaryl and fused-ring BACE1 inhibitors

…, X Cheng, H Yuan, DC Lankin, SO Abdul-Hay…

Index: Chirapu, Srinivas Reddy; Pachaiyappan, Boobalan; Nural, Hikmet F.; Cheng, Xin; Yuan, Hongbin; Lankin, David C.; Abdul-Hay, Samer O.; Thatcher, Gregory R.J.; Shen, Yong; Kozikowski, Alan P.; Petukhov, Pavel A. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 1 p. 264 - 274

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Citation Number: 16

Abstract

A series of transition state analogues of beta-secretases 1 and 2 (BACE1, 2) inhibitors containing fused-ring or biaryl moieties were designed computationally to probe the S2 pocket, synthesized, and tested for BACE1 and BACE2 inhibitory activity. It has been shown that unlike the biaryl analogs, the fused-ring moiety is successfully accommodated in the BACE1 binding site resulting in the ligands with excellent inhibitory activity. Ligand 5b ...