Discovery of Novel Small Molecule Orally Bioavailable C− X− C Chemokine Receptor 4 Antagonists That Are Potent Inhibitors of T-Tropic (X4) HIV-1 Replication

…, JB Crawford, Y Zhou, B Atsma, J Langille…

Index: Skerlj, Renato T.; Bridger, Gary J.; Kaller, Al; McEachern, Ernest J.; Crawford, Jason B.; Zhou, Yuanxi; Atsma, Bem; Langille, Jonathon; Nan, Susan; Veale, Duane; Wilson, Trevor; Harwig, Curtis; Hatse, Sigrid; Princen, Katrien; De Clercq, Erik; Schols, Dominique Journal of Medicinal Chemistry, 2010 , vol. 53, # 8 p. 3376 - 3388

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Citation Number: 56

Abstract

The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure− activity relationship (SAR) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4. 3 in MT-4 cells. As a result of lead optimization, we identified (S)-N′-((1 H-benzo [d] imidazol-2-yl) methyl)-N′ ...