Xue C-B, Chen L, Cao G, … Keller D, et al. 2010. Discovery of INCB9471, a potent, selective, and orally bioavailable CCR5 antagonist with potent anti-HIV-1 activity. ACS Med Chem Lett 1(9):483–487, doi: 10.1021/ml1001536.
To identify a CCR5 antagonist as an HIV-1 entry inhibitor, we designed a novel series of indane derivatives based on conformational considerations. Modification on the indane ring led to the discovery of compound 22a (INCB9471) that exhibited high affinity for CCR5, potent anti-HIV-1 activity, high receptor selectivity, excellent oral bioavailability, and a tolerated safety profile. INCB9471 has entered human clinical trials.Keywords (keywords): CCR5; antagonist; coreceptor; HIV-1; antiviral