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Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity.

ABSTRACT: 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.

SUBMITTER: Xue CB

PROVIDER: S-EPMC4007949 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity.

Xue Chu-Biao CB Chen Lihua L Cao Ganfeng G Zhang Ke K Wang Anlai A Meloni David D Glenn Joseph J Anand Rajan R Xia Michael M Kong Ling L Huang Taisheng T Feng Hao H Zheng Changsheng C Li Mei M Galya Laurine L Zhou Jiacheng J Shin Niu N Baribaud Fredric F Solomon Kim K Scherle Peggy P Zhao Bitao B Diamond Sharon S Emm Tom T Keller Douglas D Contel Nancy N Yeleswaram Swamy S Vaddi Kris K Hollis Gregory G Newton Robert R Friedman Steven S Metcalf Brian B

ACS medicinal chemistry letters 20100825 9

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. ...[more]

PMID: 24900235

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