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Xue CB, Chen L, Cao G, et al. Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity. ACS Med Chem Lett. 2010;1(9):483-7doi: 10.1021/ml1001536.
Xue, C. B., Chen, L., Cao, G., Zhang, K., Wang, A., Meloni, D., Glenn, J., Anand, R., Xia, M., Kong, L., Huang, T., Feng, H., Zheng, C., Li, M., Galya, L., Zhou, J., Shin, N., Baribaud, F., Solomon, K., Scherle, P., Zhao, B., Diamond, S., Emm, T., Keller, D., Contel, N., Yeleswaram, S., Vaddi, K., Hollis, G., Newton, R., Friedman, S., & Metcalf, B. (2010). Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity. ACS medicinal chemistry letters, 1(9), 483-7. https://doi.org/10.1021/ml1001536
Xue, Chu-Biao, et al. "Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity." ACS medicinal chemistry letters vol. 1,9 (2010): 483-7. doi: https://doi.org/10.1021/ml1001536
Xue CB, Chen L, Cao G, Zhang K, Wang A, Meloni D, Glenn J, Anand R, Xia M, Kong L, Huang T, Feng H, Zheng C, Li M, Galya L, Zhou J, Shin N, Baribaud F, Solomon K, Scherle P, Zhao B, Diamond S, Emm T, Keller D, Contel N, Yeleswaram S, Vaddi K, Hollis G, Newton R, Friedman S, Metcalf B. Discovery of INCB9471, a Potent, Selective, and Orally Bioavailable CCR5 Antagonist with Potent Anti-HIV-1 Activity. ACS Med Chem Lett. 2010 Aug 25;1(9):483-7. doi: 10.1021/ml1001536. eCollection 2010 Dec 09. PMID: 24900235; PMCID: PMC4007949.
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ACS Med Chem Lett. 2010 Aug 25;1(9):483-7. doi: 10.1021/ml1001536. eCollection 2010 Dec 09.

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

ACS medicinal chemistry letters

Chu-Biao Xue, Lihua Chen, Ganfeng Cao, Ke Zhang, Anlai Wang, David Meloni, Joseph Glenn, Rajan Anand, Michael Xia, Ling Kong, Taisheng Huang, Hao Feng, Changsheng Zheng, Mei Li, Laurine Galya, Jiacheng Zhou, Niu Shin, Fredric Baribaud, Kim Solomon, Peggy Scherle, Bitao Zhao, Sharon Diamond, Tom Emm, Douglas Keller, Nancy Contel, Swamy Yeleswaram, Kris Vaddi, Gregory Hollis, Robert Newton, Steven Friedman, Brian Metcalf

Affiliations

  1. Incyte Corporation, Experimental Station E336, Wilmington, Delaware 19880.

PMID: 24900235 PMCID: PMC4007949 DOI: 10.1021/ml1001536

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.

Keywords: CCR5; HIV-1; antagonist; antiviral; coreceptor

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