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Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor.

ABSTRACT: Iterative structure-activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described.

SUBMITTER: Parcella K

PROVIDER: S-EPMC5512134 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Improving Metabolic Stability with Deuterium: The Discovery of BMT-052, a Pan-genotypic HCV NS5B Polymerase Inhibitor.

Parcella Kyle K Eastman Kyle K Yeung Kap-Sun KS Grant-Young Katharine A KA Zhu Juliang J Wang Tao T Zhang Zhongxing Z Yin Zhiwei Z Parker Dawn D Mosure Kathy K Fang Hua H Wang Ying-Kai YK Lemm Julie J Zhuo Xiaoliang X Hanumegowda Umesh U Liu Mengping M Rigat Karen K Donoso Maria M Tuttle Maria M Zvyaga Tatyana T Haarhoff Zuzana Z Meanwell Nicholas A NA Soars Matthew G MG Roberts Susan B SB Kadow John F JF

ACS medicinal chemistry letters 20170629 7

Iterative structure-activity analyses in a class of highly functionalized furo[2,3-b]pyridines led to the identification of the second generation pan-genotypic hepatitis C virus NS5B polymerase primer grip inhibitor BMT-052 (14), a potential clinical candidate. The key challenge of poor metabolic stability was overcome by strategic incorporation of deuterium at potential metabolic soft spots. The preclinical profile and status of BMT-052 (14) is described. ...[more]

PMID: 28740615

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