Design and synthesis of several small-size HTLV-I protease inhibitors with different hydrophilicity profiles |
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| Authors: | Nguyen Jeffrey-Tri Kato Keiko Hidaka Koushi Kumada Henri-Obadja Kimura Tooru Kiso Yoshiaki |
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| Institution: | Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan |
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| Abstract: | The human T cell leukemia/lymphotropic virus type 1 (HTLV-I) is clinically associated with adult T cell leukemia/lymphoma, HTLV-I associated myelopathy/tropical spastic paraparesis, and a number of other chronic inflammatory diseases. To stop the replication of the virus, we developed highly potent tetrapeptidic HTLV-I protease inhibitors. In a recent X-ray crystallography study, several of our inhibitors could not form co-crystal complexes with the protease due to their high hydrophobicity. In the current study, we designed, synthesized and evaluated the HTLV-I protease inhibition potency of compounds with hydrophilic end-capping moieties with the aim of improving pharmaceutic and pharmacokinetic properties. |
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| Keywords: | Human T cell lymphotropic virus HAM/TSP Adult T cell leukemia Aspartic protease Inhibitor |
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