2. Academic Validation
  3. Design and synthesis of several small-size HTLV-I protease inhibitors with different hydrophilicity profiles

Design and synthesis of several small-size HTLV-I protease inhibitors with different hydrophilicity profiles

  • Bioorg Med Chem Lett. 2011 Apr 15;21(8):2425-9. doi: 10.1016/j.bmcl.2011.02.066.
Jeffrey-Tri Nguyen 1,  Keiko Kato,  Koushi Hidaka,  Henri-Obadja Kumada,  Tooru Kimura,  Yoshiaki Kiso
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
PMID: 21392990 DOI: 10.1016/j.bmcl.2011.02.066
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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