Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2425-9. doi: 10.1016/j.bmcl.2011.02.066. Epub 2011 Feb 18.
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.
人类 T 细胞白血病/淋巴瘤病毒 1 型（HTLV-I）与成人 T 细胞白血病/淋巴瘤、HTLV-I 相关脊髓病/热带痉挛性截瘫以及许多其他慢性炎症性疾病有关。为了阻止病毒的复制，我们开发了高效的四肽 HTLV-I 蛋白酶抑制剂。在最近的 X 射线晶体学研究中，由于我们的抑制剂具有很高的疏水性，因此无法与蛋白酶形成共晶复合物。在本研究中，我们设计、合成并评估了具有亲水端封基团的化合物对 HTLV-I 蛋白酶的抑制作用，旨在改善药物和药代动力学性质。
