4HLE
Compound 21 (1-alkyl-substituted 1,2,4-triazoles)
4HLE の概要
エントリーDOI | 10.2210/pdb4hle/pdb |
分子名称 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-4,5-dihydrothieno[3,2-d][1]benzoxepine-8-carboxamide (2 entities in total) |
機能のキーワード | lipid kinase, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
由来する生物種 | Homo sapiens (human) |
細胞内の位置 | Cytoplasm: P48736 |
タンパク質・核酸の鎖数 | 1 |
化学式量合計 | 111081.53 |
構造登録者 | |
主引用文献 | Staben, S.T.,Blaquiere, N.,Tsui, V.,Kolesnikov, A.,Do, S.,Bradley, E.K.,Dotson, J.,Goldsmith, R.,Heffron, T.P.,Lesnick, J.,Lewis, C.,Murray, J.,Nonomiya, J.,Olivero, A.G.,Pang, J.,Rouge, L.,Salphati, L.,Wei, B.,Wiesmann, C.,Wu, P. Cis-Amide isosteric replacement in thienobenzoxepin inhibitors of PI3-kinase. Bioorg.Med.Chem.Lett., 23:897-901, 2013 Cited by PubMed Abstract: Substructural class effects surrounding replacement of a 'cis' N-methyl aniline amide within potent and selective thienobenzoxepin PI3-kinase inhibitors are disclosed. While a simple aryl to alkyl switch was not tolerated due to differences in preferred amide conformation, heterocyclic amide isosteres with maintained aryl substitution improved potency and metabolic stability at the cost of physical properties. These gains in potency allowed lipophilic deconstruction of the arene to simple branched alkyl substituents. As such, overall lipophilicity-neutral, MW decreases were realized relative to the aniline amide series. The improved properties for lead compound 21 resulted in high permeability, solubility and bioavailability. PubMed: 23265894DOI: 10.1016/j.bmcl.2012.10.121 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.78 Å) |
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