4hle | pdb_00004hle

Compound 21 (1-alkyl-substituted 1,2,4-triazoles)

spinqualitylabelsall models 4hle, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hle is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 17V Gene: p110 gamma, PIK3CG (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed 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. Cis-Amide isosteric replacement in thienobenzoxepin inhibitors of PI3-kinase.,Staben ST, Blaquiere N, Tsui V, Kolesnikov A, Do S, Bradley EK, Dotson J, Goldsmith R, Heffron TP, Lesnick J, Lewis C, Murray J, Nonomiya J, Olivero AG, Pang J, Rouge L, Salphati L, Wei B, Wiesmann C, Wu P Bioorg Med Chem Lett. 2012 Nov 5. pii: S0960-894X(12)01423-0. doi:, 10.1016/j.bmcl.2012.10.121. PMID:23265894 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoinositide 3-Kinases

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