5xui
From Proteopedia
Crystal structure of PDE10A in complex with 2-methyl-5-[2-([1,2,4]triazolo[1,5-a]pyrimidin-2-yl)et hyl]pyrazolo[1,5-a]pyrimidin-7-ol
Structural highlights
FunctionPDE10_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.[1] Publication Abstract from PubMedIn this study, we report the identification of potent pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties. Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.,Chino A, Seo R, Amano Y, Namatame I, Hamaguchi W, Honbou K, Mihara T, Yamazaki M, Tomishima M, Masuda N Chem Pharm Bull (Tokyo). 2018;66(3):286-294. doi: 10.1248/cpb.c17-00836. PMID:29491261[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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