3815-69-8Relevant articles and documents
Purin-6-One Derivatives as Phosphodiesterase-2 Inhibitors
Yuan, Wei,Zhao, Xin-Yun,Chen, Xi,Zhan, Chang-Guo
, (2016/03/23)
A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC50 values of 1.73, 0.18, and 3.43 M, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of the catalytic active site of PDE2, where a Tyr655 residue was found to be important in binding with compound 2p, the most potent inhibitor identified in this study. Our present study provides useful information for the future design of novel PDE2 inhibitors.
Dimroth-type rearrangement of 1-benzyl- and 1-glycosyl-5-aminoimidazoles to 4-(N-substituted amino)imidazoles
Costanzi, Stefano,Rouse, Sean P.N.,Vanbaelinghem, Laurence,Prior, Timothy J.,Ewing, David F.,Boa, Andrew N.,MacKenzie, Grahame
supporting information; experimental part, p. 412 - 415 (2012/02/06)
An efficient route is described to an unusual exocyclic 4-β-d-ribofuranosyl-aminoimidazole nucleoside, related 4-N- benzylaminoimidazoles and imidazole analogues of precursors in the de novo biosynthesis of purines, via a regiospecific and stereoselective
Reactions of ring-expanded xanthines containing the imidazo[4,5- e][1,4]diazepine ring system
Bhan,Hosmane
, p. 1453 - 1462 (2007/10/02)
4,5,7,8-Tetrahydro-6H-imidazo[4,5-e][1,4]diazepine-5,8-dione underwent bromination at the 2-position with or without substituents at the 3-, 4- or 7-position, using bromine, N-bromosuccinimide, or acetyl hypobromite. The activation of position 6 with an ester functionality, as in 7, did not alter the site of bromination. The base-catalyzed bromination of the ring-open precursor, diethyl 2-[N-(1-benzyl-5-nitroimidazolyl-4- carbonyl)amino]malonate (5), resulted either in introduction of an alkoxy functionality in the above aminomalonate side-chain, yielding 17 when the reaction was quenched with an alcohol, or in degradation of the side-chain, yielding 1-benzyl-5-nitroimidazole-4-carboxamide (19) when the reaction was quenched with water. Both 17 and 19 are formed by oxidative bromination of 5 via the bromo intermediate 15. An indirect evidence for the latter was obtained by base-catalyzed methylation of 5 which gave diethyl 2-methyl-2- [N-(1-benzyl-5-nitroimidazolyl-4-carbonyl)amino]malonate (21). The base- catalyzed bromination of 5 with N-bromosuccinimide gave rise to two products, the dimer 24a and the monomer 24b that contained the substituted 2,2- diaminomalonate side-chain. The structure of 24b was confirmed by single- crystal X-ray diffraction analyses. Reduction of the 5-nitro group of 17 to the corresponding amino derivative 25, followed by ring-closure with sodium methoxide/methanol, yielded three products, a 5:6-fused system 26 and two 5:7 fused systems 27 and 28. The structures of 26 and 27 were confirmed by single-crystal X-ray diffraction analyses. A tentative reaction pathway for the formation of all three products has been proposed. Hydrolysis of 27 with aqueous hydrochloric acid resulted in ring-opening to form 5-amino-1- benzylimidazole-4-carboxamide (40). A mechanism for the hydrolysis reaction has been proposed. Catalytic hydrogenation of 5 in acetic acid yielded the aminoimidazolone derivative 11 which upon ring-closure with sodium methoxide in methanol produced imidazo[4,5-e][1,4]-diazepine-2,5,8-trione (12).
