66376-75-8Relevant academic research and scientific papers
HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase
Even?s, Johan,Edfeldt, Fredrik,Lepist?, Matti,Svitacheva, Naila,Synnergren, Anna,Lundquist, Britta,Gr?nse, Mia,R?nnholm, Anna,Varga, Mikael,Wright, John,Wei, Min,Yue, Sherrie,Wang, Junfeng,Li, Chong,Li, Xuan,Chen, Gang,Liao, Yong,Lv, Gang,Tj?rnebo, Ann,Narjes, Frank
, p. 1315 - 1321 (2014/03/21)
The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.
Structural studies on bioactive compounds. Part 29: Palladium catalysed arylations and alkynylations of sterically hindered immunomodulatory 2-amino- 5-halo-4,6-(disubstituted)pyrimidines
Hannah, Duncan R.,Sherer, Edward C.,Davies, Roy V.,Titman, Roger B.,Laughton, Charles A.,Stevens, Malcolm F. G.
, p. 739 - 750 (2007/10/03)
The immunological agent bropirimine 5 is a tetra-substituted pyrimidine with anticancer and interferon-inducing properties. Synthetic routes to novel 5-aryl analogues of bropirimine have been developed and their potential molecular recognition properties analysed by molecular modelling methods. Sterically challenged 2-amino-5-halo-6-phenylpyrimidin-4-ones (halo=Br or I) are poor substrates for palladium catalysed Suzuki cross-coupling reactions with benzeneboronic acid because the basic conditions of the reaction converts the amphoteric pyrimidinones to their unreactive enolic forms. Palladium-mediated reductive dehalogenation of the pyrimidinone substrates effectively competes with cross-coupling. 2-Amino-5-halo-4-methoxy-6- phenylpyrimidines can be converted to a range of 5-aryl derivatives with the 5-iodopyrimidines being the most efficient substrates. Hydrolysis of the 2- amino-5-aryl-4-methoxy-6-phenylpyrimidines affords the required pyrimidin-4- ones in high yields. Semi-empirical quantum mechanical calculations show how the nature of the 5-substituent influences the equilibrium between the 1H- and 3H-tautomeric forms, and the rotational freedom about the bond connecting the 6-phenyl group and the pyrimidine ring. Both of these factors may influence the biological properties of these compounds. (C) 2000 Elsevier Science Ltd.
On the Reaction of Diphenylcyclopropenone with Guanidines
Eicher, Thoephil,Franke, Guenter
, p. 1337 - 1353 (2007/10/02)
Diphenylcyclopropenone (6) reacts with 1,1,3,3-tetraalkylguanidines (7a-d) forming 2-amino-4,5-diphenyl-3H-pyrrol-3-ones 11, which are characterized as cyclomerocyanines by their spectroscopic behaviour.With guanidine (7e), 1-alkyl- and 1-phenylsubstituted guanidines (7f-h), 1,2-diphenyl, and 1,2,3-triphenylguanidine (7i,j) as well as 2-aminobenzimidazole (36) compound 6 yields exclusively 5,6-dihydro-5,6-diphenyl-4(1H)-pyrimidinones (22, 23, 28-32, 33, 34, 38), the constitution and configuration of which at C-5/C-6 is established.A mechanism for the formation of the abovementioned five- and six-membered heterocyclic systems is discussed.
