108512-01-2Relevant articles and documents
Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors
Anderson, Malcolm,Andrews, David M.,Barker, Andy J.,Brassington, Claire A.,Breed, Jason,Byth, Kate F.,Culshaw, Janet D.,Finlay, M. Raymond V.,Fisher, Eric,McMiken, Helen H.J.,Green, Clive P.,Heaton, Dave W.,Nash, Ian A.,Newcombe, Nicholas J.,Oakes, Sandra E.,Pauptit, Richard A.,Roberts, Andrew,Stanway, Judith J.,Thomas, Andrew P.,Tucker, Julie A.,Walker, Mike,Weir, Hazel M.
scheme or table, p. 5487 - 5492 (2009/05/30)
An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.
DERIVATIVES OF 4- (IMIDAZOL-5-YL)-2-(4-SULFOANILINO) PYRIMIDINE WITH CDK INHIBITORY ACTIVITY
-
Page/Page column 55, (2008/06/13)
Compounds of the formula (I): wherein R1, R2, R3, R4, R5 and p are as defined within and a pharmaceutically acceptable salts and in vivo hydrolysable esters are described. Also described are processes for their preparation and their use as medicaments, particularly medicaments for producing a cell cycle inhibitory (anti-cell-proliferation) effect in a warm-blooded animal, such as man.
Synthesis of 4(5)-Acyl-, 1-Substituted 5-Acyl, and 1-Substituted 4-Acyl-1H-imidazoles from 4-Aminoisoxazoles
Reiter, Lawrence A.
, p. 2714 - 2726 (2007/10/02)
4-Aminoisoxazoles can be acylated with a wide variety of activated carboxylic acids.Hydrogenation of the resulting amides gives α-(acylamino)enaminones, which cyclize to 4(5)-acylimidazoles upon treatment with base.This method allows for the synthesis of acylimidazoles with a wide range of substituents at C-2.Utilization of N-substituted 4-aminoisoxazoles in the same sequence of reactions yields 1-substituted 5-acylimidazoles, a substitution pattern not otherwise easily prepared.Treatment of α-(acylamino)enaminones, derived from N-unsubstituted isoxazoles, with primary amines leads to incorporation of the amine at the β-position with concomitant expulsion of ammonia.This sequence efficiently yields 1-substituted and 1,2-disubstituted 4-acylimidazoles but does not give satisfactory yields of 5-substituted 4-acylimidazoles due to steric inhibition of the amine exchange.
