Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors.
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.
Anderson
Malcolm
M
AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
Andrews
David M
DM
Barker
Andy J
AJ
Brassington
Claire A
CA
Breed
Jason
J
Byth
Kate F
KF
Culshaw
Janet D
JD
Finlay
M Raymond V
MR
Fisher
Eric
E
McMiken
Helen H J
HH
Green
Clive P
CP
Heaton
Dave W
DW
Nash
Ian A
IA
Newcombe
Nicholas J
NJ
Oakes
Sandra E
SE
Pauptit
Richard A
RA
Roberts
Andrew
A
Stanway
Judith J
JJ
Thomas
Andrew P
AP
Tucker
Julie A
JA
Walker
Mike
M
Weir
Hazel M
HM
D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D018797:Cell Cycle Proteins; D007093:Imidazoles; D018844:Cyclin-Dependent Kinases; C023650:aniline