| Title : 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases: highly potent 2,6-Difluorophenacyl analogues - Misra_2003_Bioorg.Med.Chem.Lett_13_2405 |
| Author(s) : Misra RN , Xiao H , Rawlins DB , Shan W , Kellar KA , Mulheron JG , Sack JS , Tokarski JS , Kimball SD , Webster KR |
| Ref : Bioorganic & Medicinal Chemistry Lett , 13 :2405 , 2003 |
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Abstract :
Structure-activity studies of 1H-pyrazolo[3,4-b]pyridine 1 have resulted in the discovery of potent CDK1/CDK2 selective inhibitor 21h, BMS-265246 (CDK1/cycB IC(50)=6 nM, CDK2/cycE IC(50)=9 nM). The 2,6-difluorophenyl substitution was critical for potent inhibitory activity. A solid state structure of 21j, a close di-fluoro analogue, bound to CDK2 shows the inhibitor resides coincident with the ATP purine binding site and forms important H-bonds with Leu83 on the protein backbone. |
| PubMedSearch : Misra_2003_Bioorg.Med.Chem.Lett_13_2405 |
| PubMedID: 12824044 |
Misra RN, Xiao H, Rawlins DB, Shan W, Kellar KA, Mulheron JG, Sack JS, Tokarski JS, Kimball SD, Webster KR (2003)
1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases: highly potent 2,6-Difluorophenacyl analogues
Bioorganic & Medicinal Chemistry Lett
13 :2405
Misra RN, Xiao H, Rawlins DB, Shan W, Kellar KA, Mulheron JG, Sack JS, Tokarski JS, Kimball SD, Webster KR (2003)
Bioorganic & Medicinal Chemistry Lett
13 :2405