Cell division cycle 7 kinase inhibitors: 1H-pyrrolo[2,3-b]pyridines, synthesis and structure-activity relationships.
Cdc7 kinase has recently emerged as an attractive target for cancer therapy and low-molecular-weight inhibitors of Cdc7 kinase have been found to be effective in the inhibition of tumor growth in animal models. In this paper, we describe synthesis and structure-activity relationships of new 1H-pyrrolo[2,3-b]pyridine derivatives identified as inhibitors of Cdc7 kinase. Progress from (Z)-2-phenyl-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylene)-3,5-dihydro-4H-imidazol-4-one (1) to [(Z)-2-(benzylamino)-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylene)-1,3-thiazol-4(5H)-one] (42), a potent ATP mimetic inhibitor of Cdc7 kinase with IC(50) value of 7 nM, is also reported.
Ermoli
Antonella
A
Nerviano Medical Sciences, 20014 Nerviano, Milano, Italy.
Bargiotti
Alberto
A
Brasca
Maria Gabriella
MG
Ciavolella
Antonella
A
Colombo
Nicoletta
N
Fachin
Gabriele
G
Isacchi
Antonella
A
Menichincheri
Maria
M
Molinari
Antonio
A
Montagnoli
Alessia
A
Pillan
Antonio
A
Rainoldi
Sonia
S
Sirtori
Federico Riccardi
FR
Sola
Francesco
F
Thieffine
Sandrine
S
Tibolla
Marcellino
M
Valsasina
Barbara
B
Volpi
Daniele
D
Santocanale
Corrado
C
Vanotti
Ermes
E
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases