937012-15-2Relevant articles and documents
Further modifications of 1H-pyrrolo[2,3-b]pyridine derivatives as inhibitors of human neutrophil elastase
Giovannoni, Maria P.,Cantini, Niccolò,Crocetti, Letizia,Guerrini, Gabriella,Iacovone, Antonella,Schepetkin, Igor A.,Vergelli, Claudia,Khlebnikov, Andrei I.,Quinn, Mark T.
, p. 617 - 628 (2019/04/30)
Human neutrophil elastase (HNE) is a potent protease that plays an important physiological role in many processes and is considered to be a multifunctional enzyme. HNE is also involved in a variety of pathologies affecting the respiratory system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here a new series of pyrrolo[2,3-b]pyridine derivatives of our previously reported potent HNE inhibitors. Our results show that position 2 of the pyrrolo[2,3-b]pyridine scaffold must be unsubstituted, and modifications of this position resulted in loss of HNE inhibitory activity. Conversely, the introduction of certain substituents at position 5 was tolerated, with retention of HNE inhibitory activity (IC50 = 15–51 nM) after most substitutions, indicating that bulky and/or lipophilic substituents at position 5 probably interact with the large pocket of the enzyme site and allow Michaelis complex formation. The possibility of Michaelis complex formation between Ser195 and the ligand carbonyl group was assessed by molecular docking, and it was found that highly active HNE inhibitors are characterized by geometries favorable for Michaelis complex formation and by relatively short lengths of the proton transfer channel via the catalytic triad.
Cell division cycle 7 kinase inhibitors: 1H-pyrrolo[2,3-b]pyridines, synthesis and structure-activity relationships
Ermoli, Antonella,Bargiotti, Alberto,Brasca, Maria Gabriella,Ciavolella, Antonella,Colombo, Nicoletta,Fachin, Gabriele,Isacchi, Antonella,Menichincheri, Maria,Molinari, Antonio,Montagnoli, Alessia,Pillan, Antonio,Rainoldi, Sonia,Sirtori, Federico Riccardi,Sola, Francesco,Thieffine, Sandrine,Tibolla, Marcellino,Valsasina, Barbara,Volpi, Daniele,Santocanale, Corrado,Vanotti, Ermes
experimental part, p. 4380 - 4390 (2010/01/16)
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 IC50 value of 7 nM, is also reported.
Azaindolylidene derivatives as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
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Page/Page column 37, (2010/11/27)
The present invention is directed to compounds of the formula or pharmaceutically acceptable salts, prodrug, solvate or optical isomer thereof, pharmaceutical compositions containing same and use thereof for treating diseases linked to disregulated cell p
