Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors

Joaquín Pastor; Julen Oyarzabal; Gustavo Saluste; Rosa María Alvarez; Virginia Rivero; Francisco Ramos; Elena Cendón; Carmen Blanco-Aparicio; Nuria Ajenjo; Antonio Cebriá; M I Albarrán; David Cebrián; Ana Corrionero; Jesús Fominaya; Guillermo Montoya; Marco Mazzorana

doi:10.1016/j.bmcl.2011.12.130

Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1591-7. doi: 10.1016/j.bmcl.2011.12.130. Epub 2012 Jan 5.

Authors

Joaquín Pastor¹, Julen Oyarzabal, Gustavo Saluste, Rosa María Alvarez, Virginia Rivero, Francisco Ramos, Elena Cendón, Carmen Blanco-Aparicio, Nuria Ajenjo, Antonio Cebriá, M I Albarrán, David Cebrián, Ana Corrionero, Jesús Fominaya, Guillermo Montoya, Marco Mazzorana

Affiliation

¹ Experimental Therapeutics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. jpastor@cnio.es

PMID: 22266039
DOI: 10.1016/j.bmcl.2011.12.130

Abstract

PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described.

MeSH terms

Drug Design*
Enzyme Activation / drug effects
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Models, Molecular*
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacology
Triazoles / chemical synthesis*
Triazoles / chemistry
Triazoles / pharmacology

Substances

Protein Kinase Inhibitors
Pyridines
Triazoles
Proto-Oncogene Proteins c-pim-1
proto-oncogene proteins pim