File(s) under permanent embargo
Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs
journal contributionposted on 2012-04-01, 00:00 authored by C Wang, Trent Ashton, A Gustafson, N D Bland, S O Ochiana, R K Campbell, M P Pollastri
Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.
JournalBioorganic & medicinal chemistry letters
Pagination2579 - 2581
LocationAmsterdam, The Netherlands
Publication classificationC Journal article; C1.1 Refereed article in a scholarly journal
Copyright notice2012, Elsevier Ltd.
AnimalsBiological AssayHumansPhosphodiesterase 5 InhibitorsPhosphoric Diester HydrolasesPiperazinesProtozoan ProteinsPurinesSildenafil CitrateSolutionsStructure-Activity RelationshipSulfonesTrypanocidal AgentsTrypanosoma brucei bruceiScience & TechnologyLife Sciences & BiomedicinePhysical SciencesChemistry, MedicinalChemistry, OrganicPharmacology & PharmacyChemistryNeglected diseaseTrypanosoma bruceiTarget repurposingPhosphodiesterase inhibitorsTbrPDEB1PDE5SildenafilPARASITEDISEASESTARGETSENZYMESDRUGOrganic Chemistry