|Chemical and physical data|
|Molar mass||477.554 g/mol g·mol−1|
|3D model (JSmol)|
RPL-554 (LS-193,855) is a drug candidate for respiratory diseases. It is an analog of trequinsin and, like trequinsin, is a highly selective inhibitor of the phosphodiesterase enzyme, PDE3; indeed, it is >3000-times more potent against PDE3 than PDE4. As of October 2015, inhaled RPL-554 delivered via a nebulizer was in development for COPD and had been studied in asthma.
RPL554 was part of a family of compounds invented by Sir David Jack, former head of R&D for GlaxoSmithKline, and Alexander Oxford, a medicinal chemist; the patents on their work were assigned to Vernalis plc.:19-20
In 2005, Rhinopharma Ltd, acquired the rights to the intellectual property from Vernalis.:19-20 Rhinopharma was a startup founded in Vancouver, Canada in 2004 by Michael Walker, Clive Page, and David Saint, to discover and develop drugs for chronic respiratory diseases,:16 and intended to develop RPL-554, delivered with an inhaler, first for allergic rhinitis, then asthma, then for COPD.:16-17 RPL554 was synthesized at Tocris, a contract research organization, under the supervision of Oxford, and was studied in collaboration with Page's lab at King’s College, London. In 2006 Rhinopharma recapitalized and was renamed Verona Pharma plc.
- Boswell-Smith V et al. The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]. J Pharmacol Exp Ther. 2006 Aug;318(2):840-8. PMID 16682455
- Nick Paul Taylor for FierceBiotech. October 1, 2015 Verona sets sights on PhIIb after COPD drug comes through early trial
- Turner MJ et al. The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L59-70. PMID 26545902
- see US20040171828, identified in the citations of PMID 16682455
- ISIS Resources, PLC. August 23, 2006 Proposed Acquisition of Rhinopharma