1426531-86-3Relevant academic research and scientific papers
Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension
Shaw, Duncan E.,Baig, Ferheen,Bruce, Ian,Chamoin, Sylvie,Collingwood, Stephen P.,Cross, Sarah,Dayal, Satish,Drückes, Peter,Furet, Pascal,Furminger, Vikki,Haggart, Deborah,Hussey, Martin,Konstantinova, Irena,Loren, Jon C.,Molteni, Valentina,Roberts, Sonia,Reilly, John,Saunders, Alex M.,Stringer, Rowan,Sviridenko, Lilya,Thomas, Matthew,Thomson, Christopher G.,Tomlins, Christine,Wen, Ben,Yeh, Vince,Pearce, Andrew C.
, p. 7901 - 7914 (2016/10/12)
A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension. Examination of PK/PD data from the optimization effort has revealed in vitro:in vivo correlations which link duration of action in vivo with low permeability and high basicity and demonstrate that nonspecific binding to lung tissue increases with lipophilicity.
COMPOUNDS AND COMPOSITIONS AS PDGFR KINASE INHIBITORS
-
, (2013/03/28)
The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase
BICYCLIC HETEROCYCLE DERIVATIVES FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION
-
Page/Page column 136, (2013/03/28)
Bicyclic heterocyclic derivatives of formula (I) useful in inhibiting PDGF receptor mediated biological activity. Wherein A is and R1, R1a, R2, R3, R4, R5, R6 and X are as defined herein.
