Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors was written by Brameld, Ken A.;Owens, Timothy D.;Verner, Erik;Venetsanakos, Eleni;Bradshaw, J. Michael;Phan, Vernon T.;Tam, Danny;Leung, Kwan;Shu, Jin;LaStant, Jacob;Loughhead, David G.;Ton, Tony;Karr, Dane E.;Gerritsen, Mary E.;Goldstein, David M.;Funk, Jens Oliver. And the article was included in Journal of Medicinal Chemistry in 2017.Synthetic Route of C28H41N7O3 The following contents are mentioned in the article:
Aberrant signaling of the FGF/FGFR pathway occurs frequently in cancers and is an oncogenic driver in many solid tumors. Clin. validation of FGFR as a therapeutic target has been demonstrated in bladder, liver, lung, breast, and gastric cancers. Our goal was to develop an irreversible covalent inhibitor of FGFR1-4 for use in oncol. indications. An irreversible covalent binding mechanism imparts many desirable pharmacol. benefits including high potency, selectivity, and prolonged target inhibition. Herein we report the structure-based design, medicinal chem. optimization, and unique ADME assays of our irreversible covalent drug discovery program which culminated in the discovery of compound 34 (PRN1371), a highly selective and potent FGFR1-4 inhibitor. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Synthetic Route of C28H41N7O3).
1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. The pyrimidine nitrogenous bases are derived from the organic compound pyrimidine through the addition of various functional groups. Drugs having the pyrimidine motif have manifested to exhibit gratifying biological activity like anticancer, antiviral, anti-inflammatory, antibacterial, and antihypertensive activities.Synthetic Route of C28H41N7O3
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia