Smaill, Jeff B. et al. published their research in Journal of Medicinal Chemistry in 1999 |CAS: 175357-98-9

The Article related to phenylaminoquinazoline acrylamide preparation egfr inhibitor, phenylaminopyridopyrimidine acrylamide preparation egfr inhibitor, epidermal growth factor receptor inhibitor acrylamide, antitumor quinazoline pyridopyrimidine acrylamide, acrylamide quinazoline pyridopyrimidine egfr inhibitor antitumor and other aspects.Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

On May 20, 1999, Smaill, Jeff B.; Palmer, Brian D.; Rewcastle, Gordon W.; Denny, William A.; McNamara, Dennis J.; Dobrusin, Ellen M.; Bridges, Alexander J.; Zhou, Hairong; Showalter, H. D. Hollis; Winters, R. Thomas; Leopold, Wilbur R.; Fry, David W.; Nelson, James M.; Slintak, Veronika; Elliot, William L.; Roberts, Billy J.; Vincent, Patrick W.; Patmore, Sandra J. published an article.Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine The title of the article was Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. And the article contained the following:

A series of 6- and 7-acrylamide derivatives of the 4-(phenylamino)quinazoline and -pyridopyrimidine classes of epidermal growth factor receptor (EGFR) inhibitors, I (R = Br, Cl, Me, X = CH, N), II (R = 3-Br, 3-Cl, 3-Me, 3-CF3, 3-Br-4-F, 3-Cl-4-F, 4-OPh, 4-OCH2Ph), III (R = 3-Br, 3-Br-4-F, 3-Cl-4-F), and IV, were prepared from the corresponding amino compounds by reaction with either acryloyl chloride/base or acrylic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. All of the 6-acrylamides, but only the parent quinazoline 7-acrylamide, were irreversible inhibitors of the isolated enzyme, confirming that the former are better-positioned, when bound to the enzyme, to react with the critical cysteine-773. Quinazoline, pyrido[3,4-d]pyrimidine, and pyrido[3,2-d]pyrimidine 6-acrylamides were all irreversible inhibitors and showed similar high potencies in the enzyme assay (likely due to titration of the available enzyme). However, the pyrido[3,2-d]pyrimidine analogs were 2-6-fold less potent than the others in a cellular autophosphorylation assay for EGFR in A431 cells. The quinazolines were generally less potent overall toward inhibition of heregulin-stimulated autophosphorylation of erbB2 (in MDA-MB-453-cells), whereas the pyridopyrimidines were equipotent. Selected compounds were evaluated in A431 epidermoid and H125 non-small-cell lung cancer human tumor xenografts. The compounds showed better activity when given orally than i.p. All showed significant tumor growth inhibition (stasis) over a dose range. The poor aqueous solubility of the compounds was a drawback, requiring formulation as fine particulate emulsions. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

The Article related to phenylaminoquinazoline acrylamide preparation egfr inhibitor, phenylaminopyridopyrimidine acrylamide preparation egfr inhibitor, epidermal growth factor receptor inhibitor acrylamide, antitumor quinazoline pyridopyrimidine acrylamide, acrylamide quinazoline pyridopyrimidine egfr inhibitor antitumor and other aspects.Name: 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia