Category: 175357-98-9

On June 11, 2007, Harbottle, Gareth W.; Feeder, Neil; Gibson, Karl R.; Glossop, Mel; Maw, Graham N.; Million, William A.; Morel, Florence F.; Osborne, Simon; Poinsard, Cedric published an article.Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine The title of the article was Microwave-assisted synthesis of mGluR1 ligands: carbon, nitrogen, and oxygen linked derivatives of pyrido[3,4-d]pyrimidin-4-ylamines. And the article contained the following:

The syntheses of 6-fluoropyrido[3,4-d]pyrimidin-4-ylamine derivatives is reported herein. Methods for generating C-, N-, and O-linked analogs by subsequent nucleophilic aromatic substitution of fluoride with alcs. or amines under microwave irradiation are described. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

The Article related to pyridopyrimidinylamine mglur1 ligand preparation, fluoropyridopyrimidinylamine amine nucleophilic aromatic substitution, alc fluoropyridopyrimidinylamine nucleophilic aromatic substitution and other aspects.Application In Synthesis of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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

On February 26, 1998, Rewcastle, Gordon W.; Murray, Donna K.; Elliott, William L.; Fry, David W.; Howard, Curtis T.; Nelson, James M.; Roberts, Billy J.; Vincent, Patrick W.; Showalter, H. D. Hollis; Winters, R. Thomas; Denny, William A. published an article.Formula: C7H3ClFN3 The title of the article was Tyrosine Kinase Inhibitors. 14. Structure-Activity Relationships for Methyl- amino-Substituted Derivatives of 4-[(3-Bromophenyl)amino]-6-(methylamino)- pyrido[3,4-d]pyrimidine (PD 158780), a Potent and Specific Inhibitor of the Tyrosine Kinase Activity of Receptors for the EGF Family of Growth Factors. And the article contained the following:

PD 158780 (I) is a very potent in vitro inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) (IC50 = 0.08 nM), and other members of the erbB family, by competitive binding at the ATP site of these signal transduction enzymes. A series of analogs of PD 158780 bearing solubilizing functions off the 6-methylamino substituent were prepared by reaction of the 6-fluoro derivatives with appropriate amine nucleophiles. These were evaluated for their ability to inhibit the tyrosine phosphorylating action of EGF-stimulated full-length EGFR enzyme and for inhibition of autophosphorylation of the EGFR in A431 human epidermoid carcinoma cells in culture. The most effective analogs were those bearing weakly basic substituents through a secondary amine linkage, which proved water-soluble (>10 mM) and potent (IC50s generally <1 nM). No clear SAR could be discerned for these compounds with respect to amine base strength or the distance of the cationic center from the chromophore, suggesting that 6-substituents are in a favorable area of bulk tolerance in the enzyme binding site. More distinct SAR emerged for the ability of the compounds to inhibit EGFR autophosphorylation in A431 cells, where analogs bearing lipophilic weak bases were preferred. Representative analogs were evaluated for antitumor effectiveness against four in vivo tumor models. Significant in vivo activity was observed in estrogen-dependent MCF-7 breast and A431 epidermoid tumors. Marginal activity was seen in an EGFR-transfected tumor model, suggesting that while this cell line requires EGF for clone formation in soft agar, other growth factors may be able to replace EGF in vivo. Also, activity was seen against the SK-OV-3 ovarian cancer model, which is known to express other EGF receptor family members (although it is not clear whether these are absolutely required for growth in vivo). While substantial growth delays were seen in A431 and MCF-7 tumor models, the treated tumors remained approx. the same size throughout therapy, suggesting that the compounds are cytostatic rather than cytotoxic under these test conditions. It remains to be determined if more prolonged therapy has cytotoxic effects in vivo, resulting in net tumor cell kill. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Formula: C7H3ClFN3

The Article related to pd 158780 analog preparation structure activity, antitumor activity pd 158780 analog preparation, tyrosine kinase inhibitor pd 158780 analog, autophosphorylation inhibitor pd 158780 analog preparation, epidermal growth factor receptor inhibitor preparation and other aspects.Formula: C7H3ClFN3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia