119584-70-2

Usage

Synthesis Reference(s)

Journal of Medicinal Chemistry, 33, p. 434, 1990 DOI: 10.1021/jm00163a067

InChI:InChI=1/C8H7FN4/c9-4-2-1-3-5-6(4)7(10)13-8(11)12-5/h1-3H,(H4,10,11,12,13)

Upstream product

• 1897-52-5 2,6 difluorobenzonitrile 
• 124-46-9 guanidine hydrogen carbonate 
• 29671-92-9 chloroformamidine hydrochloride 
• 77326-36-4 2-amino-6-fluorobenzonitrile 
• 113-00-8 guanidine nitrate 
• 593-85-1 diguanidine carbonate 
• 143306-27-8 2-fluoro-6-nitrobenzonitrile 

Downstream Products

• 133528-62-8 4-(((2,4-diamino-5-fluoro-6-quinazolinyl)amino)methyl)benzoic acid 
• 133528-61-7 methyl 4-(((2,4-diamino-5-fluoro-6-quinazolinyl)amino)methyl)benzoate 
• 133528-57-1 5-fluoro-5,8-dideazaisoaminopterin 
• 133528-60-6 di-t-butyl N-(4-(((2,4-diamino-5-fluoro-6-quinazolinyl)amino)methyl)benzoyl)-L-glutamate 
• 215925-72-7 2,4-Diamino-5-(3-trifluoromethylphenoxy)quinazoline 
• 143745-23-7 N^δ-(tert-butyloxycarbonyl)-N^α-(5-fluoro-5,8-dideazaisopteroyl)-L-ornithine 
• 143745-10-2 N^α-(5-fluoro-5,8-dideazaisopteroyl)-L-ornithine 
• 1025814-91-8 4-{[(2-Amino-5-fluoro-4-oxo-3,4-dihydro-quinazolin-6-yl)-(2,2,2-trifluoro-acetyl)-amino]-methyl}-benzoic acid 
• 143745-20-4 methyl 5-fluoro-2-pivaloyl-5,8-dideazaisopteroate 
• 143745-21-5 methyl 5-fluoro-5,8-dideazaisopteroate 
• 143745-22-6 5-fluoro-5,8-dideazaisopteroic acid 

Relevant academic research and scientific papers

SNAr reaction in aqueous medium in the presence of mixed organic and inorganic bases

N-Arylation of amines with fluorobenzonitriles in aqueous medium is described. A mixture of N,N-diisopropylethyl amine and Na2CO3 (1:1) is found to achieve maximum conversion by refluxing for 3 hours in water. The product can be easily isolated by solvent extraction.

Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors

The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC50 = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC50 = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

Antifolate and Antibacterial Activities of 5-Substituted 2,4-Diaminoquinazolines

A series of 5-substituted 2,4-diaminoquinazolines (3) has been synthesized and evaluated as inhibitors of the enzyme dihydrofolate reductase (DHFR) from both bacterial and mammalian sources.The best compounds (e.g. 53) show good activity against Escherichia coli DHFR, but there is no significant selectivity for the bacterial over the mammalian enzyme.The structure-activity relationships for enzyme inhibition appear to be complex and not amenable to simple analysis; a hypotesis to explain the observed qualitative structure-activity relationships is proposed.The inhibitory activities of the compounds against the growth of intact bacterial cells in vitro closely parallel those for the inhibition of the isolated bacterial enzymes, suggesting that their antifolate action is responsible for their antibacterial effects.Five of the compounds were tested for their ability to cure a systemic E. coli infection in the mouse, but they showed no therapeutic effects at their maximum tolerated doses.

Direct Synthesis of 2,4-Diaminoquinazolines from 2-Fluorobenzonitriles

In a search for new methods for preparing 2,4-diaminoquinazolines having a diversity of substituents in the benzenoid ring, it was found that the reaction of 2,6-difluorbenzonitrile with guanidine carbonate gave 2,4-diamino-5-fluoroquinazoline in excellent yield.Extension of this approach to other 2-fluorobenzonitriles, some of which were elaborated for the first time, showed that this reaction possesses considerable generality.The cyclization was sucessful even when electron donating groups were present at position six.Only in two cases where a primary or secondary amino group was also present ortho to the cyano group was this transformation unsucessful.