129175-87-7

Upstream product

• 108-48-5 2,6-dimethylpyridine 
• 84228-45-5 methyl-2-nitro-4-amino-benzoate 
• 129175-89-9 4--N-prop-2-ynylamino>-2-nitrobenzoic acid 
• 106-96-7 propargyl bromide 

Downstream Products

• 129175-88-8 methyl 4--N-prop-2-ynylamino>-2-nitrobenzoate 
• 129175-59-3 diethyl N-<4--N-prop-2-ynylamino>-2-nitrobenzoyl>-L-glutamate 
• 129175-35-5 (S)-2-{4-[(2-Methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-2-nitro-benzoylamino}-pentanedioic acid 
• 129175-89-9 4--N-prop-2-ynylamino>-2-nitrobenzoic acid 

Relevant academic research and scientific papers

Quinazoline derivatives possessing anti-tumor activity

The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-tumor activity; to processes for their manufacture; and to pharmaceutical compositions containing them. The invention provides a quinazoline of the formula: STR1 wherein R1 is hydrogen or amino, or alkyl or alkoxy each of up to 6 carbon atoms; or R1 is substituted alkyl or alkoxy each of up to 3 carbon atoms; R2 is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, halogenoalkyl or cyanoalkyl each of up to 6 carbon atoms; Ar is phenylene or heterocyclene; L is a group of the formula --CO.NH--, --NH.CO--, --CO.NR3 --, --NR3. CO--, --CH=CH--, --CH2 O--, --OCH2, --CH2 S--, --SCH2 --, --CO.CH2 --, --CH2.CO-- or --CO.O--, wherein R3 is alkyl of up to 6 carbon atoms; and Y is aryl or heteroaryl or a hydrogenated derivative thereof: or Y is a group of the formula --A--Y1 in which A is alkylene, cycloalkylene, alkenylene or alkynylene each of up to 6 carbon atoms and Y1 is aryl or heteroaryl or a hydrogenated derivative thereof; or a pharmaceutically-acceptable salt thereof.

Quinazoline antifolate thymidylate synthase inhibitors: Benzoyl ring modifications in the C2-methyl series

The synthesis of nine new 2-methyl-10-propargylquinazoline antifolates with substituents in the p-aminobenzoyl ring is described. In general the synthetic route involved the coupling of the appropriate ring-substituted diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate with 6-(bromomethyl)-3,4-dihydro-2-methyl-4-oxoquinazoline (11) followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 thymidylate synthase (TS). They were also examined for their inhibition of the growth L1210 cells in culture. Compared to the parent compound 1a the 2'-fluoro analogue 2a exhibited enhanced potency in both systems whereas the 3'-fluoro analogue 3a showed enhanced growth inhibitory properties against L1210 cells despite being a poorer inhibitor of the isolated enzyme. Chloro, hydroxy, methoxy, and nitro substituents in the 2'-position were also well tolerated by the enzyme but failed to give enhanced growth inhibition. The series was extended to cover analogues of the 2'-fluoro, 3'-fluoro, 2'-chloro, 2'-methyl, 2'-amino, 2'-methoxy, and 2'-nitro derivatives with modified alkyl substituents at N10.