157701-46-7

Upstream product

• 18144-47-3 tert-butyl 4-aminobenzoate 
• 174487-97-9 2-methyl-3-(2,2-dimethylpropionyloxymethyl)-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazoline-4,6-dione 
• 157701-44-5 dimethyl 2-{p-[N-(2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzamido}suberate 
• 157701-45-6 6-Bromo-2-methyl-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]-quinazolin-4-one 

Downstream Products

• 902777-34-8 tert-butyl 4-[N-(2-methyl-3-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-methylamino]benzoate 
• 902777-37-1 tert-butyl 4-[N-(2-methyl-3-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoate 
• 902777-40-6 tri-tert-butyl N-{4-[N-(2-methyl-3-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-methylamino]benzoyl}-L-γ-glutamyl-D-glutamate 
• 902777-63-3 tri-tert-butyl N-{4-[N-(2-methyl-3-(2,2-dimethylpropionyloxymethyl)-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)amino]benzoyl}-L-γ-glutamyl-D-glutamate 

Relevant academic research and scientific papers

Targeting the α-folate receptor with cyclopenta[g]quinazoline-based inhibitors of thymidylate synthase

The α-FR has been reported to be overexpressed in many carcinomas, in particular those of the ovary and uterus. The high expression of α-FR in some tumours compared with normal tissues has been exploited over the last decade for folate-mediated targeting of macromolecules, anticancer drugs, imaging agents and nucleic acids to cancer cells. CB300638, a cyclopenta[g]quinazoline-based inhibitor of thymidylate synthase (TS), has been reported to have high affinity for the receptor and selectivity for α-FR overexpressing tumour cell lines. In this study, the structural features of the molecule, in particular modifications at the 2-position, have been investigated with respect to TS inhibition, affinity for the α-FR and reduced folate carrier (RFC) and activity in A431-FBP cells (transfected with human α-FR) compared with neo-transfected A431 cells. Compounds 1a,b, 2a,b and 3a,b were synthesised utilising multistep sequences. It was found that the 2-substituent does not affect the affinity for the α-FR; however, it greatly affects selectivity for A431-FBP cells, and suggests that there are factors other than TS inhibition and α-FR affinity that are important for the activity of these compounds. Compound 2b (2-CH2OH derivative) displayed the highest selectivity for the A431-FBP cells compared with A431 cells.

Tricyclic compounds with pharmaceutical activity

The invention relates to tricyclic compounds of formula (I) STR1 wherein R1 is hydrogen, amino, (1-4C)alkyl, (1-4C)alkoxy, hydroxy-(1-4C)alkyl or fluoro-(1-4C)alkyl; R2 is hydrogen, (1-4C)alkyl, (3-4C)alkenyl, (3-4C)alkynyl, hydroxy-(2-4C)alkyl, halogeno-(2-4C)alkyl or cyano-(1-4C)alkyl; Ar is optionally-substituted phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl; and R3 includes a group of the formula --NHCH(CO2 H)--A1 --Y1 wherein A1 is (1-6C)alkylene and Y1 is carboxy, tetrazol-5-yl, N-?(1-4C)alkylsulphonyl!carbamoyl, N(phenylsulphonyl)carbamoyl, tetrazol-5-ylthio, tetrazol-5-ylsulphinyl or tetrazol-5-ylsulphonyl; or pharmaceutically-acceptable salts or esters thereof; to processes for their manufacture; to pharmaceutical compositions containing them; and to their use as anti-cancer agents.