164724-29-2

Upstream product

• 14533-84-7 pentafluorophenyl trifloroacetate 
• 174487-71-9 4-{N-[(6R/6S)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid 
• 157701-39-8 4-{N-[(6S)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid 
• 157701-32-1 diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)-N-(prop-2-ynyl)-amino]benzoyl}-L-glutamate 
• 157701-31-0 diethyl N-{p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoyl}-L-glutamate 
• 157701-04-7 N-(4-{N-[(6RS)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoyl)-L-glutamic acid 
• 157701-05-8 N-(4-{N-[(6S)-2-Methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoyl)-L-glutamic acid 
• 174487-97-9 2-methyl-3-(2,2-dimethylpropionyloxymethyl)-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazoline-4,6-dione 
• 157701-36-5 2-methyl-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]-quinazolin-4-one 
• 157701-35-4 2-Methyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4-one 
• 157701-34-3 5-acetamido-6-cyanoindane 
• 59856-06-3 5-acetamidoindane 
• 157701-33-2 5-acetylamino-6-bromoindane 
• 24425-40-9 indan-5-amine 

Downstream Products

• 416852-44-3 2-{4-[(2-methyl-4-oxo-4,6,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)-prop-2-ynyl-amino]-benzoylamino}-5-(1H-[1,2,4]triazole-3-sulfonyl)-pentanoic acid methyl ester 
• 416852-42-1 4-[3-tert-butoxycarbonyl-1-(1H-tetrazol-5-yl)-propylcarbamoyl]-2-{4-[(2-methyl-4-oxo-4,6,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)-prop-2-ynyl-amino]-benzoylamino}-butyric acid tert-butyl ester 
• 238413-07-5 Pentafluorophenyl 4-{N-[(6S)-2,3-dimethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoate 

Relevant academic research and scientific papers

Cyclopenta[g]quinazoline-based antifolates: The effect of the chirality at the 6-position on the inhibition of thymidylate synthase (TS)

Cyclopenta[g]quinazoline-based inhibitors of thymidylate synthase (TS) possess a chiral centre at the 6-position of the molecule. The effect of this chirality on the inhibition of TS was investigated by synthesising compounds 6S-1a-c, 6R-1a-c. It was shown, in particular with the diastereoisomers 6S-1c, 6R-1c, that the inhibitory activity against TS is mainly due to the 6S diastereoisomer rather than the 6R diastereoisomer, which is virtually inactive.

Chemoenzymatic preparation of the novel antifolate thymidylate synthase inhibitor N-(4-{N-[(65)-2-methyl-4-oxo-3, 4, 7, 8-tetrahydro-6-cydopenta[#]quinazolin-6-yl]-Ar-(prop-2-ynyl)amino}-benzoyl)-L- glutamic acid and its glutamyl cleavage product

5-Aminoindane was converted in six steps to the cyclopenta[g]quinazoline ketone 13. Condensation of 13 with diethyl 4-aminobenzoyl-L-glutamate, followed by in situ reduction, produced the secondary amine 15. W-Propargylation of 15, followed by deprotection, gave the diacid 17 as a mixture of diastereoisomers. Treatment of 17 with the bacterial enzyme carboxypeptidase G2 resulted in removal of the L-glutamic acid residue from (6/J)-17 to give a chromatographically separable mixture of the monoacid 18 and the antifolate 5 [(65)-17], which was assayed as an inhibitor of thymidylate synthase (Kfpp = 3 nM). Treatment of isolated diacid 5 with carboxypeptidase G2 produced the monoacid 19 in ;. 98% enantiomeric excess. The (65) stereochemistry of compound 19 has been established by X-ray crystal structure determination of the amide derivative 24.