157701-31-0Relevant academic research and scientific papers
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
Marriott, Jonathan H.,Neidle, Stephen,Matusiak, Zbigniew,Bavetsias, Vassilios,Jackman, Ann L.,Melin, Camille,Boyle, F. Thomas
, p. 1495 - 1503 (2007/10/03)
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.
Anti-cancer compounds
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, (2008/06/13)
Cyclopentaquinazoline of the formula (I): STR1 wherein R1 is hydrogen, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 hydroxyalkyl or C1-4 fluoroalkyl; wherein R2 is hydrogen, C1-4 alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or C1-4 cyanoalkyl; Ar1 is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C1-4 alkyl and C1-4 alkoxy; and wherein R3 is a group of the formula: in which A1, A2, Y1 and Ar2 are defined in claim 1; or a pharmaceutically acceptable salt or ester there of are of therapeutic value particularly in the treatment of cancer.
Tricyclic compounds with pharmaceutical activity
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, (2008/06/13)
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.
