139988-05-9Relevant academic research and scientific papers
Pharmaceutically active benzoquinazoline compounds
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Page 13-14, (2010/11/29)
Compounds of formula (I) or salts thereof, wherein the dotted line represents a single or double bond, R1is alkyl or amino optionally substituted by alkyl, alkanoyl or benzyl group; R2, R3, R4and R5are the same or different and each is selected from hydrogen, phenyl, halo, nitro, a group S(O)nR8wherein n is the integer 0, 1 or 2 and R8is halo or alkyl or a group NR9R10wherein R9and R10are both hydrogen, a group NR11R12wherein R11and R12are the same or different and each is hydrogen or alkyl, a group OR13wherein R13is hydrogen or C1-4alkyl optionally substituted by halo; a C1-4aliphatic group optionally substituted by a group OR14or NR14R15wherein R14and R15are the same or different and each is hydrogen or alkyl; or two of R2to R5are linked together to form a benzo group, or one of R2to R5is a group -X-Y-R16wherein X is CH2, NR17, CO or S(O)m, and Y is CH2, NR17, O, or S(O)m, or -X-Y- is a group -O-, -NR17-, -CH=CH- or -N=N-, are disclosed as pharmacological agents useful in the treatment of tumours. Pharmaceutical compositions and methods for the preparation of compounds of formula (I) are also described.
Benzoquinazoline inhibitors of thymidylate synthase: Enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin- 1(2H)-ones
Pendergast,Johnson,Dickerson,Dev,Duch,Ferone,Hall,Humphreys,Kelly,Wilson
, p. 2279 - 2291 (2007/10/02)
The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p- aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 μM.
