49681-96-1

Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.

The invention discloses a preparation method of a 2-thioxo-2,3-dihydroquinazoline-4(1H)-one compound. The preparation method of the compound of formula I includes the following steps: a compound of formula II and a compound of formula III are subjected to a condensation reaction in an organic solvent under the action of an organic base to obtain the compound of the formula I, wherein the reactiontemperature is 70-155 DEG C, X1, X2, X3 and X4 are independently hydrogen or halogen, and R is hydrogen or one of alkyl groups of C1-C4. The preparation method provided by the invention is mild in conditions, environment-friendly, low in cost, high in yield, simple and efficient, and is suitable for industrial production. The formula of the reaction is shown in the description.

Based on a pharmacophore model of the benzodiazepine-binding site of GABAA receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c] quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity lig

the resent invention relates to novel compounds of the general formula (I) having anxiolytic, anticonvulsant, sedative-hypnotic and myorelaxant conditions as well as anxiogenic, somnolytic and convulsant conditions in mammals, including humans, as GABAA receptor modulator.

A facile and convenient method to the one-pot synthesis of 2-mercapto-4(3H)-quinazolinones is described from the reaction of anthranilic acid derivatives with thiourea in PEG.

This invention provides the treatment of viral infections with a 4,6- disubstituted or 2,4,6-trisubstituted quinazoline derivative represented by the structural formula [(I)] wherein: R2 is selected from the group consisting of hydrogen, NR'R"

This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR'R", C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7

We have studied the electronic effect of substituents, steric factors, the medium, and the nature of the oxidizing agent on oxidative cyclocondensation of 2-thioxo-4-quinazolone and its substituted derivatives. We have found that electron-donor substituents promote the reaction while electronacceptor substituents inhibit the reaction. 2006 Springer Science+Business Media, Inc.

The invention provides low molecular compounds having activity which inhibits binding of CCR3 ligands to CCR3 on target cells, i.e. CCR3 antagonists. The invention also provides 4,4-(disubstituted)piperidine derivatives represented by formula (I) below, pharmaceutically acceptable acid adducts thereof, or pharmaceutically acceptable C1-C6 alkyl adducts thereof, as well as pharmaceutical compositions comprising them as effective ingredients, which are useful for treatment or prevention of diseases associated with CCR3, such as asthma and allergic rhinitis.

Starting from 2-thioxoquinazolin-4-one, the synthesis of 2-amino-4(3H)- one derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described.

-

-