Synthesis of Substituted 4-Oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and 4-Oxo-3,4-dihydroquinazoline-2-thioles

Abstract

We have developed a liquid-phase synthesis of combinatorial libraries of new disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and trisubstituted 4-oxo-3,4-dihydroquinazoline-2-thioles. The former were prepared using two general procedures: (i) cyclization of substituted methyl anthranilates with isothiocyanates, or (ii) cyclization of substituted 2-(methylcarboxy)benzeneisothiocyanates with primary amines or hydrazines. 4-Oxo-3,4-dihydroquinazoline-2-thioles were prepared by S-alkylation of disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines with alkyl or aryl halides. The hydrolysis of methyl benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxylate led to the corresponding acid. This acid was utilized in the synthesis of new benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxamide and S-substituted 6-mecaptobenzimidazo[1,2-c]quinazoline-3-carboxamide libraries.

Quinazoline-4(3H)-one-7-carboxamide Derivatives as Human Soluble Epoxide Hydrolase Inhibitors with Developable 5-Lipoxygenase Activating Protein Inhibition

“…Chemistry. The reaction of dimethyl aminoterephthalate 6 with the phenyl isothiocyanate in refluxing pyridine generated the 3-phenyl-2-thioxoquinazoline-4-one (7) intermediate, 31 which was reacted with the appropriate benzyl halide to produce the corresponding benzylated derivatives 8 and 9. Subsequently, hydrolysis of the ester group yielded the carboxy intermediates 10, 11, which was subsequently coupled with the appropriate amines to afford the expected amide derivatives 12−14 (Scheme 1).…”

Synthesis and Biological Activity Evaluation of 3-[2-(1h-Imidazol-2-Yl)alkyl]-2-Thioxo-2,3-Dihydroquinazolin-4 (1h) -One Derivatives

“…Analysis of the computer prediction results for a virtual library of 3-[2-(1H-imidazol-2-yl)alkyl]-2-thioxo-2,3-dihydroquinazolin-4(1H)ones showed high level of probability of antimicrobial and antifungal activity and allowed to generate the library of the most perspective compounds 4 {1-30} for further biological investigations [ Table 1]. In continuation of investigations conducting at the National University of Pharmacy, which lead to suitable synthetic methods, providing high yields and purity of 3-substituted condensed 2-thioxopyrimidin-4-ones, [12][13][14][15] we examined the possibility of use 2-(α,β,ω-aminoalkyl) imidazoles as amine components due to presence of primary amino group in the heterocyclization reaction with ortho-isothiocyanato esters. Synthesis of intermediate methyl 2-isothiocyanatobenzoates 2{1-6} was carried out by treatment of substituted methyl 2-aminobenzoates 1{1-6} with thiophosgene in a two-phase system of chloroform -water at room temperature [ Figure 1].…”

Synthesis of substituted 2-hydrazinoquinazolin-4-ones as intermediates for heterocyclic compounds synthesis

“…У спек- трах гідразинів 5{1-27} цей сигнал відсутній, але присутній сигнал NH-2 групи гідразинового фрагменту при 4,30-4,50 м.ч. Вихідні 2-тіоксохіназолін-4-они 3{1-20} були отримані при взаємодії естерів 2-ізотіоціанатобензойних кислот 1 з первинними амінами 2 [5] або гідразингідратом при кип'ятінні в і-пропанолі впродовж декількох хвилин [16]. В цих умовах при використанні гідразингідрату ще не відбувається заміщення атому сульфуру, та утворюється 3-аміно-2-тіоксохіназолін-4-он 3{1}.…”