1095658-90-4

Upstream product

• 157864-32-9 N⁴-benzyl-2-chloroquinazolin-4-amine 
• 104-84-7 para-methylbenzylamine 
• 607-68-1 2,4-dichloroquinazoline 
• 118-92-3 anthranilic acid 
• 86-96-4 1,2,3,4-tetrahydro-quinazoline-2,4-dione 
• 100-46-9 benzylamine 

Relevant academic research and scientific papers

SAR refinement of antileishmanial N2,N4-disubstituted quinazoline-2,4-diamines Dedicated to the memory of Martin John Rogers for his sincere efforts to facilitate neglected disease research, particularly in the area of drug discovery and development

Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. We previously showed that N2,N4-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular Leishmania, and lead compound N4-(furan-2-ylmethyl)-N2-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis. In the present work, thirty-one N2,N4-disubstituted quinazoline-2,4-diamines that had not previously been examined for their antileishmanial activity were evaluated for their potency and selectivity against Leishmania donovani, the causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with aromatic substituents at both N2 and N4 exhibited potent in vitro antileishmanial activity but relatively low selectivity, while compounds substituted with small alkyl groups at either N2 or N4 generally showed lower antileishmanial potency but were less toxic to a murine macrophage cell line. Based on their in vitro antileishmanial potency, N4-benzyl-N2-(4-chlorobenzyl)quinazoline-2,4-diamine (15) and N2-benzyl-N4-isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of their pharmacokinetic and antileishmanial properties. While 15 displayed a longer plasma half-life and a greater area under the curve than 40, both compounds showed low efficacy in an acute murine visceral leishmaniasis model. Although the present study did not identify new quinazoline-2,4-diamines with promising in vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl groups at either N2 or N4 may provide clues for the design of safe and effective antileishmanial quinazolines.

Antibacterial activity of a series of N2, N4- disubstituted quinazoline-2,4-diamines

A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against multidrug resistant Staphylococcus aureus. A structure-activity and structure-property relationship study was conducted to identify new hit compounds. This study led to the identification of N2,N4-disubstituted quinazoline-2,4- diamines with minimum inhibitory concentrations (MICs) in the low micromolar range in addition to favorable physicochemical properties. Testing of biological activity revealed limited potential for resistance to these agents, low toxicity, and highly effective in vivo activity, even with low dosing regimens. Collectively, these characteristics make this compound series a suitable platform for future development of antibacterial agents.

USE OF COMPOUNDS FOR PREPARING ANTI-TUBERCULOSIS AGENTS

Compounds of a compound of compound of general formula (I) wherein X1, X2, A, R1R2, R3 and R4 are as defined herein; are useful as anti-mycobacterial agents, especially agents for the treatment of tuberculosis.