1791-50-0Relevant 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
Zhu, Xiaohua,Van Horn, Kurt S.,Barber, Megan M.,Yang, Sihyung,Wang, Michael Zhuo,Manetsch, Roman,Werbovetz, Karl A.
, p. 5182 - 5189 (2015/03/18)
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.
Ligand-free palladium assisted insertion of isocyanides to urea derivatives for cascade synthesis of phenylamino-substituted quinazolinones
Sharma, Siddharth,Jain, Abhilasha
, p. 6051 - 6054 (2015/01/09)
Palladium catalyzed cascade coupling of substituted urea derivatives and tert-butyl isocyanide for the efficient synthesis of phenylamino-substituted quinazolinones has been developed in moderate to good yields. This method provides a short and alternative approach for the synthesis of quinazolinones derivatives which are valuable compounds with biological and pharmacological potentials. A plausible mechanistic scheme is proposed.
Continuous recycling of homogeneous Pd/Cu catalysts for cross-coupling reactions
Sharma, Siddharth,Basavaraju,Singh, Ajay K.,Kim, Dong-Pyo
supporting information, p. 3974 - 3977 (2014/08/18)
Given the importance of homogeneous catalysts recycling in organic chemistry, we have developed a unique microfluidic loop system for automated continuous recirculation of a soluble polymer supported metal catalyst for novel isocyanide cross-coupling reactions under thermomorphic multicomponent solvent (TMS) conditions. Our system provides an innovative approach for the chemical library synthesis of quinazolinone derivatives as well as an important intermediate of Merck's LTD4 antagonist "Singulair" with efficient continuous homogeneous catalyst recycling.
Odorless isocyanide chemistry: An integrated microfluidic system for a multistep reaction sequence
Sharma, Siddharth,Maurya, Ram Awatar,Min, Kyoung-Ik,Jeong, Guan-Young,Kim, Dong-Pyo
supporting information, p. 7564 - 7568 (2013/07/26)
Can't smell this: An integrated continuous-flow microfluidic setup enables in situ generation, extraction, separation, and reaction of foul-smelling isocyanides with little exposure to the surroundings. Isocyanides were generated by dehydration of the corresponding N-substituted formamides, and several representative isocyanide-based organic reactions were successfully performed. DIPEA=N,N-diisopropylethylamine. Copyright
Synthesis of 2-aminoquinazoline-4(3H)-one derivatives as potential potassium channel openers
Erb, Benedicte,Akue, Rufine,Rigo, Benoit,Pirotte, Bernard,Couturier, Daniel
, p. 253 - 260 (2007/10/03)
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.
Synthesis of 4(3H)-Quinazolinones from Derivatives of Methyl 2-Isothiocyanatobenzoate
Dean, William D.,Papadopoulos, Eleftherios P.
, p. 1117 - 1124 (2007/10/02)
Ethyl N-((2-methoxycarbonylphenyl)thiocarbamate (2), N-(2-ethoxycarbonylphenyl)-4-methoxythiobenzamide (3b), and 2-(4-methoxyphenyl)4H,-3,1-benzothiazin-4-one (4a), react with nucleophilic reagents containing at least one primary amino group to yield a variety of 2-substituted and 2,4-disubstituted 4(3H)-quinazolinones, as well as some tricyclic and tetracyclic products.
