144511-93-3

Upstream product

• 607-68-1 2,4-dichloroquinazoline 
• 7087-68-5 N-ethyl-N,N-diisopropylamine 
• 118-92-3 anthranilic acid 
• 86-96-4 1,2,3,4-tetrahydro-quinazoline-2,4-dione 
• 62-53-3 aniline 

Downstream Products

• 1589476-72-1 N²-isopropyl-N⁴-phenylquinazoline-2,4-diamine 
• 1589476-73-2 N²-butyl-N⁴-phenylquinazoline-2,4-diamine 
• 1251839-69-6 N-phenyl-2-(3,4,5-trimethoxyphenyl)quinazolin-4-amine 
• 40288-70-8 2-phenyl-4-phenylaminoquinazoline 
• 1304764-81-5 4-anilino-2-(3-fluorophenyl)quinazoline 
• 1589476-75-4 N²-benzyl-N⁴-phenylquinazoline-2,4-diamine 
• 1080622-96-3 2-(4-methylpiperazin-1-yl)-N-phenylquinazolin-4-amine 
• 27142-44-5 N²,N⁴-diphenylquinazoline-2,4-diamine 

Relevant academic research and scientific papers

A Diverse Range of Hemozoin Inhibiting Scaffolds Act on Plasmodium falciparum as Heme Complexes

A diverse series of hemozoin-inhibiting quinolines, benzamides, triarylimidazoles, quinazolines, benzimidazoles, benzoxazoles, and benzothiazoles have been found to lead to exchangeable heme levels in cultured Plasmodium falciparum (NF54) that ranged over an order of magnitude at the IC50. Surprisingly, less active compounds often exhibited higher levels of exchangeable heme than more active ones. Quantities of intracellular inhibitor measured using the inoculum effect exhibited a linear correlation with exchangeable heme, suggesting formation of heme-inhibitor complexes in the parasite. In an effort to confirm this, the presence of a Br atom in one of the benzimidazole derivatives was exploited to image its distribution in the parasite using electron spectroscopic imaging of Br, an element not naturally abundant in cells. This showed that the compound colocalized with iron, consistent with its presence as a heme complex. Direct evidence for this complex was then obtained using confocal Raman microscopy. Exchangeable heme and inhibitor were found to increase with decreased rate of killing, suggesting that slow-acting compounds have more time to build up exchangeable heme complexes. Lastly, some but not all compounds evidently cause pro-oxidant effects because their activity could be attenuated with N-acetylcysteine and potentiated with t-butyl hydroperoxide. Collectively, these findings suggest that hemozoin inhibitors act as complexes with free heme, each with its own unique activity.

DIACYLGLYCEROL KINASE MODULATING COMPOUNDS

The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.

Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1H)-pyrazole Derivatives as JAKs Inhibitors

Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1H)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Res

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.

Antileishmanial activity of a series of N2, N 4-disubstituted quinazoline-2,4-diamines

A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg-1 day-1 for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N2,N 4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.

Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach

From a series of small fragments that was designed to probe the histamine H4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H 4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloro-N-(furan-3-ylmethyl)2-(4-methylpiperazin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl) quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pKi ) 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine H 1 receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quinazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.

POTASSIUM CHANNEL MODULATING AGENTS AND THEIR MEDICAL USE

This invention relates to novel potassium channel modulating agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or

Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists

The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity. The synthesis and SAR towards CGP71683A is described. (C) 2000 Elsevier Science Ltd. All rights reserved.

Synthesis and bioactivities of novel piperidylpyrimidine derivatives: Inhibitors of tumor necrosis factor-alpha production

New piperidylpyrimidine derivatives, including quinazolines, were prepared, and their abilities to inhibit TNF-α production evaluated. Some compounds showed potent inhibitory activity in mouse macrophages stimulated with LPS. The synthesis and structure-activity relationships of these compounds are described. (C) 2000 Elsevier Science Ltd. All rights reserved.