1027345-16-9

Upstream product

• 80517-22-2 2-amino-4-fluorobenzonitrile 
• 24424-99-5 di-tert-butyl dicarbonate 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 4110-33-2 2,4-dinitrobenzonitrile 
• 1027345-15-8 tert-butyl 4-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate 

Downstream Products

• 1027345-23-8 7-(4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl)quinazolin-4-ol 
• 1027345-24-9 4-chloro-7-(4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl)quinazoline 
• 1027344-89-3 N-{7-[4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl]quinazolin-4-yl}-4-(((R)-3-dimethylamino-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-nitrobenzenesulfonamide 
• 1027345-25-0 7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazolin-4-ol 
• 1027345-26-1 4-chloro-7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazoline 
• 1027344-93-9 N-{7-[4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl]quinazolin-4-yl}-4-(((R)-3-(morpholin-4-yl)-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-nitrobenzenesulfonamide 
• 1027344-91-7 N-{7-[4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl]quinazolin-4-yl}-4-(((R)-3-dimethylamino-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-(trifluoromethanesulfonyl)benzenesulfonamide 
• 1027344-95-1 N-{7-[4-((4'-chloro-(1,1'-biphenyl)-2-yl)methyl)piperazin-1-yl]quinazolin-4-yl}-4-(((R)-3-(morpholin-4-yl)-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-(trifluoromethanesulfonyl)benzenesulfonamide 
• 1027344-97-3 N-(7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazolin-4-yl)-4-(((R)-3-dimethylamino-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-nitrobenzenesulfonamide 
• 1027345-01-2 N-(7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazolin-4-yl)-4-(((R)-3-(morpholin-4-yl)-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-nitrobenzenesulfonamide 
• 1027344-99-5 N-(7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazolin-4-yl)-4-(((R)-3-dimethylamino-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-(trifluoromethanesulfonyl)benzenesulfonamide 
• 1027345-03-4 N-(7-{4-[(2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl)methyl]piperazin-1-yl}quinazolin-4-yl)-4-(((R)-3-(morpholin-4-yl)-1-(phenylsulfanylmethyl)prop-1-yl)amino)-3-(trifluoromethanesulfonyl)benzenesulfonamide 

Relevant academic research and scientific papers

Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment

Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 ± 0.08 nM; 2a, EC50 = 0.58 ± 0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 ± 6.60 nM; 2a, IC50 = 22.10 ± 5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 ± 0.217 μM, BuChE IC50 = 0.34 ± 0.03 μM; 2a, AChE IC50 = 2.36 ± 0.34 μM, BuChE IC50 = 0.10 ± 0.01 μM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment.

Quinazoline sulfonamides as dual binders of the proteins B-cell lymphoma 2 and B-cell lymphoma extra long with potent proapoptotic cell-based activity

ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-xL and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.

ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti apoptotic protein family member.

ARYLSULFONAMIDE COMPOUNDS

The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mim