174415-29-3

Upstream product

• 1979-36-8 2',5'-difluoroacetophenone 
• 298-12-4 Glyoxilic acid 
• 108-31-6 maleic anhydride 
• 540-36-3 para-difluorobenzene 

Downstream Products

• 174415-25-9 4-p-methoxybenzyloxy-6,9-bis<<2-ethyl>amino>benzisoquinoline-5,10-dione 
• 157355-26-5 4-benzyloxy-6,9-bis<<2-ethyl>amino>benzisoquinoline-5,10-dione 
• 174415-34-0 4-p-methoxybenzyloxy-6,9-bis<<2-(dimethylamino)ethyl>amino>benzisoquinoline-5,10-dione 
• 157355-24-3 4-benzyloxy-6,9-bis<<2-(dimethylamino)ethyl>amino>benzisoquinoline-5,10-dione 
• 174415-28-2 4-p-methoxybenzyloxy-6,9-difluorobenzisoquinoline-5,10-dione 
• 157355-23-2 4-benzyloxy-6,9-difluorobenzisoquinoline-5,10-dione 
• 174415-33-9 methyl 6-methyl-4-(2,5-difluorobenzoyl)-5-hydroxynicotinate 
• 174415-31-7 methyl 5-hydroxy-4-(2,5-difluorobenzoyl)nicotinate 

Relevant academic research and scientific papers

Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile

Proline racemases (PRAC), catalyzing the l-proline and d-proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T.?cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C.?difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4-oxopent-2-enoic acid TcPRAC irreversible inhibitors, we synthesized 4-aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C.?difficile. This study resulted in promising candidates and allowed for identification of (E)-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.

Synthesis of 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-diones and conversions to 4-hydroxy-6,9-bis[(aminoalkyl)amino]-benz[g]isoquinoline-5,10-diones

Synthetic procedures have been developed which lead to 4-hydroxy-6,9-difluorobenz[g]isoquinoline-5,10-dione (4a) and its 3-methyl analogue 4b. Attempts to displace the fluorides from 4a with N,N-dimethylethylenediamine were unsuccessful. Analogue 4a on treatment with N-(t-butoxycarbonyl)ethylene diamine led to 15, formed from addition of the nucleophilic amine to C-3. On the other hand, analogue 4b, on treatment with N,N-dimethylethylenediamine led to the anticipated difluoride displacement product 3c. The protection of the hydroxy group of 4a by benzylation with phenyldiazomethane led to 4c which on treatment with N-(t-butoxycarbonyl)ethylene diamine or N,N-dimethylethylenediamine led to the corresponding 6,9-bis-substituted analogues 18a and 18b, respectively. Reductive debenzylations of 18a and 18b by hydrogenation over Pearlman's catalyst also effected partial reductions of the quinone. However, air oxidation of the over reduced products led to 3a and 3b, respectively. Treatment of 3a with hydrogen chloride gas led to the hydrochloride salt of 3d. Addition of O-p-Methoxybenzyl-N,N'-diisopropylurea to 4a led to the p-methoxybenzyl analogue 4d. Treatment of 4d with N,N-dimethylethylene diamine or N-(t-butoxycarbonyl)ethylene diamine led to displacements of the fluorides to yield 18c and 18d, respectively. Deprotection of 18c to 3b was accomplished using methanesulfonic acid. Treatment of 18d with trifluoroacetic acid followed by addition of maleic acid led to dimaleate salt of 3d.