878650-03-4

Upstream product

• 19227-11-3 N'-hydroxy-2-phenylethanimidamide 
• 762-42-5 dimethyl acetylenedicarboxylate 
• 140-29-4 phenylacetonitrile 
• 19227-11-3 (Z)-N'-hydroxy-2-phenylacetimidamide 

Downstream Products

• 1026055-06-0 5-benzoyloxy-6-hydroxy-2-(phenyl-piperidin-1-yl-methyl)-pyrimidine-4-carboxylic acid methyl ester 
• 519031-81-3 methyl 5,6-bis(benzoyloxy)-2-[bromo(phenyl)methyl]pyrimidine-4-carboxylate 
• 1027272-12-3 5-benzoyloxy-6-hydroxy-2-(morpholin-4-yl-phenyl-methyl)-pyrimidine-4-carboxylic acid methyl ester 
• 519031-80-2 methyl 5,6-bis(benzoyloxy)-2-benzylpyrimidine-4-carboxylate 
• 1027839-33-3 5-benzoyloxy-2-(dimethylamino-phenyl-methyl)-6-hydroxy-pyrimidine-4-carboxylic acid methyl ester 
• 519032-07-6 methyl 2-benzyl-5,6-dihydroxypyrimidine-4-carboxylate 

Relevant academic research and scientific papers

Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors

Human immunodeficiency virus type-1 (HIV-1) integrase, one of the three constitutive viral enzymes required for replication, is a rational target for chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order to examine effects on HIV-integrase inhibitory potencies. One of the most interesting compounds for this series is 2-[1-(dimethylamino)-1-methylethyl]-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine- 4-carboxamide 38, with a CIC95 of 78 nM in the cell-based assay in the presence of serum proteins. The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent.

2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: Discovery, SAR, modeling, and mutagenesis

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2- thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 μM), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.