955016-61-2

Upstream product

• 501-53-1 benzyl chloroformate 
• 112257-24-6 tert-butyl 3-(aminocarbonyl)piperazine-1-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 150407-69-5 [2S]-1-benzyloxycarbonyl-4-t-butoxycarbonylpiperazine-2-carboxylic acid 
• 126937-41-5 1-(benzyloxycarbonyl)-4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid 

Downstream Products

• 519032-09-8 1-benzyl 4-tert-butyl 2-[5-(benzoyloxy)-4-hydroxy-6-(methoxycarbonyl)pyrimidin-2-yl]-piperazine-1,4-dicarboxylate 
• 940868-26-8 methyl 5-(benzoyloxy)-2-{1-[(benzyloxy)carbonyl]-4-methylpiperazin-2-yl}-6-hydroxypyrimidine-4-carboxylate 
• 940868-25-7 methyl 5-(benzoyloxy)-2-{1-[(benzyloxy)carbonyl]piperazin-2-yl}-6-hydroxypyrimidine-4-carboxylate 
• 940868-24-6 1-benzyl 4-tert-butyl 2-[amino(hydroxyimino)methyl]piperazine-1,4-dicarboxylate 
• 955016-62-3 1-benzyl 4-(tert-butyl) 2-cyanopiperazine-1,4-dicarboxylate 

Relevant academic research and scientific papers

COMPOUNDS FOR USE IN THE TREATMENT OF KINETOPLASTID INFECTION

The present invention relates to a class of novel heterocyclic compounds, to pharmaceutical compositions comprising the compounds and their use in the treatment of kinetoplastid infections.

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.

Discovery and synthesis of HIV integrase inhibitors: Development of potent and orally bioavailable N-methyl pyrimidones

The human immunodeficiency virus type-1 (HIV-1) encodes three enzymes essential for viral replication: a reverse transcriptase, a protease, and an integrase. The latter is responsible for the integration of the viral genome into the human genome and, therefore, represents an attractive target for chemotherapeutic intervention against AIDS. A drug based on this mechanism has not yet been approved. Benzyl-dihydroxypyrimidine-carboxamides were discovered in our laboratories as a novel and metabolically stable class of agents that exhibits potent inhibition of the HIV integrase strand transfer step. Further efforts led to very potent compounds based on the structurally related N-Me pyrimidone scaffold. One of the more interesting compounds in this series is the 2-N-Me-morpholino derivative 27a, which shows a CIC95 of 65 nM in the cell in the presence of serum. The compound has favorable pharmacokinetic properties in three preclinical species and shows no liabilities in several counterscreening assays.