519032-08-7

Usage

Uses

Used in Pharmaceutical Industry:
4-PYRIMIDINECARBOXYLIC ACID, 1,6-DIHYDRO-5-HYDROXY-2-[1-METHYL-1-[[(PHENYLMETHOXY)CARBONYL]AMINO]ETHYL]-6-OXO-, METHYL ESTER is used as an intermediate in the synthesis of HIV-integrase inhibitors for the development of antiretroviral drugs. These inhibitors play a vital role in suppressing the replication of the HIV virus, thus helping to manage and treat HIV/AIDS.
Used in Research and Development:
In the field of research and development, 4-PYRIMIDINECARBOXYLIC ACID, 1,6-DIHYDRO-5-HYDROXY-2-[1-METHYL-1-[[(PHENYLMETHOXY)CARBONYL]AMINO]ETHYL]-6-OXO-, METHYL ESTER serves as a valuable compound for studying the structure-activity relationships of HIV-integrase inhibitors. This knowledge can be applied to design and develop more potent and selective inhibitors, ultimately contributing to the advancement of HIV treatment options.

InChI:InChI=1/C17H19N3O6/c1-17(2,20-16(24)26-9-10-7-5-4-6-8-10)15-18-11(14(23)25-3)12(21)13(22)19-15/h4-8,21H,9H2,1-3H3,(H,20,24)(H,18,19,22)

Upstream product

• 518047-98-8 [1-(N'-hydroxycarbamimidoyl)-1-methyl-ethyl]carbamic acid benzyl ester 
• 762-42-5 dimethyl acetylenedicarboxylate 
• 1064707-10-3 C₁₈H₂₃N₃O₇ 
• 501-53-1 benzyl chloroformate 
• 100134-82-5 (cyano-dimethyl-methyl)carbamic acid benzyl ester 
• 518047-98-8 benzyl [2-amino-2-(hydroxyimino)-1,1-dimethylethyl]carbamate 
• 1064707-10-3 2-[(2-benzyloxycarbonylamino-2-methyl-propionimidoyl)-aminooxy]-but-2-enedioic acid dimethyl ester 

Downstream Products

• 518048-00-5 methyl 5-(benzoyloxy)-2-(1-{[(benzyloxy)carbonyl]amino}-1-methylethyl)-6-hydroxypyrimidine-4-carboxylate 
• 888504-27-6 2-(1-benzyloxycarbonylamino-1-methyl-ethyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid methyl ester 
• 1415000-05-3 C₂₃H₂₄N₄O₅ 
• 1415000-06-4 C₂₃H₂₃ClN₄O₅ 
• 1415000-07-5 C₂₄H₂₆N₄O₅ 
• 1415000-08-6 C₂₄H₂₃F₃N₄O₅ 
• 1415000-09-7 C₂₄H₂₆N₄O₆ 
• 1415000-10-0 C₂₆H₃₀N₄O₈ 
• 1415000-11-1 C₂₄H₂₅FN₄O₅ 
• 1415000-12-2 C₂₄H₂₆N₄O₅ 
• 1415000-13-3 benzyl 2-(4-(2-(1H-indol-2-yl)ethylcarbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-ylcarbamate 
• 1415000-17-7 C₁₆H₁₉N₅O₅ 
• 1415000-14-4 benzyl 2-(5-hydroxy-4-(2-methoxyethylcarbamoyl)-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-ylcarbamate 
• 1415000-15-5 benzyl 2-(5-hydroxy-4-(3-methoxypropylcarbamoyl)-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-ylcarbamate 

Relevant academic research and scientific papers

Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity

A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC50 values of 0.14 and 0.15 μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).

Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection

Human immunodeficiency virus type-1 (HIV-1) integrase is one of the three virally encoded enzymes required for replication and therefore a rational target for chemotherapeutic intervention in the treatment of HIV-1 infection. We report here the discovery of Raltegravir, the first HIV-integrase inhibitor approved by FDA for the treatment of HIV infection. It derives from the evolution of 5,6-dihydroxypyrimidine-4-carboxamides and N-methyl-4- hydroxypyrimidinone-carboxamides, which exhibited potent inhibition of the HIV-integrase catalyzed strand transfer process. Structural modifications on these molecules were made in order to maximize potency as HIV-integrase inhibitors against the wild type virus, a selection of mutants, and optimize the selectivity, pharmacokinetic, and metabolic profiles in preclinical species. The good profile of Raltegravir has enabled its progression toward the end of phase III clinical trials for the treatment of HIV-1 infection and culminated with the FDA approval as the first HIV-integrase inhibitor for the treatment of HIV-1 infection.

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.