73941-29-4

Usage

InChI:InChI=1/C8H11NO2.ClH/c9-11-7-6-10-8-4-2-1-3-5-8;/h1-5H,6-7,9H2;1H

Upstream product

• 122-99-6 2-Phenoxyethanol 
• 589-10-6 phenoxyethyl bromide 
• 338406-38-5 N-(2-phenoxyethoxy)phthalimide 
• 622-86-6 2-chloroethoxybenzene 

Downstream Products

• 191472-00-1 C₁₇H₂₄N₂O₄S₂ 
• 41776-67-4 3-[(2-phenoxy-ethoxyimino)-methyl]-rifamycin 
• 191472-69-2 5-Isopropyl-6-methanesulfonyl-1-(2-phenoxy-ethoxy)-1H-pyrimidine-2,4-dione 
• 191472-43-2 5-Isopropyl-6-methylsulfanyl-1-(2-phenoxy-ethoxy)-1H-pyrimidine-2,4-dione 

Relevant academic research and scientific papers

A new supported reagent for the parallel synthesis of primary and secondary O-alkyl hydroxylamines through a base-catalyzed Mitsunobu reaction

The growing field of applications of O-alkyl hydroxylamines in medicinal chemistry and chemical biology has motivated the search for a parallel synthesis. A solid-phase approach based on the alkylation by alcohols of a new supported N-hydroxyphthalimide reagent using a Mitsunobu reaction followed by methylaminolysis has been optimized. This study points out the importance of the linker and a specific base effect for the Mitsunobu reaction. A large variety of alcohols can be used to give with moderate to high yields diverse O-alkyl hydroxylamines in high purity.

Synthesis and anti-HIV-1 activity of a series of 1-alkoxy-5-alkyl-6- (arylthio)uracils

A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl- 3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio)acryloyl)ureas (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing a catalytic amount of p-TsOH produced 1-alkoxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5- positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-1 activity (EC50: 6-((3,5- dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 μM; 6-((3,5- dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 μM). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.