338406-38-5

Upstream product

• 524-38-9 N-hydroxyphthalimide 
• 122-99-6 2-Phenoxyethanol 
• 589-10-6 phenoxyethyl bromide 

Downstream Products

• 191472-43-2 5-Isopropyl-6-methylsulfanyl-1-(2-phenoxy-ethoxy)-1H-pyrimidine-2,4-dione 
• 191472-00-1 C₁₇H₂₄N₂O₄S₂ 
• 191472-69-2 5-Isopropyl-6-methanesulfonyl-1-(2-phenoxy-ethoxy)-1H-pyrimidine-2,4-dione 
• 5397-72-8 O-(2-phenoxy-ethyl)-hydroxylamine; hydrochloride 
• 1597430-53-9 C₁₇H₂₁N₃O₇ 
• 73941-29-4 O-(2-phenoxyethyl)hydroxylamine 

Relevant academic research and scientific papers

4-alkyloxyimino derivatives of uridine-5′-triphosphate: Distal modification of potent agonists as a strategy for molecular probes of P2Y 2, P2Y4, and P2Y6 receptors

Extended N4-(3-arylpropyl)oxy derivatives of uridine-5′-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N4-(3- phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N 4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N4-(3- arylpropyl)oxy group accessed a structurally permissive region on three G q-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.

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.