81015-02-3

Upstream product

• 874-90-8 4-methoxybenzonitrile 
• 51517-88-5 5-(4-hydroxyphenyl)-1H-1,2,3,4-tetrazole 
• 616-38-6 carbonic acid dimethyl ester 
• 3424-93-9 4-methoxyphenylacetamide 
• 43131-50-6 methyl 4-(2-methyl-2H-tetrazol-5-yl)phenyl ether 

Downstream Products

• 1433892-83-1 tert-butyl 4-(3-(4-(2-methyl-2H-tetrazol-5-yl)phenoxy)-2-oxopyrrolidin-1-yl)piperidin-1-carboxylate 
• 1262107-94-7 2-methyl-5-{4-[(3-(3-nitrophenyl)-5-isoxazolyl)methoxy]phenyl}-2H-tetrazole 
• 1262107-98-1 2-methyl-5-{4-[(3-(4-nitrophenyl)-5-isoxazolyl)methoxy]phenyl}-2H-tetrazole 
• 1027529-98-1 toluene-4-sulfonic acid 3-methyl-5-[4-(2-methyl-2H-tetrazol-5-yl)-phenoxy]-pentyl ester 

Relevant academic research and scientific papers

An Environmentally Friendly Method for N-Methylation of 5-Substituted 1H-Tetrazoles with a Green Methylating Reagent: Dimethyl Carbonate

An environmentally friendly method was established for the N-methylation of the 5-substituted 1H-tetrazoles with a green reagent: DMC. DABCO was the optimal catalyst, and hazardous chemicals were avoided in this protocol. A plausible catalytic mechanism is proposed, which consists of a DABCO-activated process and a thermally induced rearrangement of tetrazole carbamates.

Design, synthesis, and antipicornavirus activity of 1-[5-(4-arylphenoxy) alkyl]-3-pyridin-4-ylimidazolidin-2-one derivatives

A series of pyridylimidazolidinone derivatives was synthesized and tested in vitro against enterovirus 71 (EV71). On the basis of compound 33 (DBPR103), introduction of a methyl group at the 2- or 3-position of the linker between the imidazolidinone and the biphenyl resulted in markedly improved antiviral activity toward EV71 with IC50 values of 5.0 nM (24b) and 9.3 nM (14a), respectively. Increasing the branched chain to propyl resulted in a progressive decrease in activity, while inserting different heteroatoms entirely rendered the compound only weakly active. The introduction of a bulky group (cyclohexyl, phenyl, or benzyl) led to loss of activity against EV71. The 4-chlorophenyl moiety in 14a was replaced with bioisosteric groups such as oxadiazole (28a-d) or tetrazole (32a,b), dramatically improving anti-EV71 activity and selectivity indices. Compounds 14a, 24b, 28b, 28d, and 32a exhibited a strong activity against lethal EV71, and no apparent cellular toxicity was observed. Three of the more potent imidazolidinone compounds, 14a, 28b, and 32b, were subjected to a large group of picornaviruses to determine their spectrum of antiviral activity.

Progress in the proxifan class: heterocyclic congeners as novel potent and selective histamine H3-receptor antagonists

Histamine H3 receptors are critically involved in the pathophysiology of several disorders of the central nervous system (CNS). Among other families of H3-receptor ligands, the proxifan class has recently been described to contain numerous potent histamine H3-receptor antagonists, e.g. ciproxifan or imoproxifan. In the present study, we report on the design of novel heterocyclic proxifan analogues and their antagonist potencies at histamine H3 receptors. The new compounds were tested for in vitro and in vivo H3-receptor antagonist potencies in different species as well as for H3-receptor selectivity vs. H1 and H2 receptors. In vitro, all compounds investigated proved to be potent H3-receptor antagonists in the rat as well as in the guinea-pig. In addition, they showed good to high oral CNS potency in vivo in mice. Especially, oxadiazole derivatives 24-26 displayed nanomolar antagonist activity in vitro and high potency in vivo (ED50=0.47-0.57 mg/kg). The results show that the additional heteroaromatic moieties might act as bioisosteres of the ketone or oxime moieties of ciproxifan or imoproxifan, respectively, and might cause divergent pharmacokinetic properties. Thus, these novel H3-receptor antagonists are interesting leads for further development. Copyright

Phenoxy- and phenoxyalkyl-piperidines as antiviral agents

Compounds of the formula STR1 wherein R1 is selected from STR2 Y is a bond or lower alkylene; R2 and R3 are independently hydrogen, lower-alkyl or halogen; R4 is STR3 R5 is hydrogen, lower-alkyl or halogen; R6 is hydrogen, lower-alkyl or halogen; R7 is hydrogen or lower-alkyl; R8 is hydrogen, lower-alkyl, or trifluoromethyl; R9 is lower-alkyl; R10 is lower-alkyl, trifluoromethyl or difluoromethyl; or pharmaceutically acceptable acid addition salts thereof are useful as antiviral agents.