N-Phenyl-N'-pyridinylureas as anticonvulsant agents

Abstract

A series of N-phenyl-N'-pyridinylureas was examined for anticonvulsant activity. Extensive structure/activity investigations revealed optimal activity in the N-(2,6-disubstituted-phenyl)-N'-(4-pyridinyl)urea series, with 37 exhibiting the best overall anticonvulsant profile. Compound 37 was effective against seizures induced by maximal electroshock but did not protect mice from clonic seizures produced by the convulsant pentylenetetrazol. The overall pharmacological profile suggests that 37 would be of therapeutic use in the treatment of generalized tonic-clonic and partial seizures. Compound 37 was selected for Phase 1 clinical trials.

Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants

“…55 While this class of compounds has been described to promote cell growth and differentiation in plants, 54 initially anticonvulsant activity was observed with N- (2,6-dimethyl-phenyl)-N'-(4-pyridinyl)-urea. To achieve an improvement in potency as well as greater separation between the protection doses and those exhibiting undesirable behavioral side effects, the researchers examined some structural modifications by varying the substituents on the phenyl ring as is shown in Table XVII.…”

Activity of Amidine-containing Diphenylureas Against P. falciparum

“…Monoamidine-containing diphenylureas 4a -4d were synthesized as outlined in Scheme 1. Commercially available 4-phenoxy anilines 2a -2d were reacted with equimolar 4-cyanophenyl isocyanate in dry THF at reflux for 6 hr to give the corresponding 1-(4-cyanophenyl)-3-(4-phenoxyphenyl)ureas 3a -3d [10]. Yields in this reaction were excellent (89% or greater).…”

Phosgene-free synthesis of N-aryl-N'-4-pyridinylureas via selenium-catalyzed oxidative carbonylation of 4-aminopyridine with aromatic amines

“…Many of them exhibit distinguished biological activities, and they are frequently employed as antibacterial agents, 1 anticonvulsant drugs, 2,3 plant cytokinins, 4,5 and Rho kinase inhibitors ( Figure 1). 6 In addition, these compounds can also be used as thermal latent initiators on ring-opening polymerization of epoxides in the production of epoxy resins.…”