The Preparation and Pharmacology of Some Phenolic Carbamates and Allophanates

Abstract A series of alkyl-substituted phenyl carbamates has been screened for analgesic activity by two methods and the ED50 of a representative number has been determined by one of them. An attempt has been made to correlate the analgesic activity with chemical constitution and the following points emerge: (i) at least one m-alkyl group is essential for significant activity, (ii) where only one substituent is present, maximal activity occurs when this is ethyl, (iii) two o-substituents abolish the activity, (iv) 2,4,5-trimethylphenyl carbamate (compound 686) possesses the highest activity, (v) the most active compounds are in general also the most toxic, compound 688 being a notable exception, (vi) o-substitution by a group larger than methyl tends to reduce activity, (vii) substitution on the carbamate N, except by hydroxyl, strongly reduces the activity. The toxicity of some of the compounds could not be attributed to their anticholinesterase activity.