4-aryl-4-aminocyclohexanones and their derivatives, a novel class of analgesics. 3. m-Hydroxyphenyl derivates.
Derivatives of 4-aryl-4-(dimethylamino)cyclohexan-1-ones substituted by m-hydroxy groups were obtained by using as a key reaction the displacement of cyanide from the alpha-aminonitrile of 1,4-cyclohexanedione ketal, with the THP ether of m-hydroxyphenylmagnesium bromide. A number of the products show narcotic antagonist activity. Amino alcohols obtained on reaction of the free ketones with phenethyl Grignard reagents are potent analgetics, though devoid of antagonist activity. Systematic variation of the substituent on nitrogen revealed nonclassical structure-activity relationships; the dimethylamino group gives the most potent antagonist.
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D003510:Cyclohexanes / Q000138:chemical synthesis*; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D051379:Mice; D013329:Structure-Activity Relationship
D000700:Analgesics; D003510:Cyclohexanes; D003512:Cyclohexanones