Details

Autor(en) / Beteiligte

• Lednicer, Daniel
• Von Voigtlander, Philip F
• Emmert, D. Edward

Titel

4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

Ist Teil von

• Journal of medicinal chemistry, 1980-04, Vol.23 (4), p.424-430

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

1980

Quelle

MEDLINE

Beschreibungen/Notizen

• Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.