SAR of Diphenyl Heptanone (Methadone Series)

SAR of Diphenyl Heptanone (Methadone Series)

• The reduction of keto and acetylation of resulting hydroxyl group gives the acetyl methadol, the useful anti-diarrhoeal opioids, for example, diphenoxylate and loperamide.

• Removal of any of the phenyl group sharply decreases the activity.

• Placement of m-hydroxy group in the phenyl ring decreases analgesic activity.

• The levo-isomer of methadone and isomethadone are twice as effective as their racemic mixture.

• Substitution of terminal dimethylamino group by piperidine group decreases activity.

• Substitution of propionyl group by hydrogen, hydroxyl or acetoxyl decreases the activity, whereas amide analogue, pyrrolidinoyl and terminal morpholino moiety enhance the activity by several time.