Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.

A simple and efficient method for the preparation of secondary N-alkylarylamines via reductive amination of ketones with primary aromatic amines using activated zinc/acetic acid is described. It requires only equimolar amounts of the starting compounds and affords good yields of the corresponding amines (50-90%). It is not applicable to aldehydes nor aliphatic amines.

A simplified, one-pot preparation of 16-dehydropregnenolone acetate (4) from diosgenin (1) using normal pressure and a much reduced temperature compared to known procedure was developed in an overall yield varied from 65 to 69 %. The method lends itself very well to industrial scale methodology.

Phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent result in the formation of α,β-unsaturated carboxylic acids. The reaction was performed at room temperature for 24 h. The corresponding conjugated acids were obtained from cyclic or aromatic ketones, whereas bromo acids were obtained from 4-oxo-piperidine-1-carboxylic acid ethyl ester (13) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14).