Phenylpiperidine class

Figure 7.5 Chemical structures of the phenylpiperidine class of opioids. several days for normal neurological functions to return.

The dopamine D2 agonist SAR area has been reviewed by Hacksell and coworkers from the perspective of stereochemistry and pharmacological profiles of the enantiomers of the compounds synthesized by that research group during a period of 10 years. The structural classes surveyed were 3-phenylpiperidines, 2-aminotetralins and their ring-methylated analogues and octahydrobenzo[/]quinolines (OHB[f]Qs) [60]. 

PHENYLPIPERIDINES, PYRROLIDINES AND RELATED COMPOUNDS ACYCLIC AND MISCELLANEOUS CLASSES ANTAGONISTS OF ANALGESICS... 

Chemical Class Opiate derivative phenylpiperidine derivative DEA Class Schedule II... 

The first agent of this class to be introduced in the clinic, haloperidol (18-8), interestingly shares the 4-phenylpiperidine structural fragment found in the central analgesic agent meperidine and its derivatives (see Chapter 7). The former compound may well have been discovered in the course of further SAR studies on the opiate [20]. An unusual synthesis of haloperidol starts with the product (18-1) from Friedel-Crafts acylation of 4-fluorobenzene with succinic anhydride. Successive protection of the... 

In spite of the SAR discrepancies between the fentanyl and pethidine groups so far noted, the agonist (albeit weak) rather than antagonist activities of N-allyl and 3,3-dimethylallyl analogs (MHP potencies fentanyl, 470 N-allyl, 0.4 N-dimethylallyl, 0.5 pethidine l)(18)poiht to a closer relationship of the anilide group with the 4-phenylpiperidine than the morphine class of analgesic. 

Analgesics of the 4-arylpiperidine class mimic the geometry of a large portion of morphine when in the axial phenyl chair conformation 33a and were thus earlier believed capable of accommodation at the proposed receptor. This view later fell into disrepute as a result of conformational considerations and particularly the radically different structure-activity relationships in regard to N-substituents and the influence of phenolic hydroxyl between the 4-arylpiperidine and morphine groups. There is evidence that reversed esters of pethidine and other 4-phenylpiperidines with C-4 oxygen functions bind in the equatorial 4-phenyl chair conformation 33b, and receptor modifications necessary to allow uptake of both ax and eq 4-phenyl chairs are discussed... 

Chemical/Pharmaceutical/Other Class Synthetic opioid analgesic a phenylpiperidine derivative... 

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