Abstract: After systematic structural modification of 3-methylfentanyl derivatives; N-1-(β-hydroxy-β-phenylethyl)-3-methyl-4-piperidyl-N-phenyl propanamide (7302) was found to be the most potent analgesic agent in this series. There are three chiral centers in the 7302 molecule, so there are four diastereoisomeric pairs. In view of the high stereoselective recognition of opiate receptor to its ligands, we had separated the diastereoisomers of 7302 and of related compounds, cis-7303 and trans-7303, all as racemic pairs,by fractional crystallization. Pharmacological results showed that the configuration of the three chiralities in 7302 was very important for analgesic potency. The activity ratio for cis-A-7302/cis-B-7302 was 5.3; trans-A-7302/trans-B-7302 was about 2. Among the four diastereoisomers of, 7302, cis-A-7302 was the most potent compound with a potency 6000 times of morphine and 3 times of etorphine. Compound 7302 in our previous report⁽²⁾ was actually the purified form which we now designate as cis-A-7302.