Synthesis of some conformationally restricted analogs of fentanyl

Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure-analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues

“…The ED 50 values were measured in all analogues and the LD 50 value only for acetylfentanyl (12). The analgesic activities of all of these compounds were lower than fentanyl, but higher than morphine.…”

“…Fentanyl analogues with a methyl group (e.g., α-methyl, 3-methyl, p-methyl, n-butyryl, and isobutyryl) were synthesized in accordance with previous reports [6,7,[10][11][12][13][14][15].…”

“…For determination of ED 50 and LD 50 values, ddy-mice (weight 23-26 g) were orally administered a dilute sample solution of a fentanyl analogue and 0.1 ml of acetic acid per 10 g body weight was given intraperitoneally [10][11][12][13][14][15]. The number of writhing episodes after 5 min up to 15 min was counted, and the results were compared with those from control animals that received 0.9% NaCl instead of the dilute fentanyl analogue.…”

“…These compounds had high potential for abuse, because of their ease of synthesis and high analgesic activity. The structures of fentanyl (1) and 11 synthesized analogues (2-12) examined in this study are shown in Tables 1-4. Although there are a number of reports regarding the analgesic activities of some of these analogues [8][9][10][11][12][13][14][15], there have been only a few reports on the actually abused analogues [8]; there have been no reports on α-methylfentanyl (2), the most widely abused analogue. Furthermore, comparison of their analgesic activities with those of morphine and fentanyl was not described.…”

γ-Carbolines and their hydrogenated derivatives. 2.* Hydrogenated derivatives of γ-carbolines: methods of synthesis (review)

“…Here the obtained compounds are configurationally uniform and represent a racemic mixture of the two possible cis isomers. By using NaBH 3 CN instead of NaBH 4 it is possible to avoid the formation of the N-alkyl-substituted compounds completely [126][127][128], while the stereoselectivity here remains the same as before.…”