The most effective influence of 17-(3-ethoxypropyl) substituent on the binding affinity and the agonistic activity in KNT-127 derivatives, δ opioid receptor agonists

Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists

“…1), 14 and reported that these substitutions led to increased selectivities for the KOR or DOR, respectively, but decreased the binding affinities compared with the parent compounds. 10,15 The agonistic activities of 17-fluoroalkyl derivatives also decreased. 10,15 As our previous investigation dealt with agonists, we next attempted to apply these substitutions to DOR antagonist, naltrindole (NTI) 9,16 and compound 1.…”

“…10,15 The agonistic activities of 17-fluoroalkyl derivatives also decreased. 10,15 As our previous investigation dealt with agonists, we next attempted to apply these substitutions to DOR antagonist, naltrindole (NTI) 9,16 and compound 1. 17 Herein, we report the synthesis of derivatives of NTI and compound 1 with the 17-fluoroethyl and 17-alkyl substituents, which were of similar size to the introduced fluorinated ethyl groups.…”

“…10 Therefore, intense effort has been made to investigate 17-substituents, but only a few compounds possessing the 17-fluoroalkyl have been reported. We recently synthesized 17-fluoroalkyl derivatives of the selective KOR agonist nalfurafine ( Fig.…”

“…Such tendencies as mentioned above were observed with both nalfurafine and KNT-127 derivatives. 10,15 The tendencies obtained in nalfurafine and KNT-127 derivatives were explained from the viewpoint of the message-address concept. 9,16,19 In a similar way, these observations on 4c-e and 6c-e could be explained.…”

Delta opioid agonists: a concise update on potential therapeutic applications

“…179 Additional DOR agonists, for example conformationally constrained analogues of SNC-80, have been reported. 180 Mixed, bivalent, heteromeric and biased ligands These topics are beyond the scope of the present review, but they deserve mention and reference to recent reviews.…”