Synthesis and biological activity of a series of aryl tropanyl esters and amides chemically related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester. Development of a 5-HT4 agonist endowed with potent antinociceptive activity.
A series of aryl tropanyl esters and amides related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester (ICS 205930, CAS 89565-68-4) were synthesized and evaluated for antinociceptive activity using the hot-plate test. Of these, the benzofurane-3-carboxylic ester of tropine (1) was found powerfully to increase the pain threshold, with a cholinergic mechanism of action. Despite the structural similarity with ICS 205930, the analgesia induced by 1 seems not to be due to 5-HT3 receptor interaction, and there is evidence of involvement of the central 5-HT4 receptor.
Romanelli
M N
MN
Ghelardini
C
C
Dei
S
S
Matucci
R
R
Mori
F
F
Scapecchi
S
S
Teodori
E
E
Bartolini
A
A
Galli
A
A
Giotti
A
A
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000077526:Tropisetron
D000700:Analgesics; D007211:Indoles; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D009270:Naloxone; D000077526:Tropisetron