Synthesis and pharmacological evaluation of perhydropyrrolo [3,4-c]pyridine derivatives.
Several N,N'-bis-alkyl-perhydropyrrolo[3,4-c]pyridines 4 and the corresponding bis-quaternary derivatives 5 have been prepared through standard methods starting from the bicyclic dilactam 2. Compounds 4 and 5 were evaluated for their inhibitory properties against acetylcholine (ACh), 1,1-dimethylphenyl piperazinium iodide (DMPP), 5-hydroxytryptamine (5-HT) and histamine (H1), and the guinea pig isolated ileum. Pharmacological data indicated that the strongest anticholinergic activity was shown by the dibenzyl amine 4 g, which among the tested molecules presented also a rather potent effect at the ganglia level, resulting about three times more potent than hexamethonium as ganglionic blocking agent. The preliminary SAR coming from the analysis of the pharmacological results are presented and discussed.
Altomare
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Dipartimento Farmaco-Chimico, Università di Bari, Italy.
Carotti
A
A
Casini
G
G
Cellamare
S
S
Ferappi
M
M
Brigiani
G S
GS
Persichella
M
M
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004246:Dimethylphenylpiperazinium Iodide / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000138:chemical synthesis; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; D011725:Pyridines; D011758:Pyrroles; D012702:Serotonin Antagonists; D004246:Dimethylphenylpiperazinium Iodide; D000109:Acetylcholine