Thiolupinine and some derivatives of pharmacological interest.
The (quinolizidin-1 alpha-yl)methanthiol (thiolupinine) was prepared and, utilizing the thiol group reactivity, several S-substituted derivatives were obtained among which was a group of 3-[(lupinylthio)methyl]indoles. Eight of the prepared compounds were subjected to a broad pharmacological screening that evidentiated for many of them good level of the following activities in vivo and in vitro: antiarrhythmic, local anesthetic, negative chronotropic on isolated atria, calcium antagonism on ileum and atria, inhibition of spontaneous contraction of isolated trachea, inhibition of guinea pig ileum contractions induced by angiotensin I and II, bradykinin and cholecystokinin, inhibition of platelet aggregation induced by PAF and ADP. Single compounds were remarkable for additional antagonistic activities: 4 against P1-purine receptor, 8 against substance P, 12 against methacholine and 13 strongly inhibited arachidonate induced platelet aggregation. Very peculiar was the ability of compound 6 to protect mice from PAF induced mortality.
Novelli
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Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Sparatore
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D000779:Anesthetics, Local / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D002491:Central Nervous System Agents; D004232:Diuretics; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D011807:Quinolizines; D018047:Receptors, Purinergic P1; C084215:thiolupinine