title: Synthesis, local anaesthetic and antiarrhythmic activities of N-alkyl derivatives of proline anilides.
abstract: We describe here the design, synthesis and evaluation of in vivo local anaesthetic and antiarrhythmic activities of a series of N-alkylproline anilides. Most of the compounds demonstrated surface anaesthetic activity higher than that of lidocaine, ropivacaine and bupivacaine. We established that the local anaesthetic activity was sensitive to structural variations in the substitution pattern at the aromatic ring and the type of alkyl group at the proline nitrogen atom. Some of the prepared N-alkylproline anilides possessed significant antiarrhythmic activity with higher therapeutic indexes than the reference drugs.
authors.affiliation: Perm State Pharmaceutical Academy, 2 Polevaya Street, Perm 614990, Russian Federation.
authors.forename: Dmitrii V
authors.initials: DV
authors.lastname: Kalinin
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Pantsurkin
authors.forename: Boris Ya
authors.initials: BY
authors.lastname: Syropyatov
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Kalinina
authors.forename: Irina P
authors.initials: IP
authors.lastname: Rudakova
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Vakhrin
authors.forename: Anton V
authors.initials: AV
authors.lastname: Dolzhenko
mesh_terms: D000473:Alkanes / Q000737:chemistry; D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control; D001767:Blinking / Q000187:drug effects; D002045:Bupivacaine / Q000737:chemistry / Q000494:pharmacology; D002122:Calcium Chloride; D004558:Electric Stimulation; D008012:Lidocaine / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D011392:Proline / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D016896:Treatment Outcome
chemical_list: D000473:Alkanes; D000577:Amides; D000779:Anesthetics, Local; D000813:Anilides; D000889:Anti-Arrhythmia Agents; D000077212:Ropivacaine; D008012:Lidocaine; D011392:Proline; D002122:Calcium Chloride; D002045:Bupivacaine