title: Synthesis of new 2-(aminomethyl)-4-phenylpyrrolo[1,2-a]-quinoxalines and their preliminary in-vivo central dopamine antagonist activity evaluation in mice.
abstract: In the search for antipsychotic agents that are not associated with extrapyramidal side effects, efforts have been focused on finding selective D4-receptor antagonists and investigating their pharmacology. Our laboratory has developed a synthesis program for new pyrroloquinoxalines with therapeutic potential. We have described the synthesis of some new pyrroloquinoxalines with substituted arylpiperazino or aryltetrahydropyrido chain at position 3 of the quinoxaline ring (2-(4-phenylpiperazin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3a), 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3b), 2-[4-(3-trifluoromethylphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3c), 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3d), 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3e), and 2-(4-phenyl1,2,3,6-tetrahydropyridin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3f)). A preliminary pharmacological study of these products was conducted using climbing behaviour induced by apomorphine (2.5 mg kg(-1), s.c.) in mice. The derivatives were administered intraperitoneally 30 min before apomorphine. Haloperidol, chlorpromazine and clozapine were used as references. Among this series, 3b, 3c and 3f revealed a central dopamine antagonist activity. The most active derivative was 3b, which exhibited a profile relatively close to clozapine.
authors.affiliation: Synthéval, Caen, France.
authors.forename: J
authors.initials: J
authors.lastname: Guillon
authors.forename: M
authors.initials: M
authors.lastname: Boulouard
authors.forename: V
authors.initials: V
authors.lastname: Lisowski
authors.forename: S
authors.initials: S
authors.lastname: Stiebing
authors.forename: V
authors.initials: V
authors.lastname: Lelong
authors.forename: P
authors.initials: P
authors.lastname: Dallemagne
authors.forename: S
authors.initials: S
authors.lastname: Rault
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002490:Central Nervous System; D018492:Dopamine Antagonists / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011810:Quinoxalines; D011954:Receptors, Dopamine