Synthesis of New 2-(Aminomethyl)-4-phenylpyrrolo[1,2-a]-quinoxalines and their Preliminary In-vivo Central Dopamine Antagonist Activity Evaluation in Mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Pharmacy and Pharmacology Année : 2000

Synthesis of New 2-(Aminomethyl)-4-phenylpyrrolo[1,2-a]-quinoxalines and their Preliminary In-vivo Central Dopamine Antagonist Activity Evaluation in Mice

J Guillon
  • Fonction : Auteur
M Boulouard
  • Fonction : Auteur
V Lisowski
  • Fonction : Auteur
S Stiebing
  • Fonction : Auteur
V Lelong
  • Fonction : Auteur
S Rault
  • Fonction : Auteur

Résumé

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-phenylpyr-rolo[1,2-a]quinoxalinium oxalate (3a), 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3b), 2-[4-(3-trinuoromethylphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[l,2-a]quinoxalinium oxalate (3c), 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3d), 2-(4-pyridin-2-ylpiper-azin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3e), and 2-(4-phenyl-1,2,3,6-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.

Domaines

Chimie

Dates et versions

hal-03970210 , version 1 (02-02-2023)

Identifiants

Citer

J Guillon, M Boulouard, V Lisowski, S Stiebing, V Lelong, et al.. Synthesis of New 2-(Aminomethyl)-4-phenylpyrrolo[1,2-a]-quinoxalines and their Preliminary In-vivo Central Dopamine Antagonist Activity Evaluation in Mice. Journal of Pharmacy and Pharmacology, 2000, 52 (11), pp.1369-1375. ⟨10.1211/0022357001777522⟩. ⟨hal-03970210⟩
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