Synthesis and Monoamine Oxidase Inhibitory Activities of some 3-(4-Fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide Derivatives

Abstract

28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The derivatives substituted by halogen on the fifth position of pyrazole ring, inhibited MAO-A enzyme with a high selectivity index. On the other hand, compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate selectivity index. Docking studies were done to highlight the interactions of the most active derivative with the active site of MAO-A. In addition, in vivo antidepressant and anxiolytic activities of the compounds having selective MAO-A inhibitory effects, were investigated by using Porsolt forced swimming and elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.

3-(3,4-Dimethoxyphenyl)-5-(2-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole

“…The uniqueness of their properties makes fluorinated organic compounds an interesting option to synthesize and evaluate their pharmacological effects [3]. Some fluorinated compounds (e.g., fluorinated pyrazolines) have been reported for their significant biological activities, such as antibacterial, antifungal, antitubercular [2], anticancer [4], antiproliferative [5], and monoamine oxidase inhibitory activities [6]. Generally, these compounds are prepared from substituted acetophenones and benzaldehydes via two-step reactions.…”

1,3,5-triaril-4,5-dihidro-1h-pirazol türevi bazı bileşiklerin benzodiazepin reseptörleri aracılıklı anksiyolitik-benzeri etkileri

“…Bu yapıya sahip bileşiklerin santral sinir sitemine geçerek önemli farmakolojik aktiviteler gösterdikleri çok kez rapor edilmiştir. Bunlardan en dikkat çekici olanlar söz konusu bileşiklerin antidepresan [17][18][19][20][21][22][23][24] , antikonvülzan 22,[25][26][27] , nöroprotektif [28][29][30] ve anksiyolitik 18,20 etkilerinin bildirildiği çalışmalardır. Bazı 4,5-dihidro-1H-pirazol türevlerinin antinosiseptif etkilerini de santral mekanizmalar ile ilişkilendiren çalışmalara rastlamak mümkündür 6,8,10,31 .…”