1‐N‐Substituted Thiocarbamoyl‐3‐phenyl‐5‐thienyl‐2‐pyrazolines: Synthesis and Evaluation as MAO Inhibitors

Abstract

Twelve new 1-N-substituted thiocarbomoyl-3-phenyl-5-thienyl-2-pyrazoline derivatives were synthesized and evaluated their for antidepressant, anxiogenic and mammalian monoamine oxidase (MAO)-A and Binhibitory activities by in vivo and in vitro tests. MAO was isolated and purified from the mitochondrial pellet of bovine liver homogenates and human platelets. All of the new compounds inhibited the total MAO activity of liver homogenates and the inhibition was found to be time-dependent. Four compounds (3 i-3 l) inhibited MAO-B selectively and irreversibly in a classical non-competitive manner with IC(50) values in the range of 22.00-91.50 microM. The rest of the compounds appeared to be non-selective reversible inhibitors. It was suggested that the p-methoxy group on the phenyl ring in the compounds increased the inhibitory effect and selectivity toward MAO-B. The reversible and unselective inhibition of MAO by the remaining compounds was suggested to be related to their properties of acting ability to act as both as substrate and inhibitor at the same time. However, none of the novel compounds showed antidepressant activity as expected suggesting formation of inactive metabolites. We conclude that the compounds appeared as which functioned as selective MAO-B inhibitors might have promising features as therapeutic properties in the treatment of Parkinson disease. In vivo studies are needed to verify this hypothesis.

Evaluation of antidepressant-like effect of 2-pyrazoline derivatives

“…The MAO inhibitors which have hydrazine and amine moiety such as isocarboxazid (Shader and Greenblatt, 1999), phenelzine (Urichuk, et al, 2000), and moclobemide (Ferigolo et al, 1998) show prominent antidepressant activity in animals and man. The antidepressant activity of 1-N-substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines was found to be similar to those of MAO inhibitors (Gökhan et al, 2003). Additionally, it has been shown that 1,3,5-triphenyl-2-pyrazolines (Prasad et al, 2005), 1-thiocarbamoyl-3,5-diphenyl-2-pyrazolines (Bilgin et al, 1993), bicyclic pyrazoline 8-thiocarbamoyl-7,8-diazabicyclo[4.3.0]non-6-ene derivatives (Palaska et al, 1996), and 3,5-difenil-2-pirazolines (Palaska et al, 2001) have antidepressant activity in forced swimming test.…”

Synthetic Studies on Erythromycin Derivatives: Reactivity of the C12-21 Alkene

“…NMR spectral analysis of compound 6 demonstrated that the regiochemical preference of the electron-withdrawing substitutent is toward to the N-portion of the dipole [6,7], affording a C-12-∆ 1 -pyrazoline derivative. Since pyrazoline derivatives have been demonstrated to possess many different biologically activities [8,9], compound 6 might be an intermediate from which active antibiotics could be made. …”

Characteristics Of The GC-MS Mass Spectra Of Terpenoids (C10H16)

“…However, pyrazolines are still least explored compounds for anticonvulsant profile even, their function is quite stable [14]. In view of this and our continued interest in the synthesis of bioactive heterocyclic compounds with a stable fragment, it was thought of interest to synthesize some new pyrazolines starting from chalcone and semicarbazide [15].…”