1-N-substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines: synthesis and evaluation as MAO inhibitors. 2003

Nesrin Gökhan, and Akgül Yeşilada, and Gülberk Uçar, and Kevser Erol, and A Altan Bilgin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. nesringokhan@hotmail.com

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.

UI MeSH Term Description Entries
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008996 Monoamine Oxidase Inhibitors A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414) MAO Inhibitor,MAO Inhibitors,Reversible Inhibitors of Monoamine Oxidase,Monoamine Oxidase Inhibitor,RIMA (Reversible Inhibitor of Monoamine Oxidase A),Reversible Inhibitor of Monoamine Oxidase,Inhibitor, MAO,Inhibitor, Monoamine Oxidase,Inhibitors, MAO,Inhibitors, Monoamine Oxidase
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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