Selective Inhibitors of Monoamine Oxidase. 3. Structure−Activity Relationship of Tricyclics Bearing Imidazoline, Oxadiazole, or Tetrazole Groups

Abstract

Inhibition of monoamine oxidase A (MAO A) is believed to cause antidepressant and possibly antianxiety effects. The previous paper had developed structure-activity relationships (SAR) for in vitro MAO A inhibition by tricyclic N-arylamides. It is shown in this paper that the same in vitro SAR can be carried over to tricyclics whose potentially toxic amide function is replaced by an appropriately substituted imidazoline, a 1,2,4- or 1,3,4-oxadiazole, or an alkylated tetrazole moiety. Dialysis of the inhibitor from the enzyme was used as a measure of reversibility which correlates with a low ability to cause a blood pressure rise with ingested tyramine ("cheese effect").

Synthesis and Local Anesthetic Activity of Some Novel N‐[5‐(4‐Substituted)phenyl‐1,3,4‐oxadiazol‐2‐yl]‐2‐(Substituted)‐Acetamides

“…IR data also confirm the presence of specific functional groups present in the final synthesized compounds. In 13 C-NMR spectra, C-2 and C-5 of the oxadiazole nucleus were seen around 171 and 168 ppm, respectively. The chemical shift of all other carbons of final compounds was seen as expected.…”

“…The structures of the title compounds were elucidated on the basis of elemental analysis, IR, 13 C-NMR, and mass spectral data. The rationale for using 13 C-NMR rather than 1 H-NMR spectroscopy for characterization of compounds is that the nucleus of the title compounds, i. e. oxadiazole does not possess any proton(s), thus to confirm the formation of nucleus, 13 C-NMR is more essential than 1 H-NMR spectroscopy. IR data of the synthesized oxadiazole analogues clearly show C=N stretching and C -O absorption bands around 1660 cm -1 and around 1090 cm -1 , respectively, which indicates ring closure of 1,3,4-oxadiazole ring.…”

“…1,3,4-Oxadiazoles are well known for their variety of biological activities including anti-inflammatory [6 -8], hypoglycemic [9,10], anticonvulsant [11,12], anti-anxiety and antidepressant [13] activities.…”

Green Approach Towards Synthesis of 3-Substituted-5-Carbonylmetyl-1,2,4-Oxadiazoles Without Any Solvent and Catalyst via Transamidoximation.

“…The construction of new heterocyclic scaffold derivatives which illustrate pharmacological and biological significance stands for a most important assignment in synthetic and medicinal chemistry. 1,2,4-Oxadiazoles are amazing classes of N-heterocyclic compounds showing their broad spectrum of valuable promising biological activities, such as muscarinic agonists, 4 serotoninergic (5-HT3) antagonists, 5 benzodiazepine receptor agonists, 6 dopamine ligands, 7 inhibitors of monoamine oxidase, 8 sphingosine-1-phosphate-1 (S1P 1 ) receptor agonist 9 can say that 1,2,4-oxaziazole core unit have been explored in past years. 1,2,4-Oxadiazoles have often been used as hydrolysis-resisting bioisosteric replacements for esters and amides 10 and as dipeptide mimetics 11 Bearing in mind the noteworthy relevancies in the fields of medicinal, biological and synthetic organic chemistry, there has been marvelous curiosity in developing efficient procedures for the synthesis of 1,2,4-oxadiazoles and quite number of synthetic procedures have been accounted in the literature for the synthesis of 1,2,4-oxadiazoles derivatives, which include the reaction of amidoxime with activated carboxylic acid derivatives such as acid chlorides, 12 fluorides, 13 anhydrides (BOP-Cl), 14 or active esters 15 using coupling reagents like, DCC, 16 DIC/HOBt, 17 TBTU, 18 CDI.…”

Synthesis of Schiff bases of 2-amino-5-aryl-1, 3, 4-oxadiazoles and their evaluation for antimicrobial activities

“…These include anti-inflammatory (Omar et al, 1996;Palaska et al, 2002;Ramalingum and Sattur, 1990;Raman et al, 1993), hypoglycemic (Girges, 1994;Husain et al, 1986), antianxiety and antidepressant (Harfenist et al, 1996), and antimitotic (Rai and Linganna, 2000) activities. In addition to these, a number of researchers have reported antimicrobial activities (Giri et al, 1976;Mir et al, 1971;Mishra, 1983;Sahin et al, 2002;Singh and Yadav, 1976).…”