Sinteza 2-(1H-indol-3-il)acetil-N-(supstituiranih fenil)hidrazinkarbotioamida i srodnih heterocikličkih spojeva te procjena njihovog antikonvulzivnog djelovanja i toksičnosti

A series of new 5-(1H-indol-3-yl)methyl-4-(substituted aryl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (4a-g), 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-oxadiazol-2-amines (5a-g) and 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-thiadiazol-2-amines (6a-g) were prepared by treating 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine carbothioamides (3a-g) with suitable reagents. All the newly synthesized compounds were screened for their anticonvulsant activity in the MES model and were compared with the standard drugs phenytoin sodium and carbamazepine. Out of the twenty-one compounds studied, 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d and 6e showed comparable MES activity to phenytoin and carbamazepine after 0.5 h. Compound 5b showed to be more potent than carbamazepine after 4 h. Compounds 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f and 6g showed lower neurotoxicity than phenytoin.Reakcijom 2-(1H-indol-3-il)acetil-N-(supstituiranih fenil)hidrazinkarbotioamida (3a-g) s odgovarajućim reaktantom sintetizirana je serija novih 5-(1H-indol-3-il)metil-4-(supstituiranih aril)-2,4-dihidro-3H-1,2,4-triazol-3-tiona (4a-g), 5-(1H-indol-3-yl)metil-N-(supstituiranih aril)-1,3,4-oksadiazol-2-amina (5a-g) i 5-(1H-indol-3-il)metil-N-(supstituiranih aril)-1,3,4-tiadiazol-2-amina (6a-g). Ispitano je antikonvulzivno djelovanje sintetiziranih spojeva na MES modelu i uspoređeno s djelovanjem fenitoin natrija i karbamazepina. Spojevi 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d i 6e pokazali su MES djelovanje usporedivo s djelovanjem fenitoina i karbamazepina nakon 0,5 h, dok je spoj 5b nakon 4 sata imao snažnije djelovanje od karbamazepina. Osim toga, spojevi 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f i 6g su manje neurotoksični od fenitoina

4-[(E)-2,6-Dichloro­benzyl­ideneamino]-3-{1-[4-(2-methyl­prop­yl)phen­yl]eth­yl}-1H-1,2,4-triazole-5(4H)-thione

In the title Schiff base compound, C21H22Cl2N4S, the triazole ring makes dihedral angles of 2.15 (11) and 87.48 (11)° with the 2,6-dichloro­phenyl and methyl­propyl­phenyl rings, respectively. Weak intra­molecular C—H⋯S and C—H⋯Cl inter­actions generate S(6) and S(5) ring motifs, respectively. In the crystal structure, centrosymmetrically related mol­ecules are linked into dimers by N—H⋯S hydrogen bonds. These dimers are arranged into sheets parallel to the ab plane and are stacked along the c axis. C—H⋯π inter­actions involving the methyl­propyl­phenyl ring and π–π inter­actions involving the dichloro­phenyl ring [centroid–centroid distance = 3.5865 (3) Å] are also observed

Arylhydrazone derivatives of naproxen as new analgesic and anti-inflammatory agents: Design, synthesis and molecular docking studies

A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)-N�-(pyridine-4-yl)methylenepropanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)-N�-4-nitrobenzylidenepropanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (RCOX-2/COX-1 = 1.94) and higher affinity rather than naproxen in COX-2 active site (RCOX-2/naproxen=1.28). Moreover, the structural analyses confirmed that the E-ap rotamer is the preferred structure for the arylidenehydrazone derivatives. © 2016 Elsevier Inc

Design, synthesis, and preliminary pharmacological evaluation of novel thiazolidinone derivatives as potential benzodiazepine agonists

Abstract: Thiazolidinones are well-known heterocycles that demonstrate promising biological effects such as anticonvulsant activity. Hybridization of these chemicals with scaffold, which has necessary pharmacophores for binding to the benzodiazepine receptors, can prompt a novel structure possessing extensive anticonvulsant effects. In this study, novel derivatives of thiazolidinone as new benzodiazepine agonists were designed, synthesized, and biologically evaluated. Compound 5h, 4-chloro-2-(2-fluorophenoxy)-N-(4-oxo-2-(p-tolyl)thiazolidin-3-yl)benzamide, exhibited considerable anticonvulsant activity, proper sedative�hypnotic effect, no memory impairment, and no muscle relaxant effect. The pharmacological effects of the designed compounds were antagonized by flumazenil, which confirmed the benzodiazepine receptors� involvement in their biological effects. Based on in silico calculations of ADME properties of our novel compounds, they could be active oral agents potentially. Graphic abstract: In this study, we designed novel structures by the hybridization of thiazolidinone moiety with scaffold which has necessary pharmacophores for binding to the benzodiazepine receptors. The results are very promising for developing new lead compounds as benzodiazepine agonists possess anticonvulsant effects.Figure not available: see fulltext.. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature