Ispitivanje antidepresivnog, sedativnog i analgetskog djelovanja novih fuzioniranih derivata tiofena

This study was aimed at the synthesis of fused benzothiophene derivatives containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea derivatives 2a,b. Cyclization of the latter products gave the annulated benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a series of heterocyclization reactions through the reaction with some chemical reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also, this work was extended to study the potential role of the novel synthesized thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg1 body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in the forced-swimming test. No compound showed sedative effect. Visceral pain evoked by i.p. injection of acetic acid in mice was significantly inhibited by all compounds at a high doses.U radu je opisana sinteza fuzioniranih derivata benzotiofena koji sadrže heterociklički ostatak bitan za farmakološko djelovanje. Tiourea derivati 2a,b dobiveni su reakcijom derivata tetrahidrobenzo[b]tiofena 1a,b s etoksikarbonilizotiocijanatom. Iz njih su dalje priređeni anulirani derivati benzo[b]tienopirimidina 3a,b. Spojevi 2a,b i 3a prevedeni su reakcijama heterociklizacije u benzo[b]tienopirimidine 5a,b-8a-c. Ispitivano je antidepresivno, sedativno i analgetsko djelovanje novosintetiziranih derivata tiouree 2a i benzo[b]tienopirimidina 3a, 5b, 6a i 8b u dvije doze (15 ili 30 mg kg1 tjelesne mase). Spojevi 2a, 3a i 5b pokazali su blago antidepresivno djelovanje u testu forsiranog plivanja, dok sedativni učinak nije pokazao niti jedan ispitivani spoj. Visceralna bol inducirana i.p. injekcijom octene kiseline u miševa značajno je inhibirana sa svim spojevima, ali u visokim dozama

The Reaction of Cyclopentanone with Cyanomethylene Reagents: Novel Synthesis of Pyrazole, Thiophene, and Pyridazine Derivatives

The reaction of cyclopentanone with either malononitrile or ethyl cyanoacetate gave the corresponding condensated products. The latter underwent some heterocyclic reactions to give new pyrazole, thiophene, and pyridazine derivatives. The antitumor evaluation of the newly synthesized products against the three cancer cells, namely, breast adenocarcinoma (MCF-7), nonsmall cell lung cancer (NCI-H460), and CNS cancer (SF-268) showed that some of them have high inhibitory effect towards three cell lines which is higher than the standard

Synthesis and anti-tumor evaluation of novel hydrazide-hydrazone derivatives

The reaction of cyclopentanone with cyanoacetylhydrazine gave the 2-cyano-2-cyclopentylideneacetohydrazide (1). Treatment of compound 1 with elemental sulphur in the presence of triethylamine afforded the 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbohydrazide (2) which in-turn formed the corresponding intermediate diazonium salt. The latter was coupled with either ethyl cyanoacetate or ethyl acetoacetate to form the 2-cyano-2-(3-(hydrazinecarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)hydrazono)acetate (3) and ethyl 2-(2-(3-(hydrazinecarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)hydrazono)-3-oxobutanoate (4), respectively. On the other hand, the reaction of compound 1 with either benzaldehyde or acetophenone afforded N\u27-benzylidene-2-cyano-2-cyclopentylideneacetohydrazide (7) and 2-cyano-2-(2-cyclopentylidene)phenylacetohydrazide (10), respectively. Moreover, compound 1 was used to synthesise the 2-cyano-2-cyclopentylidene-N\u27-(arylthiazol-2(3H)-ylidene)acetohydrazides 6a,b, 2-(2-benzylidenecyclopentylidene)-2-cyanoacetohydrazide (8), 2-amino-N\u27-benzylidene-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbohydrazide (9), 2-cyano-2-(2-(2-phenylhydrazono)cyclopentylidene)acetohydrazide (11), N\u27-(1-chloropropan-2-ylidene)-2-cyano-2-cyclopentylideneacetohydrazide (12), and the 2-cyclopentylidene-3-(3,5-disubstituted-1H-pyrazol-1-yl)-3-oxopropanenitriles 13a,b through its reaction with the respective reagents. The antitumor evaluation of the newly synthesized compounds against the three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of the described compounds exhibit higher inhibitory effects towards the three tumor cell lines than the reference compound doxorubicin