Reinvestigation of the Reaction of Phenacy lMalononitrile with Hydrazines under Solvent Conditions

Phenacylmalononitrile 3 reacts with hydrazine hydrate in refluxing dioxan to afford the iminopyridazine derivative 6 and the pyrazolo[3,4-c]pyridazine derivative 7.Compound 3 reacts also with phenylhydrazine in refluxing ethanol to afford the iminopyridazine derivative 11 along with the phenylhydrazone derivative 12. Compound 12 could be cyclized into the pyrazolo[3,4-c]pyridazine derivative 13 upon reflux with sodium ethoxide

Studies with aza-heterocyclic N-oxides: Synthesis of some new aromatic N-oxide derivatives

Benzofuroxan derivative (1a) reacts with the cyanoacetanilides (2a-d) to give the benzimidazole derivatives (3a-d). Benzofuroxan (1b) reacts with rhodanine derivatives (4a,b) in presence of sodium ethoxide to give the arylaminobenzoimidazole derivatives (6a,b); while the last reaction afforded the thiazolidinone derivatives (8a,b) and the o-benzoquinone dioxime derivatives (9a,b) when it was repeated in the presence of sodium acetate. Moreover, a series of quinoxalinyl 1,4-di-N-oxide derivatives were prepared starting from quinoxalin-1,4-di-N-oxide derivatives (10a-c). Plausible mechanisms to account for the formation of the products are discussed

Synthesis of some novel pyridine and naphthyridine derivatives

2-[1-(Furan- or thiophen-2-yl)ethylidene)malononitriles (1a,b) undergo dimerization reactions in ethanol catalyzed by sodium ethoxide to afford 2-[4,6-di(furan- or thiophen-2-yl)-3-cyano-6-methyl-5,6-dihydropyridin-2(1H)-ylidene]malononitrile derivatives (2a,b), respectively. Compounds 2a and 2b couple with arene diazonium salts (3a-c) to afford the hydrazo derivatives (4a-f). They react also with hydrazines (5a,b) to afford the pyrazolo[3,4-H][1,6]naphthyridine derivatives (6a-d) and with urea derivatives (7a-c) to afford the pyrimido[4,5-H][1,6]naphthyridine derivatives (8a-f), respectively

Facile synthesis of some novel triazolo[3,4-<i>b</i>]thiadiazines and triazolo[4,3-<i>b</i>]tetrazines

<p>4-Amino-5-ethyl-4<i>H</i>-1,2,4-triazole-3-thiol was used as a key intermediate for the synthesis of triazolo[3,4-<i>b</i>][1,3,4]thiadiazines, triazolo[4,3-<i>b</i>][1,2,4,5]tetrazines and Schiff’s base via reactions with various hydrazonoyl halides and salicyaldehyde, respectively. Moreover triazolyl-<i>N</i>-<i>N</i>′-triazole derivatives were prepared from reaction of Schiff’s base with various hydrazonoyl halides. The structures of all the newly synthesized heterocyclic compounds were established by considering elemental analysis and spectral data.</p

Synthesis and Biological Evaluation of Thiazolyl-Ethylidene Hydrazino-Thiazole Derivatives: A Novel Heterocyclic System

The reaction of 2-(1-(2-(2-(4-methoxybenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethylidene)hydrazinecarbothioamide with a range of hydrazonoyl chlorides and α-halo-compounds yielded three new series of thiazole derivatives. Chemical and physical techniques were used to analyze all newly prepared derivatives (1H-NMR, 13C-NMR, FT-IR and mass spectrometry). The potential antimicrobial and anticancer properties of the synthesized derivatives were investigated using various in vitro biological experiments. Most of the thiazole compounds tested were effective against Gram-positive and Gram-negative bacteria. In addition, a minimum inhibition concentration was determined for the antibiotic properties of the most active produced substances. The cytotoxic activities were tested on HepG-2 (liver carcinoma), HCT-116 (colorectal carcinoma) and MDA-MB-231 (breast carcinoma) cell lines in comparison with cisplatin reference drug and using colorimetric MTT assay. The results detected that compound 10c was the most potent against the three tested cell lines. Interestingly, when the tested compounds were evaluated for their toxicity against normal (MRC-5) cells, they exhibited low toxic effects indicating the safe use of most of them that may require further in vivo and pharmacological studies

Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca²⁺ Pathway

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats