Deniz S. Dogruer

Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity.

Nineteen new [6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]‐acetamide (1—10) and 3‐[6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]propanamide (11—19) derivatives have been synthesized in this study. The structures of the compounds have been elucidated by their IR and NMR spectral data and elemental analysis. Antinociceptive activity of the compounds has been investigated by modified Kosters Test in mice, using aspirin as a reference. All the compounds (at 100 mg/kg dose) except >1 and 9 have been found more potent than aspirin. Compound 6 in the group of acetamide derivatives and compound 15 in the group of propanamides exhibited the highest antinociceptive activity. In addition, the propanamides have generally been found more potent than acetamides. In addition to these studies, the quantitative relation‐ships between some structural parameters (such as log P, parachor, molar refractivity, and molecular connectivity indices) and antinociceptive activity of the compounds have been investigated. Statistical regression analysis has shown a close relationship to exist between the first‐order molecular connectivity index (1 χ) and the antinociceptive activity.

Synthesis and antinociceptive activity of 6-substituted-3-pyridazinone derivatives.

A series of 3-pyridazinones carrying morpholino, arylpiperidino and arylpiperazino moiety in the position 6 IIa-g were synthesized and evaluated for antinociceptive activity. In the modified Koster test in mice 4-(4-fluorophenyl) piperazine, IIf, was found the most active compound. All the compounds except IId were more active than aspirin in the antinociceptive activity test.

Anti-nociceptive and anti-inflammatory activity of some (2-benzoxazolone-3-yl and 2-benzothiazolone-3-yl) acetic acid derivatives

Sixteen (2-benzothiazolone-3-yl and 2-benzoxazolone-3-yl) acetic acid derivatives 5 have been tested for anti-nociceptive and anti-inflammatory activity in this study, 4-[2-(6-Benzoyl-2-benzoxazolone-3-yl)acetyl]morpholine (5c), 4-¿2-[6-(2-chloro-benzoyl)-2-benzoxazolone-3-yl]acetyl¿morpholine (5d), 1-[2-(5-chloro-2-benzoxazolone-3-yl)acetyl]pyrrolidine (5f), methyl (6-methyl-2-benzoxazolone-3-yl)acetate (5k) and N,N-diethyl-2-(2-benzothiazolone-3-yl)acetamide (5m) have shown more potent anti-nociceptive activity than others. Among these compounds, 5c, 5d and 5m have exhibited good anti-inflammatory activity, with 5f, and to a lesser extent, the other molecules displaying some toxic potential.

Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives

In this study, new 3-[(1(2H)-phthalazinone-2-yl(methyl/ethyl]-4-aryl-1,2,4-triazole-5-thione and 2-[[1(2H)-phthalazinone-2-yl]methyl/ethyl]-5-arylamino-1,3,4-thiadiazole derivatives were synthesized. Antimicrobial properties of the title compounds were investigated against two Gram (+) bacteria (S. aureus, B. subtilis), two Gram ( − ) bacteria (P. aeruginosa, E. coli) and two yeast-like fungi (C. albicans and C. parapsilosis) using the broth microdilution method. Generally the compounds were found to be active against B. subtilis and the fungi. Derivatives carrying a 1,3,4-thiadiazole ring generally showed higher antimicrobial activity against B. subtilis and the fungi when compared to other synthesized compounds.

Synthesis and antinociceptive activity of (5-chloro-2-benzothiazolinon-3-yl)acetamide derivatives.

The synthesis of (5‐chloro‐2‐benzothiazolinon‐3‐yl)acetamide derivatives is reported. The structure of these compounds is supported by their IR and 1H‐NMR spectra. The compounds were tested for antinociceptive activity.

The in vitro effects of new non-steroidal antiinflammatory compounds on antioxidant system of human erythrocytes.

It has been reported by our group that some benzoxazolone and benzothiazolone derivatives showed significant antinociceptive and anti-inflammatory activity [DOGRUER et al. 1997]. It has been speculated that nonsteroidal anti-inflammatory drugs (NSAIDs) can act as the free radical scavengers and possess antioxidant activity. It is also well documented that oxidative stress can play an important role in the side effects of many xenobiotics including NSAIDs. Therefore, in the present study, the effects of six of the above mentioned benzoxazolone and benzothiazolone derivatives bearing 2-pyridylaminocarbonylmetyl moiety at the position 3 (I) on the antioxidant system-related parameters of human erythrocytes have been investigated. Diclofenac and nimesulid were also tested in the same systems as the control, because they are commonly used as NSAIDs. Our results showed that these compounds made significant changes in the antioxidant system of human erythrocyte.

Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities

In this study, 12 new 3(2H)-pyridazinone derivatives carrying 4-substituted phenylpiperazinylethyl moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 9c showed the best analgesic and anti-inflammatory activities without causing any gastric effect in stomachs of tested animals. In addition, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains.

Synthesis and antinociceptive activity of some 3-substituted benzothiazolone derivatives

Thirteen 3-substituted benzothiazolone derivatives have been synthesized. Their chemical structures have been elucidated by IR and NMR spectral data and by elemental analyses. Among these compounds, 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]morpholine (5b); 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]-4-benzylpiperidine++ + (5c); 1-¿3-[2(3H)-benzothiazolon-3-yl[-propanoyl]-4-phenylpiperazine (5d); 3-[3-(4-benzylpiperidine-1-yl)propyl]-2(3H)-benzothiazolone (5k); 3-[3-(4-benzylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5I); 3-[3-(4-phenylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5m) have been found to be significantly more active than the others.

Synthesis and antinociceptive activity of (1-benzyl-2(3H)-benzimidazolon- 3-yl) acetic acid derivatives.

Eight (1-benzyl-2(3H)-benzimidazolon-3-yl)acetic acid derivatives have been synthesized and tested for antinociceptive activity in this study. All compounds but one, at the oral dose of 100 mg/kg were comparable with aspirin. Ethyl (1-benzyl-2(3H)-benzimidazolon-3-yl)acetate (3), 4-[(1-benzyl-2(3H)-benzimidazolon-3-yl)acetyl]morpholine (6a) and 1-[(1-benzyl-2(3H)-benzimidazolon-3-yl)acetyl]pyrrolidine (6b) have shown more potent antinociceptive activity than others.

Synthesis of some 3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives incorporating aminothiazole moiety and investigation of their antioxidant, acetylcholinesterase, and butyrylcholinesterase inhibitory activities

Abstract In this study, 12 new compounds were synthesized, six of which were 3(2H)-pyridazinone (9a–f) and the others were 1(2H)-phthalazinone (10a–f) derivatives. The chemical structures of new compounds were confirmed by 1H-NMR, 13C-NMR, mass, and elemental analysis. The antioxidant properties of all the synthesized compounds were evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assays. Moreover, cholinesterase inhibitory profiles of the synthesized compounds were determined using an in vitro assay based on a modified version of the Ellman protocol. Almost all the synthesized compounds displayed promising antioxidant activity, particularly in the DPPH radical scavenging assay, however, their inhibitory activities on cholinesterase enzymes pointed out structure specific interactions .