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.

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)-pyridazin-one-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 Koster's 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 relationships 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 chi) and the 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.

The in vitro hepatic metabolism of 1-phenyl-2-(2-benzothiazolinone-3-yl)ethanone and their reduced derivatives.

The in vitro hepatic microsomal metabolism of 1-phenyl-2-(2-benzothiazolinone-3-yl)ethanone (I) and (+/-)-1-Phenyl-2-(2-benzothiazolinone-3-yl)ethanol (II) was studied using both rat microsomal preparations and soluble fractions fortified with NADPH. These two substrates and their potential dealkylation metabolite 2-benzothiazolinone were synthesized and their structures were elucidated by spectral methods. The results showed that (I) was metabolised to (II), the corresponding alcohol by reduction. More alcohol metabolite was observed with microsomes than those obtained with the soluble fractions. No dealkylation of (I) was observed in the experiments using both microsomes and soluble fractions. (II) was metabolised to (I), the corresponding ketone by oxidation. However, compared to the metabolism of (I), more ketone metabolite was observed with soluble fractions than microsomes. (II) was also dealkylated to (III) with only soluble fractions but no dealkylated metabolites were found in the microsomes. In addition, a common unknown metabolite was observed with each substrates.

The in vitro hepatic microsomal metabolism of methyl 2-(2(3H)-benzoxazolone-3-yl)acetate in rats.

The in vitro hepatic microsomal metabolism of methyl 2-(2(3H)-benzoxazolone-3-yl)acetate (I) was studied using hepatic washed rat microsomal preparations fortified with NADPH. The substrate (I) and its potential hydrolytic metabolite 2-(2(3H)-benzoxazolone-3-yl)acetic acid (II) and 2(3H)-benzoxazolone (III), a potential dealkylation metabolite, were separated using a reverse phase HPLC system which consisted of a C18 column and a mobile phase of acetonitrile: 0.02 M phosphate buffer (30:70, final pH 7) at a flow rate of 1 ml/min with UV detection at 254 nm. The substrate (I) was incubated with rat microsomal preparations, extracted into DCM, and finally evaporated under nitrogen. The results from HPLC studies showed that (I) was metabolised to (II) and (III) by rat microsomes in the presence of NADPH.

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 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.

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.

N-(2-pyridinyl)-2-[2(3H)-benzazolone-3-yl]acetamides: synthesis, antinociceptive and anti-inflammatory activity.

Eighteen N-(2-Pyridyl)-2-[2(3H)-benzazolone-3-yl]acetamide derivatives have been synthesized. The chemical structure of the compounds have been elucidated by elemental analysis, IR and 1H NMR spectral data and their antinociceptive and anti-inflammatory activities were tested in mice. Compound VII o has shown the highest antinociceptive activity, and VII g, j, k, r exhibited relatively high antinociceptive activity. In addition, compounds VII d, f, j, p showed statistically significant anti-inflammatory activity.