Syntheses and biological evaluation of indole-2 and 3-carboxamides: new selective cyclooxygenase-2 inhibitors.

A series of indol-2 and 3-carboxamides were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1). Substitution on indol nitrogen with benzyl and p-fluorobenzyl group of indole-2 carboxamides 8, 10, 11 provides fairly active COX-2 enzyme inhibitors.

Synthesis and receptor docking studies of N-substituted indole-2-carboxylic acid esters as a search for COX-2 selective enzyme inhibitors.

A series of N-substituted indole-2-carboxylic acid esters have been prepared by replacing the benzoyl group of indomethacin with a benzyl and a phenyl group. The carbocyclic acid side chain was extended via creating an ester structure by using several dialkylaminoalkyl groups. The receptor docking studies were performed to investigate the docking mode of each compound by using DOCK 4.0. All the compounds were shown to be docked at the site where intact flurbiprofen was embedded for COX-1 and s-58 (1-phenylsulphonamide-3-trifluoromethyl-5-para-bromophenylpyrazole) for COX-2. It was predicted that N-phenyl-indole-2-carboxylic acid piperazine ester 22 can be a fairly strong COX-2 selective compound which was compared to the others. Other predicted COX-2 selective compounds included are N--H indole-2-carboxylic acid diethyl 30 and piperazine 34 esters. In view of these findings, compounds 22, 30 and 34 were chosen for the in vitro biological assays.

Determination of tetrahydrozoline hydrochloride and fluorometholone in pharmaceutical formulations by HPLC and derivative UV spectrophotometry.

Two methods for the quantitative determination of tetrahydrozoline hydrochloride (1) and fluorometholone (2) in pharmaceutical eye drops (Efemoline) are described. The procedures are based on derivative UV spectrophotometry and HPLC. In the former method, d2A/d lambda 2 values were measured in methanol at 226 and 282 nm for 1 and 2, respectively. The relative standard deviations for the method were found to be 1.06% for 1 and 0.98% for 2. The latter method based on a reversed phase HPLC system using a Partisil 5 ODS analytical column. The mobile phase used for the separation of 1, 2 and internal standard (lidocaine) was methanol/acetonitrile/water (50:50:10 v/v) and the compounds in the eye drops were detected at 220 nm using an UV detector. The relative standard deviations for the HPLC method were determined to be 0.61% and 0.50% for 1 and 2, respectively. The proposed methods, which give thoroughly comparable data, are simple, rapid, and allow precise and accurate results and could be used for commercial formulations containing tetrahydrozoline hydrochloride and fluorometholone in combination.

Quantitative determination of acrivastine and pseudoephedrine hydrochloride in pharmaceutical formulation by high performance liquid chromatography and derivative spectrophotometry.

In this study, fourth derivative spectrophotometry and high performance liquid chromatography (HPLC) have been used and described for the quantitative determination of acrivastine (I) and pseudoephedrine hydrochloride (II) in their pharmaceutical capsules form (Duact). In the former method, d4A/d gamma 4 values were measured in methanol at 315 and 269 nm for (I) and (II) respectively. The relative standard deviations (RSD) for the method were found to be 1.16% for (I) and 0.94% for (II). The latter method based on reversed phase HPLC system using LiChrosorb C18 analytical column. The mobile phase used for separation of (I), (II) and internal standard (p-hydroxymethylbenzoate) were the water/acetonitrile/methanol/perchloric acid/n-octylamine (500:130:25:13:0.3 v/v) and the detection of the compounds in the capsules were at 260 nm using UV detector. The RSD for the HPLC method were determined to be 0.79 and 0.88% for (I) and (II) respectively. The proposed methods, which give thoroughly comparable data, are simple, rapid, and allow precise and accurate results and could be used for commercial formulations containing acrivastine and pseudoephedrine hydrochloride in combination.

Mechanisms underlying enhanced glycogenolysis in livers of 3,5,3'-triiodothyronine-treated rats.

Rats trained on a diurnal controlled meal-feeding schedule and injected with a single dose of 3,5,3'-triiodothyronine (T3) failed to accumulate liver glycogen and incorporated less D-[6-3H]glucose into glycogen than normally observed during the feeding period. In the experimental group, the concentration of liver adenosine 3',5'-cyclic monophosphate (cAMP) did not fall during feeding and the pattern of activities of glycogen phosphorylase, glycogen synthase, and phosphorylase kinase remained conductive to glycogenolysis. Liver lysosomal alpha-glucosidase activity normally fell during feeding periods. After T3 treatment the activities of alpha-glucosidase and two lysosomal cathepsins (B1 and D) were elevated. The evidence suggests that T3 may induce both liver phosphorylase kinase and lysosomal alpha-glucosidase. This outcome of T3 excess, in concert with previously described T3-inducible systems, provides a plausible explanation for the failure of glycogen accumulation in this experimental model.