The Chemistry and Bio-Medicinal Significance of Pyrimidines & Condensed Pyrimidines.

This review discusses the biological and medicinal significance of one of the most important and interesting heterocyclic ring systems, the pyrimidine and its condensed derivatives. Herein, various physiologically important molecules, as well as, therapeutically used drugs having a pyrimidine or condensed pyrimidine system in their chemical structures, have been covered. The chemistry and synthesis of pyrimidines have also been briefly discussed.

Development and Validation of a Reversed-phase HPLC Method for Simultaneous Determination of Aspirin, Atorvastatin Calcium and Clopidogrel Bisulphate in Capsules.

A simple, accurate, rapid and precise isocratic reversed-phase high-performance liquid chromatographic method has been developed and validated for simultaneous determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in capsules. The chromatographic separation was carried out on an Inertsil ODS analytical column (150×4.6 mm; 5 µm) with a mixture of acetonitrile:phosphate buffer pH 3.0 adjusted with o-phosphoric acid (50:50, v/v) as mobile phase; at a flow rate of 1.2 ml/min. UV detection was performed at 235 nm. The retention times were 1.89, 6.6 and 19.8 min. for aspirin, atorvastatin calcium and clopidogrel bisulphate, respectively. Calibration plots were linear (r(2)>0.998) over the concentration range 5-30 µg/ml for atorvastatin calcium and 30-105 µg/ml for aspirin and clopidogrel bisulphate. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The proposed method was successfully used for quantitative analysis of capsules. No interference from any component of pharmaceutical dosage form was observed. Validation studies revealed that method is specific, rapid, reliable, and reproducible. The high recovery and low relative standard deviation confirm the suitability of the method for routine determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in bulk drug and capsule dosage form.

Development of novel, alternative, facile, ecofriendly, high yield synthetic process for prazosin.

Industrial chemistry in the new millennium is widely adopting the concept of "Green chemistry" to meet the fundamental scientific challenges. Antihypertensive drugs include several of the most widely prescribed drugs like diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, and α-1 adrenoreceptor blockers. The discovery of prazosin, with very high index of α1/α2 affinity has triggered off a renaissance of interest in α1-adrenoceptor antagonist drugs for treatment of hypertension. The three reported routes for synthesis and manufacture of the α-adrenoceptor antagonist- prazosin had some disadvantages. In present study we had developed new methods for the synthesis of prazosin by using microwave. The most important aspect is the overall yield of this process was ~25 % higher than the other reported methods excluding the use of banned substances.

Stability indicating HPLC method for simultaneous determination of mephenesin and diclofenac diethylamine.

A simple, specific, accurate and stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of mephenesin and diclofenac diethylamine, using a Spheri-5-RP-18 column and a mobile phase composed of methanol: water (70:30, v/v), pH 3.0 adjusted with o-phosphoric acid. The retention times of mephenesin and diclofenac diethylamine were found to be 3.9 min and 14.5 min, respectively. Linearity was established for mephenesin and diclofenac diethylamine in the range of 50-300 mug/ml and 10-60 mug/ml, respectively. The percentage recoveries of mephenesin and diclofenac diethylamine were found to be in the range of 99.06-100.60% and 98.95-99.98%, respectively. Both the drugs were subjected to acid, alkali and neutral hydrolysis, oxidation, dry heat, photolytic and UV degradation. The degradation studies indicated, mephenesin to be susceptible to neutral hydrolysis, while diclofenac diethylamine showed degradation in acid, H(2)O(2), photolytic and in presence of UV radiation. The degradation products of diclofenac diethylamine in acidic and photolytic conditions were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of mephenesin and diclofenac diethylamine in bulk drugs and formulations.

Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle biopsy: clinical importance.

PURPOSE: To assess the outcome of papillary lesions, radial scars, or lobular carcinoma in situ (LCIS) diagnosed at stereotactic core-needle biopsy (SCNB). MATERIALS AND METHODS: Retrospective review of 1,236 lesions sampled with SCNB yielded 22 papillary lesions, nine radial scars, and five LCIS lesions. Diffuse lesions such as papillomatosis, papillary ductal hyperplasia, papillary ductal carcinoma in situ (DCIS), and atypical lobular hyperplasia were not included. The mammographic findings, associated histologic features, and outcome were assessed for each case. RESULTS: Sixteen papillary lesions were diagnosed as benign at SCNB. Of these, five were benign at excision, and 10 were unremarkable at mammographic follow-up. At excision of an unusual lesion containing a microscopic papillary lesion, DCIS was found. Three of four papillary lesions suspicious at SCNB proved to be papillary carcinomas; the fourth had no residual carcinoma at excision. Eight of nine radial scars were excised, which revealed atypical hyperplasia in four scars but no malignancies. One LCIS lesion was found at excision to contain DCIS. CONCLUSION: Benign or malignant papillary lesions were accurately diagnosed with SCNB in the majority of cases. Cases diagnosed as suspicious for malignancy or with atypia or unusual associated histologic findings should be excised. No malignancies were found at excision of radial scars diagnosed at SCNB. Surgical removal of these lesions following SCNB may not be routinely necessary. DCIS was found in one lesion diagnosed as LCIS at SCNB, which suggests that removal of these lesions may be prudent.

Mechanism of the antihyperlipaemic activity and pharmacokinetics of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-o ne.

The pharmacokinetics and the mechanism of action of the antihyperlipaemic compound 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-on e (CAS 89587-03-3, LM-1554) have been studied. Serum concentrations were determined by reverse phase HPLC using methanol : water (60 : 40) as the solvent system. The results of pharmacokinetic studies suggest that the compound LM-1554 is poorly absorbed from the gastrointestinal tract after the oral administration in dogs and rabbits. The volume of distribution (Vd) was found to be low. The poor bioavailability (3-4%) and low volume of distribution of the compound LM-1554 suggest the gastrointestinal tract as the site of action for the antihyperlipaemic activity. This hypothesis is substantiated by the observations that the compound was found active in rabbits only when administered orally and found inactive by the parenteral route. Further, the cholesterol levels were found to increase in blood samples collected from the portal vein after oral administration of cholesterol in coconut oil to rats. This increase was found to be prevented by the compound LM-1554. In conclusion, the compound LM-1554 has a potential to be developed as an antihyperlipaemic agent. The mechanism of action of the compound LM-1554 appears to consist in the inhibition of cholesterol absorption in the gastrointestinal tract.

Synthesis and QSAR of some 3-amino-2-(substituted)aminomethyl-5,6-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones as novel H1-receptor antagonists.

The present study describes the synthesis and quantitative structure activity relationships (QSAR) of novel 3-amino-2-(substituted)aminomethyl-5,6-disubstitutedthieno[2,3-d] pyrimidin-4(3H)-ones for their potent H1-receptor antagonist activity on the guinea pig ileum. With the IC50 values in the range of 10(-5) gms/lit, all the compounds tested were found to possess ten fold higher affinity to the H1-receptor than diphenhydramine and cetirizine, but lower than astemizole and loratidine. The sedative potential of these compounds was found to be lower than cetirizine and astemizole but comparable to loratidine. The QSAR study indicates a parabolic relationship of the biological activity mainly with the steric parameters and partly with the lipophilic parameters.

Synthesis and quantitative structure-activity relationships of antihyperlipaemic 2-substituted thieno[3,2-d]pyrimidin-4(3H)-ones.

The synthesis, antihyperlipaemic evaluation and quantitative structure-activity relationships (QSAR) of two series of thieno[3,2-d]pyrimidin-4-one derivatives are reported. While most of the compounds in these series were found to exhibit antihyperlipaemic activity, the QSAR study of these two series indicated a positive influence of only the electronic nature of the 2-substitutents on the biological activity. The lipophilic and the steric parameters did not appear to be significant.

Synthesis and pharmacological study of antihyperlipaemic activity of 2-substituted thieno(2,3-d)pyrimidin-4(3H)-ones.

A series of 2-substituted thieno(2,3-d)pyrimidin-4-(3H) ones (1-15) was prepared by the reaction of thiophene ortho-aminoester (IV) with a variety of nitriles (V) under acidic conditions, and screened for antihyperlipaemic activity in various animal models. While most of these compounds were found active, 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d) pyrimidin-4(3H)-one (5) was found to be the most active of all. The serum triglyceride lowering activity exhibited by 5 was found comparable to that of clofibrate and riboflavin tetrabutyrate. Compound 5 was also found to be safe as indicated by acute and chronic toxicity studies in mice and rats.