An Open label, Prospective, Multi-Center, Observational Study to Evaluate the Lipid Lowering Efficacy and Safety of Rosuvastatin in Indian Dyslipidemics in Routine Clinical Practice.

Altered cholesterol levels in the blood or dyslipidemia is a major modifiable risk factor for CVD and is closely associated with the pathophysiology of CVD. Asians, particularly Indians, have a unique pattern of dyslipidemia; with lower HDL cholesterol, increased triglyceride levels and higher proportion of small dense LDL cholesterol, with characteristic centripetal obesity. ‘Statins’ belong to the group of 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors that have been shown to reduce levels of total and LDL cholesterol. Study Objective: To evaluate the lipid lowering efficacy and safety of Rosuvastatin in Indian dyslipidemics in routine clinical practice by measuring the percent change in Total Cholesterol, LDL, TG and HDL over a period of 16 weeks. Methodology : This was a multicentric, open-labeled, post-marketing surveillance study. A committee of key opinion leaders was formed. A total of 1200 doctors were approached of whom 800 provided us with subject data. Each participating doctor was given case report forms and requested to recruit patients according to the inclusion and exclusion criteria. Lipid profile of each recruited patient was done before initiating therapy and at the end of 4 months. Rosuvastatin was given at a dose of either 5mg/ 10mg OD for 4 months. Results : A total of 11, 656 subjects were recruited into this study out of which 10, 410 complete case report forms were considered (n=10410). The study included 65% males and 35% females. Majority of the subjects were in the age group of 46-55years (35.2%) and 56-65 years (29.4%). In this study, the total cholesterol (TC), LDL-C, Triglycerides (TG) has significantly decreased by 46.13%, 53.74% and 41.93% respectively. Also the HDLC levels increased by 26.84%, thereby, indicating a significant change in the levels of all the dyslipidemic indicators. With the reported number of adverse events (n=4) related to Rosuvastatin, it is evident that the drug is safe and tolerable. There were no significant changes observed in the liver and renal function tests with Rosuvastatin reiterating their safety. Conclusion : Rosuvastatin has shown greater efficacy in lowering LDL cholesterol and non-HDL-cholesterol concentrations. It has been shown to enable more patients to reach their LDL cholesterol goals and to do so with an acceptable safety profile.

Some reactions of 3-methyl- 1- phenyl-4- [phenylamino-thiocarbonyl] -2- pyrazolin-5-one

The title compound 1 was prepared via reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one with phenylisothiocyanate. Then, it was converted to pyrazolopyrazole, pyrazolopyrimidine, pyrazolopyridine, and the amino derivatives through reaction with hydrazines, urea, thiourea, malononitrile and aromatic amines. Compound [1] prepared via addition of activated nucleophilic carbon of 3-methyl-1-phenyl-2-pyrazolin-5-one to the electrophilic carbon of phenylisothiocyanate seemed to be suitable to annulation through its reactive center. The reaction of [1] with hydrazine hydrate and phenyl-hydrazine in boiling ethanol gave the pyrazolopyrazole derivatives [2a] and [2b], respectively. The mass spectrum of [2a] showed the parent ion peak at m/z 289 and the following abundant peaks 185, 105, 91, 77, and 51. Structure of [2a] was further established by its reaction with ethyl bromoacetate to give [3]. The latter afforded the hydrazide derivative [4] on reaction with hydrazine hydrate

Synthesis and pharmacological evaluation of some new quinazoline- [1,2-C] quinazoline and 1,2,4-triazino [4,3-C] quinazoline analogs

Some new quinazolino [1,2-c] quinazolin-13-ones and 2,3,4,5-tetrahydro-2,5,-dioxo-1H-1,2,4 triazino [4,3-c] quinazolines were synthesized an characterized by both elemental and spectral analyses. Pharmacological evaluation of these erivatives showed that some viny1 derivatives of quinazolinoquinazolinone possess a significant hypnotic activity compared with phenobarbitone, whereas, other quinazolinoquinazolinones and trizinoquinazolins, showed mild non-narcotic analgesic activity compared with paracetamol

Synthesis and reactions of some new substituted cyclo-hexenone tetrahydropyrimidine derivatives of expected biological activity

4-[P-chlorophenyl]-[4H]-6-[substituted styryl-cyclo-hexenonyl]- 1,2,3,4-tetrahydropyrimidine-2-thione [IV] and 5-[p-chlorophenyl]-[5H] [7-substituted styryl-cyclohexenonely]-1,2,3,4-tetrahydrothiazolo- [3,2a]-pyrimidine-3 one derivatives [V] have been synthesized. The 2- aryl-methylene [VI] and the 2-aryl-hydrazono-[VII] were also synthesized. Some of these compounds have been tested for their antimicrobial activity

Cytogenetic studies on the pyrazolo [1,5-a] pyrimidine derivatives on mice cells

Pyrazolo [1,5-a] pyrimidine derivatives has a possible antianxiety properties and anti-inflammatory actions. The two pyrazolo [1,5-a] pyrimidine derivatives; 3-acetyl-5,7-dimethyl pyrazolo [1,5-a] pyrimidine as compound A and 3-chloro-5,7 dimethyl pyrazolo [1,5-a] pyrimidine as compound B were examined to evaluate their clastogenic or mutagenic properties through the induction of chromosomal aberrations in the somatic [bone-marrow] and germ [1ry spermatocyte] cells of mice. Mice treated orally by gavage with either compound A or compound B with a single dose [1/8, 1/4 and 1/2 LD50] and multiple doses with 1/8 LD50 for five consecutive days. Both compounds A and B were found to produce a significant increase in chromosomal aberrations in somatic and germ cells except with the low dose of compound A [1/8 LD50]. This increase was dose-dependent in both types of cells. Multiple treated animals caused a significant increase 24 hours after three and five days of treatment. Concerning the sperm abnormalities, compound B induced a significant increase in the sperm-head abnormalities. Slight inhibition of sperm count and sperm motility occurred after treatment of mice with 1/8 LD50 of compound B. The results showed that compound A had a low clastogenic effect than compound B

Synthesis and antitumor activity of certain thienopyridine and pyridothienopyrimidine derivatives

A series of cyclopenteno[b] or tetrahydrobenzo[b]thiophenes, tetrahydrothieno[2,3-c]pyridines and tetrahydropyrido[4',3' :4,5]thieno[2,3-d]pyrimidines was synthesized as antitumor agents. Most of the tested compounds showed cytotoxic effect [GI[50] < 10 [micro]M] against the growth of P388 leukemia cells. Ethyl2-phenylsulphonamido-4,5,6,7-tetrahydrobenzo[b]thiophen-3-carboxylate [lla], Ethyl 2-[4- bromo-phenylsulphonamido]-4,5,6,7-tetrahydrobenzo[b]thiophen-3-carboxylate [llb], Ethyl 2-[4-methylphenyl-sulphonamido]-4,5,6,7-tetrahydrobenzo[b]thiophen-3-carboxylate [IIc], Ethyl 2-[4-methoxybenzamido]-4,5,6,7 -tetrahydro[b]thiophen-3-carboxylate [IIIc] and N-[4-methylphenyl] N-[3-carbo-ethoxy-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c] pyridin-2-yl] thiourea [lVc] showed strong potency [GI [50]; 0.8, 1.15,2.09, 1.3,2.25 [micro]M; respectively]. The detailed synthesis, spectroscopic and biological data are reported

Enaminonitrile in heterocyclic synthesis: synthesis of thiazolo [4,5-b] pyridine and thiazolo [4,5-d] pyrimidine derivatives

Ammoniumn- phenyldithiocarbamate reacted with bromomalononitrile and alpha chloroacetylacetone to afford thiazole derivatives 3a, b. Compound 3a reacted with benzylidenemalononitrile, malononitrile, phenylisothiocyanate, benzoylisothiocyanate, trichloroacetonitrile, formamide, carbon disulphide and triethylorthoformate to afford thiazolo [4,5-b] pyridine derivatives 6,9 and thiazolo [4,5-d] pyrimidine derivatives 13, 16, 18, 19, 20 and 21. Most of the synthesized products show high fungicidal and bactericidal activities

Enamine rearrangement of pyrimidinium salts Part XI: Novel synthesis of some pyrazolo and triazolopyrimidine derivatives

The pyrazolo [1,5-a] pyrimidine derivatives IV and VI underwent pyrimidine ring opening, then recyclized when heated with aqueous alcoholic alkali solution to give the corresponding pyrazolo [3,4-b] pyridine V and VII, respectively. In a similar manner, the triazolo [4,3-a] pyrimidine VIII underwent recyclization to the corresponding triazolo [1,5-a] pyrimidine IX

Condensed pyrimidines XV

The ring systems pyrrolo [1,2-c] pyrimidine and pyrimido [1,6-a] azepine [I] were subjected to acylation giving rise to a tricyclic nuclei, pyrimido [5,4-e] pyrrolo [1,2-c] pyrimidine and pyrimido [4',5': 4,5] pyrimido [1,6-a] azepine [II]. These compounds were reacted with different amines to give the corresponding 3-alkylaminopropyl derivatives [IV]. The tetracycles pyrrolo [1,2-a] pyrrolo [1',2': 1,6] pyrimido [4',5'-a] pyrimidine and pyrrolo [1",2": 1',2'] pyrimido [4',5': 4,5] pyrimido [1,6-a] azepine [V] were prepared through different routes