MXPA99009495A

MXPA99009495A - Method of using cyclooxygenase-2 inhibitors in the prevention of cardiovascular disorders

Info

Publication number: MXPA99009495A
Application number: MXPA/A/1999/009495A
Authority: MX
Inventors: Seibert Karen; Needleman Philip; Roniker Barbara; J Lachapelle Richard; T Connolly Daniel
Original assignee: T Connolly Daniel; Gd Searle & Co; J Lachapelle Richard; Needleman Philip; Roniker Barbara; Seibert Karen
Priority date: 1997-04-18
Filing date: 1999-10-15
Publication date: 2000-12-06

Abstract

This invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing cardiovascular disorders.

Description

METHOD FOR USING INHIBITORS OF THE ENZYME CYGLOGY ÍGlÍt £ SÁ-2"IN THE PREVENTION OF CARDIOVASCULAR DISORDERS FIELD OF THE INVENTION The present invention pertains to the field of the prevention of cardiovascular disorders. More specifically, the present invention relates to the use of 2-cyclooxygenase inhibitors. or derivatives thereof, to prevent cardiovascular diseases including atherosclerosis. BACKGROUND OF THE INVENTION Prostaglandins play a major role in the inflammation process and. The inhibition of prostaglandin production, especially the production of PGG2, PGH2 and 1"dE2, has been a common target for the discovery of anti-inflammatory drugs, however, non-steroidal anti-inflammatory drugs (AIR) common that are active in the reduction of pain induced by prostaglandins and in the swelling associated with the process of inflammation, are also active in affecting other processes regulated by prostaglandins and that are not associated with the process of inflammation. Thus, the use of high doses of the most common NSAIDs can produce serious side effects, including ulcers that REF .: 31419 they endanger life, which limit their therapeutic potential. "- -d H-" alternative to NSAIDs is the use of corticosteroids, which also produce shallow side effects, especially in cases of long-term therapies. It has been found that AIRE prevents the production of prostaglandins by inhibiting enzymes in the arachidonic acid / prostaglandin pathway in humans, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated cor-inflammation (called "cyclooxygenase-2 (COX-2)" or "prostaglandin G / H synthetase II") provides a viable target of inhibition that more effectively reduces inflammation and produces less Side effects and less drastic. Recently the role of inflammation in cardiovascular diseases has been better understood. Ridker et al. ,. { New Eng. J. Med., 336, 973-9 (1997)) describes a possible function of inflammation in cardiovascular diseases. J. Boyle (*. Path. R 181, 93-9 (1997)) describes the association of plaque rupture and atherosclerotic inflammation. Compounds that selectively inhibit cyclooxygenase-2 have been described in U.S. Patent Nos. 5,380,738; 5,344,991; 5,393,790; 5,434,178; ,474,995; 5,510,368 and in international documents WO96 / 06840 -, - t = Wd3 * 6 / O33"88-, WO96 / 03387, W096 / 19469, WO96 / 25405, W095 / 15316, W094 / 15932, WO94 / 27980, O95 / 00501 , W094 / 13635, WO94 / 20480 and W094 / 26731. [Pyrazol-1-yl] -benzenesulfonamides have been described as inhibitors of cyclooxygenase-2 and have shown promise in the treatment of inflammation, arthritis and pain, with effects Minimal side effects in preclinical and clinical studies Its use for the treatment of inflammation in vascular diseases has been described in US Patent No. 5,466,823, however, its use to prevent related cardiovascular diseases has not been previously described. refers to the use of cyclooxygenase-2 inhibitors for the prevention of inflammation related to cardiovascular disorders, More specifically, the present invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof for to develop cardiovascular diseases. DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for preventing cardiovascular disorders in a subject in need of such prevention, wherein the method comprises treating the subject with a therapeutically effective amount of a cyclooxygenase-2 inhibitor or a derivative or a pharmaceutically salt thereof. The above "-" or "" would be useful for, but not limited to, the prevention of inflammation related to cardiovascular disorders in a subject.The method would be useful for the prevention of coronary artery disease., aneurysm, arteriosclerosis, atherosclerosis, including atherosclerosis by heart transplantation, myocardial infarction, emboli, heart attack, thrombosis, including venous thrombosis, angina including unstable angina, inflammation of the coronary plaque, inflammation induced by bacteria including inflammation induced by Chlamydia, virus-induced inflammation and inflammation associated with surgical procedures such as vascular grafts including coronary artery bypass surgery (bypass), revascularization procedures including angioplasty, placement of graft clips, endoarterectomy or other invasive procedures involving arteries, veins and capillaries. The term "prevention" includes either preventing the emergence of clinically evident cardiovascular disorders or preventing the establishment of a preclinically evident stage of a cardiovascular disorder in individuals, including the prophylactic treatment of those at risk of developing a cardiovascular disorder.

The term "therapeutically effective" aims to qualify - "= ra = * 1ca * ntídad of each agent that will achieve the goal of an improvement in the severity of the disorder and the frequency of the incidence with the treatment of each agent by itself, while which avoids the adverse side effects typically associated with alternative therapies The term "subject" for the purposes of treatment includes any human being or animal subject that is susceptible to any of the known cardiovascular disorders and preferably the subject is a human being The subject may be at risk because of diet, exposure to bacterial or viral infections, because common markers are present, to be genetically predisposed to cardiovascular disorders, and the like In the above method, the cardiovascular disorder includes, but it is not limited to, those disorders that are known to have a component of inflammation and those that can be mediated s by cyclooxygenase-2. Inhibitors of the cyclooxygenase-2 pathway in the metabolism of arachidonic acid used in the prevention of cardiovascular disorders can inhibit the activity of the enzyme through a variety of mechanisms. For example, the inhibitors used in the methods described herein, can block the activity of IcTTpzimá "directly by acting as a substrate for the enzyme.The use of selective inhibitors of cyclooxygenase-2 is highly advantageous since it minimizes gastric side effects. which may occur with non-selective NSAIDs, especially when prolonged prophylactic treatment is expected.The term "cyclooxygenase-2 inhibitor" denotes a compound capable of inhibiting the enzyme cyclooxygenase-2 without significantly inhibiting the enzyme cyclooxygenase-1. Preferably, it includes compounds that have an IC 50 of cyclooxygenase-2 less than about 0.2 μM and also have a cyclooxygenase-2 inhibition selectivity ratio over the inhibition of cyclooxygenase-1, of at least 50, and more preferably of at least 100. Even more preferably, the compounds have an IC 50 of cyclooxygenase-1, greater than about 1 μM and preferably greater than 10 μM. The method that is provided herein, refers to the use of cyclooxygenase-2 inhibitors or derivatives thereof, in the prevention of a cardiovascular disorder related to inflammation. In preferred embodiments, the cyclooxygenase-2 inhibitor is selected from the group consisting of meloxicam (Boehringe-r ^ rpgelheim) **, nimesulide (Helsinn), MK-966 (Merck &Co), L-783003 (Merck). &Co), T-614 (Toyama), D-1367 (Chiroscience), L-748731 (Merck &Co), CT3 (Atlantic Pharmaceutical), CGP-28238 (Novartis), BF-389 (Biofor / Scherer) , GR-253035 (Glaxo Wellcome), (E) -4- (1, 3-bis- (cyclohexyl) -1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8- acid il) -cinnamic (Glaxo Wellcome), L-745337 (Merck &Co) and compounds of Formula I wherein A is a substituent selected from the group consisting of partially unsaturated or unsaturated heterocyclic rings and partially unsaturated or unsaturated carbocyclic rings; wherein R is at least one substituent selected from the group consisting of heterocyclyl, cycloalkyl, cycloalkenyl and aryl radicals, wherein R is optionally substituted in a substitutable position with one or more radicals that are selected from the group consisting of alsuyl radicals , haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, halo, alkoxy and thioalkyl; - "= a ==: =: -:" where R is a methyl or amino radical; and wherein R is a radical selected from the group consisting of hydride, halo, alkyl, alkenyl, alkynyl, oxo, cyano, carboxyl, cyanoalkyl, heterocyclyloxy, alkyloxy, thioalkyl., Alkylcarbonyl, cycloalkyl, aryl, haloalkyl, heterocyclyl, cycloalkenyl, aralkyl, heterocyclylalkyl, acyl, alkylthioalkyl, hydroxyalkyl, alkoxycarbonyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkoxyalkyl, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, to inocarbonilalquilo, alkylaminocarbonyl, N-arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, alkylaminocarbonylalkyl, carboxyalkyl, alkylamino, N-arylamino, N-aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N-arylamino, aminoalkyl, alkylaminoalkyl, N- Arylaminoalkyl, N-aralkylaminoalkyl, N-alkyl-N-aralkylaminoalkyl, N-alkyl-N-arylaminoalkyl, aryloxy, aralkoxy, thioaryl, thioaralkyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, N-arylaminosulfonyl, arylsulfonyl, N-alkyl-N- Arylaminosulfonyl; or a pharmaceutically acceptable salt thereof. ** pr * eferida of compounds that inhibit cyclooxygenase-2, consists of meloxican (Boehringer Ingelheim), nimesulide (Helsinn), MK-966 (Merck &Co), L-783003 (Merck &Co), T- 614 (Toyama), D-1367 (Chiroscience), L-748731 (Merck &Co), L-745337 (Merck &Co) and compounds of Formula I wherein A is selected from the group consisting of heterocyclyl rings of 5 or 6 partially unsaturated members, unsaturated 5 or 6 membered heterocyclyl, unsaturated condensed 9 or 10 membered heterocyclyl, lower cycloalkenyl and phenyl; wherein R is selected from the group consisting of 5- and 6-membered heterocyclyl, lower cycloalkyl, lower cycloalkenyl and aryl, which is selected from phenyl, biphenyl and naphthyl, wherein R is optionally substituted in a substitutable position with one or more radicals which are selected from the group consisting of lower alkyl, lower haloalkyl, cyano, carboxyl, lower alkoxycarbonyl, hydroxyl, lower hydroxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino, lower alkoxyalkyl, lower alkylsulfinyl, halo, lower alkoxy and lower thioalkyl; wherein R is a methyl or amino radical; and wherein R is a radical that is selected from the group consisting of hydride, oxo, cyano, carbonyl, lower akoxycarbonyl, lower carboxyalkyl, lower cyanoalkyl, halo, lower alkyl, alkyloxy- ^? fff-erior; - lower cycloalkyl, phenyl, lower haloalkyl, 5- or 6-membered heterocyclyl, hydroxylalkyl, lower aralkyl, acyl, phenylcarbonyl, lower alkoxyalkyl, 5- or 6-membered heteroaryloxy, aminocarbonyl, lower alkylaminocarbonyl, lower alkylamino, lower aminoalkyl, lower alkylaminoalkyl, phenyloxy and lower aralkoxy; or a pharmaceutically acceptable salt thereof. A more preferred class of compounds that inhibit cyclooxygenase-2, consists of meloxican (Boehringer Ingelhei), nimesulide (Helsinn), MK-966 (Merck &Co), L-783003 (Merck &Co), T-614 (Toyama), D-1367 (Chiroscience), L-748731 (Merck &Co), L-745337 (Merck &Co) and compounds of Formula I wherein A is selected from the group consisting of oxazolyl, isoxazolyl radicals , furyl, thienyl, dihydrofuryl, pyrrolyl, pyrazolyl, thiazolyl, imidazolyl, isothiazolyl, benzofuryl, cyclopentenyl, cyclopentadienyl, phenyl and pyridyl; wherein R1 is selected from the group consisting of pyridyl radicals optionally substituted in a substitutable position with one or more methyl radicals; and phenyl optionally substituted in a substitutable position with one or more radicals that are selected from the group consisting of methyl, ethyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, tTT "" radicals. " "Cfano-, carboxyl, methoxycarbonyl, ethoxycarbonyl, hydroxyl, hydroxymethyl, trifluoromethoxy, amino, N-methylamino, N, N-dimethylamino, N-ethylamino, N, N-dipropylamino, N-butylamino, N-methyl-N-ethylamino , phenylamino, methoxymethyl, methylsulfinyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, pentoxy and thiomethyl, wherein R is a methyl or amino radical, and wherein R is a radical selected from the group consists of hydride, oxo, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, carboxypropyl, carboxymethyl, carboxyethyl, cyanomethyl, fluoro, chloro, bromo, methyl, ethyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, difluoromethyl, trifluoromethyl radicals , pentafluoroethyl, heptafluor opropyl, difluoroethyl, difluoropropyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, cyclohexyl, phenyl, pyridyl, thienyl, thiazolyl, oxazolyl, furyl, pyrazinyl, hydroxymethyl, hydroxypropyl, benzyl, formyl, phenylcarbonyl, methoxymethyl, furylmethyloxy, aminocarbonyl, N-methylaminocarbonyl, N, N-dimethylaminocarbonyl, N, N-dimethylamino, N-ethylamino, N, N-dipropylamino, N-butylamino, N-methyl-N-ethylamino, aminomethyl, N, N-dimethylaminomethyl, N-methyl- N-ethylaminomethyl, benzyloxy and phenyloxy; or a pharmaceutically acceptable salt thereof.

A family of specific compounds of particular interest is composed of compounds and pharmaceutically acceptable salts of the following compounds: meloxican (Boehringer Ingelheim), nimesulide (Helsinn), MK-966 ( Merck &Co), L-783003 (Merck &Co), T-614 (Toyama), D-1367 (Chiroscience), L-748731 (Merck &Co), L-745337 (Merck &Co); 8-acetyl-3- (4-fluorophenyl) -2- (4-methylsulfonyl) -phenylimidazo- (1, 2-a) -pyridine; 5, 5-dimethyl-4- (4-methylsulfonyl) -phenyl-3-phenyl-2- (5H) -furanone; 5- (4-fluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -3- (trifluoromethyl) -pyrazol; 4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -l-phenyl-3- (trifluoromethyl) -pyrazol; 4- (5- (4-chlorophenyl) -3- (4-methoxyphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (3, 5-bis- (4-methylphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chlorophenyl) -3-phenyl-1H-pyrazol-1-yl) -benzenesulfonamide; 4- (3, 5-bis- (4-methoxy phenyl) -IH-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chlorophenyl) -3- (4-methylphenyl) -IH-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chlorophenyl) -3- (4-nitrophenyl) -lH-pyrazol-1-yl) -benzenesuITfüSamide; ~ -4- (5- (4-chlorophenyl) -3- (5-chloro-2-thienyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (4-chloro-3,5-diphenyl-lH-pyrazol-1-yl) -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5-phenyl-3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-fluorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-methoxyphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (difluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [4-chloro-5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (4-methylphenyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5-phenyl-lH-pyrazol-1-yl] -benzenesulfonamy a; 4- [3- (difluoromethyl) -5- (4-methoxyphenyl) -lH-pyrazol-1-yl] -benzenesulfomanide; 4- [3-cyano-5- (4-fluorophenyl) -lH-pyrazol-1-yl] -benzenesphidopamide-7 -4- [3- (difluoromethyl) -5- (3-fluoro-4-methoxyphenyl) -lH -pyrazol-1-yl] -benzenesulfonamide; 4- [5- (3-fluoro-4-methoxyphenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide; 4- [4-chloro-5-phenyl-lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (hydroxymethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-N, N-dimethylamino) -phenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 4- [6- (4-fluorophenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesulfonamide; 6- (4-fluorophenyl) -7- [4- (methylsulfonyl) -phenyl] -spiro- [3,4] -octa-6-ene; 5- (3-chloro-4-methoxyphenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 4- [6- (3-chloro-4-methoxyphenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesulfonamide; 5- (3,5-dichloro-4-methoxyphenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 5- (3-Chloro-4-fluorophenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 4- [6- (3, -dichlorophenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesuhamid; -2- (3-chloro-4-fluorophenyl) -4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -thiazole; 2- (2-chlorophenyl) -4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -thiazole; 5- (4-fluorophenyl) -4- (4-methylsulfonylphenyl) -2-methylthiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2-trifluoromethylthiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2- (2-thienyl) -thiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2- benzylaminothiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2- (1-propylamino) -thiazole; 2- [(3,5-dichlorophenoxy) -methyl) -4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -thiazole; 5- (4-fluorophenyl) -4- (4-methylsulfonylphenyl) -2-trifluoromethylthiazole; l-methylsulfonyl-4- [1,1-dimethyl-4- (4-fluorophenyl) -cyclopenta-2,4-dien-3-yl] -benzene; 4- [4- (4-fluorophenyl) -1,1-dimethylcyclopenta-2,4-dien-3-yl] -benzenesulfonamide; 5- (4-flurophenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hepta-4,6-diene; 4- [6- (4-fluorophenyl) -spiro- [2,4] -hepta-4,6-dien-5-yl] -benzenesuy bnamida; 6- (4-fluorophenyl) -2-methoxy-5- [4- (methylsulfonyl) -phenyl] -pyridine-3-carbonitrile; 2-bromo-6- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -pyridine-3-carbonitrile; 6- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -2- phenylpyridine-3-carbonitrile; 4- [2- (4-methylpyridin-2-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (5-Methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (2-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 3- [1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -1H-imidazol-2-yl] -pyridine; 2- [1- [4- (methylsulfonyl) -phenyl-4- (trifluoromethyl) -1H-imidazol-2-yl] -pyridine; 2-methyl-4- [1- [4- (methylsulfonyl) -phenyl-4- (trifluoromethyl) -lH-imidazol-2-yl] -pyridine; 2-methyl-6- [1- [4- (methylsulfonyl) -phenyl-4- (trifluoromethyl) -lH-imidazol-2-yl] -pyridine; 4- [2- (6-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 2- (3, -difluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -lH-imidazole; 4- [2- (4-met-? ¥ f ñ? L) * - 4- = (txifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 2- (4-chlorophenyl) -1- [4- (ethylsulfonyl) -phenyl] -4-methyl-lH-imidazole; 2- (4-chlorophenyl) -1- [4- (methylsulfonyl) -phenyl] -4-phenyl-lH-imidazole; 2- (4-chlorophenyl) -4- (4-fluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -1H-imidazole; 2- (3-fluoro-4-methoxyphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -1H-imidazole; 1- [4- (Methylsulfonyl) -phenyl] -2-phenyl-4-trifluoromethyl-1H-imidazole; 2- (4-methylphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- trifluoromethyl-lH-imidazole; 4- [2- (3-chloro-4-methylphenyl) -4- (trifluoromethyl) -lH-1-idazol-1-yl] -benzenesulfonamide; 2- (3-fluoro-5-methylphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -lH-imidazole; 4- [2- (3-fluoro-5-methylphenyl) -4- (trifluoromethyl) -1H-imidazol-1-yl] -benzenesulfonamide; 2- (3-methylphenyl) -l- [4- (methylsulfonyl) -phenyl] -4- trifluoromethyl-1H-imidazole; 4- [2- (3-methylphenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 1- [4- (Methylsulfonyl) -phenyl] -2- (3-chlorophenyl) -4- trifluoromethyl-lH-imi azol; 4- [2- (3-chlorophenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 4- [2-phenyl-4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (4-methoxy-3-chlorophenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; l-allyl-4- (4-fluorophenyl) -3- [4- (methylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazole; 4- [1-ethyl-4- (4-fluorophenyl) -5- (trifluoromethyl) -lH-pyrazol-3-yl] -benzenesulfonamide; N-phenyl- [4- (4-fluorophenyl) -3- [4- (methylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazol-1-yl] -acetamide; [4- (4-fluorophenyl) -3- [4- (ethylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazol-1-yl] -acetic acid ethyl ester; 4- (4-fluorophenyl) -3- [4- (ethylsulfonyl) -phenyl] -1- (2-phenylethyl) -IH-pyrazole; 4- (4-fluorophenyl) -3- [4- (methylsulfonyl) -phenyl] -1- (2-phenylethyl) -5- (trifluoromethyl) -pyrazol; l-ethyl-4- (4-fluorophenyl) -3- [4- (methylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazole; 5- (4-fluorophenyl) -4- (4-methylsulfonylphenyl) -2- trifluoromethyl-1H-imidazole; 4- [4- (ethylsulfonyl) -phenyl] -5- (2-thiophenyl) -2- (trifluoromethyl) -IH-imidazole; 5- [4- (Methylsulfonyl) -phenyl] -6- (trifluoromethyl) -pyridine; 2-ethoxy-5- (4-fluorophenyl) -4- [4- (methylsulfonyl) -phenyl] -6- (trifluoromethyl) -pyridine; 5- (4-fluorophenyl) 4- [4- (ethylsulfonyl) -phenyl] -2- (2-propynyloxy) -6- (trifluoromethyl) -pyridine; 2-bromo-5- (4-fluorophenyl) -4- [4- (methylsulfonyl) -phenyl] -6- (trifluoromethyl) -pyridine; 4- [2- (3-chloro-4-methoxyphenyl) -4,5-difluorophenyl] -benzenesulfonamide; 1- (4-fluorophenyl) -2- [4- (methylsulfonyl) -phenyl] -benzene; 5-difluoromethyl-4- (4-methylsulfonylphenyl) -3-phenylisoxazole; 4- [3-ethyl-5-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-difluoromethyl-3-phenylispxazol-4-yl] -benzenesulfonamide; 4- [5-hydroxymethyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-methyl-3-phenyl-isoxazol-4-yl] -benzenesulfonamide; 1- [2- (4-fluorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-fluoro-2-methylphenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-chlorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (2,4-dichlorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-trif? Udr "omethyl-phenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-methylthiophenyl) -cyclopenten-1-yl] - 4- (methylsulfonyl) benzene; 1- [2- (4-fluorophenyl) -4, -dimethylcyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (4-fluorophenyl) -4, - dimethylcyclopenten-1-yl] -benzenesulfonamide; 1- [2- (4-chlorophenyl) -4,4-dimethylcyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (4-chlorophenyl) - 4-dimethylcyclopenten-1-yl] -benzenesulfonamide; 4- [2- (4-fluorophenyl) -cyclopenten-1-yl] -benzenesulfonamide; 4- [2- (4-chlorophenyl) -cyclopenten-1-yl] - benzenesulfonamide; 1- [2- (4-methoxyphenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (2,3-difluorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (3-fluoro-4-methoxyphenyl) -cyclopenten-1-yl] -benzenesulfonamide; 1- [2- (3-chloro-4-methoxyphenyl) -cyclopenten-1-yl ] -4- (methylsulfonyl) -benzene; 4- [2- (3-chloro-4-fluorophenyl) -cyclopenten-1-yl] -benzenesulfonamide; 4- [2- (2-methylpyridin-5-yl) -cyclopenten-1-yl] benzenesulfonamide; ~ 2- [4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -oxazol-2-yl] -2-benzyl-ethyl acetate; 2- [4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -oxazol-2-yl] -acetic acid; 2- (tert-butyl) -4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -oxazole; 4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -2-phenyloxazole; 4- (4-fluorophenyl) -2-methyl-5- [4- (methylsulfonyl) -phenyl] -oxazole; and 4- [5- (3-fluoro-4-methoxyphenyl) -2-trifluoromethyl-4-oxazolyl] -benzenesulfonamide. A family of specific compounds of particular particular interest, consists of pharmaceutically acceptable compounds and salts of the following compounds: MK-966 (Merck &Co); L-752,860 (Merck &Co); L-783003 (Merck &Co); T-614 (Toyama); D-1367 (Chiroscience); L-748731 (Merck &Co); L-745337 (Merck &Co); and the compounds of Formula I 4- [5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; - [5- (3-fluoro-4-methoxyphenyl) -3- (difluoromethyl) -lH-pyrazol-1-yl] -SeTlc-n-sul "fonamide; 3- [1- [4- (methylsulfonyl) -phenyl] ] -4-trifluoromethyl-lH-imidazol-2-yl] -pyridine; -methyl-5- [1- [4- (methylsulfonyl) -phenyl] -4-trifluoromethyl-lH-imidazol-2-yl] -pyridine; 4- [2- (5-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 4- [5-methyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-hydroxymethyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; [2-trifluoromethyl-5- (3,4-difluorophenyl) -4-oxazolyl] -benzenesulfonamide; 4- [2-methyl-4-phenyl] -5-oxazolyl] -benzenesulfonamide and 4- [5- (3-fluoro-4-methoxyphenyl-2-trifluoromethyl) -4-oxazolyl] -benzenesulfonamide A subclass of inhibitors of cyclooxygenase-2 is selected from the group consisting of of the compounds of Formula II wherein R is selected from the group consisting of hydride, alkyl, haloalkyl, alkoxycarbspx? s- "- ~ - cyano, cyanoalkyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, carboxyalkylaminocarbonyl, carboxyalkyl, aralkoxycarbonylalkylaminocarbonyl, aminocarbonylalkyl, alkoxycarbonylcyanoalkenyl, and hydroxyalkyl, wherein R is selected from the group consisting of hydride, alkyl, cyano, hydroxyalkyl, cycloalkyl, alkylsulfonyl and halo radicals, and wherein R is selected from the group consisting of aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic radicals; where R is optionally substituted in a substitutable position with one or more radicals which are selected from the group consisting of halo, thioalkyl, alkylsulfonyl, cyano, nitro, haloalkyl, alkyl, hydroxyl, alkenyl, hydroxyalkyl, carboxyl, cycloalkyl, alkylamino, dialkylamino radicals , alkoxycarbonyl, aminocar bonyl, alkoxy, haloalkoxy, sulfamyl, heterocyclic and amino; or a pharmaceutically acceptable salt or derivative thereof. A class of compounds of particular interest consists of those compounds of Formula I wherein R is selected from the group consisting of hydride, lower alkyl, lower halochyl, lower alkoxycarbonyl, - "- t = -scta ?? 5 - ~ cyanoalkyl, radicals lower, carboxyl, aminocarbonyl, lower alkylaminocarbonyl, lower cycloalkylaminocarbonyl, arylaminocarbonyl, lower carboxyalkylaminocarbonyl, lower aminocarbonylalkyl, lower aralkoxycarbonylalkylaminocarbonyl, lower carboxyalkyl, lower alkoxycarbonylcyanoalkenyl, and lower hydroxyalkyl, wherein R is selected from the group consisting of hydride, lower alkyl, cyano, radicals, lower hydroxyalkyl, lower cycloalkyl, lower alkylsulfonyl and halo, and wherein R is selected from the group consisting of aralkenyl, aryl, cycloalkyl, cycloalkenyl 4 and heterocyclic radicals, wherein R is optionally substituted in a substitutable position with one or more radicals that are selected from the group consisting of halo radicals, lower thioalkyl, lower alkylsulfonyl, cyano, nitro, lower haloalkyl, lower alkyl, hydroxyl, lower alkenyl, hydroxyalkyl, carbonyl, lower cycloalkyl, lower alkylamino, lower dialkylamino, lower alkoxycarbonyl, aminocarbonyl, lower alkoxy, lower haloalkoxy, sulfamyl, five or six membered heterocyclic and amino; or a pharmaceutically acceptable salt or derivative thereof. A family of specific compounds of particular interest with Formula I, consists of pharmaceutically acceptable compounds, derivatives, "al", of the following compounds: 4- [5- (4-chlorophenyl) -3- (trifluoromethyl) -lH- pyrazol-1-yl] -benzenesulfonamide; 4- [5-phenyl-3- (trifluoromethyl) -IH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-fluorophenyl) -3- (trifluoromethyl) - lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-methoxyphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) - 3- (difluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [4- chloro-5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (4-methylphenyl) -lH-pyrazole-1- il] -benzenesulfonamide; 4- [3- (difluoromethyl) -5-phenyl-1H-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (4-methoxyphenyl) -lH-pyrazole- 1-yl] -benzenesulfonamide; [3-cyano-5- (4-fluorophenyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (3-fluoro-4-methoxyphenyl) -lH-pyrazol-1-yl] -JDerrcensu? Fsnamide; 4- [5- (3-fluoro-4-methoxyphenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide; 4- [4-chloro-5-phenyl-lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (hydroxymethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; and 4- [5- (4- (N, N-dimethylamino) -phenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide. A family of specific compounds of particular particular interest with Formula I, consists of compounds and pharmaceutically acceptable salts or derivatives of the following compounds: 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -lH-pyrazole-1 -yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (difluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; and 4- [5- (3-fluoro-4-methoxyphenyl) -3- (difluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide. The term "derivatives" as used herein, encompasses any compound that is structurally related to cyclooxygenase-2 inhibitors or which possesses substantially equivalent biological activity. As an example, such inhibitors may influence, but be limited to, prodrugs thereof. The "erm" not "~" hydride "as used herein, denotes a simple hydrogen atom (H) The hydride radical may be attached, for example, to an oxygen atom to form a hydroxyl radical or two hydride radicals can be attached to a carbon atom to form a methylene radical (-CH2-) The term "alkyl" when used either alone or together with other terms such as "haloalkyl", "alkylsulfonyl", "alkoxyalkyl" "e" hydroxyalkyl "means straight or branched chain radicals having from one to about twenty carbon atoms or, preferably, from one to about twelve carbon atoms.The most preferred alkyl radicals are" lower alkyl "radicals that they have from one to about ten carbon atoms The more preferred lower alkyl radicals have from one to about six carbon atoms Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl radicals or, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, hexyl and the like. The term "alkenyl" as used herein, includes straight or branched chain radicals having at least one carbon-carbon double bond and having from two to about twenty carbon atoms or, preferably, from two to about twelve carbon atoms. The most preferred alkyl radicals are "lower alkenyllo" radicals having from two to about six carbon atoms. Examples of alkenyl radicals include the ethenyl, propenyl, allyl, butenyl and 4-methylbutenyl radicals. The term "alkynyl" as used herein, denotes straight or branched chain radicals having from two to about twenty carbon atoms or, preferably, from two to about twelve carbon atoms. The most preferred alkynyl radicals are the "lower alkynyl" radicals having from two to about ten carbon atoms. The most preferred lower alkynyl radicals have from two to about six carbon atoms. Examples of such radicals include propargyl, butynyl radicals and the like. The terms "alkenyl", "lower alkenyl", as used herein, refer to radicals having "cis" and "trans" orientations or, alternatively, "E" orientations. The term "cycloalkyl" as used present, it includes saturated carbocyclic radicals having from three to twelve carbon atoms The most preferred cycloalkyl radicals are the "lower cycloalkyl" radicals having from three to about eight carbon atoms Examples of such radicals include cyclopropyl radicals , cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl The term "c ^ cxoalquerril®" as used herein, includes partially unsaturated carbocyclic radicals having from three to twelve carbon atoms. The most preferred cycloalkenyl radicals are the "lower cycloalkenyl" radicals having from four to about eight carbon atoms. Examples of such radicals include the cyclobutenyl, cyclopentenyl, cyclopentadienyl and cyclohexenyl radicals. The term "halo" as used herein, means halogens such as fluorine, chlorine, bromine or iodine. The term "haloalkyl" as used herein, includes radicals wherein any of the carbon atoms of the alkyl radical is substituted with a halo group such as defined above. Specifically include monohaloalkyl, dihaloalkyl and polyhaloalkyl. A monohaloalkyl radical, for example, may have either an iodine, bromine, chlorine or fluorine atom within the radical. The dihalo and polyhaloalkyl radicals can have two or more of the same halo atom or a combination of different halo radicals. The term "lower haloalkyl" as used herein, includes radicals having from one to six carbon atoms. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, T-diodepthafluoropropyl. , difluorochloromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. The term "hydroxyalkyl" as used herein, includes straight or branched chain alkyl radicals having from one to about ten carbon atoms, any of which may be substituted with one or more hydroxyl radicals. The most preferred hydroxyalkyl radicals are the "hydroxyalkyl lower" radicals having from one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include the hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl radicals. The terms "alkoxy" and "alkyloxy" as used herein, include straight or branched chain radicals containing oxy radicals, each having alkyl portions of one to about ten carbon atoms. The most preferred alkoxy radicals are the "lower alkoxy" radicals having from one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy radicals. The term "alkoxyalkyl" as used herein, includes alkyl radicals having one or more alkoxy radicals attached to the alkyl radical; that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. The "alkoxy" α-demifs- "radicals can be substituted with one or more halo atoms, such as fluoro, chloro or bromo, to obtain haloalkoxy radicals The most preferred haloalkoxy radicals are the" lower haloalkoxy "radicals having from one to six carbon atoms and one or more halo radicals Examples of such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy radicals The term "aryl" as used herein, by itself or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached in a pendent manner or in a fused manner The term "aryl" as used herein, includes aromatic radicals such as phenyl, naphthyl , tetrahydronaphthyl, "indane and biphenyl. The aryl moieties may also be substituted in a substitutable position with one or more substituents that are independently selected from the group consisting of alkyl, alkoxyalkyl, alkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkoxy, aralkoxy, hydroxyl, amino, halo, nitro, alkylamino, acyl, cyano, carboxy, aminocarbonyl, alkoxycarbonyl and aralkoxycarbonyl. The term "heterocyclyl" as used herein, includes ring-shaped radicals that are saturated, partially saturated, or unsaturated, containing heteroatoms, wherein the heteroetoms may be selected from the group consisting of nitrogen, sulfur and oxygen Examples of saturated heterocyclyl radicals include the 3 to 6 membered heteromonocyclic group containing 1 to 4 nitrogen atoms (eg, pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.), a heteromonocyclic group of 3 to 6 saturated members containing 1 to 2 oxygen atom and 1 to 3 nitrogen atoms (eg, morpholinyl, etc.), a saturated 3 to 6 membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (eg, thiazolidinyl, etc.) Examples of partially unsaturated heterocyclyl radicals include the dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole radicals. "aryl" as used herein, includes unsaturated heterocyclyl radicals. Examples of unsaturated heterocyclyl radicals, also referred to as "heteroaryl" radicals, include the unsaturated 3 to 6 membered heteromonocyclic group containing from 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (eg, 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (eg, 1H-tetrazolyl, 2H- tetrazolyl, etc.), etc .; a heterocyclic unsaturated cis-unsaturated group containing from 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolpiridazinyl (eg, tetrazolo- [1, 5] b) -pyridazinyl, etc.), etc., an unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, furyl, etc., an unsaturated 3 to 6-membered heteromonocyclic group containing sulfur atom, for example, thienyl, etc., an unsaturated 3 to 6 membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl (eg, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1, 2, 5-oxadiazolyl, etc.), etc., a condensed unsaturated heterocyclyl group containing 1 to 2 oxygen atoms and 1 to 3 Nitrogen atoms (eg, benzoxazolyl, benzoxadiazolyl, etc.), a heteromonocyclic group 3 to 6 membered unsaturated containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example thiazolyl, thiadiazolyl (e.g., 1,2,4-thiadiazolyl); 1, 3, 4-thiadiazolyl; 1, 2, 5-thiazolyl; etc etc.; a condensed unsaturated heterocyclyl group having 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms (e.g., benzothiazolyl, benzothiadiazolyl, etc.) and the like. The term also includes radicals in which "heterocyclyl radicals are fused to aryl radicals." Examples of such bicyclic fused radicals include benzofuran, benzothiophene and the like, said "heterocyclyl group" may have from 1 to 3 substituents such as alkyl radicals, hydroxyl, halo, alkoxy, oxo, amino and alkylamino The term "thioalkyl" as used herein, includes radicals containing a straight or branched chain alkyl radical of one to about ten carbon atoms attached to a carbon atom. divalent sulfur The most preferred thioalkyl radicals are "lower thioalkyl" radicals having alkyl radicals of one to six carbon atoms Examples of such lower thioalkyl radicals are the thiomethyl, thioethyl, thiopropyl, thiobutyl and thiohexyl radicals The term "alkylthioalkyl" "as used herein, includes radicals that contain a bound thioalkyl radical through the divalent sulfur to an alkyl radical of one to about ten carbon atoms. The most preferred alkylthioalkyl radicals are the "lower alkylthioalkyl" radicals having alkyl radicals of one to six carbon atoms. Examples of such lower alkylthioalkyl radicals include the methylthiomethyl radical. The term "alkylsulfinyl" as used herein, includes radicals containing an alkoxy radical-linear or branched chain of one to ten carbon atoms, linked to a divalent -S (= 0) radical. The most preferred alkylsulfinyl radicals are the "lower alkylsulfinyl" radicals having alkyl radicals of 1 to 6 carbon atoms. Examples of such lower alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl radicals. The term "sulfonyl" whether used alone or linked to other terms such as alkylsulfonyl, as used herein, refers respectively to divalent -S02- radicals. The term "alkylsulfonyl" as used herein, includes alkyl radicals attached to a sulfonyl radical, wherein the alkyl is as defined above. The most preferred alkylsulfonyl radicals are "lower alkylsulfonyl" radicals having from one to six carbon atoms. Examples of such lower alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl and propylsulfonyl radicals. The "alkylsulfonyl" radicals can additionally be substituted with one or more halo atoms, such as fluoro, chloro or bromo, to obtain haloalkylsulfonyl radicals. The terms "sulfamyl", "aminosulfonyl" and "sulfone idyl" as used herein, refer to NH2O2S- radicals. The term "acyl" as used herein denotes a radical obtained by removal of the hydroxyl residue from an organic acid Examples of such acyl radicals include alkanoyl and aroyl radicals Examples of such lower alkanoyl radicals include the radicals formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, trifluoroacetyl The term "carbonyl", whether used alone or together with other terms such as "alkoxycarbonyl" as used herein, denotes radicals - (C = 0) - The term "aroyl" as used herein, includes aryl radicals with a carbonyl radical such as defined above Examples of aroyl radicals include benzoyl, naphthoyl and the like radicals and the aryl portion of said aroyl radical may additionally be substituted.The terms "carboxy" or "carboxyl", whether used alone or together with other such terms as "carboxyalkyl" as used herein, denote radicals -CO2H. The term "carboxyalkyl" as used herein, includes alkyl radicals substituted with a carboxy radical. Most preferred are "lower carboxyalkyl" radicals which include lower alkyl radicals such as those defined above and may additionally be substituted on the alkyl radical with a halo group. Examples of such lower carboxyalkyl radicals include the carboxymethyl, carboxyethyl and carboxypropyl radicals. The term "alkoxycarbonyl" as used herein, refers to a radical containing an alkoxy radical such as defined above, linked, via an oxygen atom, to a carbonyl radical. Most preferred are "lower alkoxycarbonyl" radicals whose alkyl portions have from 1 to 6 carbon atoms. Examples of such lower alkoxycarbonyl (ester) radicals include radicals, substituted or unsubstituted, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The terms "alkylcarbonyl", "arylcarbonyl" and "aralkylcarbonyl" as used herein, include radicals having alkyl, aryl and aralkyl groups such as those defined above, attached to a carbonyl radical. Examples of such radicals include the radicals, substituted or unsubstituted, methylcarbonyl, ethylcarbonyl, phenylcarbonyl and benzylcarbonyl. The term "aralkyl" as used herein, includes alkyl radicals substituted with aryl groups such as benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The aryl group of said aralkyl radicals can additionally be substituted with -IraTor "al * qurlo, alkoxy, haloalkyl and haloalkoxy groups The terms" benzyl "and" phenylmethyl "are interchangeable The term" heterocyclylalkyl "as used in present, includes alkyl radicals substituted with saturated and partially unsaturated heterocyclyl groups, such as pyrrolidinylmethyl and alkyl radicals substituted with heteroaryl groups such as pyridylmethyl, quinolylmethyl, thienylmethyl, furylethyl and quinolylethyl The heteroaryl group of said heteroaralkyl radicals may additionally be substituted with halo groups , alkyl, alkoxy, haloalkyl and haloalkoxy The term "aralkoxy" as used herein, includes aralkyl radicals attached through an oxygen atom to other radicals The term "aralkoxyalkyl" as used herein, includes aralkoxy radicals attached through an oxygen atom to a radi lime alguilo. The term "thioaralkyl" as used herein, includes aralkyl radicals attached to a sulfur atom. The term "aralkylthioalkyl" as used herein, includes thioaralkyl radicals attached through a sulfur atom to an alkyl radical. The term "aminoalkyl" as used herein, includes alkyl radicals substituted with one or more amino radicals. The most preferred are the lower aminoalkyl radicals. Examples of such radicals include aminomethyl, aminoethyl, and the like. The term "alkylamino" as used herein, denotes amino groups that have been substituted >; with one or two alkyl radicals. Preferred are "N-lower alkylamino" radicals having alkyl portions of 1 to 6 carbon atoms. Suitable lower alkylamino radicals may be monoalkylamino or dialkylamino radicals such as N-methylamino, N-ethylamino, N, N-dimethylamino, N, N-diethylamino or the like. The term "arylamino" as used herein, denotes amino groups that have been substituted with one or two aryl radicals, such as N-phenylamino. The "arylamino" radicals can also be substituted in the aryl ring portion of the radical. The term "aralkylamino" as used herein, includes aralkyl radicals attached through an amino nitrogen atom, to other radicals. The terms "N-arylaminoalkyl" and "N-aryl-N-alkylaminoalkyl" as used herein, denote amino groups which have been substituted with an aryl radical or with an aryl radical and an alkyl radical, respectively, and whose amino group is attached to an alkyl radical. Examples of such radicals include the N-phenylaminomethyl and N-phenyl-N-methylaminomethyl radicals. The term "aminocarbonyl" as used herein, denotes an amide group of the Formula -C (= 0) NH2. The term "arylaminocarbonyl" as used herein, denotes an aminocarbonyl group which has been substituted with one or two alkyl radicals on the nitrogen atom of the amino group.The preferred ones are the "N-alkylaminocarbonyl" radicals, "N, N-dialkylaminocarbonyl." The most preferred are the "lower N-alkylaminocarbonyl" and "N, N-dialkylaminocarbonyl lower" radicals, wherein the lower alkyl portions are as defined above, the term "alkylaminoalkyl" as used herein. used herein, includes radicals having one or more alkyl radicals attached to an aminoalkyl radical The term "aryloxyalkyl" as used herein, includes radicals having an aryl radical attached to an alkyl radical through an atom Divalent Oxygen The term "arylthioalkyl" as used herein includes radicals having an aryl group attached to an alkyl group through a divalent sulfur atom. The compounds used in the methods of the present invention may be present in the form of free bases or pharmaceutically acceptable acid addition salts thereof. The term "pharmaceutically acceptable salts" as used herein, includes the salts commonly used to form salts which are "alkali metal" and to form addition salts of free acids or bases. The salt is not critical, provided that it is pharmaceutically acceptable The pharmaceutically acceptable acid addition salts of the compounds of the Formula I can be prepared from an inorganic acid or an organic acid Examples of such inorganic acids are the acid hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric The appropriate organic acids can be selected from the group consisting of aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulphonic acids, examples of which are formic acid, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, gluc uronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, 4-hydroxybenzoic, phenylacetic, mandelic, and bonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, 2-hydroxyethanesulfonic, toluenesulfonic, sulphanilic, cyclohexylaminosulfonic, stearic, algénico, ß-hidroxibutírico, salicílico, galactárico and galacturónico. Suitable pharmaceutically acceptable basic addition salts of the compounds of Formula I include metal salts prepared from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc; or organic salts prepared from N, N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All these salts can be prepared by conventional means from the corresponding compounds of Formula I, by reacting, for example, the appropriate acid or base with the compound of Formula I. Biological Evaluation Several animal models are available they are appropriate for the evaluation of the prevention of cardiovascular disorders, including the prevention of atherosclerosis. See Stehbens, Prog. Card. Dis. , XXIX, 1007-28 (1986) and Zhang et al. , Sci ence, 258, 468-71 (1992). An APOe mouse model of atherosclerosis has been described by Roselear et al. (Arteri oscle, Thromb. Vasc. Biol., 16, 1013-18 (1996) The cyclooxygenase-2 inhibitor must be active at a dose of 20 mg / kg to prevent atherosclerotic lesions. pharmaceutical composition for the prevention of cardiovascular disorders, which includes a therapeutically effective amount of a compound of Formula I in association with at least one pharmaceutically acceptable carrier, adjuvant or diluent (collectively referred to herein as "vehicle materials") ") Y, if desired, other active ingredients. The active compounds of the present invention can be administered by any suitable route known to those skilled in the art, preferably in the form of a pharmaceutical composition adapted for such a route and in an effective dose for the intended treatment. The active compounds and composition, for example, can be administered orally, intravascularly, intraperitoneally, intranasally, intrabronchially, subcutaneously, intramuscularly or topically (including aerosol). The methods and compositions used in the present invention can be used alone or in conjunction with additional therapies known to those skilled in the art, in the prevention of cardiovascular disorders. The methods and compositions described herein can be used as adjunctive therapy. As an example, the cyclooxygenase-2 inhibitor can be administered alone or in conjunction with other agents, drugs or nutrients. There are a large number of cardiovascular treatment agents commercially available, in clinical evaluation and in preclinical development, which can be selected for use with a selective inhibitor of cyclooxygenase-2 for the prevention of cardiovascular disorders. drug combination therapy. Such an agent may be one or more agents that are selected, but not limited to, several major categories, for example, a drug that lowers lipids, including an inhibitor of IBAT, a fibrate, niacin, a statin, an inhibitor of CETP and a bile acid sequestrant, an antioxidant including vitamin E and probucol, an antagonist of IlblIIa (including xemilofiban and orbofiban), an aldosterone inhibitor (including spirolactone and epoxymexrenone), an antagonist of AII (including losartan), an β-blocker, aspirin, a cycle diuretic and an ACE inhibitor. The term "combination therapy" (or "adjunctive therapy") as used herein to define the use of a cyclooxygenase-2 inhibiting agent and one or more other pharmaceutical agents, means that it encompasses the administration of each agent in a sequential manner in a regimen that will provide beneficial effects of the drug combination and also encompasses the co-administration of these agents in a substantially simultaneous manner, for example in a single formulation having a fixed ratio of these active agents, or in multiple formulations separately for each agent.

For oral administration, the pharmaceutical composition will be in the form, for example, of a tablet, a capsule, a suspension or a liquid. The pharmaceutical composition is preferably prepared in the form of a dosage unit (pharmaceutical form) containing a particular amount of the active ingredient. Examples of such dosage forms are capsules, tablets, powders, granules or a suspension, with conventional additives such as lactose, mannitol, corn starch or potato starch; with binders such as crystalline cellulose, cellulose derivatives, acacia gum, corn starch or gelatin; with disintegrants such as corn starch, potato starch or sodium carboxymethyl cellulose; and with lubricants such as talc or magnesium stearate. The active ingredient can also be administered by injection in the form of a composition in which, for example, saline, dextrose or water can be used as a suitable vehicle. For intravenous, intramuscular, subcutaneous or intraperitoneal administration, the compound can be combined with a sterile aqueous solution which is preferably isotonic with the blood of the recipient, such formulations can be prepared by dissolving the solid active ingredient in water containing physiologically compatible substances such as sodium chloride, 4b-glycine and the like, and having a pH compatible with the SiOIogical conditions, to produce an aqueous solution, and said solution is subjected to sterilization .The formulations may be present in containers. Single-dose or multiple-dose preparations, for example sealed vials or flasks, Formulations suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active compound, which is preferably prepared isotonic. can formulate by suspending or emulsifying the compounds in a non-aqueous solvent, such as a vegetable oil, glycerides of synthetic aliphatic acids, esters of higher aliphatic acids or propylene glycol. Formulations for topical application include known gels, creams, oils and the like. For aerosol application, the compounds can be formulated with the known aerosol excipients, such as saline, and can be administered using commercially available nebulizers. The formulation in a source of fatty acids can be used to increase biocompatibility. Aerosol application is the preferred method of administration to the lungs for prevention applications.

For rectal administration, the active ingredient is formulated into suppositories using bases that are solid at room temperature and that melt or dissolve at body temperature Commonly used bases include cocoa butter, gelatin glycerinate, hydrogenated vegetable oil, polyethylene glycols of various molecular weights and fatty esters of polyethylene stearate The dosage form and amount can be easily established with reference to the known treatment or to prophylactic regimens The amount of therapeutically active compound that is administered and the regimen of Dosage for the treatment of a disease with the compounds and / or compositions of the present invention, depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration and the particular compound employed, the location as well as the properties pharmacokinetics of the treated individual and, therefore, said amount of therapeutically active compound can vary widely. The dosage will usually be lower if the compounds are administered locally rather than systemically and for prevention rather than for treatment. Such treatments may be administered as often as necessary and for the periods of time deemed necessary by the treating physician. "~" A technician in the field will observe that the dose regimen or the therapeutically effective amount of the inhibitor to be administered., it may be necessary to optimize for each individual. The pharmaceutical compositions may contain the active ingredient in a range of about 0.1 to 2000 mg, preferably in the range of about 0.5 to 500 mg and more preferably between about 1 and 200 mg. A daily dose of about 0.01 to 100 mg / kg of body weight, preferably between about 0.5 and about 50 mg / kg of body weight, and more preferably of about 0.1 to 20 mg / kg of body weight may be appropriate. The daily dose can be administered in one to four doses per day. All of the patent documents referred to herein are incorporated by reference. Although the present invention has been described with respect to specific modalities, the details of these modalities should not be considered as limitations. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects to which it relates.

Claims

CLAIMS Having described the invention as an antecedent, the content of the following claims is claimed as property: 1. The use of a therapeutically effective amount of a compound selected from the group consisting of L-783003 (Merck &Co) , L-748731 (Merck &Co), L-745337 (Merck &Co) and a compound of For I wherein A is a substituent selected from the group consisting of partially unsaturated or unsaturated heterocyclyl rings and partially unsaturated or unsaturated carbocyclic rings; wherein R is at least one substituent selected from the group consisting of heterocyclyl, cycloalkyl, cycloalkenyl and aryl radicals, wherein R is optionally substituted in a substitutable position with one or more radicals that are selected from the group consisting of radicals alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, halo, alkoxy and thioalkyl; wherein R "is a methyl or amino radical, and wherein R is a radical selected from the group consisting of hydride, halo, alkyl, alkenyl, alkynyl, oxo, cyano, carboxyl, cyanoalkyl, heterocyclyloxy, alkyloxy, thioalkyl radicals , alkylcarbonyl, cycloalkyl, aryl, haloalkyl, heterocyclyl, cycloalkenyl, aralkyl, heterocyclylalkyl, acyl, alkylthioalkyl, hydroxyalkyl, alkoxycarbonyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkoxyalkyl, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxyaralkoxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, aminocarbonyl, alkylaminocarbonyl , N-arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, alkylaminocarbonylalkyl, carboxyalkyl, alkylamino, N-arylamino, N-aralkylamino, N-alkyl-N-aralkylamino, N-alkyl-N-arylamino, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl , N-aralkylaminoalkyl, N-alkyl-N-aralkylaminoalkyl, N-alkyl-N-arylaminoalkyl, aryloxy, aral coxy, thioaryl, thioaralkyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, N-arylaminosulfonyl, arylsulfonyl, N-alkyl-N-arylaminosulfonyl; provided that the compound is not 3-chloro-l- (4-fluorophenyl) -5- (4-methylsulfonyl) -pyrazol; or a pharmaceutically acceptable salt thereof; for the manufacture = í ^ = ~ uñ -medicamento for the prevention of inflammation related to a cardiovascular disorder in a subject. 2. Use in accordance with the claim 1, characterized in that A is selected from the group consisting of partially unsaturated 5 or 6 membered heterocyclyl radicals, unsaturated 5 or 6 membered heterocyclyl, unsaturated condensed 9 or 10 membered heterocyclyl, cycloalkenyl of 4 to 8 carbon atoms and phenyl; wherein R is selected from the group consisting of 5- and 6-membered heterocyclyl radicals, cycloalkyl 3 to 8 carbon atoms, cycloalkenyl of 4 to 8 carbon atoms and aryl which is selected from the group consisting of phenyl, biphenyl and naphthyl, wherein R is optionally substituted in a substitutable position with one or more radicals which are selected from group consisting of alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, cyano, carboxyl, alkoxycarbonyl of 1 to 6 carbon atoms, hydroxyl, hydroxyalkyl of 1 to 6 carbon atoms, haloalkoxy of 1 to 6 carbon atoms, amino, alkylamino of 1 to 6 carbon atoms, phenylamino, alkoxy of 1 to 6 carbon atoms- (alkyl of 1 to 6 carbon atoms), alkylsulfinyl of 1 to 6 carbon atoms, halo, alkoxy from 1 to 6 carbon atoms and thioalkyl of 1 to 6 carbon atoms; wherein R is a methyl amino radical; and wherein R is a radical selected from the group consisting of hydride, oxo, cyano, carboxyl, alkoxycarbonyl radicals of 1 to 6 carbon atoms, carboxy- (alkyl of 1 to 6 carbon atoms), cyanoalkyl of 1 to 6 carbon atoms, halo, alkyl of 1 to 6 carbon atoms, alkyloxy of 1 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, phenyl, haloalkyl of 1 to 6 carbon atoms, 5 or 6 membered heterocyclyl, hydroxy of 1 to 6 carbon atoms- (alkyl of 1 to 6 carbon atoms), aryl- (alkyl of 1 to 6 carbon atoms), acyl, phenylcarbonyl, alkoxy of 1 to 6 atoms carbon- (alkyl of 1 to 6 carbon atoms), heteroaryloxy of 5 or 6 members, aminocarbonyl, alkylaminocarbonyl of 1 to 6 carbon atoms, alkylamino of 1 to 6 carbon atoms, aminoalkyl of 1 to 6 carbon atoms, alkylaminoalkyl of 1 to 6 carbon atoms, phenyloxy and aryl- (alkoxy of 1 to 6 carbon atoms); or a pharmaceutically acceptable salt thereof. 3. The use according to claim 2, characterized in that A is selected from the group consisting of oxazolyl, isoxazolyl, furyl, thienyl, dihydrofuryl, pyrrolyl, pyrazolyl, thiazolyl, imidazolyl, isothiazolyl, benzofuryl, cyclopentenyl, cyclopentadienyl, phenyl and pyridyl; wherein R is selected from the group consisting of pyridyl radicals optionally substituted in a substitutable position with one or more methyl radicals, and optionally substituted phenyl in a substitutable position with one or more radicals that are selected from the group consisting of methyl radicals ethyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, hydroxyl, hydroxymethyl, trifluoromethoxy, amino, N-methylamino, N, N-dimethylamino, N -ethylamino, N, N-dipropylamino, N-butylamino, N-methyl-N-ethylamino, phenylamino, methoxymethyl, methylsulfinyl, fluoro, chloro, bromo, methoxy, ethoxy, propoxy, n-butoxy, pentoxy and 2-thiomethyl; R is a methyl or amino radical, and wherein R is a radical selected from the group consisting of hydride, oxo, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, carboxypropyl, carboxymethyl, carboxyethyl, cyanomethyl, flu radicals gold, chlorine, bromine, methyl, ethyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, pentafluoropropyl, difluroethyl, difluoropropyl, methoxy, ethoxy, propoxy, n-butoxy, pentoxy, cyclohexyl, phenyl, pyridyl, thienyl, thiazolyl, oxazolyl, furyl, pyrazinyl, hydroxymethyl, hydroxypropyl, benzyl, formyl, phenylcarbonyl, methoxymethyl-1T2- "fyrylmethyloxy, aminocarbonyl, N-methylaminocarbonyl, N, N-dimethylaminocarbonyl, N, N -dimethylamino, N-ethylamino, N, N-dipropylamino, N-butylamino, N-methyl-N-ethylamino, aminomethyl, N, N-dimethylaminomethyl, N-methyl-N-ethylaminomethyl, benzyloxy and phenyloxy; or a pharmaceutically acceptable salt thereof. 4. Use in accordance with the claim 1, characterized in that the compound is selected from compounds and their pharmaceutically acceptable salts from the group consisting of L-783003 (Merck &Co); L-748731 (Merck &Co); L-745337 (Merck &Co); 8-acetyl-3- (4-fluorophenyl) -2- (4-methylsulfonyl) -phenylimidazo- (1, 2-a) -pyridine; 5, 5-dimethyl-4- (4-methylsulfonyl) -phenyl-3-phenyl-2- (5H) -furanone; 5- (4-fluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -3- (trifluoromethyl) -pyrazol; 4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -1-phenyl-3- (trifluoromethyl) -pyrazol; 4- (5- (4-chlorophenyl) -3- (4-methoxyphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (3, 5-bis- (4-methylphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chloro-phenyl) -3-phenyl-1H-pyrazole-1-ii; benzenesulfonamide; 4- (3,5-bis- (4-methoxyphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide;; 4- (5- (4-chlorophenyl) -3- (4-methylphenyl) -lH-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chlorophenyl) -3- (4-nitrophenyl) - 1H-pyrazol-1-yl) -benzenesulfonamide; 4- (5- (4-chlorophenyl) -3- (5-chloro-2-thienyl) -lH-pyrazol-1-yl) -benzenesulfonamide; chloro-3, 5-diphenyl-lH-pyrazol-1-yl) -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 5-phenyl-3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-fluorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; - [5- (4-methoxyphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (difluoromethyl) -lH-pyrazole-1- il] -benzenesulfonamide; 4- [5- (4-methylphenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [4-chloro-5- (4-chlorophenyl) -3- (trifluoromethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (4-methylphenyl) -lH-pyrazol-1-yl] - benzenesu? Phiamide -4- [3- (difluoromethyl) -5-phenyl-1H-pyrazol-1-yl ] - benzenesulfonamide; 4- [3- (difluoromethyl) -5- (4-methoxyphenyl) -lH-pyrazol-1-yl] -benzenesulfomanide; 4- [3-cyano-5- (4-fluorophenyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [3- (difluoromethyl) -5- (3-fluoro-4-methoxyphenyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (3-fluoro-4-methoxyphenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide; 4- [4-chloro-5-phenyl-lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-chlorophenyl) -3- (hydroxymethyl) -lH-pyrazol-1-yl] -benzenesulfonamide; 4- [5- (4-N, N-dimethylamino) -phenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl] -benzenesulfonamide; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 4- [6- (4-fluorophenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesulfonamide; 6- (4-fluorophenyl) -7- [4- (methylsulfonyl) -phenyl] -spiro- [3,4] -octa-6-ene; 5- (3-chloro-4-methoxyphenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hept-5-ene; 4- [6- (3-chloro-4-methoxyphenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesuT-hamidide; -5- (3,5-dichloro-4-methoxyphenyl) ) -6- [4- (Methylsulfonyl) -phenyl] * spiro- [2,4] -hept-5-ene; 5- (3-chloro-4-fluorophenyl) -6- [4- (methylsulfonyl) -phenyl] - spiro- [2] -hept-5-ene; 4- [6- (3, 4-dichlorophenyl) -spiro- [2,4] -hept-5-en-5-yl] -benzenesulfonamide; 2- (3- chloro-4-fluorophenyl) -4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -thiazole; 2- (2-chlorophenyl) -4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -thiazole; 5- (4-fluorophenyl) -4- (4-methylsulfonylphenyl) -2-methylthiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2- trifluoromethylthiazole; 4- (4-fluorophenyl) -5 - (4-Methylsulfonylphenyl) -2- (2-thienyl) -thiazole; 4- (4-fluorophenyl) -5- (4-methylsulfonylphenyl) -2- benzylaminothiazole; 4- (4-fluorophenyl) -5- (4- methylsulfonylphenyl) -2- (1-propylamino) -thiazole; 2- [(3,5-dichlorophenoxy) -methyl) -4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -thiazole; - (4-fluorophenyl) -4- (4-methylsulfonylphenyl) - 2- trifluoromethylthiazole;

l-methylsulfonyl-4- [1, l-dimethyl-4- (4-fluorophenyl: cycloperite-r27"4-dien-3-l] -benzene; 4- [4- (4-fluorophenyl) -1, l- dimethylcyclopenta-2,4-dien-3-yl] -benzenesulfonamide; 5- (4-fluorophenyl) -6- [4- (methylsulfonyl) -phenyl] -spiro- [2,4] -hepta-4,6-diene; 4- [6- (4-fluorophenyl) -spiro- [2,4] -hepta-4,6-dien-5-yl] -benzenesulfonamide; 6- (4-fluorophenyl) -2-methoxy-5- [4- (methylsulfonyl) -phenyl] -pyridine-3-carbonitrile; 2-bromo-6- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -pyridine-3-carbonitrile; 6- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -2-phenyl-pyridine-3-carbonitrile; 4- [2- (4-methylpyridin-2-yl) -4- (trifluoromethyl) -IH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (5-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (2-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 3- [1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -1H-imidazol-2-yl] -pyridine; 2- [1- [4- (methylsulfonyl) -phenyl-4- (trifluoromethyl) -1H-imidazol-2-yl] -pyridine; 2-methyl-4- [1- [4-methylsulfonyl) -phenyl-4- (trifluoromethyl) -1H-imidazol-2-yl] -pyridine; (methylsulfonyl) -phenyl-4- (trifluoromethyl) -lH-imidazol-2-yl] -pyridine; 4- [2- (6-methylpyridin-3-yl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 2- (3,4-difluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -1H-imidazole; 4- [2- (4-methylphenyl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 2- (4-chlorophenyl) -1- [4- (methylsulfonyl) -phenyl] -4-methyl-lH-imidazole; 2- (4-chlorophenyl) -1- [4- (methylsulfonyl) -phenyl] -4-phenyl-lH-imidazole; 2- (4-chlorophenyl) -4- (4-fluorophenyl) -1- [4- (methylsulfonyl) -phenyl] -lH-imidazole; 2- (3-fluoro-4-methoxyphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -IH-imidazole; 1- [4- (Methylsulfonyl) -phenyl] -2-phenyl-4-trifluoromethyl-1H-imidazole; 2- (4-methylphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- trifluoromethyl-lH-imidazole; 4- [2- (3-chloro-4-methylphenyl) -4- (trifluoromethyl) -lH-imidazol-1-yl] -benzenesulfonamide; 2- (3-fluoro-5-methylphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- (trifluoromethyl) -lH-imidazole; 4- [2- (3-fluoro-5-methylphenyl) -4- (trifluoromethyl) -1H- imidazoT ^ F ^ ll] -benzenesulfonamide; 2- (3-methylphenyl) -1- [4- (methylsulfonyl) -phenyl] -4- trifluoromethyl-1H-imidazole; 4- [2- (3-methylphenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 1- [4- (methylsulfonyl) -phenyl] -2- (3-chlorophenyl) -4- trifluoromethyl-1H-imidazole; 4- [2- (3-chlorophenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 4- [2-phenyl-4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; 4- [2- (4-methoxy-3-chlorophenyl) -4-trifluoromethyl-lH-imidazol-1-yl] -benzenesulfonamide; l-allyl-4- (4-fluorophenyl) -3- [4- (ethylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazole; 4- [1-ethyl-4- (4-fluorophenyl) -5- (trifluoromethyl) -lH-pyrazol-3-yl] -benzenesulfonamide; N-phenyl- [4- (4-fluorophenyl-3- [4- (ethylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazol-1-yl] -acetamide; [4- (4-fluorophenyl) - 3- [4- (Methylsulfonyl) -phenyl] -5- (trifluoromethyl) -IH-pyrazol-1-yl] -acetic acid ethyl ester; 4- (4-fluorophenyl) -3- [4- (methylsulfonyl) -phenyl] -1- (2-phenylethyl) -lH-pyrazole; 4- (4-fluorophenyl) -3- [4- (ethylsulfonyl) -phenyl] -1- (2-phenylethyl) -5- (trifluoromethyl) -pyrazole; -ethyl-4- (4-^? X? Orofeñi) -3- [4- (methylsulfonyl) -phenyl] -5- (trifluoromethyl) -lH-pyrazole; 5- (4-fluorophenyl) -4- (4- methylsulfonylphenyl) -2- trifluoromethyl-lH-imidazole; 4- [4- (methylsulfonyl) -phenyl] -5- (2-thiophenyl) -2- (trifluoromethyl) -1H-imidazole; 5- (4-fluorophenyl) -2 -methoxy-4- [4- (methylsulfonyl) -phenyl] -6- (trifluoromethyl) -pyridine; 2-ethoxy-5- (4-fluorophenyl) -4- [4- (methylsulfonyl) -phenyl] -6- ( trifluoromethyl) -pyridine; 5- (4-fluorophenyl) 4- [4- (methylsulfonyl) -phenyl] -2- (2-propynyloxy) -6- (trifluoromethyl) -pyridine; 2-bromo-5- (4-fluorophenyl) ) -4- [4- (methylsulfonyl) -f enyl] -6- (trifluoromethyl) -pyridine; 4- [2- (3-chloro-4-methoxyphenyl) -4,5-difluorophenyl] -benzenesulfonamide; 1- (4-fluorophenyl) -2- [4- (methylsulfonyl) -phenyl] -benzene; 5-difluoromethyl-4- (4-methylsulfonylphenyl) -3-phenylisoxazole; 4- [3-ethyl-5-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-difluoromethyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-hydroxymethyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; 4- [5-methyl-3-phenylisoxazol-4-yl] -benzenesulfonamide; 1- [2- (4-fluorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-flusro = 2'-me "t? Rphenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-chlorophenyl) -cyclopenten-1- il] -4- (methylsulfonyl) -benzene; 1- [2- (2,4-dichlorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-trifluoromethylphenyl) - Cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 1- [2- (4-methylthiophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) benzene; 1- [2- (4-fluorophenyl) -4,4-dimethylcyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (4-fluorophenyl) -4,4-dimethylcyclopenten-1-yl] -benzenesulfonamide; 1- [2- ( 4-chlorophenyl) -4,4-dimethylcyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (4-chlorophenyl) -4,4-dimethylcyclopenten-1-yl] -benzenesulfonamide; [2- (4-fluorophenyl) -cyclopenten-1-yl] -benzenesulfonamide; 4- [2- (4-chlorophenyl) -cyclopenten-1-yl] -benzenesulfonamide; 1- [2- (4-methoxyphenyl) -cyclopenten; -1-yl] -4- (methylsulfonyl) -benzene; 1- [
2- (2,
3-difluorophenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene;
4- [2- (3-fluoro-4-methoxyphenyl) -cyclopenten-1-yl] -benzenesulfonamide; ~ 1- [2- (3-chloro-4-methoxyphenyl) -cyclopenten-1-yl] -4- (methylsulfonyl) -benzene; 4- [2- (3-chloro-4-fluorophenyl) -cyclopenten-1-yl] -benzenesulfonamide; 4- [2- (2-methylpyridin-
5-yl) -cyclopenten-1-yl] -benzenesulfonamide; 2- [4- (4-fluorophenyl) -5- [4- (ethylsulfonyl) -phenyl] -oxazol-2-yl] -2-benzyl-ethyl acetate; 2- [4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -oxazol-2-yl] -acetic acid; 2- (tert-butyl) -4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -oxazole; 4- (4-fluorophenyl) -5- [4- (methylsulfonyl) -phenyl] -2-phenyloxazole; 4- (4-fluorophenyl) -2-methyl-5- [4- (methylsulfonyl) -phenyl] -oxazole; and 4- [5- (3-fluoro-4-methoxyphenyl) -2-trifluoromethyl-4-oxazolyl] -benzenesulfonamide. 5. Use in accordance with the claim 1, characterized in that the cardiovascular disorder is selected from the group consisting of prevention of disease - of coronary arteries, aneurysm, arteriosclerosis, atherosclerosis including atherosclerosis by heart transplantation, myocardial infarction, embolism, heart attack, "thrombosis including venous thrombosis, angina including unstable angina, inflammation of coronary plaque, bacterial-induced inflammation, including Chlamydia-induced inflammation, virus-induced inflammation and inflammation associated with surgical procedures such as vascular grafts, including coronary artery bypass surgery, revascularization procedures including angioplasty, placement of graft clips, endoarterectomy and other invasive procedures involving arteries, veins and capillaries 6. The use of a therapeutically effective amount of a compound of Formula II characterized in that R is selected from the group consisting of hydride, alkyl, haloalkyl, alkoxycarbonyl, cyano, cyanoalkyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, carboxyalkylaminocarbonyl, carboxyalkyl, aralkoxycapsilonyl, aminocarbonyl, alkoxycarbonylcyanoalkenyl and hydroxyalkyl; Wherein R is selected from the group consisting of hydride, alkyl, cyano, hydroxyalkyl, cycloalkyl, alkylsulfonyl and halo radicals; and wherein R is selected from the group consisting of aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic radicals; wherein R is optionally substituted in a substitutable position with one or more radicals which are selected from the group consisting of halo, thioalkyl, alkylsulfonyl, cyano, nitro, haloalkyl, alkyl, hydroxyl, alkenyl, hydroxyalkyl, carboxyl, cycloalkyl, alkylamino, dialkylamino, alkoxycarbonyl, aminocarbonyl, alkoxy, haloalkoxy, sulfamyl, heterocyclic and amino; or a pharmaceutically acceptable salt or derivative thereof; for the manufacture of a medicament for preventing inflammation related to a cardiovascular disorder in a subject. 7. Use in accordance with the claim 6, characterized in that R is selected from the group consisting of hydride radicals, alkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, alkoxycarbonyl of 1 to 6 carbon atoms, cyano, cyanoalkyl of 3 to 8 atoms carbon, carboxyl, aminocarbonyl &T ^ aTkylaminocarbonyl of 1 to 6 carbon atoms, cycloalkylaminocarbonyl of 3 to 8 carbon atoms, arylaminocarbonyl, carboxy- (alkylaminocarbonyl of 1 to 6 carbon atoms), aminocarbonyl- (alkyl of 1) to 6 carbon atoms), aryl- (alkoxycarbonylalkylaminocarbonyl of 1 to 6 carbon atoms), carboxy (alkyl of 1 to 6 carbon atoms), alkoxycarbonylcyanoalkenyl of 1 to 6 carbon atoms and hydroxyalkyl of 1 to 6 carbon atoms; wherein R is selected from the group consisting of hydride radicals, alkyl of 1 to 6 carbon atoms, cyano, hydroxyalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, alkylsulfonyl of 1 to 6 carbon atoms and halo; and wherein R is a radical selected from the group consisting of aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic radicals; wherein R is optionally substituted in a substitutable position with one or more radicals which are selected from the group consisting of halo, thioalkyl radicals of 1 to 6 carbon atoms, alkylsulfonyl of 1 to 6 carbon atoms, cyano, nitro, haloalkyl 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, hydroxyl, alkenyl of 2 to 6 carbon atoms, hydroxyalkyl of 1 to 6 carbon atoms, carboxyl, cycloalkyl of 3 to 8 carbon atoms, alkylamino of 1 to 6 carbon atoms, dialkylamino of 1 to 6 atoms - ^ Se -carbon- "alkoxycarbonyl of 1 to 6 carbon atoms, aminocarbonyl, alkoxy of 1 to 6 carbon atoms, haloalkoxy of 1 to 6 carbon atoms, sulfamyl, Five or six membered heterocyclic and amino; or a pharmaceutically acceptable salt or derivative thereof. The use according to claim 6, characterized in that the cardiovascular disorder related to inflammation is selected from the group consisting of prevention of coronary artery disease, aneurysm, arteriosclerosis, atherosclerosis including atherosclerosis by heart transplantation, myocardial infarction, embolism , heart attack, thrombosis including venous thrombosis, angina including unstable angina, inflammation of the coronary plaque, bacterial-induced inflammation including Chlamydia-induced inflammation, virus-induced inflammation and inflammation associated with surgical procedures such as vascular graft including bypass surgery (bypass ) of the coronary arteries, revascularization procedures including angioplasty, placement of graft clips, endoartectomy and other invasive procedures involving the arteries, veins and capillaries.