SUBSTITUTED BENZENESULFONAMIDE DERIVATIVES AS PRODRUGS OF COX-2 INHIBITORS

• Main Authors: GRANETO, Matthew J, WEIER, Richard M, MALECHA, James W, NAGARAJAN, Srinivasan, KHANNA, Ish K, TALLEY, John J, CARTER, Jeffrey, BERTENSHAW, Stephen, XU, Xiangdong, ROGIER, Donald J, Jr, LI, Jinglin, BROWN, David L, PENNING, Thomas D
• Format: Patent
• Language: English
• Published: 10.10.2011
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Ovaj pronalazakse odnosi na pro-lekove jedinjenja sledeće formule I Ovaj pronalazakse odnosi na pro-lekove jedinjenja sledeće formule I         u kojoj A, R1,R2 i R3 imaju značenje data u 1. patentnom zahtevu, akoji selektivno sprečavaju ciklooksigens-2.Ova jedinjenja su opisana kao korisna pri lečenju zapaljenja kao i poremećaja povezanihsa zapaljenjima. u kojoj A, R 1 ,R 2 i R 3 imaju značenje data u 1. patentnom zahtevu, akoji selektivno  sprečavaju ciklooksigens-2.Ova jedinjenja su opisana kao korisna pri lečenju zapaljenja  kao i poremećaja povezanihsa zapaljenjima. Prodrugs of COX-2 inhibitors of formula (I) are described as being useful in treating inflammation and inflammation-related disorders wherein A is a ring substituent selected from partially unsaturated heterocyclyl, heteroaryl, cycloalkenyl and aryl, wherein A is optionally substituted at a substitutable position with one or more radicals selected from alkylcarbonyl, formyl, halo, alkyl, haloalkyl, oxo, cyano, nitro, carboxyl, alkoxy, aminocarbonyl, alkoxycarbonyl, carboxyalkyl, cyanoalkyl, hydroxyalkyl, haloalkylsulfonyloxy, alkoxyalkyloxyalkyl, carboxyalkoxyalkyl, cycloalkylalkyl, alkenyl, alkynyl, heterocyclyloxy, alkylthio, cycloalkyl, aryl, heterocyclyl, cycloalkenyl, aralkyl, heterocyclylalkyl, alkylthioalkyl, arylcarbonyl, aralkylcarbonyl, aralkenyl, alkoxyalkyl, arylthioalkyl, aryloxyalkyl, aralkylthioalkyl, aralkoxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylaminocarbonyl, N-arylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, alkylaminocarbonylalkyl, 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, arylthio, aralkylthio, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, N-arylaminosulfonyl, arylsulfonyl, and N-alkyl-N-arylaminosulfonyl; wherein R is selected from heterocyclyl, cycloalkyl, cycloalkenyl, and aryl, wherein R is optionally substituted at a substitutable position with one or more radicals selected from alkyl, haloalkyl, cyano, carboxyl, alkoxycarbonyl, hydroxyl, hydroxyalkyl, haloalkoxy, amino, alkylamino, arylamino, nitro, alkoxyalkyl, alkylsulfinyl, halo, alkoxy and alkylthio; wherein R is selected from hydrido and alkoxycarbonylalkyl; and wherein R is selected from alkyl, carboxyalkyl, acyl, alkoxycarbonyl, heteroarylcarbonyl, alkoxycarbonylalkylcarbonyl, alkoxycarbonylcarbonyl, amino acid residue, and alkylcarbonylaminoalkylcarbonyl; provided A is not tetrazolium, or pyridinum; and further provided A is not indanone when R is alkyl or carboxyalkyl; or a pharmaceutically-acceptable salt thereof.