compostos inibidores de sglt2, composição farmacêutica e uso dos referidos compostos

• Main Authors: Gang Wu, William N. Washburn, Philip M. Sher, Bruce Ellsworth, Wei Meng
• Format: Patent
• Language: Portuguese
• Published: 24.09.2019
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; DERIVATIVES THEREOF; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SUGARS

compostos inibi dores de sglt2, composição farmacêutica e uso dos referidos compostos são fornecidos compostos inibidores sglt2 tendo a fórmula (i) onde r1 e r2 são independentemente hidrogênio, oh, or5 , alquila (c 1-c8 ), cf3 , ochf2, ocf3 , sr5i ou halogênio, ou r1 e r2 juntamente com os carbonos aos quais são ligados formam -och20-; r3 e r4 são independentemente hidrogênio, oh, orsa' ofenila, och2fenila, alquila ( cl -cs) i cicloexila, cf3, - ochf2, -ocf3, halogênio, -c02r5b, -c02h, cor6b, -ch (oh) r6c, -nhcor5c, -nhs02r5ct, -nhs02fenila, fenila, -srse' -sor5f, -s02r5g, -s02fenila, tiadiazolila, tetrazolila, ou r3 e r4 juntos formam -och20-; r5, r5a, r5b, r5c, r5d, r5e, r5f, r5g e r5i são independentemente alquila ( c1-c8) ; r6b e r6c são independentemente hidrogênio ou alquila (c 1-c8 ); a é o, s, nh, ou ( ch2) n onde n é o - 3, ou um sal farmaceuticamente aceitável do mesmo ou estereoisômero do mesmo; com a condição de que onde a é (ch2)n onde n é o, 1, 2, ou 3 ou a é o, e pelo menos um dentre r1 e r2 é oh ou or5, então pelo menos um dentre r1 e r2 é cf3 , ocf3 ou ochf2 e/ou pelo menos um dentre r3 e r4 e cf3, - ochf 2, - ocf 3, -co2r5b, ch (oh) r6c, cor6b, -nhcor5c, -nhso2r5d, -nhso2fenila, fenila, -sr5e, -sor5f, -so2r5g ou -so2fenila. SGLT2 inhibiting compounds are provided having the formulawhereR1, R2, and R2a are independently hydrogen, OH, OR5, lower alkyl, CF3, OCHF2, OCF3, SR5i or halogen, or two of R1, R2 and R2a together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle;R3 and R4 are independently hydrogen, OH, OR5a, OAryl, OCH2Aryl, lower alkyl, cycloalkyl, CF3, -OCHF2, -OCF3, halogen, -CN, -CO2R5b, -CO2H, -COR6b, -CH(OH)R6c, -CH(OR5h)R6d, -CONR6R6a, -NHCOR5c, -NHSO2R5d, -NHSO2Aryl, Aryl, -SR5e, -SOR5f, -SO2R5g, -SO2Aryl, or a five, six or seven membered heterocycle, or R3 and R4 together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle;R5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h and R5i are independently lower alkyl;R6, R6a, R6b, R6c and R6d are independently hydrogen, alkyl,aryl, alkylaryl or cycloalkyl, or R6 and R6a together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle;A is O, S, NH, or (CH2)n where n is 0-3.A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.