Trifluorobenzothiazol indole acetic acid compounds which interact with and inhibit aldose reductase

摘要

A compound of formula (I) wherein A is a C1-C4 alkylene group optionally substituted with C1- C2 alkyl or mono-or disubstituted with halogen; Z is a bond; R1 is hydrogen, alkyl having 1-6 carbon atoms, halogen, or phenyl, where the phenyl or pyridyl is optionally substituted with up to three groups selected from halogen, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl, nitro, amino, or mono- or di (C1-C6)alkylamino ; R2, R3, R4 and R5 are each independently hydrogen, halogen, nitro, or an alkyl group of 1-6 carbon atoms (which may be substituted with one or more halogens); OR7, SR7, S(0)R7, S(O)2N(R7)2, C(O)N(R7)2, or N(R7)2, wherein each R7 is independently hydrogen, an alkyl group of 1-6 carbon atoms (which may be substituted with one or more halogens) or benzyl, where the phenyl portion is optionally substituted with up to three groups independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, and mono- or di (C1-C6)) alkylamino; phenyl where phenyl is optionally substituted with up to three groups independently selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, and mono- or di (C1-C6) alkylamino; phenoxy where the phenyl portion is optionally substituted with up to three groups independently selected from halogen, (C1-C6)alkyl, (C1- C6)alkoxy, amino, and mono-or di (C1-C6) alkylamino; or a group of the formula (II) where J is a bond, CH2, oxygen, or nitrogen; and each r is independently 2 or 3; R6 is hydroxy or (C1-C6)alkoxy; Ra is hydrogen, (C1-C6)alkyl, fluoro, or trifluoromethyl; Ar represents a benzothiazole ring optionally substituted on the benzo protion by one of iodo, cyano, nitro, perfluoroethyl, trifluoroacetyl, or (C1-C6)) alkanoyl, one or two of fluoro, chloro, bromo, hydroxy, (C1-C6)alkyl, (C1- C6)alkoxy, (C1-C6)alkylthio, trifluoromethoxy, trifluoromethylthio, (C1-C6)alkylsulfinyl, (C1- C6)alkylsulfonyl or trifluoromethyl, or two fluoro or two trifluoromethyl with one hydroxy or one (C1-C6)alkoxy, or one or two fluoro and one trifluoromethyl, or three fluoro. Is described. The compound can be used in a pharmaceutical composition for the treatment of chronic complications arising from diabetes mellitus, which can included diabetic cataracts, retinopathy, nephropathy and neuropathy.