Steroidal glycosides as antihyperlipidemic agents

A compound of structural formula (I):

• ##STR55## and the pharmaceutically acceptable salts and hydrates thereof wherein:
• R.sup.1 is selected from:
• a) --O--X,
• b) --O--phenyl substituted at the 3 or 4 position with X,
• c) -phenyl-4-O--X or .beta.-phenyl-3-O--X, and
• wherein X is a sugar selected from .beta.-D-cellobiosyl, .beta.-D-glucopyranosyl, .beta.-D-galactopyranosyl, .beta.-D-2-acetamido-2-deoxy-glucopyranosyl, .beta.-D-fucopyranosyl, .beta.-D-maltosyl, .beta.-D-lactosyl, .beta.-D-cellotriosyl and .beta.-D-maltotriosyl;
• R.sup.2 is selected from:
• a) --C.sub.1 -C.sub.8 -alkyl, --C.sub.3 -C.sub.8 alkenyl or --C.sub.3 -C.sub.7 -cycloalkyl unsubstituted or wherein each may be substituted with one to three substituents selected from:
• halogen, --O--C.sub.1 -C.sub.4 alkyl, aryl, heteroaryl, O-aryl and O--heteroaryl,
• b) aryl,
• c) --CH.sub.2 OC(O)NH--R.sup.3,
• d) --CH.sub.2 O(CO)NH--SO.sub.2 --R.sup.3,
• e) --CH.sub.2 OC(O)--R.sup.3,
• f) --OR.sup.3,
• g) --OC(O)NH--R.sup.3,
• h) --O(CO)NH--SO.sub.2 --R.sup.3,
• i) --OC(O)--R.sup.3,
• j) --CH.sub.2 --NR.sup.3 R.sup.4,
• k) --CH.sub.2 NHC(O)R.sup.3,
• l) --CH.sub.2 NHC(O)OR.sup.3,
• m) --CH.sub.2 NHC(O)NHR.sup.3,
• n) --NR.sup.3 R.sup.4,
• o) --NHC(O)R.sup.3,
• p) --NHC(O)OR.sup.3,
• q) --NHC(O)NHR.sup.3,
• r) --C(O)R.sup.3,
• s) --CO.sub.2 -t-Bu,
• t) --CONR.sup.3 R.sup.4,
• u) --CH=CR.sup.3 R.sup.4,
• v) ##STR56## w) ##STR57## x) ##STR58## and y) ##STR59## R.sup.3 and R.sup.4 are independently selected from:
• a) --H,
• b) C.sub.1 -C.sub.10 -alkyl, C.sub.3 -C.sub.10 alkenyl or C.sub.3 -C.sub.10 -cycloalkyl, unsubstituted or wherein each may be substituted with one to three substituents selected from:
• 1) halogen
• 2) --O--C.sub.1 -C.sub.4 alkyl,
• 3) aryl,
• 4) heteroaryl,
• 5) =O,
• 6) --C(O)-aryl,
• 7) --C(O)--C.sub.1 -C.sub.10 alkyl,
• 8) --C(O)O-aryl,
• 9) --C(O)O--C.sub.1 -C.sub.10 alkyl,
• 10) --C(O)NH-aryl,
• 11) --C(O)NH--C.sub.1 -C.sub.10 alkyl,
• 12) --N(R.sup.5).sub.2, wherein R.sup.5 is independently selected at each occurrence from the group:
• --H, --C.sub.1 -C.sub.10 alkyl, --C.sub.3 -C.sub.10 alkenyl, --C.sub.3 -C.sub.10 cycloalkyl, aryl and heteroaryl;
• c) aryl
• R.sup.3a is selected from:
• a) C.sub.1-C.sub.10 -alkyl, C.sub.3 -C.sub.10 alkenyl or C.sub.3 -C.sub.10 -cycloalkyl, unsubstituted or wherein each may be substituted with one to three substituents selected from:
• 1) halogen
• 2) --O--C.sub.1 -C.sub.4 alkyl,
• 3) aryl,
• 4) heteroaryl,
• 5) =O,
• 6) --C(O)-aryl,
• 7) --C(O)--C.sub.1 -C.sub.10 alkyl,
• 8) --COO-aryl,
• 9) --COO--C.sub.1 -C.sub.10 alkyl,
• 10) --C(O)NH-aryl,
• 11) --C(O)NH--C.sub.1 -C.sub.10 alkyl,
• 12) --N(R.sup.5).sub.2, wherein R.sup.5 is independently at each occurrence from the group:
• --H, --C.sub.1 -C.sub.10 alkyl, -C.sub.3 -C.sub.10 alkenyl, --C.sub.3 -C.sub.10 cycloalkyl, aryl and heteroaryl;
• b) aryl
• R.sup.6 and R.sup.7 are independently selected from:
• a) --H,
• b) OH,
• c) oxo (=O),
• d) =N--OR.sup.3,
• e) --NR.sup.3 R.sup.4,
• f) --NHCOR.sup.3a,
• g) --NHCONR.sup.3 R.sup.4,
• h) --NHCO.sub.2 R.sup.3a, and
• i) --SO.sub.2 R.sup.3a ;
• R.sup.8 is selected from:
• a) --H and
• b) oxo (=O);
• the line "- - - " designated as a represents a single or double bond when R.sup.6 and R.sup.7 are independently selected from --H and --SO.sub.2 R.sup.3 ;
• otherwise, a is a single bond;
• aryl is phenyl or bi-phenyl unsubstituted or wherein each may be substituted with one or two substituents selected from the group:
• halogen (F, Cl, Br, I), OH, NR.sup.3 R.sup.4, CO.sub.2 R.sup.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, NO.sub.2, CF.sub.3, C.sub.1 -C.sub.4 alkylthio, methylenedioxy, SO.sub.2 --(C.sub.1 -C.sub.8) alkyl, SO.sub.2 -aryl, and SO.sub.2 -heteroaryl;
• and
• heteroaryl is selected from
• (a) an unsubstituted, monosubstituted or disubstituted five or six membered aromatic ring which consists of carbon atoms and from one to three heteroatoms selected from the group O, N and S,
• (b) an unsubstituted, monosubstituted or disubstituted eight to ten membered bicyclic ring system which is completely or partially unsaturated and which consists of carbon atoms and from one to three heteroatoms selected from the group O, N, S, and NH;
• and wherein the substituents on the heteroaryl are independently selected from the group consisting of halogen, OH, NR.sup.3 R.sup.4, CO.sub.2 R.sup.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, NO.sub.2, CF.sub.3, C.sub.1 -C.sub.4 alkylthio, SO.sub.2 --(C.sub.1 -C.sub.8) alkyl, SO.sub.2 -aryl, and SO.sub.2 -heteroaryl.