Inhibitors of microsomal triglyceride transfer protein and method

A compound having the structure ##STR738## wherein Q is ##STR739## Z is a bond;

• R.sup.5 is phenyl substituted with aryl, wherein aryl is phenyl substituted with trifluoromethyl;
• R.sup.6 is H;
• R.sup.13 and R.sup.15 are each H;
• R.sup.12 --Z.sup.2 is ##STR740## R.sup.11 is (CH.sub.2).sub.4 ;
• Z.sup.1 is a bond or N-oxides ##STR741## thereof;
• or pharmaceutically acceptable salts thereof.

A compound which has the structure ##STR747## where Q is ##STR748## R.sup.1 is an indenyl-type group of the structure ##STR749## Z.sup.1 and Z.sup.2 are the same or different and are independently a bond O, S, ##STR750## R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;

• arylene or mixed arylene-alkylene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, heteroaryl, heteroarylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the provisos that
• (1) when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, then Z.sup.2 is ##STR751## or a bond;
• (2) when Z.sup.2 is a bond, R.sup.12 cannot be heteroaryl or heteroarylalkyl;
• (3) where R.sup.1 is indanyl E, if Z.sup.1 is a bond, then R.sup.12 --Z.sup.2 is other than alkyl or H;
• (4) where R.sup.1 is indenyl F, then Z.sup.2 is ##STR752## where R.sup.12 is other than alkoxy, or ##STR753## where R.sup.12 is other than alkyl;
• Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms;
• R.sup.13 and R.sup.14 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.15a and R.sup.16a are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, alkoxy, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl, or aryloxy;
• R.sup.5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloheteroalkyl, heteroaryloxy, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl, heteroarylcarbonyl, amino, alkyl-amino, arylamino, heteroarylamino, cycloalkyloxy or cycloalkylamino, all optionally substituted through available carbon atoms with 1, 2, 3 or 4 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, arylalkynyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, substituted amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl, arylsulfonylamino, heteroarylcarbonylamino, heteroarylsulfinyl, heteroarylthio, heteroarylsulfonyl and alkylsulfinyl;
• R.sup.6 is hydrogen or C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
• all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR754## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members;
• and
• N-oxides ##STR755## thereof;
• and pharmaceutically acceptable salts thereof.

A compound which has the structure ##STR765## wherein R.sup.1 is a group of the structure ##STR766## or Z.sup.1 and Z.sup.2 are the same or different and are independently a bond, O, S, ##STR767## with the proviso that with respect to B, at least one of Z.sup.1 and Z.sup.2 will be other than a bond;

• R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;
• arylene or mixed arylenealkyene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, arylalkyl, arylalkenyl, cycloalkyl, trihaloalkyl, trihaloalkylalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, heteroaryl or heteroarylalkyl;
• with the provisos that (1) when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, then Z.sup.2 is ##STR768## or a bond, and (2) when Z.sup.2 is a bond, R.sup.12 cannot be heteroaryl or heteroarylalkyl;
• Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms R.sup.13, R.sup.14, R.sup.15, and R.sup.16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, carboxy, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.5 is alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl, heteroarylcarbonyl, amino, alkylamino, arylamino, heteroarylamino, cycloalkyloxy, or cycloalkylamino, all optionally substituted through available carbon atoms with 1, 2, 3 or 4 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, arylalkynyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, substituted amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl, arylsulfonylamino, heteroarylcarbonylamino, heteroarylsulfinyl, heteroarylthio, heteroarylsulfonyl, and alkylsulfinyl;
• R.sup.6 is hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
• all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR769## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members;
• and N-oxides thereof;
• and
• pharmaceutically acceptable salts thereof;
• ##STR770##

A method for preventing or treating atherosclerosis;

• or for preventing or treating pancreatitis secondary to hypertriglyceridemia;
• hyperglycemia (1) by causing reduced absorption of dietary fat through MTP inhibition or (2) by lowering triglycerides through MTP inhibition or (3) by decreasing absorption of free fatty acids through MTP inhibition;
• or obesity by causing reduced malabsorption of dietary fat through MTP inhibion, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound which has the structure ##STR771## where R.sup.1 is a fluorenyl-type group of the structure ##STR772## or R.sup.1 is an indenyl-type group of the structure ##STR773## Z.sup.1 and Z.sup.2 are the same or different and are independently a bond, O, S, ##STR774## with the proviso that with respect to B, at least one of Z.sup.1 and Z.sup.2 will be other than a bond;
• R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;
• arylene or mixed arylenealkylene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, the Z.sup.2 is ##STR775## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms;
• R.sup.13, R.sup.14, R.sup.15, and R.sup.16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.15a and R.sup.16a are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, alkoxy, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl, or aryloxy;
• R.sup.5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloheteroalkyl, heteroaryloxy, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl or heteroarylcarbonyl, all optionally substituted through available carbon atoms with 1, 2 or 3 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl and arylsulfonylamino;
• R.sup.6 is hydrogen or C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkylenyl;
• all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR776## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members;
• or
• pharmaceutically acceptable salts thereof.

A method for lowering serum lipid levels, cholesterol and/or triglycerides, or for preventing or treating hyperlipemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia and/or hypertriglyceridemia, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound which has the structure ##STR777## wherein R.sup.1 is a fluorenyl-type group of the structure ##STR778## R.sup.1 is an indenyl-type group of the structure ##STR779## Z.sup.1 and Z.sup.2 are the same or different and are independently a bond, O, S, ##STR780## with the proviso that with respect to B, at least one of Z.sup.1 and Z.sup.2 will be other than a bond;

• R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;
• arylene or mixed arylenealkylene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, the Z.sup.2 is ##STR781## Z is a bond, O, S, or N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms;
• R.sup.13, R.sup.14, R.sup.15, and R.sup.16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.15a and R.sup.16a are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, alkoxy, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl, or aryloxy;
• R.sup.5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloheteroalkyl, heteroaryloxy, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl or heteroarylcarbonyl, all optionally substituted through available carbon atoms with 1, 2, or 3 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl and arylsulfonylamino;
• R.sup.6 is hydrogen or C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
• all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR782## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members;
• or
• pharmaceutically acceptable salts thereof.

A method for preventing or treating atherosclerosis;

• or for preventing or treating pancreatitis secondary to hypertriglyceridemia;
• hyperglycemia (1) by causing reduced absorption of dietary fat through MTP inhibition or (2) by lowering triglycerides through MTP inhibition or (3) by decreasing absorption of free fatty acids through MTP inhibition;
• or obesity by causing reduced malabsorption of dietary fat through inhibition, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound which has the structure ##STR783## R.sup.1 is a fluorenyl-type group of the structure ##STR784## Z.sup.1 and Z.sup.2 are the same or different and are independently a bond, O, S, ##STR785## with the proviso that with respect to B, at least one of Z.sup.1 and Z.sup.2 will be other than a bond;
• R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;
• arylene or mixed arylenealkylene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkyenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, then Z.sup.2 is ##STR786## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms;
• R.sup.13, R.sup.14, R.sup.15, and R.sup.16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcabonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloheteroalkyl, heteroaryloxy, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl or heteroarylcarbonyl, all optionaly substituted through available carbon atoms with 1, 2, or 3 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl and arylsulfonylamino;
• R.sup.6 is hydrogen or C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
• all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR787## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members;
• or
• pharmaceutically acceptable salts thereof.

A method for lowering serum lipid levels, cholesterol and/or triglycerides, or for preventing or treating hyperlipemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia and/or hypertriglyceridemia, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound which has the structure ##STR788## R.sup.1 is a fluorenyl-type group of the structure ##STR789## Z.sup.1 and Z.sup.2 are the same or different and are independently a bond, O, S, ##STR790## with the proviso that with respect to B, at least one of Z.sup.1 and Z.sup.2 will be other than a bond;

• R.sup.11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms;
• arylene or mixed arylenealkylene;
• R.sup.12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R.sup.12 is H, aryloxy, alkoxy or arylalkoxy, then Z.sup.2 is ##STR791## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms;
• R.sup.13, R.sup.14, R.sup.15, and R.sup.16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cycloheteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy;
• R.sup.5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloheteroalkyl, heteroaryloxy, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl or heteroarylcarbonyl, all optionally substituted through available carbon atoms with 1, 2, or 3 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, arylcycloalkyl, arylalkenyl, aryloxy, aryloxyalkyl, arylalkoxy, arylazo, heteroaryloxo, heteroarylalkyl, heteroarylalkenyl, heteroaryloxy, hydroxy, nitro, cyano, amino, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkylcarbonyl, arylcarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkynylaminocarbonyl, alkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, alkylsulfonyl and arylsulfonylamino;
• R.sup.6 is hydrogen or C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkenyl;
• all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R.sup.5 set out above;
• ##STR792## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members, or
• pharmaceutically acceptable salts thereof.