Claims for Patent: 5,739,135

Summary for Patent: 5,739,135

Title:	Inhibitors of microsomal triglyceride transfer protein and method
Abstract:	Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure defined herein.
Inventor(s):	Scott A. Biller, John K. Dickson, R. Michael Lawrence, David R. Magnin, Michael A. Poss, Richard B. Sulsky, Joseph A. Tino
Assignee:	University of Pennsylvania Penn
Application Number:	US08/472,067
Patent Claims:	1. A compound which has the structure ##STR701## where Q is ##STR702## R1 is a fluorenyl-type group of the structure ##STR703## Z1 and Z2 are the same or different and are independently a bond, O, S, ##STR704## with the proviso that with respect to B, at least one of Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, heteroaryl, heteroarylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the provisos that(1) when R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR705## or a bond and (2) when Z2 is a bond, R12 cannot be heteroaryl or heteroarylalkyl; Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 are independently hydrogen, alkyl, halo, haloalkyl, aryl, cycloalkyl, cyclo-heteroalkyl, alkenyl, alkynyl, hydroxy, alkoxy, nitro, amino, thio, alkylsulfonyl, arylsulfonyl, alkylthio, arylthio, aminocarbonyl, alkylcarbonyloxy, arylcarbonylamino, alkylcarbonylamino, arylalkyl, heteroaryl, heteroarylalkyl or aryloxy; R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R5 set out above; ##STR706## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members; and N-oxides ##STR707## thereof; and pharmaceutically acceptable salts thereof. 2. The compound as defined in claim 1 having the formula ##STR708## 3. The compound as defined in claim 1 having the formula ##STR709## 4. The compound as defined in claim 1 wherein R1 is ##STR710## 5. The compound as defined in claim 4 wherein R1 is ##STR711## Z is a bond, O or S; R13, R14, R15 and R16 are each H or one of R15 and R16 and one of R13 and R14 are halogen;Z1 is a bond or C═O; R11 is alkylene or alkenylene; R12 --Z2 is ##STR712## R12a is alkyl, fluorinated lower alkyl or polyfluorinated lower alkyl. 6. The compound as defined in claim 1 wherein R1 is ##STR713## where R11 is alkylene or alkenylene; R12 is H, alkyl, alkenyl, aralkyl, aralkenyl; and R13 is H or F; and R15 is H or F; Z is O, S or a bond. 7. The compound as defined in claim 1 having the structure ##STR714## where Q is ##STR715## Z is a bond, O or S; where R5 is cycloalkyl, phenyl, aryl, heteroaryl, or cycloalkyl, phenyl, aryl or heteroaryl, independently substituted at the ortho position with alkyl, alkoxy, haloalkyl (optionally substituted with up to 5 halogens), trifluoromethyl, aryl, aryloxy, haloalkoxy (optionally substituted with up to 5 halogens), arylalkyl or arylalkoxy;R6 is H or CH3 ; R13 and R15 are independently H or F; Z1 is a bond; R11 is alkylene; R12 --Z2 is ##STR716## or Z2 is a bond and R12 is alkyl. 8. The compound as defined in claim 7 wherein R11 is --(CH2)4 --, Z1 is a bond, and R12 --Z2 is ##STR717## 9. The compound as defined in claim 7 having the structure ##STR718## and R12 is trifluoromethylalkyl or alkyl. 10. The compound as defined in claim 7 having the structure ##STR719## where R12 is alkyl. 11. The compound as defined in claim 1 having the structure ##STR720## where Q is ##STR721## Z is a bond, O or S; where R5 is cycloalkyl, phenyl, aryl, heteroaryl, or cycloalkyl, phenyl, aryl or heteroaryl, independently substituted at the ortho position with alkyl, alkoxy, haloalkyl (optionally substituted with up to 5 halogens), trifluoromethyl, aryl, aryloxy, haloalkoxy (optionally substituted with up to 5 halogens), arylalkyl or arylalkoxy;R6 is H or CH3 ; R13 and R15 are independently H or F; Z1 is a bond; R11 is alkylene; ##STR722## R12 --Z2 is ##STR723## R12a is alkyl, fluorinated lower alkyl or polyfluorinated lower alkyl, or Z2 is a bond and R12 is alkyl. 12. The compound as defined in claim 1 which is9- 4- 4- (1,1-dimethylethoxy)carbonyl!amino!-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide; 9- 4- 4- 2-(phenoxyphenyl)carbonyl!amino!-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide; 9- 4- 4-(benzoylamino)-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide; 9- 4- 4-(acetylamino)-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide; 9- 4- 4- (1,1-dimethylethoxy)carbonyl!-amino!-1-piperidinyl!butyl!-2,7-difluoro-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4- (2-phenoxybenzoyl)amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4-(benzoylamino)-1-piperidinyl!-butyl!-2,7-difluoro-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 2,7-difluoro-9- 4- 4- (2-phenoxybenzolyl)-amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoro-ethyl)-9H-fluorene-9-carboxamide; 9- 4- 4-(benzoylamino)-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 1- 4- 9- (propylamino)carbonyl!-9H-fluoren-9-yl!butyl!-3-piperidinyl!carbamic acid, phenyl-methyl ester; 9- 4- 3-(benzoylamino)-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide; 9- 4- 4- (1,1-dimethylethoxy)carbonyl!-amino!-1-piperidinyl!butyl!-3,6-difluoro-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4-(benzoylamino)-1-piperidinyl!butyl!-3,6-difluoro-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 3,6-difluoro-9- 4- 4- (2-phenoxybenzoyl)-amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl-9H-fluorene-9-carboxamide; ##STR724## 9- 4- 4- (phenoxycarbonyl)amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4- (phenylamino)carbonyl!amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9carboxamide; 9- 4- 4- (phenylsulfonyl)amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; ##STR725## 9- 4- 4- (2-phenoxybenzoyl)amino!-1-piperidinyl!-4-oxobutyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; ##STR726## 9- 4- 4- (1,1-dimethylethoxy)carbonyl!-amino!-1-piperidinyl!pentyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4- (2-phenyoxyphenyl)sulfonyl!amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 2- 4-(benzoylamino)-1-piperidinyl!carbonyl!amino!ethyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 4- (2-phenoxybenzoyl)amino!-1-piperidinecarboxylic acid, 2- 9- (2,2,2-trifluoroethyl)amino!carbonyl!-9H-fluoren-9-yl!ethyl ester; 4- (1,1-dimethylethoxy)carbonyl!amino!-1-piperidinecarboxylic acid, 2- 9- (2,2,2-trifluoroethyl)amino!carbonyl!-9H-fluoren-9-yl!ethyl ester; 9- 4- 4- (2-phenoxybenzoyl)amino!-1-piperidinyl!pentyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 2- 4- (2-phenoxybenzoyl)amino!-1-piperidinyl!carbonyl!amino!ethyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 4-(benzoylamino)-1-piperidinecarboxylic acid, 2- 9-(2,2,2-trifluoroethyl)amino!carbonyl!-9H-fluoren-9-yl!ethyl ester; 9- 4- 4-(benzoylamino)-1-piperidinyl!pentyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide; 9- 4- 4- (1,1-dimethylethoxy)carbonyl!amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-thioxanthene-9-carboxamide; 9- 4- 4-(benzoylamino)-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-thioxanthene-9-carboxamide; 9- 4- 4- (2-phenoxyphenyl)carbonyl!amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-thioxanthene-9-carboxamide;wherein for structures bearing only 2 single bonded substituents to N, the third substituent is always H, and for structures bearing an O or S with only one single bonded substituent, the second substituent is always H; and a pharmaceutically acceptable salt of any of the above and an N-oxide of any of the above. 13. The compound as defined in claim 1 which has the structure ##STR727## where R1 is a group of the structure ##STR728## R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy, or cycloalkylalkyl, Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R5 is independently alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, arylalkoxy, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, polycycloalkyl, polycycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, polycycloalkenyl, polycycloalkenylalkyl, 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, or arylsulfonylamino; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl;pharmaceutically acceptable salts thereof. 14. The compound as defined in claim 1 which has the structure ##STR729## where R1 is a fluorenyl-type group of the structure ##STR730## Z1 and Z2 are the same or different and are independently a bond, O, S, ##STR731## with the proviso that with respect to B, at least one of Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R22 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR732## Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R5 set out above; ##STR733## are the same or different and are independently selected from heteroaryl containing 5- or 6-ring members; or pharmaceutically acceptable salts thereof. 15. A method for preventing, or treating atherosclerosis; 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 inhibition, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound as defined in claim 1. 16. A method of lowering serum lipid levels, cholesterol and/or triglycerides, or preventing and/or treating hyperlipemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia and/or hypertriglyceridemia, which comprises administering to a patient in need of treatment of a therapeutically effective amount of a compound as defined in claim 1. 17. The compound as defined in claim 7 wherein Q is ##STR734## Z is a bond; R5 is aryl or heteroaryl substituted at the ortho position with aryl or heteroaryl;R6 is H; R13 and R15 are each H; R12 --Z2 is ##STR735## 18. The compound as defined in claim 17 wherein R5 is ##STR736## and R11 is --(CH2)4 --. 19. The compound as defined in claim 1 having the structure ##STR737## 20. The compound as defined in claim 1 which is cis-9- 4- 4-(2,3-dihydro-1H-isoindol-2-yl)-1-piperidinyl!butyl!-N-propyl-9H-fluorene-9-carboxamide, N-oxide or cis-9- 4- 4 (2-phenoxybenzoyl)amino!-1-piperidinyl!butyl!-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide, N-oxide. 21. A compound having the structure ##STR738## wherein Q is ##STR739## Z is a bond; R5 is phenyl substituted with aryl, wherein aryl is phenyl substituted with trifluoromethyl;R6 is H; R13 and R15 are each H; R12 --Z2 is ##STR740## R11 is (CH2)4 ; Z1 is a bond or N-oxides ##STR741## thereof; or pharmaceutically acceptable salts thereof. 22. The compound as defined in claim 21 having the structure ##STR742## wherein alkyl is CH2, and aryl is phenyl substituted with CF3. 23. The compound as defined in claim 21 having the structure ##STR743## 24. A compound having the structure ##STR744## including the piperidine N-oxide thereof or a pharmaceutically acceptable salt thereof,Z is a bond; R5 is heteroaryl, aryl, cycloheteroalkyl or cycloalkyl, each R5 group being optionally substituted with 1, 2, 3 or 4 substituents which may be the same or different. 25. The compound as defined in claim 24 wherein the substituent on R5 is adjacent to the carbon attached to the ##STR745## group. 26. The compound as defined in claim 24 wherein R5 is phenyl substituted with heteroaryl, or phenyl which is substituted with haloalkyl or trifluoromethyl. 27. The compound as defined in claim 26 wherein R5 is ##STR746## 28. A compound which has the structure ##STR747## where Q is ##STR748## R1 is an indenyl-type group of the structure ##STR749## Z1 and Z2 are the same or different and are independently a bond O, S, ##STR750## R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylene-alkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, heteroaryl, heteroarylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the provisos that(1) when R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR751## or a bond; (2) when Z2 is a bond, R12 cannot be heteroaryl or heteroarylalkyl; (3) where R1 is indanyl E, if Z1 is a bond, then R12 --Z2 is other than alkyl or H;(4) where R1 is indenyl F, then Z2 is ##STR752## where R12 is other than alkoxy, or ##STR753## where R12 is other than alkyl; Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13 and R14 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; R15a and R16a 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; R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R5 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. 29. The compound as defined in claim 28 wherein R1 is an indenyl-type group of the structure ##STR756## 30. The compound as defined in claim 28 which has the structure ##STR757## wherein R1 is an indenyl-type group of the structure ##STR758## Z1 and Z2 are the same or different and are independently a bond, O, S, ##STR759## R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 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 R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR760## or a bond; (2) when Z2 is a bond, R12 cannot be heteroaryl or heteroarylalkyl; (3) where R1 is indanyl E, if Z1 is a bond, then R12 --Z2 is other than alkyl; and (4) where R1 is indenyl F, then Z2 is ##STR761## where R12 is other than alkoxy, or ##STR762## where R12 is other than alkyl; Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms R13 and R14 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; R15a and R16a 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; R5 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 or alkylsulfinyl; R6 is hydrogen, C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R5 set out above; ##STR763## 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. 31. A method for preventing or treating atherosclerosis; pancreatitis secondary to hypertriglyceridemia; hyperglycemia (1) by causing reduced absorption of dietary fat through MTP inhibition of (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 inhibition, in a mammalian species, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound as defined in claim 28. 32. A method of lowering serum lipid levels, cholesterol and/or triglycerides, or preventing and/or treating hyperlipemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia and/or hypertriglyceridemia, which comprises administering to a patient in need of treatment a therapeutically effective amount of a compound as defined in claim 28. 33. The compound as defined in claim 30 wherein R1 is a group of the structure ##STR764## 34. A compound which has the structure ##STR765## wherein R1 is a group of the structure ##STR766## or Z1 and Z2 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 Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkyene; R12 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 R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR768## or a bond, and (2) when Z2 is a bond, R12 cannot be heteroaryl or heteroarylalkyl; Z is bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms R13, R14, R15, and R16 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;R5 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; R6 is hydrogen, C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2, 3 or 4 groups which may independently be any of the substituents listed in the definition of R5 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## 35. 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 R1 is a fluorenyl-type group of the structure ##STR772## or R1 is an indenyl-type group of the structure ##STR773## Z1 and Z2 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 Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R12 is H, aryloxy, alkoxy or arylalkoxy, the Z2 is ##STR775## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R15a and R16a 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; R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkylenyl; all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R5 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. 36. 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 R1 is a fluorenyl-type group of the structure ##STR778## R1 is an indenyl-type group of the structure ##STR779## Z1 and Z2 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 Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R12 is H, aryloxy, alkoxy or arylalkoxy, the Z2 is ##STR781## Z is a bond, O, S, or N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R15a and R16a 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; R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R5 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. 37. 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## R1 is a fluorenyl-type group of the structure ##STR784## Z1 and Z2 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 Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkyenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR786## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R5 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. 38. 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## R1 is a fluorenyl-type group of the structure ##STR789## Z1 and Z2 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 Z1 and Z2 will be other than a bond; R11 is a bond, alkylene, alkenylene or alkynylene of up to 10 carbon atoms; arylene or mixed arylenealkylene; R12 is hydrogen, alkyl, alkenyl, aryl, haloalkyl, trihaloalkyl, trihaloalkylalkyl, arylalkyl, arylalkenyl, cycloalkyl, aryloxy, alkoxy, arylalkoxy or cycloalkylalkyl, with the proviso that when R12 is H, aryloxy, alkoxy or arylalkoxy, then Z2 is ##STR791## Z is a bond, O, S, N-alkyl, N-aryl, or alkylene or alkenylene from 1 to 5 carbon atoms; R13, R14, R15, and R16 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;R5 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; R6 is hydrogen or C1 -C4 alkyl or C1 -C4 alkenyl; all optionally substituted with 1, 2 or 3 groups which may be any of the substituents listed in the definition of R5 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.