Inhibitors of microsomal triglyceride transfer protein and method

• US 5,739,135 A
• Filed: 06/06/1995
• Issued: 04/14/1998
• Est. Priority Date: 09/03/1993
• Status: Expired due to Term

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Lawrence, R. Michael, Sulsky, Richard B., Tino, Joseph A., Poss, Michael A., Magnin, David R., Biller, Scott A., Dickson, John K.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): WONG, KING
• Application Number:
  US08/472,067
• Time in Patent Office: 1,043 Days
• Field of Search: 546/203, 546/204, 546/205, 546/197, 546/194, 546/206, 546/196, 546/198, 546/199, 546/200, 546/201, 514/325, 514/319, 514/321, 514/318, 514/329, 514/320, 514/322, 514/252, 514/266, 544/406, 544/407, 544/235, 544/238, 544/277
• US Class Current: 514/252.03
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/94 Oxygen atom, e.g. piperidine N-oxide
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 419/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: G01N 2800/044 : Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity

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 ##STR1## wherein R¹ to R⁷, Q, X and Y are as defined herein.

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## R^12a 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## R^12a 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 is4- 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;

R^15a and R^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;

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;

R^15a and R^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;

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;

R^15a and R^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;

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;

R^15a and R^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;

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.