Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method

A compound which has the structure ##STR800## including pharmaceutically acceptable salts thereof, N-oxides thereof, wherein

• A is ##STR801## where R.sup.5 is H or lower alkyl;
• B is a fluorenyl-type group of the structure ##STR802## R.sup.1 is heteroaryl, heteroarylamino, heteroaryloxy, heteroetrylsulfonylamino, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, the R.sup.1 group may optionally be substituted with 1, 2, 3 or 4 substituents, which can be any of the R.sup.3 or R.sup.1 groups or alkyl, alkenyl, alkynyl, alkoxyl, cycloalkyl cycloalkenyl, substituted alkylamino, substituted arylalkylamino, aryl, arylalkyl, arylamino, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl alkylsulfonyl --PO(R.sup.13)(R.sup.14), (where R.sup.13 and R.sup.14 are independently alkyl, aryl, alkoxy, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy, cycloheteroalkyl, cycloheteroalkylalkyl, cycloheteroalkoxy, or cycloheteroalkylalkoxy);
• aminocarbonyl (where the amino may optionally be substituted with one or two aryl, alkyl or heteroaryl groups);
• cyano, or alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, alkoxycarbonylamino, aryloxycarbonylamino, heteroaryloxylcarbonylamino, uriedo (where the uriedo nitrogens may optionally be substituted with alkyl, aryl or heteroaryl), alkylsulfonylamino, arylsulfonylamino, or heteroarylsulfonylamino;
• R.sup.2 is independently any of the groups set out for R.sup.1, alkyl, alkenyl, alkynyl, alkoxyl, (alkyl or aryl).sub.3 Si (where each alkyl or aryl group is independent), cycloalkyl, cycloalkennyl, substituted alkylamino, substituted arylalkylamino, aryl, arylalkyl, arylamino, aryloxy, arylsulfonylamino, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, --PO(R.sup.13)(R.sup.14), (where R.sup.13 and R.sup.14 are independently alkyl, aryl, alkoxy. aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy. heteroarylalkoxy. cycloheteroalkyl, cycloheteroalkylalkyl, cycloheteroalkoxy, or cycloheteroalkylalkoxy);
• aminocarbonyl (where the amino may optionally be substituted with one or two aryl, alkyl or heteroaryl groups);
• cyano, H, or polyhaloalkyl, and may be optionally substituted with one to four of any of the groups defined for R.sup.3 or substituents defined for R.sup.1 ;
• L.sup.1 is a linking group containing from 1 to 10 carbons;
• in a linear chain including alkylene, alkenylene or alkynylene, which may contain, within the linking chain any of the following:
• one or two alkenes, one or two alkynes, an oxygen, an amino group, an oxo group, and may be substituted with one to five alkyl or halo groups;
• L.sup.2 may be the same or different from L.sup.1 and may independently be any of the L.sup.1 groups set out above or a single bond;
• R.sup.3, R.sup.3', R.sup.4 and R.sup.4' may be the same or different and are independently selected from H, halogen, CF.sub.3, haloalkyl, hydroxy, alkoxy, alkyl, aryl, alkenyl, alkenyloxy, alkynyl, alkynyloxy, alkanoyl, nitro, amino, thiol, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylcarbonyloxy, alkylcarbonylamino, cyano, Ar-, Ar-alkyl, ArO, Ar-amino, Ar-thio, Ar-sulfinyl, Ar-sulfonyl, Ar-carbonyl, Ar-carbonyloxy or Ar-carbonylamino, wherein Ar is aryl or hetertoaryl and Ar may optionally include 1, 2 or 3 additional rings fused to Ar;
• R.sup.3a and R.sup.3b are the same or different and are independently any of the R.sup.3 groups except hydroxy, nitro, amino or thio;
• ##STR803## are the same or different and independently represent a 5 or 6 membered heteroaryl ring which contains 1, 2, 3 or 4 heteroatoms in the ring which are independently N, S or O;
• and including N-oxides;
• X is a bond, or is one of the following groups:
• ##STR804## wherein Y is O, N--R.sup.6 or S;
• n' is 0, 1 or 2;
• R.sup.6 is H, lower alkyl, aryl, --C(O)--R.sup.11 or --C(O)--O--R.sup.11 ;
• R.sup.7 and R.sup.8 are the same or different and are independently H, alkyl, aryl, halogen, --O--R.sup.12, or
• R.sup.7 and R.sup.8 together can be oxygen to form a ketone;
• R.sup.9, R.sup.10, R.sup.9' and R.sup.10' are the same or different and are independently H, lower alkyl, aryl or -O-R.sup.11 ;
• R.sup.9" and R.sup.10" are the same or different and are independently H, lower alkyl, aryl, halogen or --O--R.sup.11 ;
• R.sup.11 is alky or aryl;
• R.sup.12 is H, alkyl or aryl.