Heterocyclic inhibitors of microsomal triglyceride transfer protein and method

A compound which has the structure

• including a pharmaceutically acceptable salt thereof, or an N-oxide thereof,
• wherein A is
• where Z is N or CH, or where Z is
• or CH2 when is a single bond;
• Q is
• (1) —O—;
• (2) —S—;
• or
• where R5 and R5a are the same or different and are H, lower alkyl, aryl, heteroaryl or cycloalkyl;
• R is H, alkyl, alkoxy, alkenyl, alkynyl, aryl, halo, heteroaryl, cycloheteroalkyl, heteroarylalkyl, cycloalkyl or cycloalkenyl, with the proviso that R cannot be alkoxy or halo when is a single bond;
• B is an indenyl-type group of the structure
• R1 is alkyl, alkenyl, alkynyl, alkoxyl, (alkyl or aryl)3Si (where each alkyl or aryl group is independent), cycloalkyl, cycloalkenyl, substituted alkylamino, substituted arylalkylamino, aryl, arylalkyl, arylamino, aryloxy, hydroxy, amino, heteroaryl, heteroarylamino, heteroaryloxy, arylsulfonylamino, heteroarylsulfonylamino, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, cycloheteroalkyl, cycloheteroalkylalkyl, —PO(R13)(R14), (where R13 and R14 are independently alkyl, aryl, alkoxy, aryloxy, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylalkoxy, cycloheteroalkyl, cycloheteroalkylalkyl, cycloheteroalkoxy, or cycloheteroalkylalkoxy);
• carbonylamino or aminocarbonyl (where the amino may optionally be substituted with one or two aryl, alkyl or heteroaryl groups);
• cyano, 1,1-(alkoxyl or aryloxy)2alkyl (where the two aryl or alkyl substituents can be independently defined, or linked to one another to form a ring connected to L1 at the 2, 4, 5 or 6-position;
• the R1 group may optionally be substituted with 1, 2, 3 or 4 substituents, which can be any of the R3 or R1 groups or alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, alkoxycarbonylamino, aryloxycarbonylamino, heteroaryloxylcarbonylamino, uriedo (where the uriedo nitrogens may optionally be substituted with alkyl, aryl or heteroaryl), heterocyclylcarbonylamino (where the heterocycle is connected to the carbonyl group via a nitrogen or carbon atom), alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino,
• where J is:
• R23, R24 and R25 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or cycloalkylalkyl;
• R20, R21, R22 are independently hydrogen, halo, alkyl, alkenyl, alkoxy, aryloxy, aryl, arylalkyl, alkylmercapto, arylmercapto, cycloalkyl, cycloalkyl-alkyl, heteroaryl, heteroarylalkyl, hydroxy or haloalkyl;
• and these substituents may either be directly attached to R1, or attached via an alkylene at an open position;
• L1 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;
• R3 and R3′ may be the same or different and are independently selected from H, halogen, CF3, haloalkyl, hydroxy, alkoxy, alkyl, aryl, alkenyl, alkenyloxy, alkynyl, alkynyloxy, alkanoyl, nitro, amino, thiol, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxy, alkoxycarbonyl, aminocarbonyl, alkylcarbonyloxy, alkylcarbonylamino, cycloheteroalkyl, cycloheteroalkylalkyl, 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 heteroaryl and Ar may optionally include 1, 2 or 3 additional rings fused to Ar;
• R3a and R3b are the same or different and are independently any of the R3 groups;
• represents 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;
• with the provisos that
• (1) where A is the thiazole
• then B is other than indanyl
• and L1 is other than —CH2O—;
• and
• (2) where R1 is OH, then L1 contains at least 3 carbons in the chain;
• (3) where A is
• R can not be alkoxy.