Amino Bi- and tri-carbocyclic aklane bis-aryl squalene synthase inhibitors
AssigneeRhone-Poulenc Rorer Pharmaceuticals Inc.
InventorsRobert L. Morris, Kent W. Neuenschwander, Keith S. Learn, Anthony C. Scotese
Life of this patent
Estimating the term…
Abstract
This invention relates to a class of novel amino bi- and tri-carbocyclic alkane compounds having bis-aryl substitution which exhibit squalene synthase inhibition properties. The bi- and tri-carbocyclic alkane ring contains an amino group and the ring is further linked or bridged to two mono- and/or bicyclic rings. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Claims18
A compound of the formula:
- ##STR13## where:
- A is O, S, NR, SO, SO.sub.2, O.dbd.C, NR--C.dbd.O, O.dbd.C--NR, RC.dbd.CR, C.tbd.C or a bond;
- B is (CR.sub.2).sub.e, O, S, NR, SO, SO.sub.2, NR--C.dbd.O, O.dbd.C--NR, RC.dbd.CR, C.tbd.C, O.dbd.C or a bond;
- R is hydrogen or C.sub.1-6 alkyl;
- R' is hydrogen, C.sub.1-6 alkyl or acetyl or propionyl;
- R" is hydrogen or C.sub.1-6 alkyl;
- R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, chloro, fluoro, bromo, trifluoromethyl, nitro, amino, mono- or di-C.sub.1-6 alkylamino or phenyl;
- R.sub.3 is hydrogen, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy, acetyloxy, propionyloxy, amino, mono- or di-C.sub.1-6 alkylamino, acetylamino, propionylamino, chloro, fluoro, bromo or trifluoromethyl;
- R.sub.4 is hydrogen, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy, acetyloxy, propionyloxy, acetylamino, propionylamino, chloro, fluoro, bromo or trifluoromethyl;
- ##STR14## Ar I is phenylene;
- Ar II is benzoxazole;
- a and b are independently 0-3;
- a+b is 0-3;
- d is 0-3
- e is 1-3;
- m and n are 0-2;
- and
- its stereoisomers, enantiomers, diastereoisomers and racemic mixtures;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.