Fused bicyclic oxazolidinone CETP inhibitor
View Patent ↗Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.
1. A method of treating a disease or condition which is hypercholesterolemia or familial-hypercholesterolemia in a patient in need of such treatment comprising the administration of a therapeutically effective amount of a compound having Formula Ia,
or a pharmaceutically acceptable salt thereof;
wherein the dashed line in the ring in Formula Ia is an optional double bond when x is 0;
wherein R 1 is CF 3 , F, or —N(CH 3 ) 2 ;
R 5 is H or CH 3 ;
D 1 is N or CR 2 , wherein R 2 is H or —CH(CH 3 ) 2 ;
D 2 is N or CR 3 , wherein R 3 is H or CH 3 ;
D 3 is N or CR 4 , wherein R 4 is H or CH 3 ;
A 1 is phenyl, pyridyl, thienyl, furyl, cyclohexenyl, or cyclopentenyl,
wherein A 1 is optionally substituted with 1-3 groups which are each independently F, Cl, —OCH 3 , isopropyl, —CN, —CH 3 , or CF 3 , and optionally one substituent group Z;
Z is A 3 , —CH 2 CH 2 CO 2 R 8 , —CH 2 CH 2 -(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl), or —CH 2 CH 2 -(5-amino-1,3,4-oxadiazol-2-yl);
R 8 is H or —CH 3 ,
A 3 is phenyl, cyclobutyl, or pyridyl, wherein A 3 is optionally substituted with 1 group —CH 3 , and is optionally substituted with 1 group -(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl), -(5-amino-1,3,4-oxadiazol-2-yl), or —CO 2 R in which R is H or —CH 3 ;
A 2 is phenyl, which is substituted with 1-2 substituent groups which are each independently CF 3 , CH 3 , F, or Cl; and
a is 0;
to said patient.
2. The method of claim 1 , wherein the method comprises the administration of the compound
or a pharmaceutically acceptable salt thereof to said patient.
3. The method of claim 1 , wherein the method comprises the administration of the compound
or a pharmaceutically acceptable salt thereof to said patient.
4. The method of claim 1 , wherein the method comprises the administration of the compound
or a pharmaceutically acceptable salt thereof to said patient.
5. The method of claim 1 , wherein the method comprises the administration of the compound
or a pharmaceutically acceptable salt thereof to said patient.
6. The method of claim 1 , wherein the method comprises the administration of the compound
or a pharmaceutically acceptable salt thereof to said patient.
7. The method of claim 2 , wherein the disease or condition is hypercholesterolemia.
8. The method of claim 3 , wherein the disease or condition is hypercholesterolemia.
9. The method of claim 4 , wherein the disease or condition is hypercholesterolemia.
10. The method of claim 5 , wherein the disease or condition is hypercholesterolemia.
11. The method of claim 6 , wherein the disease or condition is hypercholesterolemia.
12. The method of claim 2 , wherein the disease or condition is familial hypercholesterolemia.
13. The method of claim 3 , wherein the disease or condition is familial hypercholesterolemia.
14. The method of claim 4 , wherein the disease or condition is familial hypercholesterolemia.
15. The method of claim 5 , wherein the disease or condition is familial hypercholesterolemia.
16. The method of claim 6 , wherein the disease or condition is familial hypercholesterolemia.