Heteroaryl alkyl piperazine derivatives as fatty acid oxidation inhibitors

Abstract

Novel compounds of the general formula (I): and pharmaceutically acceptable acid addition salts thereof, wherein the compounds are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.

We claim:  
     
         1 . A substituted piperazine compound having the following formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 m=1, 2, or 3;  
 q=NH, O, or S;  
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  all, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl and aryl substituent are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , and SO 2 R 22  and wherein R 1  and R 2  or R 2  and R 3  or R 3  and R 4  or R 4  and R 5  when taken together with the carbons to which they are attached may form a 6-membered aromatic ring that is optionally substituted by alkyl, trifluoroalkyl, alkoxy, or halogen;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CO 2 R 20 , CON(R 20 ) 2 , C 1-4  alkyl, or aryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , CN, OR 20 , N(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2  or aryl, wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring including from 1 to 3 carbon atoms;  
 R 17  is heteroaryl that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 20 ;  
 R 20  is selected from the group consisting of H, C 1-15  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, mono- or dialkylamino, alkyl, CN, —O—C 1-6  alkyl, or CF 3 ; and  
 R 22  is selected from the group consisting of C 1-15  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl amide, aryl amide, heteroaryl amide, CN, O—C 1-6  alkyl, CF 3 , or heteroaryl.  
 
     
     
         2 . The compound of  claim 1  wherein q=NH or O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , SO 2 N(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-4  alkyl, or wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl;  
 R 17  is heteroaryl that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2  R 2 ; and  
 R 20  is selected from the group consisting of H, C 1-15  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkylcyano, —O—C 1-6  alkyl, or CF 3 .  
 
     
     
         3 . The compound of  claim 1  wherein R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , C 1-5  alkyl, C 2-5  alkenyl, or C 2-5  alkynyl, wherein the allyl substituent is optionally substituted with CF 3 ; 
 R 6 , R 7  and R 8  are each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , or C 1-4  alkyl wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl;  
 R 17  is heteroaryl that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-8  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —O-C 1-3  alkyl, or CF 3 .  
 
     
     
         4 . The composition of  claim 1  wherein R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , C 1-3  alkyl, C 2-3  alkenyl, or C 2-3  alkynyl, wherein the alkyl is optionally substituted with CF 3 ; 
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or methyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14, R   15  and R 16  are each independently selected from the group consisting of hydrogen or C 1-2  alkyl, wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl;  
 R 17  is a heteroaryl that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-5  alkyl, C 2-3  alkenyl, C 2-3  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-5  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —OMe, or CF 3 .  
 
     
     
         5 . The composition of  claim 1  wherein m=1; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , or C 1-3  alkyl wherein the alkyl substituent is optionally substituted with CF 3 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or methyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, or methyl, wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl;  
 R 17  is a heteroaryl that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-3  alkyl, or aryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent individually selected from the group consisting of halo, —OMe, and CF 3 .  
 
     
     
         6 . The compound of  claim 1  wherein R 17  is a heteroaryl that is a fused 6,5 membered ring system containing from 1 to 5 heteroatoms each selected from the group consisting of N, O, or S that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  allyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 .  
     
     
         7 . The composition of  claim 6  wherein q=NH, O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , SO 2 N(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, heterocyclyl, aryl, or, heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22  or SO 2 R 22 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or Cl  3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-4  alkyl, or aryl wherein the alkyl and aryl substituents are each optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2  or aryl wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system containing from 1 to 4 heteroatoms each selected from the group consisting of N, O, and S that is optionally substituted with 1-3 substituents selected from the following hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 ; and  
 R 20  is selected from the group consisting of H, C 1-15  alkyl, aryl, or heteroaryl, wherein the allyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl-CN, —O—C 1-6  alkyl, or CF 3 .  
 
     
     
         8 . The composition of  claim 6  wherein q=NH or O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , C 1-5  alkyl, C 2-5  alkenyl, or C 2-5  alkynyl, wherein the alkyl substituent is optionally substituted with CF 3  or wherein R 1  and R 2  or R 2  and R 3  or R 3  and R 4  or R 4  and R 5  when taken together with the carbons to which they are attached may form a 6-membered aromatic ring that is optionally substituted by alkyl, trifluoroalkyl, alkoxy, or halogen;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-3  alkyl, or aryl wherein the alyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, N(R 20 ) 2 , and aryl or wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system containing from 1 to 3 heteroatoms selected from the group consisting of N, O, or S that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-8  alkyl, aryl, or heteroaryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —O—C 1-3  alkyl, or CF 3 .  
 
     
     
         9 . The compound of  claim 6  wherein q=NH or O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , C 1-3  alkyl, C 2-3  alkenyl, or C 2-3  alkynyl, wherein the alkyl substituent is optionally substituted with CF 3 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or methyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-3  alkyl, or aryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, N(R 20 ) 2 , or aryl wherein R 9  and R 10  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15 or R   9  and R 13  may join together to form a ring;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system containing from 1 to 2 heteroatoms selected from the group consisting of N, O, or S that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-4  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , or OR 20 ; and  
 R 20  is selected from the group consisting of H, C 1-5  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —OMe, or CF 3 .  
 
     
     
         10 . The compound of  claim 6  wherein q=NH or O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , or C 1-3  alkyl wherein the alkyl substituent is optionally substituted with CF 3  and wherein R 2  and R 3  when taken together with the carbons to which they are attached may form a 6-membered aromatic ring that is optionally substituted by alkyl, trifluoroalkyl, alkoxy, or halogen;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or methyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, or C 1-2  alkyl, wherein the alkyl substituent is optionally substituted with 1 substituent selected from the group consisting of N(R 20 ) 2 , or aryl or wherein R 9  and R 10  may together form a carbonyl;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system containing from 1 to 2 heteroatoms selected from the group consisting of N, O, or S that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , or OR 20 ; and  
 R 20  is selected from the group consisting of H, C 1-3  alkyl, or aryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —OMe, or CF 3 .  
 
     
     
         11 . The composition of  claim 10  wherein q=O; and 
 R 17  is a heteroaryl that is a fused 6,5 membered ring system selected from the group consisting of indole, benzothiazole, and benzoxazole that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , or OR 20 .  
 
     
     
         12 . The composition of  claim 10  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, CF 3 , OR 20 , or C 1-2  alkyl and wherein R 2  and R 3  when taken together with the carbons to which they are attached may form a 6-membered aromatic ring that is optionally substituted by alkyl, trifluoroalkyl, alkoxy, or halogen;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen or C 1-2  alkyl, or wherein R 9  and R 10  may together form a carbonyl;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system selected from the group consisting of indole, benzothiazole, and benzoxazole that is optionally substituted with 1 substituent selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, or aryl, wherein the allyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo or CF 3 ; and  
 R 20  is selected from the group consisting of H or C 1-3  alkyl.  
 
     
     
         13 . The compound of  claim 12  wherein R 17  is benzothiazole that is optionally substituted with 1 substituent selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, or aryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo or CF 3 .  
     
     
         14 . The compound of  claim 12  wherein R 17  is benzothiazole that is optionally substituted at the 2-position with 1 substituent selected from the group consisting of hydrogen, methyl or phenyl.  
     
     
         15 . The compound of  claim 12  wherein R 17  is 5-substituted benzothiazole that is optionally substituted with 1 substituent selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 2 ) 2 , C 1-3  alkyl, or aryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo or CF 3 . 
 R 20  is selected from the group consisting of H or methyl.  
 
     
     
         16 . A compound of  claim 12  wherein R 17  is 5-substituted benzothiazole that is optionally substituted at the 2-position with 1 substituent selected from the group consisting of hydrogen, methyl or phenyl; and 
 R 20  is selected from the group consisting of H or methyl.  
 
     
     
         17 . A compound of  claim 12  wherein q=O; 
 R 1 , R 1 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, OR 20 , or methyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 11  and R 15  are each selected from the group consisting of hydrogen or methyl, R 9 , R 10 , R 12 , R 13 , R 14  and R 16  are each hydrogen and R 9  and R 10  may together form a carbonyl;  
 R 17  is 5-substituted benzothiazole that is substituted at the 2-position with methyl; and  
 R 20  is H.  
 
     
     
         18 . A compound of  claim 12  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, OR 20 , or methyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 11  and R 15  are each selected from the group consisting of hydrogen or methyl, R 9 , R 10 , R 12 , R 13 , R 14  and R 16  are each hydrogen and R 9  and R 10  may together form a carbonyl;  
 R 17  is 5-substituted benzothiazole that is substituted at the 2-position with phenyl; and  
 R 20  is H.  
 
     
     
         19 . A compound of  claim 12  wherein q=O; 
 R 1 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, OR 20 , or methyl and wherein R 2  and R 3  when taken together with the carbons to which they are attached may form a 6-membered aromatic ring that is optionally substituted by alkyl, trifluoroalkyl, alkoxy, or halogen;  
 R 6 , R 7  and kg are each hydrogen;  
 R 11  and R 15  are each selected from the group consisting of hydrogen or methyl, R 9 , R 10 , R 12 , R 13 , R 14  and R 16  are each hydrogen and R 9  and R 10  may together form a carbonyl;  
 R 17  is 5-substituted benzothiazole that is substituted at the 2-position with methyl; and  
 R 20  is H.  
 
     
     
         20 . A compound of  claim 6  or  7  or  8  or  9  or  10  or  11  or  claim 12  or  13 , or  14  or  15  or  16  wherein R 17  is 5-substituted benzothiazole that is substituted at the 2-position with methyl.  
     
     
         21 . A compound of  claim 6  or  7  or  8  or  9  or  10  or  11  or  12  or  13  or  14  or  15 , or  16  wherein R 17  is 5-substituted benzothiazole that is substituted at the 2-position with phenyl.  
     
     
         22 . The compound of  claim 1  wherein R 17  is a heteroaryl that is a fused 6, 6 membered ring system containing from 1 to 4 nitrogen atoms that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 3 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 .  
     
     
         23 . The compound of  claim 22  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , SO 2 N(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-4  alkyl, or aryl wherein the alkyl and aryl substituents are each optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2  or aryl wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 20  is selected from the group consisting of H, C 1-15  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl-CN, —O—C 1-6  alkyl, or CF 3 ; and  
 
     
     
         24 . The compound of  claim 22  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , Cl alkyl, C 2-5  alkenyl, or C 2-5  alkynyl, wherein the alkyl substituent is optionally substituted with CF 3 ;  
 R 6 , R 7  and R 5  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-3  alkyl, or aryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, N(R 20 ) 2 , and aryl or wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 17  is a heteroaryl that is a fused 6, 6 membered ring system containing from 1 to 3 nitrogen atoms that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-8  alkyl, aryl, or heteroaryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —O—C 1-3  alkyl, or CF 3 .  
 
     
     
         25 . The compound of  claim 22  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydro-gen, OR 20 , or methyl;  
 R 6 , R 7  and R 8  each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, C 1-2  alkyl, or R 9  and R 10  may together form a carbonyl;  
 R 17  is a heteroaryl that is a fused 6, 6 membered ring system containing from 1 to 2 nitrogen atoms that is optionally substituted with methyl; and  
 R 20  is H.  
 
     
     
         26 . The compound of  claim 22  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen or methyl;  
 R 6 , R 7  and R 8  each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each hydrogen; and  
 R 17  is a heteroaryl that is a fused 6,6-membered ring system containing from 1 to 2 nitrogen atoms that is optionally substituted with methyl.  
 
     
     
         27 . The compound of  claim 1  wherein R 17  is a 5 or 6-membered ring containing from 1 to 3 heteroatoms selected from the group consisting of N, S, or O that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 .  
     
     
         28 . The compound of  claim 27  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , SO 2 N(R 20 ) 2 , CO 2 R 20 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-4  allyl, or aryl wherein the alkyl and aryl substituents are each optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2  or aryl wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl, or R 13  and R 14  may together form a carbonyl, or R 15  and R 16  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 17  is a 5 or 6-membered ring containing from 1 to 3 heteroatoms selected from the group consisting of N, S, or O that is optionally substituted with from 1 to 3 substituents selected from the group consisting of hydrogen, halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R, SO 2 R 22 , SO 2 N(R 20 ) 2 , NR 20 CO 2 R 22 , NR 20 CON(R 20 ) 2 , COR 20 , CO 2 R 20 , CON(R 20 ) 2 , NR 20 SO 2 R 22 , C 1-15  alkyl, C 2-15  alkenyl, C 2-15  alkynyl, heterocyclyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, NO 2 , CF 3 , CN, OR 20 , SR 20 , N(R 20 ) 2 , S(O)R 22 , or SO 2 R 22 .  
 R 20  is selected from the group consisting of H, C 1-15  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl-CN, —O—C 1-6  alkyl, or CF 3 ; and  
 R 22  is selected from the group consisting of C 1-15  alkyl, aryl, or heteroaryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl amide, aryl amide, heteroaryl amide, CN, O—C 1-6  alkyl, CF 3 , or heteroaryl.  
 
     
     
         29 . The compound of  claim 27  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , C 1-5  alkyl, C 2-5  alkenyl, or C 2-5  alkynyl, wherein the alkyl substituent is optionally substituted with CF 3 ;  
 R 6 , R 7  and R 8  each independently selected from the group consisting of hydrogen or C 1-3  alkyl;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, CON(R 20 ) 2 , C 1-3  alkyl, or aryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, N(R 20 ) 2 , and aryl or wherein R 9  and R 10  may together form a carbonyl, or R 11  and R 12  may together form a carbonyl with the proviso that R 11  and R 13  or R 9  and R 15  or R 9  and R 11  or R 11  and R 15  or R 9  and R 13  may join together to form a ring;  
 R 17  is a 5 or 6 membered ring including from 1 to 3 heteroatoms selected from N, S, or O nitrogen atoms that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ; and  
 R 20  is selected from the group consisting of H, C 1-8  alkyl, aryl, or heteroaryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, —O—C 1-3  alkyl, or CF 3 .  
 
     
     
         30 . The compound of  claim 29  wherein R 17  is a 6 membered ring including from 1 to 2 nitrogen atoms that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent independently selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 .  
     
     
         31 . The compound of  claim 30  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, OR 20 , or methyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen, C 1-2  alkyl, or R 9  and R 10  may together form a carbonyl;  
 R 17  is a 6 membered ring containing from 1 to 2 nitrogen atoms that is optionally substituted with methyl; and  
 R 20  is H.  
 
     
     
         32 . The compound of  claim 30  wherein q=O; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen or methyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each hydrogen; and  
 R 17  is a 6 membered ring containing 1 nitrogen atom that is optionally substituted with methyl.  
 
     
     
         33 . The composition of  claim 10  wherein q=NH; and 
 R 17  is a heteroaryl that is a fused 6,5 system containing from 1 to 2 heteroatoms selected from the group consisting of N, O, or S that is optionally substituted with from 1 to 2 substituents selected from the group consisting of hydrogen, halo, CF 3 , OR 20 , N(R 20 ) 2 , CON(R 20 ) 2 , C 1-3  alkyl, aryl, or heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF 3 , OR 20 , or N(R 20 ) 2 ;  
 
     
     
         34 . The composition of  claim 10  wherein q=NH; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, CF 3 , OR 20 , or C 1-2  alkyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each independently selected from the group consisting of hydrogen or C 1-2  alkyl, or wherein R 9  and R 10  may together form a carbonyl;  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system selected from the group consisting of benzothiazole, and benzoxazole that is optionally substituted with 1 substituent selected from the group consisting of hydrogen, CF 3 , OR 20 , C 1-3  alkyl, or aryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo or CF 3 ; and  
 R 20  is selected from the group consisting of H or C 1-3  alkyl.  
 
     
     
         35 . The composition of  claim 10  wherein q=NH; 
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen or methyl;  
 R 6 , R 7  and R 8  are each hydrogen;  
 R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  and R 16  are each hydrogen; and  
 R 17  is a heteroaryl that is a fused 6,5 membered ring system selected from the group consisting of benzothiazole, and benzoxazole that is optionally substituted with methyl.  
 
     
     
         36 . A compound selected from the group consisting of N-(2,6-dimethyl-phenyl)-2-(4-{2-hydroxy-3-[2-(3-trifluoromethylphenyl)-benzoxazol-5-yloxy]-propyl}-piperazin-1-yl)acetamide, 2-{4-[3-(benzothiazol-2-yloxy)-2-hydroxy-propyl]-piperazin-1-yl}-N-(2,6-dimethylphenyl)acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)-propyl]-piperazin-1-yl}acetamide,4-(3-{4-[(2,6-dimethylphenylcarbamoyl)-methyl]-piperazin-1-yl}-2-hydroxy-propoxy)-1H-indole-2-carboxylic acid amide, 2-{4-[3-(benzothiazol-6-yloxy)2-hydroxy-propyl]-piperazin-1-yl}-N-(2,6-dimethyl-phenyl)-acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methylbenzothiazol-6-yloxy)-propyl]-piperazin-1-yl}aceamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methyl-benzothiazol-5-yloxy)-propyl]-3,5-dimethyl-piperazine-1-yl}acetamide, 2-{4-[2-hydroxy-3-(2-methyl-benzothiazol-5-yloxy)-propyl]-piperazin-1-yl}-N-(4-hydroxyphenyl)acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-phenyl-benzothiazol-5-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-phenyl-benzoxazol-5-yloxy)-propyl)-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)2-{4-[2-hydroxy-3-(2-phenyl-benzothiazol-7-yloxy)-propyl]-piperazin-1-ylacetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methyl-benzothiazol-5-yloxy)-propyl]-2-oxo-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methyl-benzoxazol-5-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-(4-{2-hydroxy-3-[2-(4-trifluoromethyl-phenyl)-benzoxazol-5-yloxy]-propyl}-piperazin-1-yl)acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(quinoxalin-2-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(pyridin-3-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(quinolin-4-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(isoquinolin-5-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(quinolin-6-yloxy)-propyl]-piperazin-1-yl}acetamide, N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methyl-quinolin-7-yloxy)-propyl]-piperazin-1-yl}acetamide, 2-{4-[3-(benzothiazol-2-ylamino)-2-hydroxypropyl]piperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[3-(benzoxazol-2-ylamino)-2-hydroxypropyl]piperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2,5-dimethylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2,6-dimethylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-3,3-dimethylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{(3S)-4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-3-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{(2R)-4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2R)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-3-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2,6-dimethylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl](1,4-diazaperhydroepinyl)}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(4-hydroxyphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2,6-dimethylpiperazinyl}-N-(4-carboxamidophenyl)acetamide, 2-{(3S)-4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-3-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2R)-2-hydroxy-3-(2-phenylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(2,6-dimethyl-4-hydroxyphenyl)acetamide, 2-{5-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[(2S)-2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(4-sulfamoyphenyl)acetamide, 2-{(3S)-4-[(2S)-2-hydroxy-3-(2-phenylbenzoxazol-5-yloxy)propyl]-3-methylpiperazinyl}-N-(2,6-dimethylphenyl)acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-naphthylacetamide, N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-phenylacetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(3,4,5-trichlorophenyl)acetamide, 2-{4-[2-hydroxy-3-(4-methoxyphenyl)propyl]piperazinyl}-N-(3,4,5-trichlorophenyl)acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl-N-(2-chloro-4-methylphenyl)-acetamide, 2-{4-[2-hydroxy-3-(2-methylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(3,4,5-trichlorophenyl)acetamide, 2-{4-[2-hydroxy-3-(2-phenylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(3,5-dichlorophenyl)-acetamide, 2-{4-[2-hydroxy-3-(2-phenylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-(3,4-dichlorophenyl)-acetamide, 2-{4-[2-hydroxy-3-(2-phenylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-[3-methoxy-5-(trifluoromethyl)phenyl]acetamide, 2-{4-[2-hydroxy-3-(2-phenylbenzothiazol-5-yloxy)propyl]piperazinyl}-N-[3,-5-dichloro)phenyl]acetamide, and 2-{4-[2-hydroxy-3-(2-((1E)buta-1,3-dienyl)benzothiazol-5-yloxy)propyl]piperazinyl}-N-[4-chloro-2-methoxy-5-methylphenyl]acetamide.  
     
     
         37 . A method of treatment comprising administering a therapeutically effective amount of a compound of  claim 1  to a mammal in need of a treatment selected from the group consisting of protecting skeletal muscles against damage resulting from trauma, protecting skeletal muscles subsequent to muscle or systemic diseases, treating shock conditions, preserving donor tissue and organs used in transplants, or treating cardiovascular diseases.  
     
     
         38 . The method of  claim 37  wherein the cardiovascular disease is selected from the group consisting of atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, exercise induced angina, congestive heart disease, or myocardial infarction.  
     
     
         39 . The method of  claim 37  or  38  wherein the therapeutically effective amount ranges from about 0.01 to about 100 mg/kg weight of the mammal.  
     
     
         40 . The method of  claim 37  or  38  wherein the mammal is a human.  
     
     
         41 . A pharmaceutical composition of matter comprising the composition of  claim 1  and one or more pharmaceutical excipients.  
     
     
         42 . The pharmaceutical composition of matter of  claim 41  wherein the pharmaceutical composition is in the form of a solution.  
     
     
         43 . The pharmaceutical composition of matter of  claim 41  wherein the pharmaceutical composition is in a form selected from the group consisting of a tablet or a capsule.