Small molecule activators of mitochondrial function

Abstract

Methods for improving mitochondrial function, decreasing iron accumulation, and/or decreasing oxidative stress by exposing cells or treating a subject to compounds or compositions of the general formulaare described that are beneficial in treating, for example, diseases and conditions such as Friedreich's ataxia, normal aging, and various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Furthermore, such compounds are useful as probes for identifying defects in mitochondrial metabolism, mitochondrial iron accumulation, cellular stress among other mitochondrial diseases and helping to identify compounds active in overcoming such defects.

What is claimed is: 
     
         1 .- 102 . (canceled) 
     
     
         103 . A pharmaceutical composition comprising a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein A is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, stereoisomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing. 
       
     
     
         104 . The pharmaceutical composition of  claim 103  wherein the compound has formula (II): 
       
         
           
           
               
               
           
         
         wherein B is O, N or S; 
         R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; 
         R 5  is one or more hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, enantiomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing. 
       
     
     
         105 . The pharmaceutical composition of  claim 104  wherein R 3  is alkyl or aralkyl. 
     
     
         106 . The pharmaceutical composition of  claim 104  wherein R 5  is one or more halo, alkyl or alkoxy. 
     
     
         107 . The pharmaceutical composition of  claim 104  wherein the compound is selected from among N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]pentanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]propanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]-2-methylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]butanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]acetamide, N-[(8-hydroxy-5-nitroquinolin-7-yl)-thiophen-2-ylmethyl]butanamide, N-[(8-hydroxy-5-nitro-quinolin-7-yl)-thiophen-2-yl-methyl]-acetamide, N-[(8-hydroxy-5-nitro-quinolin-7-yl)-thiophen-2-yl-methyl]-propionamide, N-[2-furyl(8-hydroxy-5-nitro-7-quinolinyl)methyl]butanamide, N-[(8-hydroxyquinolin-7-yl)-thiophen-2-ylmethyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-furan-2-ylmethyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-furan-2-ylmethyl]propanamide, and N-[(5-chloro-8-hydroxyquinolin-7-yl)-furan-2-ylmethyl]pentanamide. 
     
     
         108 . The pharmaceutical composition of  claim 103  wherein the compound of formula (I) has the structure of formula (III): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; 
         R 5  is one or more hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, enantiomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing; 
         and a pharmaceutically acceptable carrier, recipient or diluent. 
       
     
     
         109 . The pharmaceutical composition of  claim 108  wherein R 3  is alkyl or aralkyl. 
     
     
         110 . The pharmaceutical composition of  claim 108  wherein R 5  is one or more halo, alkyl or alkoxy. 
     
     
         111 . The pharmaceutical composition of claim  8  wherein the compound is selected from among N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3,4-dimethoxyphenyl)methyl]propanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-methoxyphenyl)methyl]propanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-tolyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-methoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-dimethylaminophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3,4-dimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2,4-dimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3,4,5-trimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-bromophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-p-tolyl-methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-hydroxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-methoxyphenyl)methyl]-3-phenylpropanamide, N-[(8-Hydroxy-5-nitro-quinolin-7-yl)-p-tolyl-methyl]-propionamide, N-[{8-hydroxy-5-nitro-7-quinolinyl}(4-methylphenyl)methyl]acetamide, and N-[(8-hydroxyquinolin-7-yl)-(2-methoxyphenyl)methyl]pentanamide. 
     
     
         112 . A compound having the structure of formula (I): 
       
         
           
           
               
               
           
         
         wherein A is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, stereoisomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing. 
       
     
     
         113 . The compound of  claim 112  wherein R 1  is halo. 
     
     
         114 . The compound of  claim 112  wherein R 2  is hydroxy. 
     
     
         115 . The compound of  claim 112  wherein A is a substituted aryl group or an optionally substituted furyl group. 
     
     
         116 . The compound of  claim 112  wherein R 3  is an optionally substituted alkyl or aralkyl group. 
     
     
         117 . The compound of  claim 112  having the structure of formula (II): 
       
         
           
           
               
               
           
         
         wherein B is O, N or S; 
         R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; 
         R 5  is one or more hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, enantiomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing. 
       
     
     
         118 . The compound of  claim 117  wherein R 1  is hydroxy, nitro or halogen. 
     
     
         119 . The compound of  claim 117  wherein R 3  is alkyl or aralkyl. 
     
     
         120 . The compound of  claim 117  which is N-[(5-chloro-8-hydroxyquinolin-7-yl)-furan-2-ylmethyl]-3-phenylpropanamide. 
     
     
         121 . The compound of  claim 112  having the formula (III): 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , or an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 2  is hydroxy or —OR, wherein R is —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —SO 2 NR 4 R 6 , —SO 2 R 7 , —COR 7 , —COOR 7  or —CONR 4 R 6 , wherein (a) one or more of the carbon atoms in the alkyl, alkenyl or alkynyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl or alkynyl group is optionally substituted with a —C 1 -C 3 -alkyl; 
         R 3  is an optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; 
         R 4  and R 6  are each independently hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —COR 7 , —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with an oxygen, a —C 1 -C 3 -alkyl, or a —C 5 -C 7 -aryl; 
         R 5  is one or more hydrogen, hydroxy, halogen, cyano, alkyloxy, nitro, NH 2 , NHCOR 4 , NHSO 2 R 4 , CONHR 4 , COOR 4 , optionally substituted aliphatic, alicyclic, heteroaliphatic, heterocyclic, aromatic, or heteroaromatic; and 
         R 7  is hydrogen, —C 1 -C 6 -alkyl, —C 2 -C 6 -alkenyl, —C 2 -C 6 -alkynyl, —C 5 -C 7 -aryl, or —C 5 -C 10 -arylalkyl, wherein (a) one or more of the carbon atoms in the alkyl, alkenyl, alkynyl, aryl or arylalkyl group is each independently optionally replaced with a nitrogen, sulfur or oxygen atom, and (b) the alkyl, alkenyl, alkynyl, aryl or arylalkyl is optionally substituted with a halogen, a —C 1 -C 3 -alkyl, a —C 5 -C 7 -aryl, or —NR 4 R 6  or —OR 4 ; 
         or an isomer, enantiomer, racemate, prodrug, active metabolite, metal chelate, or a pharmaceutically-acceptable derivative or salt form of any of the foregoing. 
       
     
     
         122 . The compound of  claim 121  wherein R 1  is hydroxy, nitro or halogen. 
     
     
         123 . The compound of  claim 121  wherein R 5  is one or more alkyl, alkoxy, dimethylamino or halogen. 
     
     
         124 . The compound of  claim 121  wherein R 3  is an alkyl or aralkyl moiety. 
     
     
         125 . The compound of  claim 121  selected from N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-methoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-dimethylaminophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-chlorophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3,4-dimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2,4-dimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3,4,5-trimethoxyphenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-bromophenyl)methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-p-tolyl-methyl]-3-phenylpropanamide, N-[(5-chloro-8-hydroxyquinolin-7-yl)-(2-hydroxyphenyl)methyl]-3-phenylpropanamide, and N-[(5-chloro-8-hydroxyquinolin-7-yl)-(4-methoxyphenyl)methyl]-3-phenylpropanamide.