US2009143446A1PendingUtilityA1

Thiazolidinone amides, thiazolidine carboxylic acid amides, methods of making, and uses thereof

Assignee: UNIV OHIO STATE RES FOUNDPriority: Nov 18, 2003Filed: Oct 22, 2007Published: Jun 4, 2009
Est. expiryNov 18, 2023(expired)· nominal 20-yr term from priority
C07D 417/04C07D 277/14C07D 277/34C07D 277/06A61P 35/00C07D 277/56C07D 277/20
60
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Claims

Abstract

Substituted thiazolidinone carboxylic acid amides and substituted thiazolidine carboxylic acid amides according to formulae (I) and (II) are disclosed where the various substituent groups are as defined in the specification. Methods of making these compounds, pharmaceutical compositions containing the compounds, and their use, particularly for treating or preventing cancer, are also disclosed.

Claims

exact text as granted — not AI-modified
1 . A compound according to formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  and X 2  are each optional, and each can be oxygen; 
 X 3  and X 4  are each optional, and each can be oxygen or sulfur; 
 l is an integer from 1 to 12; 
 R 1  is selected from the group of phenyl, biphenyl, naphthyl, pyrimidinyl, pyridinyl, indolyl, furanyl, cycloalkyl, an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, or 
 
       
         
           
           
               
               
           
         
       
       where m is an integer from 0 to 10;
 R 2  is hydrogen, an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, R 10 —N(Z)-hydrocarbon- or R 10 -hydrocarbon- where the hydrocarbon group is an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, biphenyl, naphthyl, or 
 
       
         
           
           
               
               
           
         
       
       where n is an integer from 0 to 10;
 R 3  is hydrogen or an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon; 
 R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14  and R 15  are independently selected from the group of hydrogen, hydroxyl, an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon, alkoxy, aryloxy, nitro, cyano, chloro, fluoro, bromo, iodo, haloalkyl, dihaloalkyl, trihaloalkyl, amino, alkylamino, dialkylamino, acylamino, arylamino, aryl, C5 to C7 cycloalkyl, arylalkyl; 
 R 10  is H(Z)N—, H(Z)N-hydrocarbon-, H(Z)N-hydrocarbon —N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-O-hydrocarbon-, hydrocarbon-O-hydrocarbon-, hydrocarbon-N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-carbonyl-hydrocarbon-, hydrocarbon-carbonyl-hydrocarbon-, H(Z)N-phenyl-, H(Z)N-phenylalkyl-, H(Z)N-phenylalkyl —N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-O-hydrocarbon-, phenylalkyl-O-hydrocarbon-, phenylalkyl-N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-carbonyl-hydrocarbon-, or phenylalkyl-carbonyl-hydrocarbon-, wherein each hydrocarbon is independently an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 group, and wherein each alkyl is a C1 to C10 alkyl; and 
 Z is independently hydrogen or t-butoxycarbonyl. 
 
     
     
         2 . The compound according to  claim 1 , wherein X 3  is oxygen. 
     
     
         3 . The compound according to  claim 2 , wherein X 4  is oxygen. 
     
     
         4 . The compound according to  claim 3 , wherein R 3  is hydrogen. 
     
     
         5 . The compound according to  claim 4 , wherein R 2  is a C10 to C20 straight-chain or branched-chain, aliphatic or non-aliphatic hydrocarbon. 
     
     
         6 . The compound according to  claim 4 , wherein R 2  is a C14 to C18 straight-chain or branched-chain, aliphatic or non-aliphatic hydrocarbon. 
     
     
         7 . The compound according to  claim 4 , wherein R 1  is phenyl, pyridinyl, indolyl, furanyl, cycloalkyl, an aliphatic or non-aliphatic straight- or branched-chain C10 to C20 hydrocarbon, or 
       
         
           
           
               
               
           
         
       
       where m is an integer from 0 to 10. 
     
     
         8 . The compound according to  claim 1 , wherein the compound is selected from the group of: 
       2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-decyl-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-tetradecyl-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-octadecyl-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-octadecyl-2-(4-oxo-2-biphenylthiazolidin-3-yl)acetamide, 
       2-(2-(1-(dimethylamino)naphthalen-4-yl)-4-oxothiazolidin-3-yl)-N-octadecylacetamide, 
       2-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)-N-octadecylacetamide, 
       2-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)-N-octadecylacetamide, 
       N-octadecyl-2-(4-oxo-2-phenyl-1-sulfoxide-thiazolidin-3-yl)acetamide, 
       N-octadecyl-2-(4-oxo-2-phenyl-1-sulfonyl-thiazolidin-3-yl)acetamide, 
       N-(3,5-difluorophenyl)-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-(3,5-difluorophenyl)-2-(4-oxo-2-phenylthiazolidin-3-yl)ethanethioamide, 
       N-(3,5-bis(trifluoromethyl)phenyl)-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-(3,5-dichlorophenyl)-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-(2,4-dimethoxyphenyl)-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       N-(naphthalen-1-yl)-2-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, 
       3-(2-(octadecylamino)ethyl)-2-phenylthiazolidin-4-one, 
       N-(2-(2-phenylthiazolidin-3-yl)ethyl)octadecan-1-amine, and 
       salts thereof. 
     
     
         9 . The compound according to  claim 1 , wherein
 R 2  is R 10 —N(Z)-hydrocarbon- or R 10 -hydrocarbon- and   R 10  is selected from the group of H(Z)N-hydrocarbon-, H(Z)N-hydrocarbon-N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-carbonyl-hydrocarbon-, H(Z)N-phenyl-, H(Z)N-phenylalkyl-, and H(Z)N-phenylalkyl-N(Z)-hydrocarbon-.   
     
     
         10 . The compound according to  claim 1  wherein l is an integer from 1 to 8. 
     
     
         11 . A compound according to formula (II) 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  and X 2  are each optional, and each can be oxygen; 
 X 3  and X 4  are each optional, and each can be oxygen or sulfur; 
 l is an integer from 1 to 12; 
 R 1  is selected from the group of phenyl, biphenyl, naphthyl, pyrimidinyl, pyridinyl, indolyl, furanyl, cycloalkyl, an aliphatic or non-aliphatic straight- or 
 
       
         
           
           
               
               
           
         
       
       branched-chain C1 to C30 hydrocarbon, or where m is an integer from 0 to 10;
 R 2  is hydrogen, an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, R 10 —N(Z)-hydrocarbon- or R 10 -hydrocarbon- where the hydrocarbon group is an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, biphenyl, naphthyl, or 
 
       
         
           
           
               
               
           
         
       
       where n is an integer from 0 to 10;
 R 3  is hydrogen or an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon; 
 R 4  is optional, or can be hydrogen, an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon, acyl, acetyl, or mesyl; 
 R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , and R 15  are independently selected from the group of hydrogen, hydroxyl, an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon, alkoxy, aryloxy, nitro, cyano, chloro, fluoro, bromo, iodo, haloalkyl, dihaloalkyl, trihaloalkyl, amino, alkylamino, dialkylamino, acylamino, arylamino, aryl, C5 to C7 cycloalkyl, arylalkyl; 
 R 10  is H(Z)N—, H(Z)N-hydrocarbon-, H(Z)N-hydrocarbon —N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-O-hydrocarbon-, hydrocarbon-O-hydrocarbon-, hydrocarbon-N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-carbonyl-hydrocarbon-, hydrocarbon-carbonyl-hydrocarbon-, H(Z)N-phenyl-, H(Z)N-phenylalkyl-, H(Z)N-phenylalkyl-N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-O-hydrocarbon-, phenylalkyl-O-hydrocarbon-, phenylalkyl-N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-carbonyl-hydrocarbon-, or phenylalkyl-carbonyl-hydrocarbon-, wherein each hydrocarbon is independently an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 group, and wherein each alkyl is a C1 to C10 alkyl; and 
 Z is independently hydrogen or t-butoxycarbonyl. 
 
     
     
         12 . The compound according to  claim 11 , wherein X 3  is not oxygen. 
     
     
         13 . The compound according to  claim 11 , wherein X 3  is oxygen. 
     
     
         14 . The compound according to  claim 11 , wherein R 3  is hydrogen and R 2  is a C10 to C20 straight-chain or branched-chain, aliphatic or non-aliphatic hydrocarbon. 
     
     
         15 . The compound according to  claim 14 , wherein R 2  is a C14 to C18 straight-chain or branched-chain, aliphatic or non-aliphatic hydrocarbon. 
     
     
         16 . The compound according to  claim 14 , wherein R 1  is phenyl, biphenyl, pyridinyl, indolyl, furanyl, cycloalkyl, an aliphatic or non-aliphatic straight- or branched-chain C10 to C20 hydrocarbon, or 
       
         
           
           
               
               
           
         
       
       where m is an integer from 0 to 10. 
     
     
         17 . The compound according to  claim 16 , wherein R 1  is 
       
         
           
           
               
               
           
         
       
       where m is an integer from 0 to 10, and at least one of R 5 , R 6 , R 7 , R 9 , and R 9  is aryloxy, arylamino, aryl, C5 to C7 cycloalkyl, or arylalkyl. 
     
     
         18 . The compound according to  claim 11 , wherein the compound is selected from the group of: 
       (4R)—N-octadecyl-N-mesyl-2-phenylthiazolidine-4-carboxamide, 
       (4R)—N-octadecyl-N-acetyl-2-phenylthiazolidine-4-carboxamide, 
       (4R)—N-heptyl-2-phenylthiazolidine-4-carboxamide, 
       (4R)—N-octadecyl-2-biphenylthiazolidine-4-carboxamide, 
       (4R)-2-dodecyl-N-octadecylthiazolidine-4-carboxamide, 
       (4R)—N-octadecyl-2-(pyridin-3-yl)thiazolidine-4-carboxamide, 
       2-(furan-3-yl)-N-octadecylthiazolidine-4-carboxamide, 
       (4R)-2-cyclohexyl-N-octadecylthiazolidine-4-carboxamide, 
       (4R)-2-(1H-indol-3-yl)-N-octadecylthiazolidine-4-carboxamide, 
       (4R)-2-benzyl-N-octadecylthiazolidine-4-carboxamide, 
       (4R)-2-(3,4,5-trimethoxyphenyl)-N,N-dioctylthiazolidine-4-carboxamide, and salts thereof. 
     
     
         19 . The compound according to  claim 11 , wherein the compound is a stereoisomer. 
     
     
         20 . The compound according to  claim 11 , wherein the compound is present in the form of a pharmaceutically acceptable salt. 
     
     
         21 . A compound according to formula (II) 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  and X 2  are each optional, and each can be oxygen; 
 X 3  and X 4  are each optional, and each can be oxygen or sulfur; 
 l is an integer from 1 to 12; 
 R 1  is selected from the group of phenyl, biphenyl, naphthyl, pyrimidinyl, pyridinyl, indolyl, furanyl, cycloalkyl, an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, or 
 
       
         
           
           
               
               
           
         
       
       where m is an integer from 0 to 10;
 R 2  is R 10 —N(Z)-hydrocarbon- or R 10 -hydrocarbon- where the hydrocarbon group is an aliphatic or non-aliphatic straight- or branched-chain C1 to C30 hydrocarbon, biphenyl, naphthyl, or 
 
       
         
           
           
               
               
           
         
       
       where n is an integer from 0 to 10;
 R 3  is hydrogen or an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon; 
 R 4  is optional, or can be hydrogen, an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon, acyl, acetyl, or mesyl; 
 R 5 , R 6 , R 7 , R 8 , R 9 , R 11 , R 12 , R 13 , R 14 , and R 15  are independently selected from the group of hydrogen, hydroxyl, an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 hydrocarbon, alkoxy, aryloxy, nitro, cyano, chloro, fluoro, bromo, iodo, haloalkyl, dihaloalkyl, trihaloalkyl, amino, alkylamino, dialkylamino, acylamino, arylamino, aryl, C5 to C7 cycloalkyl, arylalkyl; 
 R 10  is H(Z)N—, H(Z)N-hydrocarbon-, H(Z)N-hydrocarbon-N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-O-hydrocarbon-, hydrocarbon-O-hydrocarbon-, hydrocarbon-N(Z)-hydrocarbon-, H(Z)N-hydrocarbon-carbonyl-hydrocarbon-, hydrocarbon-carbonyl-hydrocarbon-, H(Z)N-phenyl-, H(Z)N-phenylalkyl-, H(Z)N-phenylalkyl-N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-O-hydrocarbon-, phenylalkyl-O-hydrocarbon-, phenylalkyl-N(Z)-hydrocarbon-, H(Z)N-phenylalkyl-carbonyl-hydrocarbon-, or phenylalkyl-carbonyl-hydrocarbon-, wherein each hydrocarbon is independently an aliphatic or non-aliphatic straight- or branched-chain C1 to C10 group, and wherein each alkyl is a C1 to C10 alkyl; and 
 Z is independently hydrogen or t-butoxycarbonyl. 
 
     
     
         22 . A pharmaceutical composition comprising:
 a pharmaceutically acceptable carrier and   a compound according to  claim 1 .   
     
     
         23 . A pharmaceutical composition comprising:
 a pharmaceutically acceptable carrier and   a compound according to  claim 11 .   
     
     
         24 . A pharmaceutical composition comprising:
 a pharmaceutically acceptable carrier and   a compound according to  claim 21 .

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