US2009069396A1PendingUtilityA1

Polyene Oxazoles and Processes for Their Preparation

Assignee: THALLION PHARMACEUTICALS INCPriority: Jun 13, 2003Filed: Nov 2, 2007Published: Mar 12, 2009
Est. expiryJun 13, 2023(expired)· nominal 20-yr term from priority
A61P 35/00C12P 17/14C07D 413/12C12R 2001/60C12N 1/205C07D 263/32
52
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Claims

Abstract

This invention relates to novel biologically active polyene oxazoles, their pharmaceutically acceptable salts and derivatives, and to methods of obtaining them. One method for obtaining the compounds is by cultivation of Streptomyces sparsogenes NRRL 2940 or a mutant or variant thereof.

Claims

exact text as granted — not AI-modified
1 . A compound of Formula I: 
     
       
         
         
             
             
         
       
     
     wherein,
 R 1  is selected from H, C 1-6  alkyl, C 2-7  alkenyl, C 6-10  aryl or heteroaryl, —C(O)C 1-6  alkyl, —C(O)C 2-7  alkenyl, or —C(O)C 6-10  aryl; 
 R 2  is a hydrogen; or 
 R 1  and R 2  may be taken together to form a second bond between the attached oxygen and carbon atoms to form a carbonyl; 
 R 3  is selected from H or CH 3 ; 
 R 4  is selected from —COOH, —COOR 5 , —CH 2 OC(O)R 6  and —CH 2 OR 7    
 R 5  and R 6  are selected from C 1-6  alkyl, C 6-10  aryl or arylalkyl; 
 R 7  is selected from H or C 1-6  alkyl; 
 R 8  is selected from H, OH, —OC(O)C 1-6  alkyl, —OC(O)C 6-10  aryl or —OC(O)C 6-16  arylalkyl; 
 R 9  and R 10  are each independently selected from H and C 1-6  alkyl; or 
 R 9  and R 10  may be taken together with attached oxygen and carbon atoms to form a 1,3-dioxolane ring of formula: 
 
     
       
         
         
             
             
         
       
       R 11  and R 12  are each independently selected from H, C 1-6  alkyl, C 6-10  aryl or C 6-16  arylalkyl, and wherein R 11  and R 12  are not both H; 
     
     or a pharmaceutically acceptable salt thereof. 
   
   
       2 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , is hydrogen. 
   
   
       3 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from the group selected from C 1-6  alkyl, C 2-7  alkenyl, C 6-10  aryl and heteroaryl. 
   
   
       4 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is selected from the group selected from —C(O)C 1-6  alkyl, —C(O)C 2-7  alkenyl, and —C(O)C 6-10  aryl. 
   
   
       5 . The compound of  claim 1 , wherein said compound is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     a pharmaceutically acceptable salt thereof. 
   
   
       6 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
   
   
       7 . A pharmaceutical composition comprising a compound of  claim 5 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
   
   
       8 . A method of inhibiting growth of a tumor cell, comprising contacting a tumor cell with a compound of  claim 1 , thereby inhibiting growth of a tumor cell. 
   
   
       9 . A method of inhibiting growth of a tumor cell, comprising contacting a tumor cell with a compound of  claim 5 , thereby inhibiting growth of a tumor cell. 
   
   
       10 . The method of  claim 8 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       11 . The method of  claim 9 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       12 . A method of inhibiting growth of a tumor cell in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a pharmaceutical composition of  claim 6 , thereby inhibiting growth of a tumor cell in a subject. 
   
   
       13 . A method of inhibiting growth of a tumor cell in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a pharmaceutical composition of  claim 7 , thereby inhibiting growth of a tumor cell in a subject. 
   
   
       14 . The method of  claim 12 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       15 . The method of  claim 13 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       16 . The method of  claim 12 , wherein the subject is a human. 
   
   
       17 . The method of  claim 13 , wherein the subject is a human. 
   
   
       18 . A method of inhibiting growth of a tumor cell, comprising contacting a tumor cell with compound 1 or a pharmaceutically acceptable salt thereof, 
     
       
         
         
             
             
         
       
     
     thereby inhibiting growth of a tumor cell. 
   
   
       19 . A method of inhibiting growth of a tumor cell, comprising contacting a tumor cell with compound 2 or a pharmaceutically acceptable salt thereof, 
     
       
         
         
             
             
         
       
     
     thereby inhibiting growth of a tumor cell. 
   
   
       20 . The method of  claim 18 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       21 . The method of  claim 19 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       22 . A method of inhibiting growth of a tumor cell in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a pharmaceutical composition comprising compound 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, 
     
       
         
         
             
             
         
       
     
     thereby inhibiting growth of a tumor cell in a subject. 
   
   
       23 . A method of inhibiting growth of a tumor cell in a subject, comprising administering to a subject in need of treatment a therapeutically effective amount of a pharmaceutical composition comprising compound 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, 
     
       
         
         
             
             
         
       
     
     thereby inhibiting growth of a tumor cell in a subject. 
   
   
       24 . The method of  claim 22 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       25 . The method of  claim 23 , wherein the tumor cell is a cell a neoplasm selected from the group consisting of leukemia, melanoma, breast carcinoma, lung carcinoma, renal carcinoma, colon carcinoma, prostate cancer, bladder cancer and glioblastoma. 
   
   
       26 . The method of  claim 22 , wherein the subject is a human. 
   
   
       27 . The method of  claim 23 , wherein the subject is a human.

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