Methods of treating radiation induced gastrointestinal syndrome (rigs) and related disease states using yel002/bcn057

Abstract

The present disclosure is directed to method of treatment for treating or ameliorating various conditions caused by radiation exposure such as RIGS, enteritis, oral mucositis, mucositis, and proctitis by the administration of a compound Yel002/BCN057 or an analog thereof.

1 . A method of treating radiation induced gastrointestinal syndrome (RIGS) in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         R 1  and R 2  are independently selected from the group consisting of hydrogen, amino, amide, F, Cl, Br, I, nitro, alkoxy, hydroxyl, thiol, alkylthio, acyl carboxylic acid, ester, sulfonyl, sulfonamide, —SO 4 H, optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted phenyl; and 
         R 3  is optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted phenyl. 
       
     
     
         2 . The method of  claim 1 , wherein the compound is administered to the subject within 48 hours of the radiation exposure. 
     
     
         3 . The method of  claim 1 , wherein the compound is administered to the subject after 24 hours of the radiation exposure. 
     
     
         4 . The method of  claim 1 , wherein the analog is selected from the group consisting of Formula IB-H. 
     
     
         5 . The method of  claim 1 , wherein the compound is Formula IA. 
     
     
         6 . The method of  claim 1 , wherein the subject received radiation therapy. 
     
     
         7 . A method of treating radiation induced oral mucositis in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         R 1  and R 2  are independently selected from the group consisting of hydrogen, amino, amide, F, Cl, Br, I, nitro, alkoxy, hydroxyl, thiol, alkylthio, acyl carboxylic acid, ester, sulfonyl, sulfonamide, —SO 4 H, optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted phenyl; and 
         R 3  is optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted phenyl. 
       
     
     
         8 . The method of  claim 7 , wherein the compound is administered to the subject within 48 hours of the radiation exposure. 
     
     
         9 . The method of  claim 7 , wherein the compound is administered to the subject after 24 hours of the radiation exposure. 
     
     
         10 . The method of  claim 7  wherein the analog is selected from the group consisting of Formula IB-H. 
     
     
         11 . The method of  claim 7 , wherein the compound is Formula IA. 
     
     
         12 . The method of  claim 7 , wherein the subject received radiation therapy. 
     
     
         13 . A method of treating radiation-induced proctitis in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         R 1  and R 2  are independently selected from the group consisting of hydrogen, amino, amide, F, Cl, Br, I, nitro, alkoxy, hydroxyl, thiol, alkylthio, acyl carboxylic acid, ester, sulfonyl, sulfonamide, —SO 4 H, optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted phenyl; and 
         R 3  is optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted phenyl. 
       
     
     
         14 . The method of  claim 13 , wherein the compound is administered to the subject within 48 hours of the radiation exposure. 
     
     
         15 . The method of  claim 13 , wherein the compound is administered to the subject after 24 hours of the radiation exposure. 
     
     
         16 . The method of  claim 13 , wherein the analog is selected from the group consisting of Formula IB-IH. 
     
     
         17 . The method of  claim 13 , wherein the compound is Formula IA. 
     
     
         18 . The method of  claim 13 , wherein the subject received radiation therapy. 
     
     
         19 . A method of treating radiation induced enteritis in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         R 1  and R 2  are independently selected from the group consisting of hydrogen, amino, amide, F, Cl, Br, I, nitro, alkoxy, hydroxyl, thiol, alkylthio, acyl carboxylic acid, ester, sulfonyl, sulfonamide, —SO 4 H, optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted phenyl; and 
         R 3  is optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted phenyl. 
       
     
     
         20 . The method of  claim 19 , wherein the compound is administered to the subject within 48 hours of the radiation exposure. 
     
     
         21 . The method of  claim 19 , wherein the compound is administered to the subject after 24 hours of the radiation exposure. 
     
     
         22 . The method of  claim 19 , wherein the analog is selected from the group consisting of Formula IB-H. 
     
     
         23 . The method of  claim 19 , wherein the compound is Formula IA. 
     
     
         24 . The method of  claim 19 , wherein the subject received radiation therapy. 
     
     
         25 . A method of treating radiation induced mucositis in a subject in need thereof, the method comprising the step of administering to the subject a therapeutically effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         R 1  and R 2  are independently selected from the group consisting of hydrogen, amino, amide, F, Cl, Br, I, nitro, alkoxy, hydroxyl, thiol, alkylthio, acyl carboxylic acid, ester, sulfonyl, sulfonamide, —SO 4 H, optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted phenyl; and 
         R 3  is optionally substituted C 1 -C 20  alkyl, optionally substituted C 1 -C 20  alkenyl, optionally substituted C 1 -C 20  alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted phenyl. 
       
     
     
         26 . The method of  claim 25 , wherein the compound is administered to the subject within 48 hours of the radiation exposure. 
     
     
         27 . The method of  claim 25 , wherein the compound is administered to the subject after 24 hours of the radiation exposure. 
     
     
         28 . The method of  claim 25 , wherein the analog is selected from the group consisting of Formula IB-II. 
     
     
         29 . The method of  claim 25 , wherein the compound is Formula IA or II. 
     
     
         30 . The method of  claim 25 , wherein the subject received radiation therapy.