US2022112157A1PendingUtilityA1

Myc-max inhibitor compound therapeutics for cancer treatment, methods and uses associated therewith

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Assignee: UNIV BRITISH COLUMBIAPriority: Sep 5, 2018Filed: Sep 5, 2019Published: Apr 14, 2022
Est. expirySep 5, 2038(~12.1 yrs left)· nominal 20-yr term from priority
A61P 35/00C07D 241/24C07D 403/12C07D 403/06C07C 255/66C07D 271/12C07C 381/00C07C 233/56C07C 311/18C07C 335/18C07D 239/42C07D 261/08C07K 5/06026C07C 2603/74C07D 333/20C07D 417/12C07C 237/42C07C 237/22C07D 413/12C07D 213/40C07C 335/16C07C 271/22C07D 417/06C07C 323/60C07D 211/42C07C 237/12C07C 233/43C07D 213/61C07D 311/16C07D 307/14C07D 265/36C07D 405/12C07D 471/04C07D 409/06C07D 249/08C07D 213/75C07D 235/02C07C 275/30C07D 231/14C07C 275/24C07K 7/06C07D 265/30C07C 311/39C07D 333/38C07C 335/12C07D 277/36C07C 335/22C07C 311/19C07C 275/10C07C 2601/16C07C 235/20C07C 335/20C07C 2601/08
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Claims

Abstract

Provided herein are Myc-Max inhibitory compounds having the structure of Formula (I) and compositions thereof for use in the treatment of cancer. In particular, the Myc-Max inhibitory compounds may be useful for the treatment of cancers selected from one or more of: prostate cancer, breast cancer, colon cancer, cervical cancer, small-cell lung carcinomas, neuroblastomas, osteosarcomas, glioblastomas, melanoma and myeloid leukaemia.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A compound, the compound having the structure of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein,
 M 1  is selected from: 
 
       
         
           
           
               
               
           
         
         M 2  is selected from: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       CH 3  or NH 2 ;
 A 1  is selected from CH 2 , CH(CH 3 ), CH(CH 2 CH 3 ), CH(CH(CH 3 ) 2 ), or CHX; 
 A 2  is CH 2  or CH(CH 3 ); 
 T 1  is H or CH 3 ; 
 T2 is H or CH 3 ; 
 D 1  is O or S; 
 n 1  is 0-3, wherein if n 1  is 2 or 3, each A 1  may be independently selected from CH 2 , CH(CH 3 ), CH(CH 2 CH 3 ), CH(CH(CH 3 ) 2 ), or CHX; 
 n 2  is 0-1; 
 n 3  is 1 or 2, wherein if n 3  is 2, each D 1  may be independently selected from O or S; 
 n 4  is 0-3, wherein if n 4  is 2 or 3, each T 2  may be independently selected from H or CH 3 ; 
 n 5  is 0-3, wherein if n 5  is 2 or 3, each A 2  may be independently selected from CH 2 , CH(CH 3 ), CH(CH 2 CH 3 ), CH(CH(CH 3 ) 2 ), or CHX; 
 X is 
 
       
         
           
           
               
               
           
         
         E 1  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         E 2  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         E 3  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         E 4  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )CH 2 ) 
       
       
         
           
           
               
               
           
         
         E 5  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 (CH 2 ), 
       
       
         
           
           
               
               
           
         
         E 6  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         E 7  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         G 1  is H, OCH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ) or OCH 2 C(CH 3 )(CH 2 ); 
         L 1  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 2  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 3  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 4  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 5  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 6  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 7  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
       
       and
 provided that when M 1  is 
 
       
         
           
           
               
               
           
         
       
       and G 1  is H, then n 3  is 1; 
       wherein the compound is for use in the treatment of one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         2 . The compound of  claim 1 , wherein M 1  is selected from: 
       
         
           
           
               
               
           
         
       
       and wherein M 2  is selected from: 
       
         
           
           
               
               
           
         
       
       CH 3  or NH 2 . 
     
     
         3 . The compound of  claim 1  or  2 , wherein A 1  is selected from CH 2 , CH(CH 3 ) or CH(CH 2 CH 3 ); wherein A 2  is CH 2  or CH(CH 3 ); and wherein G 1  is H, OCH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2  or S(═O) 2 (NH 2 ). 
     
     
         4 . The compound of  claim 1 ,  2  or  3 , wherein E 1  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 2  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 3  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 4  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 5  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 6  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       E 7  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 1  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 2  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 3  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 4  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 5  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       L 6  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
       and 
       L 7  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of any one of  claims 1 - 4 , wherein the compound has the structure of Formula II: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of any one of  claims 1 - 5 , wherein the compound has the structure of Formula III: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1 , wherein the compounds is selected from TABLE 3. 
     
     
         8 . A compound, the compound having the structure of Formula IV: 
       
         
           
           
               
               
           
         
       
       wherein,
 D 2  is O or S; 
 D 3  is O or S; 
 J 1  is H, CH 3 , CH 2 CH 3 , 
 
       
         
           
           
               
               
           
         
       
       or is absent (+);
 R 1  is 
 
       
         
           
           
               
               
           
         
         M 3  is selected from: 
       
       
         
           
           
               
               
           
         
         E 8  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 9  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 10  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 11  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 12  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 13  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         E 14  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
         L 8  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 9  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 10  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 11  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 12  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, CF 3 , OCF 3 , OCF 2 , S(═O) 2 (NH 2 ), OCH 2 C(CH 3 )(CH 2 ), 
       
       
         
           
           
               
               
           
         
         L 13  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; and 
         L 14  is H, CH 3 , CH 2 CH 3 , F, Cl, Br, or CF 3 ; 
       
       wherein the compound is for use in the treatment of one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         9 . The compound of  claim 8 , wherein the compound is selected from one or more of: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound of any one of  claims 1 - 9 , for use in the treatment of cancer. 
     
     
         11 . The compound of  claim 10 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         12 . A pharmaceutical composition for treating cancer, comprising compound of any one of  claims 1 - 9  and a pharmaceutically acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         14 . Use of compound of any one of  claims 1 - 9  for treating cancer. 
     
     
         15 . Use of compound of any one of  claims 1 - 9  in the manufacture of a medicament for treating cancer. 
     
     
         16 . The use of  claim 14  or  15 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         17 . A commercial package comprising (a) compound of any one of  claims 1 - 9  and a pharmaceutically acceptable carrier; and (b) instructions for the use thereof for treating cancer. 
     
     
         18 . A commercial package comprising (a) a pharmaceutical composition comprising compound of any one of  claims 1 - 9  and a pharmaceutically acceptable carrier; and (b) instructions for the use thereof for treating cancer. 
     
     
         19 . The commercial package of  claim 17  or  18 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         20 . A compound of any one of Formulas I-IV, provided that the compound excludes all of the compounds set out in TABLES 3 and 4. 
     
     
         21 . A compound having the structure 
       
         
           
           
               
               
           
         
       
       for use in the treatment of cancer. 
     
     
         22 . The compound of  claim 21 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         23 . A pharmaceutical composition for treating cancer, comprising the compound of  claim 21  and a pharmaceutically acceptable carrier. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia. 
     
     
         25 . Use of compound having the structure 
       
         
           
           
               
               
           
         
       
       for treating cancer. 
     
     
         26 . Use of compound having the structure 
       
         
           
           
               
               
           
         
       
       in the manufacture of a medicament for treating cancer. 
     
     
         27 . The use of  claim 25  or  26 , wherein the cancer is selected from one or more of the following: prostate cancer; breast cancer; colon cancer; cervical cancer; small-cell lung carcinoma; neuroblastomas; osteosarcoma; glioblastoma; melanoma; and myeloid leukaemia.

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