Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and their use for the prevention or treatment of disease

Abstract

This invention provides compounds of Formulae (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), (IL), (II), (III), (IIIA), and (IIIB); pharmaceutically acceptable salts and solvates thereof, and compositions thereof. This invention further provides methods for treating a disease, including but not limited to, liver disease or an abnormal liver condition; cancer (such as hepatocellular carcinoma or cholangiocarcinoma); a malignant or benign tumor of the lung, liver, gall bladder, bile duct or digestive tract; an intra- or extra-hepatic bile duct disease; a disorder of lipoprotein; a lipid-and-metabolic disorder; cirrhosis; fibrosis; a disorder of glucose metabolism; a cardiovascular or related vascular disorder; a disease resulting from steatosis, fibrosis, or cirrhosis; a disease associated with increased inflammation (such as hepatic inflammation or pulmonary inflammation); hepatocyte ballooning; a peroxisome proliferator activated receptor-associated disorder; an ATP citrate lyase disorder; an acetyl-coenzyme A carboxylase disorder; obesity; pancreatitis; or renal disease.

1 .- 120 . (canceled) 
     
     
         121 . A method for treating or preventing renal cell carcinoma, comprising administering to a subject in need thereof an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         122 . The method of  claim 121 , further comprising administering an effective amount of another pharmaceutically active agent. 
     
     
         123 . The method of  claim 121 , further comprising administering to the subject sorafenib, lenvatinib, bevacizumab, avelumab, axitinib, cabozantinib, ipilimumab, pembrolizumab, nivolumab, sunitinib, temsirolimus, durvalumab, bempegaldesleukin, tremelimumab, vorolanib, toripalimab, atezolizumab, camrelizumab, cemiplimab, guadecitabine, sitravatinib, or pexastimogene devacirepvec. 
     
     
         124 . The method of  claim 121 , further comprising administering to the subject sorafenib or lenvatinib. 
     
     
         125 . A method for treating or preventing colorectal cancer, comprising administering to a subject in need thereof an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         126 . The method of  claim 125 , further comprising administering an effective amount of another pharmaceutically active agent. 
     
     
         127 . The method of  claim 125 , further comprising administering to the subject sorafenib, lenvatinib, bevacizumab, ramucirumab, pembrolizumab, nivolumab, avelumab, durvalumab, eicosapentaenoic acid, anlotinib, camrelizumab, atezolizumab, cabozantinib, trametinib, or tremelimumab. 
     
     
         128 . The method of  claim 125 , further comprising administering to the subject sorafenib or lenvatinib. 
     
     
         129 . A composition comprising:
 (i) an effective amount of a compound having the structure:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof;
 (ii) bevacizumab, avelumab, axitinib, cabozantinib, ipilimumab, pembrolizumab, nivolumab, sunitinib, temsirolimus, durvalumab, bempegaldesleukin, tremelimumab, vorolanib, toripalimab, atezolizumab, camrelizumab, cemiplimab, guadecitabine, sitravatinib, pexastimogene devacirepvec, ramucirumab, eicosapentaenoic acid, anlotinib, or trametinib; and 
 (iii) a pharmaceutically acceptable carrier or vehicle. 
 
     
     
         130 . The composition of  claim 129  comprising an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         131 . The composition of  claim 129  comprising an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof.