Hybrid scfa-hydroxyl-derivatized monosaccharides, methods of synthesis, and methods of treating disorders

Abstract

Described herein are fatty acid carbohydrate-hydroxyl-hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.

1 . A compound of formula I, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein,
 each of R 1 , R 2 , R 3 , and R 4  is independently H, —C(O)alkyl or —C(O)(CH 2 ), CH 3 ; 
 wherein at least one R 1 , R 2 , R 3 , and R 4  is H and at least one R 1 , R 2 , R 3 , and R 4  is —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 each n is independently an integer from 0-18; and 
 
         R is alkyl or alkenyl, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl. 
       
     
     
         2 . The compound of  claim 1 , of formula II, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein,
 each of R 1 , R 2 , R 3 , and R 4  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 wherein at least one R 1 , R 2 , R 3 , and R 4  is H and at least one R 1 , R 2 , R 3 , and R 4  is —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 each n is independently an integer from 0-18; and 
 
         R is alkyl or alkenyl, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl. 
       
     
     
         3 - 25 . (canceled) 
     
     
         26 . The compound of  claim 1 , of formula III, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein,
 each of R 1 , R 2 , R 3 , and R 4  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 wherein at least one R 1 , R 2 , R 3 , and R 4  is H and at least one R 1 , R 2 , R 3 , and R 4  is —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 
         each n is independently an integer from 0-18; and
 R is alkyl or alkenyl, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl. 
 
       
     
     
         27 - 30 . (canceled) 
     
     
         31 . The compound of  claim 1 , of formula IV, or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein,
 each of R 1 , R 2 , R 3 , and R 4  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; wherein at least one R 1 , R 2 , R 3 , and R 4  is H and at least one R 1 , R 2 , R 3 , and R 4  is —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 
         each n is independently an integer from 0-18; and
 R is alkyl or alkenyl, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl. 
 
       
     
     
         32 - 38 . (canceled) 
     
     
         39 . A compound of formula V: 
       
         
           
           
               
               
           
         
         wherein,
 Y is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, or heteoaralkyl; each of which may be optionally substituted by 1-3 groups selected from alkyl, alkoxy, aryl, heteroaryl, aralkyl, heteroaralkyl, hal, nitro, cyano, and acyl; 
 X is O, NH, or NR A ; 
 each of R 5  and R 7  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 each of R 6  and R 8  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 R 9  is H, alkyl, C(O)R A , C(O)OR A , or C(O)NR A R A ; and 
 R A  is H or alkyl. 
 
       
     
     
         40 . The compound of  claim 39 , of formula VI: 
       
         
           
           
               
               
           
         
         wherein,
 Y is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, or heteoaralkyl; each of which may be optionally substituted by 1-3 groups selected from alkyl, alkoxy, aryl, heteroaryl, aralkyl, heteroaralkyl, hal, nitro, cyano, and acyl; 
 X is O; 
 
         each of R 5  and R 7  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; and 
         each of R 6  and R 8  is independently —C(O)alkyl or —C(O)(CH 2 ) n CH 3 . 
       
     
     
         41 . The compound of  claim 39 , of formula VII: 
       
         
           
           
               
               
           
         
         wherein,
 Y is alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, aralkyl, or heteoaralkyl; each of which may be optionally substituted by 1-3 groups selected from alkyl, alkoxy, aryl, heteroaryl, aralkyl, heteroaralkyl, hal, nitro, cyano, and acyl; 
 X is NH or NR A ; 
 each of R 5  and R 7  is independently H, —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 R 8  is —C(O)alkyl or —C(O)(CH 2 ) n CH 3 ; 
 R 9  is alkyl, C(O)RA, C(O)OR A , or C(O)NR A R A ; and 
 R A  is H or alkyl. 
 
       
     
     
         42 . (canceled) 
     
     
         43 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         44 . The composition of  claim 43 , further comprising an additional therapeutic agent. 
     
     
         45 . The composition of  claim 44 , wherein the additional therapeutic agent is an anticancer agent. 
     
     
         46 - 49 . (canceled) 
     
     
         50 . A method of treating or preventing a subject suffering from or susceptible to a disease or disorder, the method comprising the step of administering to the subject a therapeutic amount of a compound of  claim 1  sufficient to treat the disease or disorder or symptoms thereof under conditions such that the disease or disorder is treated. 
     
     
         51 . A method of treating or preventing a subject suffering from or susceptible to a disease or disorder, the method comprising the steps of: (i) identifying the patient as in need of administration of a MUCI, MMP9, CXCR4, or NF-κB inhibitor compound; and (ii) administering to the subject a therapeutic amount of a compound of  claim 1  sufficient to treat or prevent the disease or disorder or symptoms thereof. 
     
     
         52 . The method of  claim 51 , wherein the subject is a human. 
     
     
         53 - 57 . (canceled) 
     
     
         58 . A method of sensitizing a cancer cell in a subject to anticancer agents, the method comprising the steps of identifying a subject as in need thereof and administering to the subject a therapeutic amount of a compound of  claim 1  sufficient to sensitizing a cancer cell in a subject to anticancer agents. 
     
     
         59 . A method of treating or preventing cancer in a subject, the method comprising the step of administering to the subject a therapeutic amount of a compound of  claim 1 . 
     
     
         60 . (canceled) 
     
     
         61 . A method of treating or preventing cancer in a subject, with reduced toxicity, the method comprising the steps of administering to the subject a therapeutic amount of a compound of  claim 1 . 
     
     
         62 . (canceled) 
     
     
         63 . A method of a incorporating a compound of  claim 1  in a glycan cell surface or in a glycosylation pathway, wherein toxicity is reduced. 
     
     
         64 - 67 . (canceled) 
     
     
         68 . A kit comprising an effective amount of a compound of  claim 1  in unit dosage form, together with instructions for administering the compound to a subject suffering from or susceptible to a cancer disease or disorder or symptoms thereof. 
     
     
         69 . A method of treating or preventing a disease or disorder selected from multiple sclerosis, Crohn's disease, rheumatoid arthritis, fibrosis, myocardial infarction, osteoid arthritis, Kaposi's sarcoma-associated herpes virus, Parkinson's disease, Huntington's disease, spinal muscular atrophy (increase survival motor neuron protein), cystic fibrosis, ulcerative colitis, antibiotic-associated diarrhea, stem cell fate and regenerative medicine, immune disorders, congenital abnormalities, infectious diseases and related diseases in a subject,
 the method comprising the steps of identifying a subject as in need thereof and administering to the subject a therapeutic amount of a compound of  claim 1  sufficient to treat or prevent the disease or disorder.   
     
     
         70 - 76 . (canceled)