Compounds for treatment of lipoprotein metabolism disorders

A method for treating a disorder of lipoprotein metabolism in a subject, said method comprising obtaining a level of low-density lipoprotein-C (LDL-C) in a subject and wherein, if the level of LDL-C is above 3.3 mmol/L or above 2.6 mmol/L if the subject is at risk of heart disease, then administering to the subject a composition comprising a compound having the structure of formula (I):

• or a pharmaceutically acceptable salt, solvate, polymorph, or tautomer thereof,
• wherein:
• R1 is selected from the group consisting of alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkylsulfonyl, substituted alkylsulfonyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, ester, amide, acyl, substituted acyl, amino, substituted amino, thioalkyl, substituted thioalkyl, aryl, heteroaryl, substituted aryl, hydrogen, and halogen;
• each R2 is independently selected from the group consisting of —OSO3−, —OH, —NH2, —NHSO3−, —NHOCH3 and —OPO32−;
• each R3 is independently selected from the group consisting of —OSO3−, —OH and —OPO32−;
• each R4 is independently selected from the group consisting of —OSO3−, —OH, —OPO32− and —H;
• each R5 is independently selected from the group consisting of —CH2OSO3−, —CH2OH, —COO− and —CH2OPO32−;
• n is an integer equal to, or greater than 1.

A pharmaceutical composition comprising:

• A) a compound having the general structure of formula (I):
• or a pharmaceutically acceptable salt, solvate, polymorph, or tautomer thereof, wherein:
• R1 is selected from the group consisting of alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkylsulfonyl, substituted alkylsulfonyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, ester, amide, acyl, substituted acyl, amino, substituted amino, thioalkyl, substituted thioalkyl, aryl, heteroaryl, substituted aryl, hydrogen, and halogen;
• each R2 is independently selected from the group consisting of —OSO3−, —OH, —NH2, —NHSO3−, —NHOCH3 and —OPO32−;
• each R3 is independently selected from the group consisting of —OSO3−, —OH and —OPO32−;
• each R4 is independently selected from the group consisting of —OSO3−, —OH, —OPO32− and —H;
• each R5 is independently selected from the group consisting of —CH2OSO3−, —CH2OH, —COO− and —CH2OPO32−;
• n is an integer equal to, or greater than 1;
• and
• B) at least one of:
• an antibody inhibiting binding of PCSK9 to LDLR;
• a statin;
• cholestyramine;
• ezetimibe.