Heteroaryl compounds and uses thereof

A combination comprising a Bruton's tyrosine kinase (BTK) inhibitor of Formula VI:

• or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, wherein:
• X and X′ are each independently O;
• p and q are each independently 0 or 1, wherein p and q are not both 1;
• R1 is —OR′, —OCH2CH2OR′ or —OCH2CO2H;
• R′ is —H or —CH3;
• each Glu is a glucuronyl moiety;
• A is selected from —H or
• R2 and R3 are each independently —H, —OH, —OSO3H, —OGlu, or:
• R2 and R3 are taken together to form a double bond;
• or:
• R2 and R3 are taken together with their intervening atoms to form an epoxide moiety;
• R2′ is —H, or:
• R2 and R2′ are taken together to form ═O;
• R3′ and R3″ are each —H, or:
• R3′ and R3″ are taken together to form ═O;
• R4 is —H, —OH, —OSO3H or —OGlu;
• Rx and Ry are each independently —OH, —OSO3H, or —OGlu;
• Rz, Rz′ and Rz″ are each independently —H, —CH3, —OH, —OSO3H, or —OGlu;
• or
• Rz″ and R3 are taken together to form —O—;
• m and n are each independently 0, 1, 2, 3 or 4,
• provided that when R2 and R3 are taken together to form a double bond, at least one of the following is true:
• (a) R1 is —OH, —OSO3H, —OGlu, —OCH2CH2OH, —OCH2CO2H, —OCH2CH2OSO3H or —OCH2CH2OGlu;
• (b) at least one of R4, Rx, Ry, Rz, Rz′ and Rz″ is —OH, —OSO3H or —OGlu;
• or
• (c) one of p or q is 1;
• and an additional therapeutic agent selected from:
• (i) a compound of formula A:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is an optionally substituted group selected from straight or branched C1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;
• R2 is hydrogen or an optionally substituted group selected from straight or branched C1-8 aliphatic, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl, heterocyclylalkyl, aralkyl, or cycloalkylalkyl;
• and
• R3 is hydrogen or an optionally substituted straight or branched C1-8 aliphatic group;
• wherein when an aliphatic group is substituted with one or more substituents, such substituents are independently selected from halogen;
• aliphatic;
• hydroxyl;
• alkoxy;
• alkoxyaliphatic;
• amino;
• alkylamino;
• carboxy;
• nitro;
• cyano;
• thiol;
• thioether;
• imine;
• imide;
• amidine;
• guanidine;
• enamine;
• aminocarbonyl;
• acylamino;
• phosphonato;
• phosphine;
• thiocarbonyl;
• sulfonyl;
• sulfone;
• sulfonamide;
• ketone;
• aldehyde;
• ester;
• urea;
• urethane;
• oxime;
• hydroxylamine;
• alkoxyamine;
• aralkoxyamine;
• N-oxide;
• hydrazine;
• hydrazide;
• hydrazone;
• azide;
• isocyanate;
• isothiocyanate;
• cyanate;
• thiocyanate;
• oxo (═O);
• B(OH)2, or —O(aliphatic)aminocarbonyl;
• or
• (ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:
• or a pharmaceutically acceptable salt thereof.