Therapeutic thiazolidinone compounds

A compound having formula I, or a pharmaceutically acceptable salt thereof,

• Wherein each R is independently H or —C1-C3alkyl;
• R1 is H or —C1-C3 alkyl, wherein —C1-C3 alkyl is optionally substituted with 1-5 halogens;
• A and B are each A1 or A2, wherein one of A and B is A1 and the other of A and B is A2,
• A1 has the structure:
• wherein D is selected from the group consisting of:
• (a) phenyl, and
• (b) HET(1);
• wherein ring D comprises at least two carbon atoms that are bonded to each other, wherein one of the two carbon atoms that are bonded to each other in ring D is connected to the group A3 and the other of the two carbon atoms that are bonded to each other in ring D is connected to the remainder of the structure of Formula I, so that A3 and the remainder of the structure of formula I are ortho to each other on ring D;
• wherein HET(1) is a monocyclic 5-8-membered heterocyclic or heteroaromatic ring having 1-4 heteroatom groups independently selected from N, NH, S, O, —S(O)—, —S(O)2—, —C(═O)—, and —N(O)—, wherein HET(1) optionally comprises 1-4 double bonds;
• A3 is
• (a) phenyl, or
• (b) HET(1), wherein
• A3 is optionally substituted with 1-5 substituent groups independently selected from Ra and optionally one or two groups X;
• provided that when B is A1, and D and A3 are both phenyl, then A2 is HET(1), or A3 is substituted with one group X, wherein X is phenyl or HET(1);
• A2 is
• (a) phenyl,
• (b) HET(1), or
• (c) —C3-C8 cycloalkyl optionally having 1-3 double bonds;
• wherein A2 is optionally substituted with 1-5 substituent groups independently selected from Ra;
• Each Ra is independently selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —OC2-C6alkenyl, —OC2-C6alkynyl, —C(═O)C1-C6alkyl, —C(═O)H, —OH, —NR6R7, —C(═O)NR6R7, —NR6C(═O)OC1-C6 alkyl, —NR6C(═O)NR6R7, —S(O)xC1-C6 alkyl, —S(O)yNR6R7, —NR6S(O)yNR6R7, —NR6S(O)yC1-C6 alkyl, halogen, —CN, —NO2, or a 3-7-membered heterocycle having 1-3 heteroatoms which are independently N, S or O, and optionally one group —C(═O)—, wherein the heterocycle optionally has 1-3 double bonds and is optionally substituted with 1-3 substituent groups which are independently halogen, CH3, CF3, —OCH3, or —OCF3;
• wherein for compounds in which Ra is selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —OC2-C6 alkenyl, —OC2-C6 alkynyl, —C(═O)C1-C6alkyl, —NR6C(═O)OC1-C6 alkyl, —S(O)XC1-C6 alkyl, and —NR6S(O)yC1-C6 alkyl, Ra is optionally substituted with 1-11 halogens;
• X is (a) C3-C8cycloalkyl which optionally comprises 1-2 double bonds and which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are independently halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens and optionally 1-2 groups —OH;
• (b) C1-C5 alkyl which is optionally substituted with 1-2 groups D1 and optionally with 1-2 —OH and 1-11 halogens;
• (c) phenyl which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens and optionally 1-2 groups —OH;
• (d) HET(1) which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens and optionally with 1-2 groups —OH;
• or (e) D1;
• D1 is —CO2R8, —C(O)NR6R7, SO2NR6R7, or HET(1);
• R6 and R7 are each independently H or —C1-5alkyl;
• R8 is H or —C1-5 alkyl optionally substituted with 1-7 halogens;
• p is an integer from 0-4;
• x is 0, 1, or 2;
• and
• y is 1 or 2.