Piperidine-2,6-dione derivatives which bind to cereblon, and methods of use thereof

A compound of Formula (Ia) or (Ib):

• or a pharmaceutically acceptable salt or tautomer thereof,
• wherein
• each of X1 and X2 is independently O or S;
• Z is O, S or NR2;
• T is C═O or SO2;
• each of Y1, Y2, Y3, and Y4 is independently N or CR,
• wherein at least one of Y1, Y2 and Y3 in Formula (Ia) is CR, and at least one of Y1, Y2 and Y4 in Formula (Ib) is CR;
• n is 0, 1 or 2;
• L is hydrogen, alkyl, alkenyl, aryl, heteroaryl, benzyl, haloalkyl, haloalkenyl, —C(O)R″, —CH2C(O)OR″, —C(O)OR″, —C(O)NH2, —C(O)NHR″, —C(O)NR″2, —OR″, —NR″2, or —S(O)2R″;
• each R is independently hydrogen, halogen, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heteroaryl, benzyl, haloalkyl, haloalkenyl, —NH2, —NHR″, —NR″2, —CH2NR″2, —NR″C(O)R″, —NR″C(O)CH2NR″2, —NR″C(O)CH2-heterocycloalkyl, —NR″C(O)CH(OH)R″, —CH2NR″C(O)OR″, —NR″C(O)OR″, —NR″SO2R″, —NO2, —CN, —C(O)R″, —C(O)OR″, —C(O)NH2, —C(O)NHR″, —C(O)NR″2, —OR″, —OC(O)R″, —OC(O)OR″, —OC(O)NH2, —OC(O)NHR″, —OC(O)NR″2, —NHC(S)NHR″, SR″, or —S(O)2R″, —S(O)2OR″, —S(O)2NH2, —S(O)2NHR″, or —S(O)2NR″2;
• each R″ is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl, or benzyl;
• R2 is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heteroaryl, benzyl, haloalkyl, haloalkenyl, —NH2, —NHR″, —NR″2, —NR″C(O)R″, —N[C(O)R″]2, —NR″C(O)OR″, —NO2, —CN, —C(O)R″, —C(O)OR″, —C(O)NH2, —C(O)NHR″, —C(O)NR″2, —OR″, —OC(O)R″, —OC(O)OR″, —OC(O)NH2, —OC(O)NHR″, —OC(O)NR″2, —SR″, or —S(O)2R″, —S(O)2OR″, —S(O)2NH2, —S(O)2NHR″, or —S(O)2NR″2;
• R1 is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl, or benzyl;
• wherein when Z is O, then Y2 is CR′ and
• wherein when the compound is of Formula (Ia), then
• (i) when each of Y1, Y2 and Y3 is CR, then at least one of R is not H;
• (ii) when Z is NR2, then Y2 and Y3 are CR;
• (iii) when Z is S, then Y1 is not C—OMe and Y2 is not C—OMe;
• (iv) when Z is S and Y1 is C—NHCOMe, then Y3 is not C—CH2NR″C(O)OR″;
• (v) when Z is S and Y1 is N, then Y2 is not C—H, C-aryl or C—C(O)OR″;
• and
• (vi) when Z is S and Y2 is N, then Y3 is C—NH2, C—NHR″, C—NR″2, C—NR″C(O)OR″, C—CH2NR″C(O)OR″, C-haloalkyl, C-tButyl, C—OR″, C—COOR″ or C—SR″;
• wherein when Y3 is C—NH2, C—NHR″ or C—NR″2, then Y1 is C—H;
• and when the compound is of Formula (Ib), then:
• (vii) when each of Y1, Y2 and Y4 is CR, then at least one of R is not H;
• (viii) when Z is S, then Y1 is not C—COOH or C—NHC(O)Me, and Y4 is not C—Br;
• (ix) when Z is S and Y2 is C—Br, then Y4 is C—OR″
• (x) when Z is S, Y1 is N and Y2 is C—H or C—NH2, then Y4 is not C—H
• (xi) when Z is S and Y1 is N, then Y2 is not C-halogen, C-alkyl, C-cycloalkyl, C-aryl, C-heteroaryl, C—CH2NH2, C—COOalkyl, or C—NHC(O)alkyl;
• (xii) when Z is NR2, then Y1, Y2 and Y4 are CR.