Bifunctional compounds for degrading btk with enhanced imid activity

A method of treating or preventing a disease in a subject in need thereof, comprising a step of administering to the subject an amount of a bifunctional compound, wherein said bifunctional compound is capable of inducing proteolytic degradation of Bruton's tyrosine kinase, wherein said compound has enhanced IMiD activity, wherein said amount is effective to treat or prevent the disease, wherein the administering is for at least 15 days, and wherein the bifunctional compound is a compound of Formula (A)

• or a pharmaceutically acceptable salt thereof, wherein
• W is CH or N;
• D is a bond or —NH—;
• Ring A is phenyl, a 9-10 membered bicyclic aryl, a 5-6 membered partially or fully unsaturated monocyclic heterocycle, or a 9-10 membered bicyclic heteroaryl, wherein the monocyclic heterocycle and bicyclic heteroaryl of Ring A each possess one to three heteroatoms independently selected from N, O, or S, wherein Ring A is unsubstituted or is independently substituted with up to three substituents selected from halo, —CN, —COOH, NH2, and substituted or unsubstituted C1-6 alkyl;
• Ring B is a phenyl, a 5-6 membered heteroaryl, a 4-6 membered heterocycloalkyl, or a 8-10 membered spiro bicyclic heterocycle, wherein Ring B is substituted or is unsubstituted, and wherein the heteroaryl and heterocycloalkyl of Ring B has one to three heteroatoms independently selected from N, O, or S;
• L is —X1—X2—X3—X4—X5—;
• X1 is a bond, —C(O)—N(R)—, —N(R)—C(O)—, —(O—CH2—CH2)m—, —O(C6H4)—, —(O—CH2—CH2—CH2)m—, —C1-5 alkyl-, 7-12 membered spiro or fused bicyclic heterocycloalkyl having one to three heteroatoms independently selected from N, O, or S, or 4-6 membered monocyclic heterocycloalkyl having one to two heteroatoms independently selected from N, O, or S, wherein each of the monocyclic and bicyclic heterocycloalkyl of X1 is substituted with —CH3 or is unsubstituted;
• X2 is a bond, —(O—CH2—CH2)p—, —(CH2—CH2—O)p—, —N(R)—C(O)—, —N(R)—, —C(O)—, —C1-5 alkyl-, 4-6 membered monocyclic cycloalkyl, or 4-6 membered monocyclic heterocycloalkyl having one to two heteroatoms independently selected from N, O, or S;
• X3 is a bond, —C1-8 alkyl-, —C≡C—, 4-6 membered cycloalkyl, —N(R)—, —N(R)—C(O)—, —(O—CH2—CH2)p—, —(CH2—CH2—O)p—, 4-6 membered heterocycloalkyl having one to two heteroatoms independently selected from N, O, or S, wherein the heterocycloalkyl is substituted with —CH3 or is unsubstituted;
• X4 is a bond, —CH2—CH2—N(R)—, —N(R)—, —C1-4 alkyl-, —(O—CH2—CH2—CH2)m—, a 5-6 membered saturated, partially unsaturated, or fully unsaturated carbocycle, or a 5-6 membered saturated, partially unsaturated, or fully unsaturated heterocycle having one to three heteroatoms independently selected from N, O, or S;
• X5 is a bond, —C1-4 alkyl-, —N(R)—, —O—, —C(O)—, or —C(O)—N(R)—;
• each R is independently hydrogen or —C1-3 alkyl;
• and
• each of m, n, and P is independently an integer from one to three;
• and
• Y is
• wherein each T is independently CH or N;
• and each Z is independently —CH2— or —C(O)—;
• and each R′ is hydrogen, methyl, or NH2.