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US 11,897,882 B2Granted
Tricyclic crbn ligands and uses thereof
AssigneeKymera Therapeutics, Inc.
InventorsNan Ji, Arthur F. Kluge, Matthew M. Weiss, Yi Zhang
Life of this patent
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Abstract
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
Claims19
A method of treating a CRBN-mediated disorder, disease, or condition in a patient comprising administering to said patient a compound of formula I-d:
- a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, wherein:
- X1 is —CH2— or —C(O)—;
- X2 is a carbon atom;
- X3 is —CH2—;
- R1 is hydrogen;
- each R2 is independently hydrogen, deuterium, R3, halogen, —CN, —NO2, —OR, —SR, —N(R)2, —Si(R)3, —S(O)2R, —S(O)2N(R)2, —S(O)R, —C(O)R, —C(O)OR, —C(O)N(R)2, —C(O)N(R)OR, —C(R)2N(R)C(O)R, —C(R)2N(R)C(O)N(R)2, —OC(O)R, —OC(O)N(R)2, —OP(O)R2, —OP(O)(OR)2, —OP(O)(OR)(NR2), —OP(O)(NR2)2—, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)N(R)2, —N(R)S(O)2R, —NP(O)R2, —N(R)P(O)(OR)2, —N(R)P(O)(OR)(NR2), —N(R)P(O)(NR2)2, or —N(R)S(O)2R;
- each R3 is independently an optionally substituted group selected from C1-6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- each R is independently hydrogen, or an optionally substituted group selected from C1.6 aliphatic, phenyl, a 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or:
- two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur;
- each L is independently a covalent bond or a bivalent, saturated or unsaturated, straight or branched C1-50 hydrocarbon chain, wherein 0-6 methylene units of L are independently replaced by —C(D)(H)-, —C(D)2-, —Cy-, —O—, —N(R)—, —Si(R)2—, —Si(OH)(R)—, —Si(OH)2—, —P(O)(OR)—, —P(O)(R)—, —P(O)(NR2)—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O)2—, —N(R)S(O)2—, —S(O)2N(R)—, —N(R)C(O)—, —C(O)N(R)—, —OC(O)N(R)—, —N(R)C(O)O—,
- wherein:
- each -Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, an 8-10 membered bicyclic arylenyl, a 4-7 membered saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, a 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4-7 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- Ring A is tricyclic ring
- wherein
- each of Ring B and Ring C is independently a fused ring selected from 6-membered aryl containing 0-2 nitrogens and a 5-membered heteroaryl with 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur;
- is a single or double bond;
- L1 is a covalent bond;
- each of n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
- and
- m is 0, 1, or 2.
17 more elements
Dependencies are inferred from the claim text.