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US 12,540,127 B2Granted
CRBN ligands and uses thereof
AssigneeKymera Therapeutics, Inc.
InventorsNello Mainolfi, Nan Ji, Yi Zhang, Matthew M. Weiss
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.
Claims17
A compound of formula II:
- or a pharmaceutically acceptable salt thereof, wherein:
- X1 is a bivalent moiety selected from a covalent bond, —CH2—, —C(O)—, —C(S)—, or
- R1 is hydrogen, halogen, —CN, —OR, —SR, —S(O)R, —S(O)2R, —NR2, or an optionally substituted C1-4 aliphatic;
- Ring A is a mono- or bicyclic ring selected from
- each R2 is independently hydrogen, —R4, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R)OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R;
- Ring B is selected from a 6-membered aryl containing 0-2 nitrogen atoms or a 5-membered heteroaryl with 1-3 heteroatoms independently selected from nitrogen, oxygen or sulfur;
- each R3 is independently hydrogen, —R4, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —C(O)R, —C(O)OR, —C(O)NR2, —C(O)N(R) OR, —OC(O)R, —OC(O)NR2, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR2, or —N(R)S(O)2R;
- each R4 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;
- R5 is hydrogen, C1-4 aliphatic, or —CN;
- m is 0, 1, or 2;
- n is 0, 1, 2, 3, 4 or 5;
- p is 0 or 1, wherein when p is 0, the bond connecting Ring A and Ring B terminates in a hydrogen;
- and
- 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;
- wherein said compound of formula II is other than
13 more elements
Dependencies are inferred from the claim text.