US 12,077,555 B2
STAT degraders and uses thereof
Nello Mainolfi, Belmont, MA (US); Nan Ji, Arlington, MA (US); Bin Yang, Lexington, MA (US); and Yi Zhang, Belmont, MA (US)
Assigned to Kymera Therapeutics, Inc., Watertown, MA (US)
Filed by Kymera Therapeutics, Inc., Watertown, MA (US)
Filed on May 4, 2022, as Appl. No. 17/736,669.
Application 17/736,669 is a division of application No. 16/841,095, filed on Apr. 6, 2020, granted, now 11,485,750.
Claims priority of provisional application 62/967,921, filed on Jan. 30, 2020.
Claims priority of provisional application 62/949,053, filed on Dec. 17, 2019.
Claims priority of provisional application 62/947,310, filed on Dec. 12, 2019.
Claims priority of provisional application 62/944,810, filed on Dec. 6, 2019.
Claims priority of provisional application 62/932,957, filed on Nov. 8, 2019.
Claims priority of provisional application 62/926,127, filed on Oct. 25, 2019.
Claims priority of provisional application 62/887,872, filed on Aug. 16, 2019.
Claims priority of provisional application 62/877,051, filed on Jul. 22, 2019.
Claims priority of provisional application 62/875,362, filed on Jul. 17, 2019.
Claims priority of provisional application 62/860,512, filed on Jun. 12, 2019.
Claims priority of provisional application 62/855,259, filed on May 31, 2019.
Claims priority of provisional application 62/833,331, filed on Apr. 12, 2019.
Claims priority of provisional application 62/830,095, filed on Apr. 5, 2019.
Prior Publication US 2023/0084113 A1, Mar. 16, 2023
Int. Cl. C07F 9/6561 (2006.01); C07F 9/6506 (2006.01); A61K 45/06 (2006.01)
CPC C07F 9/6561 (2013.01) [C07F 9/65068 (2013.01); A61K 45/06 (2013.01)] 14 Claims
 
1. A method of degrading STAT3 protein in a patient or biological sample comprising administering to said patient, or contacting said biological sample with a compound of formula I:

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or a pharmaceutically acceptable salt thereof, wherein:
LBM is a cereblon E3 ubiquitin ligase binding moiety;
L is 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 —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—,

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 wherein
each-Cy- is independently an optionally substituted bivalent ring selected from phenylenyl, 8-10 membered bicyclic arylenyl, 4-7 membered saturated or partially unsaturated carbocyclylenyl, 4-11 membered saturated or partially unsaturated spiro carbocyclylenyl, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclylenyl, 4-7 membered saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 4-11 membered saturated or partially unsaturated spiro heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 membered bicyclic saturated or partially unsaturated heterocyclylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and
each R is independently hydrogen, or an optionally substituted group selected from C1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 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 optionally 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;
r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and
STAT is a STAT3 protein binding moiety selected from

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