Granted Patent B2

US 12,545,659 · App. 17/597,165 · Granted Feb 10, 2026

Inventors: Nello Mainolfi (Belmont, MA); Nan Ji (Arlington, MA); Matthew M. Weiss (Boston, MA); Xiaozhang Zheng (Lexington, MA); Yi Zhang (Belmont, MA); Paul R. Fleming (Lexington, MA)

Assignee: Kymera Therapeutics, Inc.

C07D401/14C07D413/14C07D471/10C07D487/04

Abstract

Claims (36)

1 . A compound of formula I-k-15:

or a pharmaceutically acceptable salt thereof, wherein:

each R x is independently hydrogen, C 1-6 alkyl, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —CFR 2 , —CF 2 R, —CF 3 , —CR 2 (OR), —CR 2 (NR 2 ), —C(O)R, —C(O)OR, —C(O)NR 2 , —C(S)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)S(O) 2 R, —N + (O—)R 2 , —OP(O)R 2 , —OP(O)(OR) 2 , —OP(O)(OR)NR 2 , —OP(O)(NR 2 ) 2 , —P(O)R 2 , —SiR 3 , —Si(OR)R 2 , or

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 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;

each R y is independently hydrogen, C 1-6 alkyl, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —CFR 2 , —CF 2 R, —CF 3 , —CR 2 (OR), —CR 2 (NR 2 ), —C(O)R, —C(O)OR, —C(O)NR 2 , —C(S)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR 2 , —N(R)S(O) 2 R, —OP(O)R 2 , —OP(O)(OR) 2 , —OP(O)(OR)NR 2 , —OP(O)(NR 2 ) 2 , —SiR 3 , —SF 5 , or

or

a single R y and a single R x are optionally taken together with their intervening atoms to form a 8-20 membered saturated or partially unsaturated carbocyclic or heterocyclic monocyclic or bicyclic ring having 1-10 heteroatoms, independently selected from nitrogen, oxygen, and sulfur;

Ring T is phenyl,

L x is —C(O)N(H)—;

x is 0, 1, 2, 3 or 4;

y is 0, 1, 2, 3 or 4;

L is a covalent bond or a bivalent, saturated or unsaturated, straight or branched C 1-50 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)(NR 2 )—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O) 2 —, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —N(R)C(O)—, —C(O)N(R)—, —OC(O)N(R)—, —N(R)C(O)O—,

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 4-11 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 4-11 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, or an 8-10 membered bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

X 1 is —C(O)—;

X 2 is —C(O)—;

X 3 is —CH 2 — or —C(O)—;

R 1 is hydrogen or C 1-4 aliphatic;

each of R 2 is independently hydrogen, halogen, C 1-4 aliphatic or —OC 1-4 aliphatic;

Ring A is a fused ring selected from a 6-membered aryl containing 0-1 nitrogen atoms; and

m is 0, 1, 2, 3 or 4.

2 . The compound claim 1 , wherein L is a bivalent, saturated or unsaturated, straight or branched C 1-30 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)(NR 2 )—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —S(O)—, —S(O) 2 —, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —N(R)C(O)—, —C(O)N(R)—, —OC(O)N(R)—, or —N(R)C(O)O—.

3 . The compound of claim 1 , wherein said compound is selected from

or a pharmaceutically acceptable salt thereof.

4 . A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

5 . The compound of claim 1 , wherein Ring T is phenyl,

6 . The compound of claim 1 , wherein R x is hydrogen, C 1-6 alkyl, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —CF 2 R, —CF 3 , —CR 2 (OR), —CR 2 (NR 2 ), —C(O)R, —C(O)OR, —C(O)NR 2 , —C(S)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, or —N(R)S(O) 2 R.

7 . The compound of claim 1 , wherein R y is hydrogen, C 1-6 alkyl, halogen, —CN, —NO 2 , —OR, —SR, —NR 2 , —S(O) 2 R, —S(O) 2 NR 2 , —S(O)R, —CF 2 R, —CF 3 , —CR 2 (OR), —CR 2 (NR 2 ), —C(O)R, —C(O)OR, —C(O)NR 2 , —C(S)NR 2 , —C(O)N(R)OR, —OC(O)R, —OC(O)NR 2 , —N(R)C(O)OR, —N(R)C(O)R, or —N(R)S(O) 2 R.

8 . The compound of claim 1 , wherein R y is fluoro, chloro, —CN, —CF 2 Me, —CFMe 2 , methyl, or —OCF 3 .

9 . The compound of claim 1 , wherein x is 0 or 1.

10 . The compound of claim 1 , wherein m is 0 or 1.

11 . The compound of claim 1 , wherein Ring A is a 6-membered aryl.

12 . The compound of claim 1 , wherein said compound is any one of the following formulae:

or a pharmaceutically acceptable salt thereof.

13 . The compound of claim 1 , wherein

14 . The compound of claim 1 , wherein L is

Assignments (1)

Continuity (9)

References Cited (400)