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US 11,903,935 B2Granted
Inhibitors of SARM1 NADase activity and uses thereof
AssigneesWashington University, Disarm Therapeutics, Inc.
InventorsJeffrey Milbrandt, Kow Essuman, Yo Sasaki, Aaron Diantonio, Xianrong Mao, Rajesh Devraj, Raul Eduardo Krauss, Robert Owen Hughes
Life of this patent
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Abstract
The present disclosure provides compounds useful as inhibitors of SARM1 NADase activity, compositions thereof, and methods of using the same. The present disclosure provides compounds useful for treating a neurodegenerative or neurological disease or disorder, compositions thereof, and methods of using the same.
Claims3
A method of inhibiting SARM1 NADase activity, comprising contacting SARM1 with a SARM1 NADase inhibitor, wherein the SARM1 NADase inhibitor is a compound of formula IA:
- or a pharmaceutically acceptable salt thereof, wherein:
- XA is —S—, —SO— or —SO2—;
- R1A is hydrogen, C1-4 aliphatic, alkali metal, alkaline earth metal, ammonium or N+(C1-4alkyl)4;
- Ring AA is selected from a benzo fused ring and a 5-6 membered heteroaromatic fused ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- Ring BA is selected from phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- RXA and RYA are independently hydrogen, C1-4 aliphatic optionally substituted with 1-4 halogen, —ORA, —SRA, —N(RA)2, —N(RA)C(O)RA, —C(O)N(RA)2, —N(RA)C(O)N(RA)2, —N(RA)C(O)ORA, —OC(O)N(RA)2, —N(R)S(O)2RA, —S(O)2N(RA)2, —C(O)RA, —C(O)ORA, —OC(O)RA, —S(O)RA, —S(O)2RA, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- each RA is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- mA and nA are independently 0, 1, 2, or 3.
5 more elements
Dependencies are inferred from the claim text.