Cyclic vinyl sulfone wrn inhibitors

A compound, or pharmaceutically acceptable salt thereof, according to Formula I:

• wherein
• Ring A is a bivalent cyclic group selected from:
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclylene,
• phenylene,
• a 4-8 membered saturated or partially unsaturated monocyclic heterocyclylene having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-6 membered monocyclic heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• an 8-10 membered bicyclic heteroarylene ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 7-12 membered saturated or partially unsaturated bicyclic heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-12 membered saturated or partially unsaturated bicyclic carbocyclylene that is optionally bridged or spirocyclic, and
• a 5-12 membered saturated or partially unsaturated bicyclic heterocyclylene that is optionally bridged or spirocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• R1 is hydrogen, halogen, —CN, or an optionally substituted C1-6 aliphatic group;
• R2 is a C1-6 aliphatic group, a C1-6 aliphatic-Cy′ group, or a cyclic group selected from:
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring,
• phenyl,
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring that is optionally bridged or spirocyclic, and
• a 5-12 membered saturated or partially unsaturated bicyclic heterocyclic ring that is optionally bridged or spirocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• wherein R2 is substituted with y instances of RA;
• R3 and R4 are each independently selected at each occurrence from hydrogen, halogen, —CN, —NO2, —OR, —SR, —NR2, —NRC(O)R—S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —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, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)2R, a C1-6 aliphatic group optionally substituted with —C(O)NR2 or NR2, a C1-6 aliphatic-Cy″ group, or Cy″;
• wherein when m is 2 or 3, two adjacent instances of CR3R4 are optionally combined to forma carbon-carbon double bond of the formula —C(R4)═C(R4)—;
• each instance of R5 is independently selected from hydrogen, halogen, —CN, —NO2, —OR, —SR, —NR2, —S(O)2R, —S(O)2NR2, —S(O)R, —S(O)NR2, —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, —N(R)C(NR)NR2, —N(R)S(O)2NR2, —N(R)S(O)2R, a C1-6 aliphatic group substituted with z instances of RB, a C1-6 aliphatic-Cy′″ group substituted with z instances of RB, and Cy′″ substituted with z instances of RB;
• or two instances of R5 on the same atom together form oxo;
• or two instances of R5 on adjacent atoms of Ring A, taken together with said adjacent atoms, form a phenyl ring fused to Ring A, wherein said phenyl ring is substituted with 0-4 independently selected halogens;
• R6 is hydrogen, halogen, a C1-6 aliphatic group, —SF5, —OR, —SR, —S(O)2NR2, —NR2, —S(O)2R, —SiR3, or a cyclic group selected from:
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring,
• phenyl,
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring that is optionally bridged or spirocyclic,
• a 5-12 membered saturated or partially unsaturated bicyclic heterocyclic ring that is optionally bridged or spirocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• wherein the C1-6 aliphatic group and cyclic group are substituted with z instances of RB;
• each instance of RA is independently selected from hydrogen;
• a C1-6 aliphatic group optionally substituted with 1, 2, or 3 groups independently selected from halogen, —CN, —NR2, and —OR;
• halogen;
• —CN;
• —NO2;
• —OR;
• —SR;
• —NR2;
• —S(O)2R;
• —S(O)2NR2;
• —S(O)R;
• —S(O)NR2;
• —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;
• —N(R)C(NR)NR2;
• —N(R)S(O)2NR2;
• —N(R)S(O)2R;
• two instances of RA on the same atom together form oxo;
• and a cyclic group selected from:
• 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring;
• a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• wherein the cyclic group is optionally substituted with 1, 2, or 3 groups independently selected from —OR, —CR2OR, and halogen;
• each instance of RB is independently selected from hydrogen;
• a C1-6 aliphatic group optionally substituted with 1, 2, or 3 groups independently selected from halogen, —CN, —NR2, and —OR;
• halogen;
• —CN;
• —NO2;
• —OR;
• —SR;
• —NR2;
• —S(O)2R;
• —S(O)2NR2;
• —S(O)R;
• —S(O)NR2;
• —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;
• —N(R)C(NR)NR2;
• —N(R)S(O)2NR2;
• —N(R)S(O)2R;
• phenyl;
• and two instances of RB on the same atom together form oxo;
• each of Cy′, Cy″, and Cy′″ is independently an optionally substituted cyclic group selected from:
• a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring,
• phenyl,
• a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring that is optionally bridged or spirocyclic,
• a 5-12 membered saturated or partially unsaturated bicyclic heterocyclic ring that is optionally bridged or spirocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and
• an 8-10 membered bicyclic aromatic carbocyclic ring;
• each R is independently hydrogen, —C(O)N(CH3)2, —C(O)2CH3, —C(O)2C(CH3)3, —C(O)2CH(CH3)2, —S(O)2CH3, an optionally substituted C1-6 aliphatic group, an optionally substituted cyclic group selected from:
• phenyl,
• an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring,
• an optionally substituted 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur,
• or an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and/or
• two R groups on the same atom are taken together with the same atom to form a cyclic group selected from:
• an optionally substituted 4-7 membered saturated or partially unsaturated carbocycyl,
• an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and
• an optionally substituted 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• x is 0, 1, 2, 3, or 4;
• m is 0, 1, 2, or 3;
• n is 1 or 2;
• y is 0, 1, 2, or 3;
• and
• z is 0, 1, 2, or 3.