Tricyclic indole mcl-1 inhibitors and uses thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• L1 is selected from a covalent bond or an optionally substituted bivalent straight or branched C1-6 hydrocarbon chain wherein one or more methylene units are optionally and independently replaced with -Cy-, —O—, —S—, —N(R)—, —N(R)C(O)—, —N(R)S(O)2—, —C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, or —S(O)2N(R)—;
• A is —O—, —S—, —S(O)—, —S(O)2—, —N(R′)—, or optionally substituted —CH2—;
• R1 is hydrogen, —R, —OR, —SR, —S(O)R, —S(O)2R, —S(O)2N(R)2, —N(R)2, —C(O)N(R)2, —C(O)R, —C(O)OR, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRS(O)2R, —NRS(O)2N(R)2, —C(O)OH, —C(O)Rx, —S(O)2OH, or —S(O)2Ry, or is selected from
• R2 is selected from R, halo, —NH2, —CN, —NO2, —CF3—C(O)-L3-Rz, —C(O)N(R)-L3-Rz, —C(O)N(R)—C(R)2-L3-Rz, —C(O)O-L3-Rz or —C(O)S-L3-Rz;
• L3 is selected from a covalent bond or an optionally substituted bivalent straight or branched C1-8 hydrocarbon chain wherein one or more methylene units are optionally and independently replaced with -Cy-, —O—, —S—, —N(R)—, —N(R)C(O)—, —N(R)S(O)2—, —C(O)—, —C(O)N(R)—, —S(O)—, —S(O)2—, or —S(O)2N(R)—;
• -Cy- is an optionally substituted bivalent ring independently selected from phenylene, 3-8 membered saturated or partially unsaturated carbocyclylene, 5-6 membered heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 3-8 membered saturated or partially unsaturated heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Rz is hydrogen, R, —OR, —SR, —S(O)R, —S(O)2R, —S(O)2N(R)2, —N(R)2, —C(O)N(R)2, —C(O)R, —C(O)OR, —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)N(R)2, —N(R)S(O)2R, —N(R)S(O)2N(R)2, —C(O)OH, —C(O)Rx, —S(O)2OH, or —S(O)2R3, or is selected from:
• Rx is selected from —C(O)OR, —N(R)S(O)2CF3, —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)N(R)2, or —N(R)S(O)2R;
• Ry is selected from —N(R)C(O)CF3, —N(R)C(O)R, or —N(R)C(O)N(R)2;
• each R is independently selected from hydrogen or an optionally substituted group selected from C1-12 aliphatic or a ring selected from a 3-10 membered saturated or partially unsaturated carbocyclic ring, phenyl, a 6-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 3-8 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen or sulfur;
• L2 is an optionally substituted bivalent straight or branched C3-6 hydrocarbon chain wherein one or two methylene units of L2 are optionally and independently replaced with —O—, —S—, or —N(R′)—, and wherein two substituents of L2 are optionally taken together to form an optionally substituted bivalent ring selected from 3-8 membered saturated or partially unsaturated carbocyclylene or 3-8 membered saturated or partially unsaturated heterocyclylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each R′ is independently hydrogen or optionally substituted C1-4 alkyl;
• R3 is an optionally substituted ring selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 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 of R4, R5, and R6 is independently selected from R, halogen, —CN, —NO2, —CF3, —C(O)OR′, —OR′, —SR′, —C(O)N(R′)2—N(R′)2, —S(O)2N(R)2, —N(R′)S(O)2CF3, —C(O)R′, —N(R′)C(O)R′, —S(O)R′, —S(O)2R′, —N(R′)C(O)OR′, and —N(R′)S(O)2R′;
• and
• optionally R2 and -A-L1-, R2 and -L2-R3, R4 and R5, R5 and R6 and/or R6 and -A-L1- are independently taken together with their intervening atoms to form an optionally substituted ring selected from a 4-8 membered saturated or partially unsaturated carbocyclic ring, phenyl, a 4-8 membered saturated or partially unsaturated heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.