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1. A method for inhibiting HCV protease, or a mutant thereof, in a patient comprising the step of administering to a patient in need thereof a compound of formula I:or a pharmaceutically acceptable salt thereof, wherein:
R1 and R1′ are independently hydrogen or optionally substituted C1-6 aliphatic, or R1 and R1′ are taken together to form an optionally substituted 3-7 membered carbocyclic ring; R2a is —OH or —NHSO7R2; R2 is —N(R)2 or an optionally substituted group selected from C3-7 cycloalkyl, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R is independently hydrogen, optionally substituted C1-6 aliphatic, or:
two R on the same nitrogen atom are taken together with the nitrogen to form a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R3 is selected from the group consisting of:R4 is H, —NHC(O)R5, —NHC(O)OR6, or a natural or unnatural amino acid side-chain group; each R5 is independently —N(R)2 or an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R6 is an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and R7 is an optionally substituted group selected from C1-6 aliphatic, a bridged bicyclic, 6-10 membered aryl, 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 4-7 membered heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and Rz is or R4 and Rz are taken together with their intervening atoms to form an optionally substituted, saturated or unsaturated 16-22 membered ring having 2-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each occurrence of Ry is independently selected from halogen, —OR∘, —CN, —NO2, —N(R∘)2, or optionally substituted C1-4 aliphatic; R∘ is an optionally substituted group selected from C1-6 aliphatic; m is an integer from 0 to 4, inclusive; s is an integer from 0 to 4, inclusive; t is an integer from 0 to 4, inclusive; wherein the sum of s and t is non-zero.
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