主权项 |
1. A compound having the formula I-A: or a pharmaceutically acceptable salt or prodrug thereof, wherein: R1 is independently selected from fluoro, chloro, or —C(J1)2CN; J1 is independently selected from H or C1-2alkyl; or two occurrences of J1, together with the carbon atom to which they are attached, form a 3-4 membered optionally substituted carbocyclic ring; R2 is independently selected from H; halo; —CN; NH2; a C1-2alkyl optionally substituted with 0-3 occurrences of fluoro; or a C1-3aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n; R3 is independently selected from H; halo; C1-4alkyl optionally substituted with 1-3 occurrences of halo; C3-4cycloalkyl; —CN; or a C1-3aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n; R4 is independently selected from Q1 or a C1-10aliphatic chain wherein up to four methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n—; each R4 is optionally substituted with 0-5 occurrences of JQ; or R3 and R4, taken together with the atoms to which they are bound, form a 5-6 membered non-aromatic ring having 0-2 heteroatoms selected from oxygen, nitrogen or sulfur; the ring formed by R3 and R4 is optionally substituted with 0-3 occurrences of JZ; Q1 is independently selected from a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring, the 3-7 membered ring having 0-3 heteroatoms selected from oxygen, nitrogen or sulfur; or an 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; Jz is independently selected from C1-6aliphatic, ═O, halo, or →O; JQ is independently selected from —CN; halo; ═O; Q2; or a C1-8aliphatic chain wherein up to three methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n—; each occurrence of JQ is optionally substituted by 0-3 occurrences of JR; or two occurrences of JQ on the same atom, taken together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein the ring formed by two occurrences of JQ is optionally substituted with 0-3 occurrences of JX; or two occurrences of JQ, together with Q1, form a 6-10 membered saturated or partially unsaturated bridged ring system; Q2 is independently selected from a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen, or sulfur; or an 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; JR is independently selected from —CN; halo; ═O; →O; Q3; or a C1-6aliphatic chain wherein up to three methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n—; each JR is optionally substituted with 0-3 occurrences of JT; or two occurrences of JR on the same atom, together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein the ring formed by two occurrences of JR is optionally substituted with 0-3 occurrences of JX; or two occurrences of JR, together with Q2, form a 6-10 membered saturated or partially unsaturated bridged ring system; Q3 is a 3-7 membered fully saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms selected from oxygen, nitrogen, or sulfur; or an 7-12 membered fully saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms selected from oxygen, nitrogen, or sulfur; JX is independently selected from —CN; halo; or a C1-4aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n—; JT is independently selected from —CN; ═O; a C1-6aliphatic chain wherein up to two methylene units of the aliphatic chain are optionally replaced with —O—, —NR—, —C(O)—, or —S(O)n—; or a 3-6 membered non-aromatic ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; each occurrence of JT is optionally substituted with 0-3 occurrences of JM; or two occurrences of JT on the same atom, together with the atom to which they are joined, form a 3-6 membered ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; or two occurrences of JT, together with Q3, form a 6-10 membered saturated or partially unsaturated bridged ring system; JM is independently selected from halo or C1-6aliphatic; n is 0, 1 or 2; and R is independently selected from H or C1-4aliphatic.
|