| 主权项 |
1. A topical formulation comprising one or more dermatologically acceptable carriers and one or more compounds having the formula:or a pharmaceutically acceptable salt, ester, tautomer or prodrug thereof, wherein:
A is selected from the group consisting of:
phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl; B is selected from the group consisting of:
phenyl, pyridyl, pyrazinyl, pyrimidinyl, and pyridazinyl; Het-CH2—R3 is selected from the group consisting of: M is selected from the group consisting of:
a) saturated, unsaturated, or aromatic C3-14 carbocycle, and b) saturated, unsaturated, or aromatic 3-14 membered heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein a) or b) optionally is substituted with one or more R5 groups; M-L is selected from the group consisting of:
a) M-X, b) M-L1, c) M-L1-X, d) M-X-L2, e) M-L1-X-L2, f) M-X-L2, g) M-L1-X-L2-X, h) M-X—X—, i) M-L1-X—X—, j) M-X—X-L2, and k) M-L1-X—X-L2,
wherein
X, at each occurrence, independently is selected from the group consisting of: a) —O—, b) —NR4—, c) —N(O)—, d) —N(OR4)—, e) —S(O)p—, f) —SO2NR4—, g) —NR4SO2—, h) —NR4—N═, i) ═N—NR4—, j) —O—N═, k) ═N—O—, l) —N═, m) ═N—, n) —NR4—NR4—, o) —NR4C(O)O—, p) —OC(O)NR4—, q) —NR4C(O)NR4— r) —NR4C(NR4)NR4—, and L1 is selected from the group consisting of: a) C1-6 alkyl, b) C2-6 alkenyl, and c) C2-6 alkynyl, wherein any of a)-c) optionally is substituted with one or more R5 groups; andL2 is selected from the group consisting of: a) C1-6 alkyl, b) C2-6 alkenyl, and c) C2-6 alkynyl, wherein any of a)-c) optionally is substituted with one or more R5 groups; R1, at each occurrence, independently is selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) —CF3, f) —OR4, g) —CN, h) —NO2, i) —NR4R4, j) —C(O)R4, k) —C(O)OR4, l) —OC(O)R4, m) —C(O)NR4R4, n) —NR4C(O)R4, o) —OC(O)NR4R4, p) —NR4C(O)OR4, q) —NR4C(O)NR4R4, r) —C(S)R4, s) —C(S)OR4, t) —OC(S)R4, u) —C(S)NR4R4, v) —NR4C(S)R4, w) —OC(S)NR4R4, x) —NR4C(S)OR4, y) —NR4C(S)NR4R4, z) —NR4C(NR4)NR4R4, aa) —S(O)pR4, bb) —SO2NR4R4, and cc) R4; R2, at each occurrence, independently is selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) —CF3, f) —OR4, g) —CN, h) —NO2, i) —NR4R4, j) —C(O)R4, k) —C(O)OR4, l) —OC(O)R4, m) —C(O)NR4R4, n) —NR4C(O)R4, o) —OC(O)NR4R4, p) —NR4C(O)OR4, q) —NR4C(O)NR4R4, r) —C(S)R4, s) —C(S)OR4, t) —OC(S)R4, u) —C(S)NR4R4, v) —NR4C(S)R4, w) —OC(S)NR4R4, x) —NR4C(S)OR4, y) —NR4C(S)NR4R4, z) —NR4C(NR4)NR4R4, aa) —S(O)pR4, bb) —SO2NR4R4, and cc) R4; R3 is selected from the group consisting of:
a) —OR4, b) —NR4R4, c) —C(O)R4, d) —C(O)OR4, e) —OC(O)R4, f) —C(O)NR4R4, g) —NR4C(O)R4, h) —OC(O)NR4R4, i) —NR4C(O)OR4, j) —NR4C(O)NR4R4, k) —C(S)R4, l) —C(S)OR4, m) —OC(S)R4, n) —C(S)NR4R4, o) —NR4C(S)R4, p) —OC(S)NR4R4, q) —NR4C(S)OR4, r) —NR4C(S)NR4R4, s) —NR4C(NR4)NR4R4, t) —S(O)pR4, u) —SO2NR4R4, and v) R4; R4, at each occurrence, independently is selected from the group consisting of:
a) H, b) C1-6 alkyl, c) C2-6 alkenyl, d) C2-6 alkynyl, e) C3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C1-6 alkyl, h) —C(O)—C2-6 alkenyl, i) —C(O)—C2-6 alkynyl, j) —C(O)—C3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C1-6 alkyl, m) —C(O)O—C2-6 alkenyl, n) —C(O)O—C2-6 alkynyl, o) —C(O)O—C3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b)-p) optionally is substituted with one or more R5 groups; R5, at each occurrence, is independently selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) ═O, f) ═S, g) ═NR6, h) ═NOR6, i) ═N—NR6R6, j) —CF3, k) —OR6, l) —CN, m) —NO2, n) —NR6R6, o) —C(O)R6, p) —C(O)OR6, q) —OC(O)R6, r) —C(O)NR6R6, s) —NR6C(O)R6, t) —OC(O)NR6R6, u) —NR6C(O)OR6, v) —NR6C(O)NR6R6, w) —C(S)R6, x) —C(S)OR6, y) —OC(S)R6, z) —C(S)NR6R6, aa) —NR6C(S)R6, bb) —OC(S)NR6R6, cc) —NR6C(S)OR6, dd) —NR6C(S)NR6R6, ee) —NR6C(NR6)NR6R6, ff) —S(O)pR6, gg) —SO2NR6R6, and hh) R6; R6, at each occurrence, independently is selected from the group consisting of:
a) H, b) C1-6 alkyl, c) C2-6 alkenyl, d) C2-6 alkynyl, e) C3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C1-6 alkyl, h) —C(O)—C2-6 alkenyl, i) —C(O)—C2-6 alkynyl, j) —C(O)—C3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, l) —C(O)O—C1-6 alkyl, m) —C(O)O—C2-6 alkenyl, n) —C(O)O—C2-6 alkynyl, o) —C(O)O—C3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b)-p) optionally is substituted with one or more R7 groups; R7, at each occurrence, independently is selected from the group consisting of:
a) F, b) Cl, c) Br, d) I, e) ═O, f) ═S, g) ═NR8, h) ═NOR8, i) ═N—NR8R8, j) —CF3, k) —OR8, l) —CN, m) —NO2, n) —NR8R8, o) —C(O)R8, p) —C(O)OR8, q) —OC(O)R8, r) —C(O)NR8R8, s) —NR8C(O)R8, t) —OC(O)NR8R8, u) —NR8C(O)OR8, v) —NR8C(O)NR8R8, w) —C(S)R8, x) —C(S)OR8, y) —OC(S)R8, z) —C(S)NR8R8, aa) —NR8C(S)R8, bb) —OC(S)NR8R8, cc) —NR8C(S)OR8, dd) —NR8C(S)NR8R8, ee) —NR8C(NR8)NR8R8, ff) —S(O)pR8, gg) —SO2NR8R8, hh) C1-6 alkyl, ii) C2-6 alkenyl, jj) C2-6 alkynyl, kk) C3-14 saturated, unsaturated, or aromatic carbocycle, and ll) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of hh)-ll) optionally is substituted with one or more moieties selected from the group consisting of R8, F, Cl, Br, I, —CF3, —OR8, —SR8, —CN, —NO2, —NR8R8, —C(O)R8, —C(O)OR8, —OC(O)R8, —C(O)NR8R8, —NR8C(O)R8, —OC(O)NR8R8, —NR8C(O)OR8, —NR8C(O)NR8R8, —C(S)R8, —C(S)OR8, —OC(S)R8, —C(S)NR8R8, —NR8C(S)R8, —OC(S)NR8R8, —NR8C(S)OR8, —NR8C(S)NR8R8, —NR8C(NR8)NR8R8, —SO2NR8R8, and —S(O)pR8; R8, at each occurrence, independently is selected from the group consisting of:
a) H, b) C1-6 alkyl, c) C2-6 alkenyl, d) C2-6 alkynyl, e) C3-14 saturated, unsaturated, or aromatic carbocycle, f) 3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, g) —C(O)—C1-6 alkyl, h) —C(O)—C2-6 alkenyl, i) —C(O)—C2-6 alkynyl, j) —C(O)—C3-14 saturated, unsaturated, or aromatic carbocycle, k) —C(O)-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 1) —C(O)O—C1-6 alkyl, m) —C(O)O—C2-6 alkenyl, n) —C(O)O—C2-6 alkynyl, o) —C(O)O—C3-14 saturated, unsaturated, or aromatic carbocycle, and p) —C(O)O-3-14 membered saturated, unsaturated, or aromatic heterocycle comprising one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
wherein any of b)-p) optionally is substituted with one or more moieties selected from the group consisting of F, Cl, Br, I, —CF3, —OH, —OCH3, —SH, —SCH3, —CN, —NO2, —NH2, —NHCH3, —N(CH3)2, —C(O)CH3, —C(O)OCH3, —C(O)NH2, —NHC(O)CH3, —SO2NH2, —SO2NHCH3, —SO2N(CH3)2, and —S(O)pCH3; m is 0, 1, 2, 3, or 4; n is 0, 1, 2, 3, or 4; and p, at each occurrence, independently is 0, 1, or 2. |
