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1. A compound having the structure:or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof,wherein
A is selected from -(a) a C1-6 alkyl group, (b) a C2-6 alkenyl group, (c) a C2-6 alkynyl group, (d) a C3-12 saturated, unsaturated, or aromatic carbocycle, (e) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more nitrogen, oxygen or sulfur atoms, (f) H, (g) —OH, (h) —SH, (i) F, (j) Cl, (k) Br, (l) I, (m) —CF3, (n) —CN, (o) —N3, (p) —NO2, (q) —NR6(CR6R6)tR9, (r) —OR9, (s) —S(CR6R6)tR9, (t) —S(O)(CR6R6)tR9, (u) —S(O)2(CR6R6)tR9 (v) —C(O)(CR6R6)tR9, (w) —OC(O)(CR6R6)tR9, (x) —OC(O)O(CR6R6)tR9, (y) —SC(O)(CR6R6)tR9, (z) —C(O)O(CR6R6)tR9, (aa) —NR6C(O)(CR6R6)tR9, (bb) —C(O)NR6(CR6R6)tR9, (cc) —C(═NR6)(CR6R6)tR9, (dd) —C(═NNR6R6)(CR6R6)tR9, (ee) —C[═NNR6C(O)R6](CR6R6)tR9, (ff) —NR6C(O)O(CR6R6)tR9, (gg) —OC(O)NR6(CR6R6)e, (hh) —NR6C(O)NR6(CR6R6)tR9, (ii) —NR6S(O)p(CR6R6)tR9, (jj) —S(O)pNR6(CR6R6)tR9, (kk) —NR6R6, (ll) —NR6(CR6R6)tR9, (mm) —SR6, (nn) —S(O)R6, (oo) —S(O)2R6, (pp) —NR6C(O)R6, (qq) —Si(R13)3, and (rr) —C(═O)H;wherein (a)-(e) optionally are substituted with one or more R14 groups;
T is a 14- or 15-membered macrolide connected via a macrocyclic ring carbon atom; X is selected from —OR15 and —SR15, R1 and R3 independently are selected from: (a) H, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) —C(O)R5, (f) —C(O)OR5, (g) —C(O)—NR4R4, (h) —C(S)R5, (i) —C(S)OR5, (j) —C(O)SR5, and (k) —C(S)—NR4R4; Alternatively, R1 and R3 are taken together with the oxygen to which R1 is attached, the nitrogen to which R3 is attached and the two intervening carbons to form a 5 or 6 membered ring, said ring being optionally substituted with one or more R5; R2 is hydrogen or —OR12; R4, at each occurrence, independently is selected from:
(a) H, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) a C6-10 saturated, unsaturated, or aromatic carbocycle, (f) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from 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)—C6-10 saturated, unsaturated, or aromatic carbocycle, (k) —C(O)-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from 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—C6-10 saturated, unsaturated, or aromatic carbocycle, (p) —C(O)O-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, and (q) —C(O)NR6R6,
wherein any of (b)-(p) optionally is substituted with one or more R5 groups; alternatively, NR6R6 forms a 3-7 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R6 groups are attached, wherein said ring is optionally substituted at a position other than the nitrogen atom to which the R6 groups are attached, with one or more substituents selected from O, S(O)p, N, and NR8; R5 is selected from:
(a) R7, (b) a C1-8 alkyl group, (c) a C2-8 alkenyl group, (d) a C2-8 alkynyl group, (e) a C3-12 saturated, unsaturated, or aromatic carbocycle, and (f) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, or two R5 groups, when present on the same carbon atom can be taken together with the carbon atom to which they are attached to form a spiro 3-6 membered carbocyclic ring or heterocyclic ring containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,wherein any of (b)-(f) immediately above optionally is substituted with one or more R7 groups; R6, at each occurrence, independently is selected from:
(a) H, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (b)-(f) optionally is substituted with one or more moieties selected from:
(aa) a carbonyl group, (bb) a formyl group, (cc) F, (dd) Cl, (ee) Br, (ff) I, (gg) CN, (hh) NO2, (ii) —OR8, (jj) —S(O)pR8, (kk) —C(O)R8, (ll) —C(O)OR8, (mm) —OC(O)R8, (nn) —C(O)NR8R8, (oo) —OC(O)NR8R8, (pp) —C(═NR8)R8, (qq) —C(R8)(R8)OR8, (rr) —C(R8)2OC(O)R8, (ss) —C(R8)(OR8)(CH2)rNR8R8, (tt) —NR8R8, (uu) —NR8OR8, (vv) —NR8C(O)R8, (ww) —NR8C(O)OR8, (xx) —NR8C(O)NR8R8, (yy) —NR8S(O)rR8, (zz) —C(OR8)(OR8)R8, (ab) —C(R8)2NR8R8, (ac) ═NR8, (ad) —C(S)NR8R8, (ae) —NR8C(S)R8, (af) —OC(S)NR8R8, (ag) —NR8C(S)OR8, (ah) —NR8C(S)NR8R8, (ai) —SC(O)R8, (aj) a C1-8 alkyl group, (ak) a C2-8 alkenyl group, (al) a C2-8 alkynyl group, (am) a C1-8 alkoxy group, (an) a C1-8 alkylthio group, (ao) a C1-8 acyl group, (ap) —CF3, (aq) —SCF3—, (ar) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (as) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur; alternatively, NR6R6 focus a 3-10 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R6 groups are attached wherein said ring is optionally substituted at a position other than the nitrogen atom to which the R6 groups are bonded, with one or more moieties selected from —O, S(O)p, N, and NR8; alternatively, CR6R6 forms a carbonyl group; R7, at each occurrence, is selected from:
(a) H, (b) ═O, (c) ═S, (d) F, (e) Cl, (f) Br, (g) I, (h) —CF3,(i) —CN, (j) —N3, (k) —NO2, (l) —NR6(CR6R6)tR9, (m) —OR9,(n) —S(O)pC(R6R6)tR9, (o) —C(O)(CR6R6)tR9, (p) —OC(O)(CR6R6)tR9,(q) —SC(O)(CR6R6)tR9, (r) —C(O)O(CR6R6)tR9, (s) —NR6C(O)(CR6R6)tR9,(t) —C(O)NR6(CR6R6)tR9, (u) —C(═NR6)(CR6R6)tR9,(v) —C(═NNR6R6)(CR6R6)tR9, (w) —C(—NNR6C(O)R6)(CR6R6)tR9,(x) —C(═NOR9)(CR6R6)tR9, (y) —NR6C(O)O(CR6R6)tR9,(z) —OC(O)NR6(CR6R6)tR9, (aa) —NR6C(O)NR6(CR6R6)tR9,(bb) —NR6S(O)p(CR6R6)tR9, (cc) —S(O)pNR6(CR6R6)tR9,(dd) —NR6S(O)pNR6(CR6R6)tR9, (ee) —NR6R6, (ff) —NR6(CR6R6), (gg) —OH,(hh) —NR6R6, (ii) —OCH3, (jj) —S(O)pR6, (kk) —NC(O)R6, (ll) a C1-6 alkyl group, (mm) a C2-6 alkenyl group, (nn) a C2-6 alkynyl group, (oo) —C3-10 saturated, unsaturated, or aromatic carbocycle, and (pp) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (ll)-(pp) optionally is substituted with one or more R9 groups; alternatively, two R7 groups taken together form —O(CH2)uO—; R8 is selected from:
(a) H, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) a C3-10 saturated, unsaturated, or aromatic carbocycle, (f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, (g) —C(O)—C1-6 alkyl, (h) —C(O)—C1-6 alkenyl, (i) —C(O)—C1-6 alkynyl, —C(O)—C3-10 saturated, unsaturated, or aromatic carbocycle, and (k) —C(O)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from -nitrogen, oxygen, and sulfur,
wherein any of (c)-(k) optionally is substituted with one or more moieties selected from—: (aa) H, (bb) F, (cc) Cl, (dd) Br, (ee) I, (ff) CN, (gg) NO2, (hh) OH, (ii) NH2, (jj) NH(C1-6 alkyl), (kk) N(C1-6 alkyl)2, (ll) a C1-6 alkoxy group, (mm) an aryl group, (nn) a substituted aryl group, (oo) a heteroaryl group, (pp) a substituted heteroaryl group, and (qq) a C1-6 alkyl group optionally substituted with one or more moieties selected from an aryl group, a substituted aryl group, a heteroaryl group, a substituted heteroaryl group, F, Cl, Br, I, CN, NO2, CF3, SCF3, and OH; R9, at each occurrence, independently is selected from:
(a) R10, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (b)-(f) optionally is substituted with one or more R16 groups; R10, at each occurrence, independently is selected from:
(a) H, (b) ═O, (c) F, (d) Cl, (e) Br, (f) I, (g) —CF3, (h) —CN, (i) —NO2,(j) —NR6R6, (k) —OR6, (l) —S(O)pR6, (m) —C(O)R6, (n) —C(O)OR6,(o) —OC(O)R6, (p) NR6C(O)R6, (q) —C(O)NR6R6, (r) —C(═NR6)R6,(s) —NR6C(O)NR6R6, (t) —NR6S(O)pR6, (u) S(O)pNR6R6,(v) —NR6S(O)pNR6R6, (w) a C1-6 alkyl group, (x) a C2-6 alkenyl group, (y) a C2-6 alkynyl group, (z) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (aa) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (w)-(aa) optionally is substituted with one or more moieties selected from R6, F, Cl, Br, I, CN, NO2, —OR6, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, a C1-6 alkoxy group, a C1-6 alkylthio group, and a C1-6 acyl group; R11 at each occurrence, independently is selected from:
(a) H, (b) F, (c) Cl, (d) Br, (e) I, (f) CN, (g) NO2, (h) OR8, (i) —S(O)pR8, (j) —C(O)R8, (k) —C(O)OR8, (l) —OC(O)R8, (m) —C(O)NR8R8,(n) —OC(O)NR8R8, (o) —C(═NR8)R8, (p) —C(R8)(R8)OR8,(q) —C(R8)2OC(O)R8,(r) —C(R8)(OR8)(CH2)r—NR8R8, (s) —NR8R8, (t) —NR8OR8,(u) —NR8C(O)R8, (v) —NR8C(O)OR8, (w) —NR8C(O)NR8R8,(x) —NR8S(O)pR8, (y) —C(OR8)(OR8)R8, (z) —C(R8)2NR8R8, (aa) —C(S)NR8R8, (bb) —NR8C(S)R8, (cc) —OC(S)NR8R8, (dd) —NR8C(S)OR8, (ee) —NR8C(S)NR8R8, (ff) —SC(O)R8, (gg) —N3, (hh) —Si(R13)3, (ii) a C1-8 alkyl group, (jj) a C2-8 alkenyl group, (kk) a C2-8 alkynyl group, (ll) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (mm) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, wherein (ii)-(mm) optionally are substituted with one or more R5 groups; R12 is selected from:
(a) H, (b) a C1-6 alkyl group, (c) a C2-6 alkenyl group, (d) a C2-6 alkynyl group, (e) —C(O)R5, (f) —C(O)OR5, (g) —C(O)—NR4R4, (h) —C(S)R5, (i) —C(S)OR5, (j) —C(O)SR5, (k) —C(S)—NR4R4, (l) a C3-10 saturated, unsaturated, or aromatic carbocycle, (m) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, (n) a —(C1-6 alkyl)-C3-10 saturated, unsaturated, or aromatic carbocycle, and (o) a —(C1-6 alkyl)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from -nitrogen, oxygen, and sulfur,
wherein (a)-(d) and (l)-(o) optionally are substituted with one or more R5 groups; R13 at each occurrence, is independently selected from (a) —C1-6 alkyl and (b) —O—(C1-6 alkyl); R14 at each occurrence is independently selected from:
(a) H, (b) F, (c) Cl, (d) Br, (e) I, (f) CN, (g) NO2, (h) OR8, (i) —S(O)pR8, (j) —C(O)R8, (k) —C(O)OR8, (l) —OC(O)R8, (m) —C(O)NR8R8,(n) —OC(O)NR8R8, (o) —C(═NR8)R8, (p) —C(R8)(R8)OR8,(q) —C(R8)2OC(O)R8,(r) —C(R8)(OR8)(CH2)rNR8R8, (s) —NR8R8, (t) —NR8OR8,(u) —NR8C(O)R8, (v) —NR8C(O)OR8, (w) —NR8C(O)NR8R8,(x) —NR8S(O)pR8, (y) —C(OR8)(OR8)R8, (z) —C(R8)2NR8R8, (aa) —C(S)NR8R8, (bb) —NR8C(S)R8, (cc) —OC(S)NR8R8, (dd) —NR8C(S)OR8, (ee) —NR8C(S)NR8R8, (ff) —SC(O)R8, (gg) —N3, (hh) —Si(R13)3, (ii) a C1-8 alkyl group, (jj) a C2-8 alkenyl group, (kk) a C2-8 alkynyl group, (ll) a C3-10 saturated, unsaturated, or aromatic carbocycle, and (mm) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, wherein (ii)-(mm) optionally are substituted with one or more R5 groups; alternatively two R14 groups are taken together to form (a) ═O, (b) ═S, (c) ═NR8, (e) ═NOR8; R15 is C1-6 alkyl, optionally substituted with from 1 to 13 fluorine atoms; n at each occurrence is 0, 1, 2, 3, or 4 p at each occurrence is 0, 1, or 2; r at each occurrence is 0, 1, or 2; t at each occurrence is 0, 1, or 2; and u at each occurrence is 1, 2, 3, or 4. |
