Macrocyclic compounds and methods of making and using the same

Abstract

The present invention provides macrocyclic compounds useful as therapeutic agents of the formula: or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein T, R 1 , R 2 , R 3 , D, E, F, and G are as defined herein. More particularly, these compounds are useful as anti-infective, antiproliferative, anti-inflammatory and prokinetic agents.

What is claimed is: 
     
         1 . A compound having the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, 
       wherein
 T is a 14-, 15-, or 16-membered macrolide connected via a macrocyclic ring carbon atom; 
 R 1  and R 3  independently are selected from the group consisting of: (a) H, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6 alkynyl group, (e) —C(O)R 5 , 
 
       (f) —C(O)OR 5 , (g) —C(O)—NR 4 R 4 , (h) —C(S)R 5 , (i) —C(S)OR 5 , (j) —C(O)SR 5 , and (k) —C(S)NR 4 R 4 ;
 R 2  is hydrogen or —OR 12 ; 
 D is selected from the group consisting of:
 (a) a single bond, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6 alkynyl group, (e) —C(O)—X—, (f) —C(O)O—X—, (g) —C(O)NR 4 R 4 —X—, 
 (h) —C(═NR 4 )—X—, (i) —C(═NR 4 )O—X—, (j) —C(═NR 4 )N—X—, 
 (k) —SO 2 —X—, (l) —C(NR 4 )NR 4 —X—, (m) —C(S)—X—, 
 (n) —C(S)NR 4 —X—, (o) —C(NR 4 )S—X—, or (p) —C(O)S—X—, wherein
 i) 0-2 carbon atoms in any of (b)-(d) of D immediately above optionally is replaced by a moiety selected from the group consisting of O, S(O) p , and NR 4 , 
 ii) each of the groups (b)-(d) immediately above optionally is substituted with one or more R 5  groups, 
 iii) alternatively when R 5  is present as an optional substituent on (b)-(d), R 3  and R 5  can be taken together with the atoms to which they are attached to form a 3-7 membered ring, and 
 iv) X is selected from the group consisting of (aa) a C 1-6 alkyl group, (bb) a C 2-6 alkenyl group, and (cc) a C 2-6 alkynyl group, wherein each of groups (aa)-(cc) optionally is substituted with one or more R 5  groups; 
 
 
 F is selected from the group consisting of:
 (a) a single bond, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, and (d) a C 2-6  alkynyl group, wherein
 i) 0-2 carbon atoms in any of (b)-(d) of F immediately above optionally is replaced by a moiety selected from the group consisting of O, S(O) p , and NR 4 , 
 ii) any of (b)-(d) of F immediately above optionally is substituted with one or more R 5  groups, and 
 iii) any of (b)-(d) of F immediately above optionally is substituted with C 1-6 alkyl-R 5  groups; 
 
 
 E is selected from the group consisting of:
 (a) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 
 (b) a 3-10 membered saturated, unsaturated, or aromatic carbocycle, 
 (c) a —W-[3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur], 
 (d) a —W-[3-10 membered saturated, unsaturated, or aromatic carbocycle], 
 (e) —C(O)—, (f) —C(O)O—, (g) —C(O)NR 4 —, (h) —C(═NR 4 )—, 
 (i) —C(═NR 4 )O—, (j) —C(═NR 4 )NR 4 —, (k) —OC(O)—, (l) —OC(O)O—, 
 (m) —OC(O)NR 4 —, (n) —NR 4 C(O)—, (O)—NR 4 C(O)O—, 
 (p) —NR 4 C(O)NR 4 —, (q) —NR 4 C(═NR 4 )NR 4 —, (r) —S(O) P —, 
 (s) —NR 4 S(O) 2 —, (t) —S(O) 2 NR 4 —, (u) —C(N—OR 4 )—, (v) —CH 2 —, 
 (w) —C(N—NR 4 R 4 )—, (x) —C(S)NR 4 —, (y) —NR 4 C(S)—, (z) —C(S)O—, or 
 (aa) —OC(S)—, wherein
 i) any of (a)-(d) immediately above optionally is substituted with one or more R 5  groups; and 
 ii) W is selected from the group consisting of:
 (aa) —OCO—, (bb) —OC(O)O—, (cc) —OC(O)NR 4 —, 
 (dd) —NR 4 C(O)O—, (ee) —OCNOR 4 —, 
 (ff) —NR 4 —C(O)O—, (gg) —C(S)(NR 4 )—, (hh) —NR 4 —, 
 (ii) —OC(S)O—, (jj) —OC(S)NR 4 —, (kk) —NR 4 C(S)O—, (ll) —OC(S)NOR 4 —, (mm) —C(S)O—, (nn) —OC(S)—, (o) —C(O)—, (pp) —C(O)O—, (qq) —C(O)NR 4 —, (rr) —C(═NR 4 )—, 
 (ss) —C(═NR 4 )O—, (tt) —C(═NR 4 )NR 4 —, (uu) —OC(O)—, (vv) —OC(O)O—, (ww) —OC(O)NR 4 —, (xx) —NR 4 C(O)—, (yy) —NR 4 C(O)O—, 
 (zz) —NR 4 C(O)NR 4 —, (aaa) —NR 4 C(═NR 4 )NR 4 —, (bbb) —S(O) p —, (ccc) —NR 4 S(O) 2 —, (ddd) —S(O) 2 NR 4 —, (eee) —C(N—OR 4 )—, (fff) —C(N—NR 4 R 4 )—, (ggg) —C(S)NR 4 —, or (hhh) —NR 4 C(S)—; 
 
 
 
 G is selected from the group consisting of: (a) B′ and (b) B′—Z—B″, wherein
 i) each B′ and B″ is independently selected from the group consisting of (aa) an aryl group, (bb) a heteroaryl group, (cc) a biaryl group, (dd) a fused bicyclic or tricyclic saturated, unsaturated or aromatic ring system optionally containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (ee) a 3-10 membered saturated or unsaturated heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (ff) a 3-10 membered saturated, or unsaturated carbocycle, wherein each (aa)-(ff) optionally is substituted with one or more R 11  groups; and 
 ii) Z is selected from the group consisting of:
 (aa) a single bond, (bb) a C 1-2 alkyl group, (cc) a C 2  alkenyl group, 
 (dd) a C 2  alkynyl group, (ee) —C(O)—, (ff) —C(O)O—, (gg) —C(O)NR 4 —, 
 (hh) —C(═NR 4 )—, (ii) —C(═NR 4 )O—, (jj) —C(═NR 4 )NR 4 —, (kk) —S(O)—, 
 (ll) —OC(O)—, (mm) —C(S)—, (nn) —C(S)NR 4 —, (O)—C(NR 4 )S—, (pp) —C(O)S—, (qq) —O—, (rr) —NR 4 —, (ss) —NR 4 C(O)—, (tt) —OC(NR 4 )—, (uu) —NC(NR 4 )—, (vv) —C(S)O—, (ww) —SC(O)—, and (xx) —OC(S)—; 
 
 
 R 4 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6 alkynyl group, (e) a C 6-10  saturated, unsaturated, or aromatic carbocycle, (f) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (g) —C(O)—C 1-6  alkyl, (h) —C(O)—C 2-6 alkenyl, (i) —C(O)—C 2-6  alkynyl, (j) —C(O)—C 6-10  saturated, unsaturated, or aromatic carbocycle, (k) —C(±)-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (1) —C(O)O—C 1-6  alkyl, (m) —C(O)O—C 2-6  alkenyl, (n) —C(O)O—C 2-6  alkynyl, 
 (o) —C(O)O—C 6-10  saturated, unsaturated, or aromatic carbocycle, p) —C(O)O-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and q) —C(O)NR 6 R 6 ,
 wherein any of (b)-(p) optionally is substituted with one or more R 5  groups; 
 
 
 alternatively, NR 4 R 4  forms a 3-7 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R 4  groups are bonded, wherein said ring is optionally substituted at a position other than the nitrogen atom to which the R 4  groups are bonded, with one or more moieties selected from the group consisting of O, S(O) p , N, and NR 8 ; 
 R 5  is selected from the group consisting of:
 (a) R 7 , (b) a C 1-8 alkyl group, (c) a C 2-8 alkenyl group, (d) a C 2-8 alkynyl group, (e) a C 3-12  saturated, unsaturated, or aromatic carbocycle, and (f) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, or two R 5  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 form the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (b)-(f) immediately above optionally is substituted with one or more R 7  groups; 
 
 
 R 6 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6 alkynyl group, (e) a C 3-10  saturated, unsaturated, or aromatic carbocycle, and (f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (b)-(f) optionally is substituted with one or more moieties selected from the group consisting of:
 (aa) a carbonyl group, (bb) a formyl group, (cc) F, (dd) Cl, (ee) Br, (ff) I, (gg) CN, (hh) NO 2 , (ii) —OR 8 , 
 (jj) —S(O) p R 8 , (kk) —C(O)R 8 , (ll) —C(O)OR 8 , 
 (mm) —OC(O)R 8 , (nn) —C(O)NR 8 R 8 , 
 (o) —OC(O)NR 8 R 8 , (pp) —C(═NR 8 )R 8 , 
 (qq) —C(R 8 )(R 8 )OR 8 , (rr) —C(R 8 ) 2 OC(O)R 8 , 
 (ss) —C(R 8 )(OR 8 )(CH 2 ) r NR 8 R 8 , (tt) —NR 8 R 8 , 
 (uu) —NR 8 OR 8 , (vv) —NR 8 C(O)R 8 , 
 (ww) —NR 8 C(O)OR 8 , (xx) —NR 8 C(O)NR 8 R 8 , 
 (yy) —NR 8 S(O) r R 8 , (zz) —C(OR 8 )(OR 8 )R 8 , 
 (ab) —C(R) 2 NR 8 R 8 , (ac) ═NR 8 , 
 (ad) —C(S)NR 8 R 8 , (ae) —NR 8 C(S)R 8 , 
 (af) —OC(S)NR 8 R 8 , (ag) —NR 8 C(S)OR 8 , 
 (ah) —NR 8 C(S)NR 8 R 8 , (ai) —SC(O)R 8 , 
 (aj) a C 1-8 alkyl group, (ak) a C 2-8 alkenyl group, (al) a C 2-8 alkynyl group, (am) a C 1-6  alkoxy group, (an) a C 1-8 alkylthio group, (ao) a C 1-8  acyl group, (ap) —CF 3 , 
 (aq) —SCF 3 , (ar) a C 3-10  saturated, unsaturated, or aromatic carbocycle, and (as) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; 
 
 
 
 alternatively, NR 6 R 6  forms a 3-10 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R 6  groups are attached wherein said ring is optionally substituted at a position other than the nitrogen atom to which the R 6  groups are bonded, with one or more moieties selected from the group consisting of O, S(O) p , N, and NR 8 ; 
 alternatively, CR 6 R 6  forms a carbonyl group; 
 R 7 , at each occurrence, is selected from the group consisting of:
 (a) H, (b) ═O, (c) F, (d) Cl, (e) Br, (f) I, (g) —CF 3 , 
 (h) —CN, (i) —N 3 , (j) —NO 2 , (k) —NR 6 (CR 6 R 6 ) t R 9 , (l) —OR 9 , (m) —S(O) p C(R 6 R 6 ) t R 9 , 
 (n) —C(O)(CR 6 R 6 ) t R 9 , (o) —OC(O)(CR 6 R 6 ) t R 9 , (p) —SC(O)(CR 6 R 6 ) t R 9 , (q) —C(O)O(CR 6 R 6 ) t R 9 , (r) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (s) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (t) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (u) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (v) —C(═NNR 6 C(O)R 6 )(CR 6 R 6 ) t R 9 , (w) —C(═NOR 9 )(CR 6 R 6 ) t R 9 , (x) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (y) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (z) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , 
 (aa) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (bb) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (cc) —NR 6 S(O) p NR 6 (CR 6 R 6 ) t R 9 , (dd) —NR 6 R 6 , (ee) —NR 6 (CR 6 R 6 ), (ff) —OH, (gg) —NR 6 R 6 , 
 (hh) —OCH 3 , (ii) —S(O) p R 6 , (jj) —NC(O)R 6 , (kk) a C 1-6  alkyl group, (ll) a C 2-6  alkenyl group, (mm) a C 2-6 alkynyl group, (nn) —C 3-10  saturated, unsaturated, or aromatic carbocycle, and (o) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (kk)-(O) optionally is substituted with one or more R 9  groups; 
 
 
 alternatively, two R 7  groups form —O(CH 2 ) u O—; 
 R 8  is selected from the group consisting of:
 (a) R 5 , (b) H, (c) a C 1-6 alkyl group, (d) a C 2-6 alkenyl group, (e) a C 2-6  alkynyl group, 
 (f) a C 3-10  saturated, unsaturated, or aromatic carbocycle, (g) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (h) —C(O)—C 1-6  alkyl, (i) —C(O)—C 1-6 alkenyl, (j) —C(O)—C 1-6  alkynyl, (k) —C(O)—C 3-10  saturated, unsaturated, or aromatic carbocycle, and (l) —C(±)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (c)-(k) optionally is substituted with one or more moieties selected from the group consisting of: (aa) H, (bb) F, (cc) Cl, (dd) Br, (ee) I, (ff) CN, (gg) NO 2 , (hh) OH, (ii) NH 2 , (jj) NH(C 1-6  alkyl), (kk) N(C 1-6  alkyl) 2 , (ll) a C 1-6 alkoxy group, (mm) an aryl group, (nn) a substituted aryl group, (oo) a heteroaryl group, (pp) a substituted heteroaryl group, and qq) a C 1-6 alkyl group optionally substituted with one or more moieties selected from the group consisting of an aryl group, a substituted aryl group, a heteroaryl group, a substituted heteroaryl group, F, Cl, Br, I, CN, NO 2 , CF 3 , SCF 3 , and OH; 
 
 
 R 9 , at each occurrence, independently is selected from the group consisting of:
 (a) R 10 , (b) a C 1-6  alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6  alkynyl group, e) a C 3-10  saturated, unsaturated, or aromatic carbocycle, and f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (b)-(f) optionally is substituted with one or more R 10  groups; 
 
 
 R 10 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) ═O, (c) F, (d) Cl, (e) Br, (f) I, (g) —CF 3 , (h) —CN, (i) —NO 2 , (j) —NR 6 R 6 , (k) —OR 6 , (l) —S(O) p R 6 , (m) —C(O)R 6 , (n) —C(O)OR 6 , (o) —OC(O)R 6 , (p) NR 6 C(O)R 6 , 
 (q) —C(O)NR 6 R 6 , (r) —C(═NR 6 )R 6 , (s) —NR 6 C(O)NR 6 R 6 , (t) —NR 6 S(O) p R 6 , (u) —S(O) p NR 6 R 6 , (v) —NR 6 S(O) p NR 6 R 6 , (w) a C 1-6  alkyl group, (x) a C 2-6  alkenyl group, 
 (y) a C 2-6  alkynyl group, (z) a C 3-10  saturated, unsaturated, or aromatic carbocycle, and 
 (aa) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (w)-(aa) optionally is substituted with one or more moieties selected from the group consisting of R 6 , F, Cl, Br, I, CN, NO 2 , —OR 6 , —NH 2 , —NH(C 1-6  alkyl), —N(C 1-6  alkyl) 2 , a C 1-6  alkoxy group, a C 1-6  alkylthio group, and a C 1-6  acyl group; 
 
 
 R 11  each occurrence, independently is selected from the group consisting of:
 (a) a carbonyl group, (b) a formyl group, (c) F, (d) Cl, (e) Br, (f) I, (g) CN, (h) NO 2 , 
 (i) OR 8 , (j) —S(O) p R 8 , (k) —C(O)R 8 , (l) —C(O)OR 8 , 
 (m) —OC(O)R 8 , (n) —C(O)NR 8 R 8 , (O)—OC(O)NR 8 R 8 , 
 (p) —C(═NR 8 )R 8 , (q) —C(R 8 )(R 8 )OR 8 , (r) —C(R 8 ) 2 OC(O)R 8 , 
 (s) —C(R 8 )(OR 8 )(CH 2 ) r NR 8 R 8 , (t) —NR 8 R 8 , (u) —NR 8 OR 8 , 
 (v) —NR C(O)R 8 , (w) —NR 8 C(O)OR 8 , (x) —NR C(O)NR 8 R 8 , (y) —NR 8 S(O) r R 8 , (z) —C(OR 8 )(OR 8 )R 8 , (aa) —C(R 8 ) 2 NR 8 R 8 , (bb) ═NR 8 , (cc) —C(S)NR 8 R 8 , (dd) —NR 8 C(S)R 8 , (ee) —OC(S)NR 8 R 8 , (ff) —NR 8 C(S)OR 8 , (gg) —NR C(S)NR 8 R 8 , (hh) —SC(O)R 8 , (ii) a C 1-8 alkyl group, (jj) a C 2-8 alkenyl group, (kk) a C 2-8 alkynyl group, 
 (ll) a C 1-8 alkoxy group, (mm) a C 1-8  alkylthio group, (nn) a C 1-8  acyl group, (O) a C 3-10  saturated, unsaturated, or aromatic carbocycle, and (pp) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein (ii)-(kk) optionally are substituted with one or more R 5  groups; 
 
 R 12  is selected from the group consisting of:
 (a) H, (b) a C 1-6 alkyl group, (c) a C 2-6 alkenyl group, (d) a C 2-6 alkynyl group, (e) —C(O)R 5 , (f) —C(O)OR 5 , (g) —C(O)—NR 4 R 4 , (h) —C(S)R 5 , (i) —C(S)OR 5 , (j) —C(O)SR 5 , (k) —C(S)—NR 4 R 4 , (1) a C 3-10  saturated, unsaturated, or aromatic carbocycle, or (m) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 
 (n) a —(C 1-6 alkyl)-C 3-10  saturated, unsaturated, or aromatic carbocycle, and (o) a —(C 1-6 alkyl)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein (a)-(d) and (l)-(O) optionally are substituted with one or more R 5  groups; 
 
 
 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; 
 u at each occurrence is 1, 2, 3, or 4; 
 provided that
 i) when T is a 14 or 15 membered macrolide D-E is not 
 
 
       
         
           
           
               
               
           
         
         
           ii) when T is a 14 or 15 membered macrolide F—B′ is not 
         
       
       
         
           
           
               
               
           
         
         
           iii) when T is a 14 or 15 membered macrolide B′—Z—B″ is not 
         
       
       
         
           
           
               
               
           
         
         
           iv) when T is a 14 or 15 membered macrolide R 11  is not 
         
       
       
         
           
           
               
               
           
         
         
           v) when the compound has formula I and T is 
         
       
       
         
           
           
               
               
           
         
         
           
             D is not a single bond or a —CH 2 —, 
           
           vi) when the compound has formula I and T is a 14 or 15 membered macrolide -D-E-F— is not a —CH 2 —, 
           vii) when the compound has formula I and T is a 14 or 15 membered macrolide -D-E-F-G- is not a chemical moiety selected from the chemical moieties listed in Table A 
         
       
       
         
           
                 
               
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         and
 viii) when the compound has formula II and T is a 16 membered macrolide
 i. -D-E- is not a glycoside attached via its anomeric carbon, 
 ii. -D-E-F-G is not a C 1-4  (alkyl), C 2-4  (alkenyl), or C 2-4  (alkynyl) chain bonded to a 5-10 membered monocyclic or bicyclic carbocyle or heterocycle or bonded to a 5 or 6 membered carbocycle or heterocycle further bonded to a 5 or 6 membered carbocycle or heterocycle, any of said carbocycles or heterocycles being optionally substituted with one or more groups selected from the group consisting of (aa) —OH, (bb) —F, (cc) —Cl, (dd) —I, and (ee) —NO 2 , and 
 iii. -D-E-F-G- is not a chemical moiety selected from the chemical moieties listed in Table B 
 
 
       
       
         
           
                 
                 
               
                   TABLE B 
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   -(t-butoxycarboxy)-3-(3-quinolyl) 
                 
                     
                 
             
                
                
               
               
                
                
               
            
           
         
       
     
     
         2 . A compound according to  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof. 
       
     
     
         3 . A compound according to  claim 2  having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof. 
       
     
     
         4 . A compound according to  claim 2  having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof. 
       
     
     
         5 . A compound according to  claim 1  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein T is a 14- or 15-membered macrolide connected via a macrocyclic ring carbon atom. 
     
     
         6 . A compound according to  claim 1  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein G is B′. 
     
     
         7 . A compound according to  claim 6  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein B′ is selected from the group consisting of: (a) an aryl group, (b) a heteroaryl group, (c) a biaryl group, and (d) a fused bicyclic or tricyclic unsaturated or aromatic ring system optionally containing one or more carbonyl groups and one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a)-(d) optionally is substituted with one or more R 11  groups. 
     
     
         8 . A compound according to  claim 6  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein E is
 (a) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 
 (b) a 3-10 membered saturated, unsaturated, or aromatic carbocycle, 
 (c) a —W-[3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur], 
 (d) a —W-[3-10 membered saturated, unsaturated, or aromatic carbocycle], 
 (e) —C(O)—, (f) —C(O)O—, (g) —C(O)NR 4 —, (h) —C(═NR 4 )—, 
 (i) —C(═NR 4 )O—, (j) —C(═NR 4 )NR 4 —, (k) —OC(O)—, (l) —OC(O)O—, 
 (m) —OC(O)NR 4 —, (n) —NR 4 C(O)—, (o) —NR 4 C(O)O—, 
 (p) —NR 4 C(O)NR 4 —, (q) —NR 4 C(═NR 4 )NR 4 —, (r) —S(O)—, 
 (s) —NR 4 S(O) 2 —, (t) —S(O) 2 NR 4 —, (u) —C(N—OR 4 )—, (v) —C(N—NR 4 R 4 )—, 
 (w) —C(S)NR 4 —, (x) —NR 4 C(S)—, (y) —C(S)O—, or (z) —OC(S)—, wherein
 i) any of (a)-(d) immediately above optionally is substituted with one or more R 5  groups; and 
 ii) W is selected from the group consisting of:
 (aa) —OCO—, (bb) —OC(O)O—, (cc) —OC(O)NR 4 —, (dd) —NR 4 C(O)O—, 
 (ee) —OCNOR 4 —, (ff) —NR 4 —C(O)O—, (gg) —C(S)(NR 4 )—, (hh) —NR 4 —, 
 (ii) —OC(S)O—, (jj) —OC(S)NR 4 —, (kk) —NR 4 C(S)O—, (ll) —OC(S)NOR 4 —, (mm) —C(S)O—, (nn) —OC(S)—, (O)—C(O)—, (pp) —C(O)O—, (qq) —C(O)NR 4 —, (rr) —C(═NR 4 )—, (ss) —C(═NR 4 )O—, (tt) —C(═NR 4 )NR 4 —, (uu) —OC(O)—, (vv) —OC(O)O—, (ww) —OC(O)NR 4 —, 
 (xx) —NR 4 C(O)—, (yy) —NR 4 C(O)O—, (zz) —NR 4 C(O)NR 4 —, (aaa) —NR 4 C(═NR 4 )NR 4 —, (bbb) —S(O) p —, (ccc) —NR 4 S(O) 2 —, (ddd) —S(O) 2 NR 4 —, (eee) —C(N—OR 4 )—, (fff) —C(N—NR 4 R 4 )—, (ggg) —C(S)NR 4 —, or (hhh) —NR 4 C(S)—. 
 
 
 
     
     
         9 . A compound according to  claim 1  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein
 D is selected from the group consisting of (a) a C 1-6 alkyl group, (b) a C 2-6 alkenyl group, and (c) a C 2-6 alkynyl group, wherein
 i) 0-2 carbon atoms in any of (a)-(c) of D immediately above optionally is replaced by a moiety selected from the group consisting of O, S(O) p , and NR 4 , 
 ii) any of (a)-(c) of D immediately above optionally is substituted with one or more R 5  groups; and 
 
 F is selected from the group consisting of (a) a single bond, (b) a C 1-6  alkyl group, (c) a C 2-6 alkenyl group, and (d) a C 2-6 alkynyl group, wherein
 i) 0-2 carbon atoms in any of (b)-(d) of F immediately above optionally is replaced by a moiety selected from the group consisting of O, S(O) p , and NR 4 ; 
 ii) any of (b)-(d) of F immediately above optionally is substituted with one or more R 5  groups; and 
 iii) any of (b)-(d) of F immediately above optionally is substituted with C 1-6  alkyl-R 5 . 
 
 
     
     
         10 . A compound according to  claim 9  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein
 E is selected from the group consisting of:
 (a) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 
 (b) a 3-10 membered saturated, unsaturated, or aromatic carbocycle, 
 (c) a —W-[3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur], 
 (d) a —W-[3-10 membered saturated, unsaturated, or aromatic carbocycle], 
 (e) —C(O)—, (f) —C(O)O—, (g) —C(O)NR 4 —, (h) —C(═NR 4 )—, (i) —C(═NR 4 )O—, (j) —C(═NR 4 )NR 4 —, (k) —OC(O)—, (l) —OC(O)O—, 
 (m) —OC(O)NR 4 —, (n) —NR 4 C(O)—, (o) —NR 4 C(O)O—, (p) —NR 4 C(O)NR 4 —, (q) —NR 4 C(═NR 4 )NR 4 —, (r) —S(O) p —, is) —NR 4 S(O) 2 —, (t) —S(O) 2 NR 4 —, (u) —C(N—OR 4 )—, 
 (v) —CH 2 —, (w) —C(N—NR 4 R 4 )—, (x) —C(S)NR 4 , (y) —NR 4 C(S)—, (Z) —C(S)O—, and 
 (aa) —OC(S)—, wherein
 i) any of (a)-(d) immediately above optionally is substituted with one or more R 5  groups; and 
 ii) W is selected from the group consisting of:
 (aa) —OCO—, (bb) —OC(O)O—, (cc) —OC(O)NR 4 —, 
 (dd) —NR 4 C(O)O—, (ee) —OCNOR 4 —, 
 (ff) —NR 4 —C(O)O—, (gg) —C(S)(NR 4 )—, (hh) —NR 4 , 
 (ii) —OC(S)O—, (jj) —OC(S)NR 4 —, (kk) —NR 4 C(S)O—, (ll) —OC(S)NOR 4 —, (mm) —C(S)O—, (nn) —OC(S), (O)—C(O)—, (pp) —C(O)O—, (qq) —C(O)NR 4 —, (rr) —C(═NR 4 )—, 
 (ss) —C(═NR 4 )O—, (tt) —C(═NR 4 )NR 4 —, (uu) —OC(O)—, (vv) —OC(O)O—, (ww) —OC(O)NR 4 —, (xx) —NR 4 C(O)—, (yy) —NR 4 C(O)O—, (zz) —NR 4 C(O)NR 4 —, (aaa) —NR 4 C(═NR 4 )NR 4 —, (bbb) —S(O) p —, (ccc) —NR 4 S(O) 2 —, (ddd) —S(O) 2 NR 4 —, (eee) —C(N—OR 4 )—, (fff) —C(N—NR 4 R 4 )—, (ggg) —C(S)NR 4 —, and (hhh) —NR 4 C(S)—. 
 
 
 
 
     
     
         11 . A compound according to  claim 10  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein
 E is selected from the group consisting of:
 (a) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and 
 (b) a 3-10 membered saturated, unsaturated, or aromatic carbocycle, wherein (a) and (b) immediately above optionally is substituted with one more R 5  groups. 
 
 
     
     
         12 . A compound according to  claim 9  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof wherein
 E is selected from the group consisting of:
 (a) —C(O)—, (b) —C(O)O—, (c) —C(O)NR 4 —, (d) —C(═NR 4 )—, 
 (e) —C(═NR 4 )O—, (f) —C(═NR 4 )NR 4 —, (g) —OC(O)—, (h) —OC(O)O—, (i) —OC(O)NR 4 —, 
 (j) —NR 4 C(O)—, (k) —NR 4 C(O)O—, (l) —NR 4 C(O)NR 4 —, (m) —NR 4 C(═NR 4 )NR 4 —, (n) —S(O) p —, (O)—NR 4 S(O) 2 —, (p) —S(O) 2 NR 4 —, (q) —C(N—OR 4 )—, (r) —CH 2 —, (s) —C(N—NR 4 R 4 )—, (t), —C(S)NR 4 , (u) —NR 4 C(S)—, (v) —C(S)O, and (w) —OC(S)—. 
 
 
     
     
         13 . A compound according to any one of according to  claim 1 , wherein T is: 
       
         
           
           
               
               
           
         
       
       or an N-oxide, pharmaceutically acceptable salt, ester or prodrug thereof,
 wherein: 
 M is selected from the group consisting of:
 (a) —C((O)—, (b) —CH(—OR 114 )—, (c) —NR 114 —CH 2 —, (d) —CH 2 —NR 114 , (e) —CH(NR 114 R 114 )—, (f) —C(═NNR 114 R 114 )—, (g) —NR 114 —C(O)—, (h) —C(O)NR 14 —, (i) —C(═NR 114 )—, and (j) —CR 115 R 115 —, (k) —C(═NOR 127 )—; 
 
 R 100  is selected from the group consisting of H and C 1-6  alkyl; 
 R 101  is selected from the group consisting of:
 (a) H, (b) Cl, (c) F, (d) Br, (e) I, (f) —NR 114 R 114 , (g) —NR 114 C(O)R 114 , (h) —OR 114 , 
 (i) —OC(O)R 114 , (j) —OC(O)OR 114 , (k) —OC(O)NR 114 R 114 , (l) —O—C 1-6 alkyl, 
 (m) —OC(O)—C 1-6 alkyl, (n) —OC(O)O—C 1-6 alkyl, (o) —OC(O)NR 114 —C 1-6 alkyl, 
 (p) C 1-6 alkyl, (q) C 1-6 alkenyl, and (r) C 1-6 alkynyl,
 wherein any of (l)-(r) optionally is substituted with one or more R 115  groups; 
 
 
 R 102  is H; 
 R 103  is selected from the group consisting of:
 (a) H, (b) —OR 114 , (c) —O—C 1-6 alkyl-R 115 , (d) —OC(O)R 114 , 
 (e) —OC(O)—C 1-6  alkyl-R 115 , (f) —OC(O)OR 114 , (g) —OC(O)O—C 1-6  alkyl-R 115 , 
 (h) —OC(O)NR 114 R 114 , (i) —OC(O)NR 114 —C 1-6  alkyl-R 115 , and 
 (j) 
 
 
       
         
           
           
               
               
           
         
         alternatively, R 102  and R 103  taken together form a carbonyl group; 
         alternatively, R 101  and R 103  taken together are a single bond between the respective carbons to which these two groups are attached thereby creating a double bond between the carbons to which R 100  and R 102  are attached; 
         alternatively, R 101  and R 103  taken together are an epoxide moiety; 
         R 104  is selected from the group consisting of:
 (a) H, (b) R 114 , (c) —C(O)R 114 , (d) —C(O)OR 114  (e) —C(O)NR 114 R 114 , (f) —C 1-6 alkyl-K—R 114 , (g) —C 2-6 alkenyl-K—R 114 , and (h) —C 2-6  alkynyl-K—R 14 ; 
 
         alternatively R 103  and R 104 , taken together with the atoms to which they are bonded, form: 
       
       
         
           
           
               
               
           
         
         K is selected from the group consisting of:
 (a) —C(O)—, (b) —C(O)O—, (c) —C(O)NR 114 —, (d) —C(═NR 114 )—, (e) —C(═NR 114 )O—, 
 (f) —C(═NR 114 )NR 114 —, (g) —OC(O)—, (h) —OC(O)O—, (i) —OC(O)NR 114 , 
 (j) —NR 114 C(O)—, (k) —NR 114 C(O)O—, (l) —NR 114 C(O)NR 114 —, 
 (m) —NR 114 C(═NR 114 )NR 14 —, and (O)—S(O) p —; 
 
         R 105  is selected from the group consisting of:
 (a) R 114 , (b) —OR 114 , (c) —NR 114 R 114 , (d) —O—C 1-6  alkyl-R 115 , (e) —C(O)—R 114 , 
 (f) —C(O)—C 1-6 alkyl-R 115 , (g) —OC(O)—R 114 , (h) —OC(O)—C 1-6 alkyl-R 115 , 
 (i) —OC(O)O—R 114 , (j) —OC(O)O—C 1-6  alkyl-R 115 , (k) —OC(O)NR 114 R 114 , 
 (l) —OC(O)NR 114 —C 1-6  alkyl-R 115 , (m) —C(O)—C 2-6 alkenyl-R 115 , and 
 (n) —C(O)—C 2-6 alkynyl-R 115 ; 
 
         alternatively, R 104  and R 105 , taken together with the atoms to which they are bonded, form: 
       
       
         
           
           
               
               
           
         
         
           wherein
 Q is CH or N, and R 126  is —OR 114 , —NR 114  or R 114 ; 
 
         
         alternatively, R 104  and R 105 , taken together with the atoms to which they are bonded, form: 
       
       
         
           
           
               
               
           
         
         
           wherein
 i) R 101  is as defined above; 
 ii) alternatively, R 101  and R 109  taken together form a carbonyl group; 
 iii) alternatively, R 101  and R 109  taken together form the group —O(CR 116 R 116 ) u O—; 
 
         
         alternatively, R 104  and R 105 , taken together with the atoms to which they are bonded, form: 
       
       
         
           
           
               
               
           
         
         
           i) R 130  is —OH, ═C(O), or R 114 , 
           ii) R 131  is —OH, ═C(O), or R 114 , 
           iii) alternatively, R 130  and R 131  together with the carbons to which they are attached form a 3-7 membered saturated, unsaturated or aromatic carbocyclic or heterocyclic ring which can optionally be substituted with one or more R 114  groups; 
         
         R 106  is selected from the group consisting of:
 (a) —OR 114 , (b) —C 1-6 alkoxy-R 115 , (c) —C(O)R 114 , (d) —OC(O)R 114 , (e) —OC(O)OR 114 , 
 (f) —OC(O)NR 114 R 114 , and (g) —NR 114 R 114 , 
 
         alternatively, R 105  and R 106  taken together with the atoms to which they are attached form a 5-membered ring by attachment to each other through a chemical moiety selected from the group consisting of:
 (a) —OC(R 115 ) 2 O—, (b) —OC(O)O—, (c) —OC(O)NR 114 —, (d) —NR 114 C(O)O—, 
 (e) —OC(O)NOR 114 —, (f) —NOR 114 —C(O)O—, (g) —OC(O)NNR 114 R 114 —, 
 (h) —NNR 114 R 114 —C(O)O—, (i) —OC(O)C(R 115 ) 2 —, (j) —C(R 115 ) 2 C(O)O—, (k) —OC(S)O—, 
 (l) —OC(S)NR 114 —, (m) —NR 114 C(S)O—, (n) —OC(S)NOR 114 —, (o) —NOR 114 —C(S)O—, 
 (p) —OC(S)NNR 114 R 114 —, (q) —NNR 114 R 114 —C(S)O—, (r) —OC(S)C(R 115 ) 2 —, and (s) —C(R 115 ) 2 C(S)O—; 
 
         alternatively, M, R 105 , and R 106  taken together with the atoms to which they are attached form: 
       
       
         
           
           
               
               
           
         
       
       wherein J is selected from the group consisting of O, S and NR 114 ;
 alternatively, M and R 104  taken together with the atoms to which they are attached form: 
 
       
         
           
           
               
               
           
         
         R 107  is selected from the group consisting of:
 (a) H, (b) —C 1-4 alkyl, (c) —C 2-4 alkenyl, which can be further substituted with C 1-12  alkyl or one or more halogens, (d) —C 2-4  alkynyl, which can be further substituted with C 1-12  alkyl or one or more halogens, (e) aryl or heteroaryl, which can be further substituted with C 1-12  alkyl or one or more halogens, (f) —C(O)H, (g) —COOH, (h) —CN, (i) —COOR 114 , (j) —C(O)NR 114 R 114 , (k) —C(O)R 114 , and (l) —C(O)SR 114 , wherein (b) is further substituted with one or more substituents selected from the group consisting of (aa) —OR 114 , (bb) halogen, (cc) —SR 114 , (dd) C 1-12  alkyl, which can be further substituted with halogen, hydroxyl, C 1-6 alkoxy, or amino, (ee) —OR 114 , (ff) —SR 114 , (gg) —NR 114 R 114 , (hh) —CN, (ii) —NO 2 , (jj) —NC(O)R 114 , (kk) —COOR 114 , (ll) —N 3 , (mm) ═N—O—R 114 , (nn) ═NR 114 , (oo) ═N—NR 114 R 114 , (pp) ═N—NH—C(O)R 114 , and (qq) ═N—NH—C(O)NR 114 R 114 ; 
 
         alternatively R 106  and R 107  are taken together with the atom to which they are attached to form an epoxide, a carbonyl, an olefin, or a substituted olefin, or a C 3 -C 7  carbocyclic, carbonate, or carbamate, wherein the nitrogen of said carbamate can be further substituted with a C 1 -C 6  alkyl; 
         R 108  is selected from the group consisting of:
 (a) C 1-6  alkyl, (b) C 2-6 alkenyl, and (c) C 2-6 alkynyl,
 wherein any of (a)-(c) optionally is substituted with one or more R 114  groups; 
 
 
         R 112  is selected from the group consisting of H, OH, and OR 114 ; 
         R 114 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) C 1-6 alkyl, (c) C 2-6 alkenyl, (d) C 2-6 alkynyl, (e) C 6-10  saturated, unsaturated, or aromatic carbocycle, (f) 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (g) —C(O)—C 1-6 alkyl, (h) —C(O)—C 2-6 alkenyl, (i) —C(O)—C 2-6 alkynyl, (j) —C(O)—C 6-10  saturated, unsaturated, or aromatic carbocycle, (k) —C(O)-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (l) —C(O)O—C 1-6 alkyl, (m) —C(O)O—C 2-6 alkenyl, (n) —C(O)O—C 2-6  alkynyl, (o) —C(O)O—C 6-10  saturated, unsaturated, or aromatic carbocycle, (p) —C(O)O-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (q) —C(O)NR 116 R 116 ,
 wherein any of (b)-(p) optionally is substituted with one or more R 115  groups, wherein one or more non-terminal carbon moieties of any of (b)-(d) optionally is replaced with oxygen, S(O) p , or —NR 116 ; 
 
 
         alternatively, NR 114 R 114  forms a 3-7 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R 114  groups are bonded and optionally one or more moieties selected from the group consisting of O, S(O) p , N, and NR 118 ; 
         R 115  is selected from the group consisting of:
 (a) R 117 , (b) C 1-8 alkyl, (c) C 2-8 alkenyl, (d) C 2-8 alkynyl, (e) C 3-12  saturated, unsaturated, or aromatic carbocycle, and (f) 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (b)-(f) optionally is substituted with one or more R 117  groups; 
 
 
         R 116 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) C 1-6  alkyl, (c) C 2-6 alkenyl, (d) C 2-6 alkynyl, (e) C 3-10  saturated, unsaturated, or aromatic carbocycle, and (f) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein one or more non-terminal carbon moieties of any of (b)-(d) optionally is replaced with oxygen, S(O) p , or —NR 114 , wherein any of (b)-(f) optionally is substituted with one or more moieties selected from the group consisting of:
 (aa) carbonyl, (bb) formyl, (cc) F, (dd) Cl, (ee) Br, (ff) I, (gg) CN, (hh) N 3 , (ii)NO 2 , (jj) OR 118 , (kk) —S(O) p R 118 , (ll) —C(O)R 118 , (mm) —C(O)OR 118 , (nn) —OC(O)R 118 , (O)—C(O)NR 118 R 118 , (pp) —OC(O)NR 118 R 118 , (qq) —C(═NR 118 )R 118 , (rr) —C(R 118 )(R 118 )OR 118 , (ss) —C(R 118 ) 2 OC(O)R 118 , (tt) —C(R 118 )(OR 118 )(CH 2 ) r NR 118 R 118 , (uu) —NR 118 R 118 , (vv) —NR 118 OR 118 , (ww) —NR 118 C(O)R 118 , (xx) —NR 118 C(O)OR 118 , (yy) —NR 118 C(O)NR 118 R 118 , (zz) —NR 118 S(O) r R 118 , (ab) —C(OR 118 )(OR 118 )R 118 , (ac) —C(R 118 ) 2 NR 118 R 118 , (ad) ═NR 118 , (ae) —C(S)NR 118 R 118 , (af) —NR 118 C(S)R 118 , (ag) —OC(S)NR 118 R 118 , (ah) —NR 118 C(S)OR 118 , (ai) —NR 118 C(S)NR 118 R 118 , (aj) —SC(O)R 118 , (ak) C 1-8 alkyl, (al) C 2-8 alkenyl, (am) C 2-8 alkynyl, (an) C 1-8 alkoxy, (ao) C 1-8 alkylthio, (ap) C 1-8  acyl, (aq) saturated, unsaturated, or aromatic C 3-10  carbocycle, and (ar) saturated, unsaturated, or aromatic 3-10 membered heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, 
 
 
 
         alternatively, NR 116 R 116  forms a 3-10 membered saturated, unsaturated or aromatic ring including the nitrogen atom to which the R 116  groups are attached and optionally one or more moieties selected from the group consisting of O, S(O) p , N, and NR 118 ; 
         alternatively, CR 116 R 116  forms a carbonyl group; 
         R 117 , at each occurrence, is selected from the group consisting of:
 (a) H, (b) ═O, (c) F, (d) Cl, (e) Br, (f) I, (g) (CR 116 R 116 ) r CF 3 , (h) (CR 116 R 116 ) r CN, 
 (i) (CR 116 R 116 ) r NO 2 , (j) (CR 116 R 116 ) r NR 116 (CR 116 R 116 ) t R 119 , (k) (CR 116 R 116 ) r OR 119 , 
 (l) (CR 116 R 116 ) r S(O) p (CR 1116 R 116 ) t R 119 , (m) (CR 116 R 116 ) r C(O)(CR 116 R 116 ) t R 119 , 
 (n) (CR 116 R 116 ) r OC(O)(CR 116 R 116 ) t R 119 , (O) (CR 116 R 116 ) r SC(O)(CR 116 R 116 ) t R 119 , 
 (p) (CR 116 R 116 ) r C(O)O(CR 116 R 116 ) t R 119 , (q) (CR 116 R 116 ) r NR 116 C(O)(CR 116 R 116 ) t R 119 , 
 (r) (CR 116 R 116 ) r C(O)NR 116 (CR 116 R 116 ) t R 119 , (s) (CR 116 R 116 ) r C(═NR 116 )(CR 116 R 116 ) t R 119 , (t) (CR 116 R 116 ) r C(═NNR 116 R 116 )(CR 116 R 116 ) t R 119 , 
 (u) (CR 116 R 116 ) r C(═NNR 116 C(O)R 116 )(CR 116 R 116 ) t R 119 , (v) (CR 116 R 116 ) r C(═NOR 119 )(CR 116 R 116 ) t R 119 , (w) (CR 116 R 116 ) r NR 116 C(O)O(CR 116 R 116 ) t R 119 , 
 (x) (CR 116 R 116 ) r OC(O)NR 116 (CR 116 R 116 ) t R 119 , 
 (y) (CR 116 R 116 ) r NR 116 C(O)NR 116 (CR 116 R 116 ) t R 119 , 
 (z) (CR 116 R 116 ) r NR 116 S(O) p (CR 116 R 116 ) t R 119 , 
 (aa) (CR 116 R 116 ) r S(O) p NR 116 (CR 116 R 116 ) t R 119 , 
 (bb) (CR 116 R 116 ) r NR 116 S(O) p NR 116 (CR 116 R 116 ) t R 119 , (cc) (CR 116 R 116 ) r NR 116 R 116 , 
 (dd) C 1-6  alkyl, (ee) C 2-6 alkenyl, (ff) C 2-6  alkynyl, (gg) (CR 116 R 116 ) r —C 3-10  saturated, unsaturated, or aromatic carbocycle, and (hh) (CR 116 R 116 ) r -3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (dd)-(hh) optionally is substituted with one or more R 119  groups; 
 
 
         alternatively, two R 117  groups form —O(CH 2 ) u O—; 
         R 118  is selected from the group consisting of:
 (a) H, (b) C 1-6 alkyl, (c) C 2-6  alkenyl, (d) C 2-6  alkynyl, (e) C 3-10  saturated, unsaturated, or aromatic carbocycle, (f) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (g) —C(O)—C 1-6 alkyl, (h) —C(O)—C 1-6 alkenyl, (g) —C(O)—C 1-6 alkynyl, (i) —C(O)—C 3-10  saturated, unsaturated, or aromatic carbocycle, and (j) —C(±)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (b)-(j) optionally is substituted with one or more moieties selected from the group consisting of: (aa) H, (bb) F, (cc) Cl, (dd) Br, (ee) I, (ff) CN, (gg) NO 2 , (hh) OH, (ii) NH 2 , (jj) NH(C 1-6  alky(l), (kk) N(C 1-6 alky(l) 2 , (ll) C 1-6 alkoxy, (mm) aryl, (nn) substituted aryl, (oo) heteroaryl, (pp) substituted heteroaryl, and (qq) C 1-6 alkyl, optionally substituted with one or more moieties selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, F, Cl, Br, I, CN, NO 2 , and OH; 
 
 
         R 119 , at each occurrence, independently is selected from the group consisting of:
 (a) R 120 , (b) C 1-6  alkyl, (c) C 2-6  alkenyl, (d) C 2-6 alkynyl, (e) C 3-10  saturated, unsaturated, or aromatic carbocycle, and (f) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; 
 
         R 120 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) ═O, (c) F, (d) Cl, (e) Br, (f) I, (g) (CR 116 R 116 ) r CF 3 , (h) (CR 116 R 116 ) r CN, 
 (i) (CR 116 R 116 ) r NO 2 , (j) (CR 116 R 116 ) r NR 116 R 116 , (k) (CR 116 R 116 ) r OR 114 , 
 (l) (CR 116 R 116 ) r S(O) p R 116 , (m) (CR 116 R 116 ) r C(O)R 116 , (n) (CR 116 R 116 ) r C(O)OR 116 , 
 (o) (CR 116 R 16 ) r OC(O)R 116 , (p) (CR 116 R 116 ) r NR 116 C(O)R 116 , 
 (q) (CR 116 R 116 ) r C(O)NR 116 R 116 , (r) (CR 116 R 116 ) r C(═NR 116 )R 116 , 
 (s) (CR 116 R 116 ) r NR 116 C(O)NR 116 R 116 , (t) (CR 116 R 116 ) r NR 116 S(O) p R 116 , 
 (u) (CR 116 R 116 ) r S(O) p NR 116 R 116 , (v) (CR 116 R 116 ) r NR 116 S(O) p NR 116 R 116 , 
 (w) C 1-6  alkyl, (x) C 2-6 alkenyl, (y) C 2-6 alkynyl, (z) (CR 116 R 116 ) r —C 3-10  saturated, unsaturated, or aromatic carbocycle, and (aa) (CR 116 R 116 ) r -3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
 wherein any of (w)-(aa) optionally is substituted with one or more moieties selected from the group consisting of R 116 , F, Cl, Br, I, CN, NO 2 , —OR 116 , —NH 2 , —NH(C 1-6  alkyl), —N(C 1-6 alkyl) 2 , C 1-6 alkoxy, C 1-6 alkylthio, and C 1-6  acyl; 
 
 
         R 121 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) —OR 118 , (c) —O—C 1-6 alkyl-OC(O)R 118 , (d) —O—C 1-6  alkyl-OC(O)OR 118 , 
 (e) —O—C 1-6  alkyl-OC(O)NR 118 R 118 , (f) —O—C 1-6 alkyl-C(O)NR 118 R 118 , (g) —O—C 1-6 alkyl-NR 118 C(O)R 118 , (h) —O—C 1-6 alkyl-NR 118 C(O)OR 118 , (i) —O—C 1-6  alkyl-NR 118 C(O)NR 118 R 118 , (j) —O—C 1-6 alkyl-NR 118 C(═N(H)NR 118 R 118 , (k) —O—C 1-6  alkyl-S(O) p R 118 , (l) —O—C 2-6 alkenyl-OC(O)R 118 , (m) —O—C 2-6 alkenyl-OC(O)OR 118 , (n) —O—C 2-6 alkenyl-OC(O)NR 118 R 118 , (o) —O—C 2-6  alkenyl-C(O)NR 118 R 118 , (p) —O—C 2-6 alkenyl-NR 118 C(O)R 118 , (q) —O—C 2-6 alkenyl-NR 118 C(O)OR 118 , (r) —O—C 2-6 alkenyl-NR 118 C(O)NR 118 R 118 , (s) —O—C 2-6 alkenyl-NR 118 C(═N(H)NR 118 R 118 , 
 (t) —O—C 2-6 alkenyl-S(O) p R 118 , 
 (u) —O—C 2-6  alkynyl-OC(O)R 118 , (v) —O—C 2-6 alkynyl-OC(O)OR 118 , 
 (w) —O—C 2-6 alkynyl-OC(O)NR 118 R 118 , (x) —O—C 2-6 alkynyl-C(O)NR 118 R 118 , (y) —O—C 2-6 alkynyl-NR 118 C(O)R 118 , (z) —O—C 2-6 alkynyl-NR 118 C(O)OR 118 , (aa) —O—C 2-6 alkynyl-NR 118 SC(O)NR 118 R 118 , 
 (bb) —O—C 2-6 alkynyl-NR 118 C(═N(H)NR 118 R 118 , (cc) —O—C 2-6 alkynyl-S(O) p R 118 , and 
 (dd) —NR 118 R 118 ; 
 
         alternatively, two R 121  groups taken together form ═O, ═NOR 118 , or ═NNR 118 R 118 ; 
         R 124 , at each occurrence, independently is selected from the group consisting of:
 (a) H, (b) F, (c) Cl, (d) Br, (e) I, (f) CN, (g) —OR 114 , (h) —NO 2 , (i) —NR 114 R 114 , (j) C 1-6  alkyl, (k) C 1-6  acyl, and (l) C 1-6 alkoxy; 
 
         R 109  is H or F; 
         R 127  is R 114 , a monosaccharide or disaccharide (including amino sugars and halo sugar(s)), —(CH 2 ) n —(O—CH 2 CH 2 —) m —O(CH 2 ) p CH 3 , or —(CH 2 ) n —(O—CH 2 CH 2 —) m —OH; 
         R 128  is R 114 ; 
         R 129  is R 114 ; 
         R 110  is R 114 ; 
         alternatively, R 109  and R 110  taken together with the carbons to which they are attached form: 
       
       
         
           
           
               
               
           
         
         alternatively, R 128  and R 129  together with the carbons to which they are attached form a 3-6 membered saturated, unsaturated or aromatic carbocyclic or heterocyclic ring which optionally be substituted with one or more R 114  groups; 
         m, at each occurrence is 0, 1, 2, 3, 4, or 5; 
         n, at each occurrence is 1, 2, or 3. 
       
     
     
         14 . A compound according to  claim 13 , wherein T is a macrolide selected from the group consisting of: 
       
         
           
           
               
               
           
         
         or an N-oxide pharmaceutically acceptable salt, ester, or prodrug thereof. 
       
     
     
         15 . A compound according to  claim 13 , wherein T is a macrolide selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or an N-oxide pharmaceutically acceptable salt, ester, or prodrug thereof. 
       
     
     
         16 . A compound according to  claim 13 , wherein T is a macrolide selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or an N-oxide pharmaceutically acceptable salt, ester, or prodrug thereof. 
       
     
     
         17 . A compound according to  claim 1 , wherein T is a macrolide selected from the group consisting of T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, T15, T16, T17, T18, T19, T20, T21, T22, T23, T24, T25, T26, T27, T28, T29, T30, T31, and T33: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof. 
       
     
     
         18 . A compound having the structure corresponding to any one of the structures listed in Table 1 or 13, or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof. 
     
     
         19 . A pharmaceutical composition comprising a compound according to  claim 1  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof and a pharmaceutically acceptable carrier. 
     
     
         20 . A method for treating or preventing a disease state in a mammal comprising administering to a mammal in need thereof an effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof.