Macrocyclic compounds and methods of making and using the same

1. A compound having the formula:

or a pharmaceutically acceptable salt, or ester thereof,

wherein

T is

wherein:

M is selected from the group consisting of:

(a) —C(O)—, (b) —CH(—OR 114 )—, (c) —C(═NNR 114 R 114 )(d) —C(═NR 114 )—, (e) —CR 115 R 115 —, (f) —C(═NOR 127 )—, (g) —NR 114 —CH 2 —, (h) —CH 2 —NR 114 —, (i) CH(NR 114 R 114 )— (j) —NR 114 —C(O)—, and (k) —C(O)NR 114 —;

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

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 114 ;

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 114 —, 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(±)-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 0, 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 , OR 118 , (kk) —S(O) p R 118 , (ll) —C(O)R 118 , (mm) —C(O)OR 118 , (nn) —OC(O)R 118 , (oo) —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) 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 0, 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 116 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 -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) alkynyl, (i) —C(O)—C 3-10 saturated, unsaturated, or aromatic carbocycle, and (j) —C(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 (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 116 ) 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 16 , (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-C(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 C(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;

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(S)R 5 , (h) —C(S)OR 5 , and (i) —C(O)SR 5 ;

R 2 is hydrogen or —OR 12 ;

D is a C 1-6 alkyl group;

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 0, 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 1,2,3 triazolyl wherein

said 1,2,3-triazolyl immediately above optionally is substituted with one or more R 5 groups;

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) p —, (ll) —OC(O)—, (mm) —C(S)—, (nn) —C(S)NR 4 —, (oo) —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(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 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 0, 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 , (oo) —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 8 ) 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 1-8 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)-(oo) 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, (O) 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 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 8 C(O)R 8 , (w) —NR 8 C(O)OR 8 , (x) —NR 8 C(O)NR 8 R 8 , (y) —NR 8 S(O) n 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 8 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, (oo) 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 , (O)—C(O)OR 5 , (g) —C(S)R 5 , (h) —C(S)OR 5 , (i) —C(O)SR 5 , (j) a C 3-10 saturated, unsaturated, or aromatic carbocycle, (k) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (l) a —(C 1-6 alkyl) —C 3-10 saturated, unsaturated, or aromatic carbocycle, and (m) 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 (j)-(m) 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; and

provided that when the compound has formula I and T is

D is not a single bond or a —CH 2 —.

2. A compound according to claim 1 , having the formula:

or a pharmaceutically acceptable salt, or ester thereof.

3. A compound according to claim 2 having the formula:

or a pharmaceutically acceptable salt, or ester thereof.

4. A compound according to claim 2 having the formula:

or a pharmaceutically acceptable salt, or ester thereof.

5. A compound according to claim 1 or a pharmaceutically acceptable salt, or ester thereof wherein G is B′.

6. A compound according to claim 5 or a pharmaceutically acceptable salt, or ester 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.

7. A compound according to claim 1 , wherein T is a macrolide selected from the group consisting of:

or a pharmaceutically acceptable salt, or ester thereof.

8. A compound according to claim 1 , wherein T is a macrolide selected from the group consisting of:

or a pharmaceutically acceptable salt, or ester thereof.

9. A compound according to claim 1 , wherein T is a macrolide selected from the group consisting of:

or a pharmaceutically acceptable salt, or ester thereof.

10. A compound according to claim 1 , wherein T is a macrolide selected from the group consisting of T1, T2, T3, T4, T5, T6, 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, or ester thereof.

11. A compound having the structure selected from

Compound

Number

Structure

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

120

121

122

123

124

142

125

126

129

130

131

132

133

134

135

136

137

138

139

140

141

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

244

245

246

247

248

249

250

251

252

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

290

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

355

356

401

402

403

404

405

406

407

408

409

410

411

412

413

414

415

416

417

425

426

427

428

429

430

431

432

433

434

435

436

437

438

439

440

441

442

443

444

445

446

447

448

449

450

451

460

461

462

463

464

465

466

550

551

552

553

554

555

556

601

602

608

610

612

613

614

615

616

617

620

621

630

701

702

703

704

705

706

707

708

709

710

711

712

713

714

715

716

717

718

719

720

721

722

723

724

725

726

727

728

729

730

731

732

733

734

735

736

737

738

742

743

744

745

746

747

748

749

750

751

752

753

754

755

756

or a pharmaceutically acceptable salt, or ester thereof.

12. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

13. A method for treating a bacterial infection in a mammal comprising administering to a mammal in need thereof an effective amount of a compound according to claim 1 .

14. The method according to claim 13 wherein the compound is administered orally, parentally, or topically.

15. A medical device containing a compound according to claim 1 .

16. The medical device according to claim 15 , wherein the device is a stent.