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)—, (oo) —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 —, (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 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 , 
  (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 1-6  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 (oo) 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(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 (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, (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 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, (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 , (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 (0o) 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 
           
         
       
       
         
           
                 
               
                   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 carbocycle 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)