Triazole compounds and methods of making and using the same
View Patent ↗The present invention provides triazole macrocyclic compounds useful as therapeutic agents. More particularly, these compounds are useful as anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. The compounds have the following structure: wherein T is the macrocyclic part.
1. A compound having the structure:
or a pharmaceutically acceptable salt, ester, or N-oxide thereof,
wherein
A is selected from: (a) a C 1-6 alkyl group, (b) a C 2-6 alkenyl group, (c) a C 2-6 alkynyl group, (d) a C 3-12 saturated, unsaturated, or aromatic carbocycle, (e) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more nitrogen, oxygen or sulfur atoms, (f) H, (g) —OH, (h) —SH, (i) F, (j) Cl, (k) Br, (l) I, (m) —CF 3 , (n) —CN, (o) —N 3 , (p) —NO 2 , (q) —NR 6 (CR 6 R 6 ) t R 9 , (r) —OR 9 , (s) —S(CR 6 R 6 ) t R 9 , (t) —C(O)(CR 6 R 6 ) t R 9 , (u) —OC(O)(CR 6 R 6 ) t R 9 , (v) —OC(O)O(CR 6 R 6 ) t R 9 , (w) —SC(O)(CR 6 R 6 ) t R 9 , (x) —C(O)O(CR 6 R 6 ) t R 9 , (y) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (z) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (aa) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (bb) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (cc) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (dd) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (ee) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (ff) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (gg) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (hh) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (ii) —NR 6 R 6 , (jj) —SR 6 , (kk) —S(O)R 6 , (ll) —NR 6 C(O)R 6 , (mm) —Si(R 13 ) 3 , and (nn) —C(═O)H,
wherein (a)-(e) optionally are substituted with one or more R 14 groups;
T is a 14- or 15-membered macrolide connected via a macrocyclic ring carbon atom;
X is selected from —OR 15 and —SR 15 ;
R 1 and R 3 independently are selected from: (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 ;
alternatively, R 1 and R 3 are taken together with the oxygen to which R 1 is attached, the nitrogen to which R 3 is attached and the two intervening carbons to form a 5 or 6 membered ring, said ring being optionally substituted with one or more R 5 ;
R 2 is hydrogen or —OR 12 ;
R 4 , at each occurrence, independently is selected from:
(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 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 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 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 6 R 6 forms a 3-7 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 attached, with one or more substituents selected from O, S(O) p , N, and NR 8 ;
R 5 is selected from:
(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 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 from 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:
(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 nitrogen, oxygen, and sulfur,
wherein any of (b)-(f) optionally is substituted with one or more moieties selected from:
(aa) a carbonyl group, (bb) a formyl group, (cc) F, (dd) Cl, (ee) Br, (ff) I, (gg) CN, (hh) 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 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 —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:
(a) H, (b) ═O, (c) ═S, (d) F, (e) Cl, (f) Br, (g) I, (h) —CF 3 , (i) —CN, (j) —N 3 , (k) —NO 2 , (l) —NR 6 (CR 6 R 6 ) t R 9 , (m) —OR 9 , (n) —S(O) p C(R 6 R 6 ) t R 9 , (o) —C(O)(CR 6 R 6 ) t R 9 , (p) —OC(O)(CR 6 R 6 ) t R 9 , (q)—SC(O)(CR 6 R 6 ) t R 9 , (r) —C(O)O(CR 6 R 6 ) t R 9 , (s) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (t) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (u) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (v) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (w) —C(═NNR 6 C(O)R 6 )(CR 6 R 6 ) t R 9 , (x) —C(═NOR 9 )(CR 6 R 6 ) t R 9 , (y) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (z) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (aa) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (bb) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (cc) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (dd) —NR 6 S(O) p NR 6 (CR 6 R 6 ) t R 9 , (ee) —NR 6 R 6 , (ff) —NR 6 (CR 6 R 6 ), (gg) —OH, (hh) —NR 6 R 6 , (ii) —OCH 3 , (jj) —S(O) p R 6 , (kk) —NC(O)R 6 , (ll) a C 1-6 alkyl group, (mm) a C 2-6 alkenyl group, (nn) a C 2-6 alkynyl group, (oo) —C 3-10 saturated, unsaturated, or aromatic carbocycle, and (pp) 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (ll)-(pp) optionally is substituted with one or more R 9 groups; alternatively, two R 7 groups taken together form —O(CH 2 ) u O—;
R 8 is selected from:
(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, (f) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, (g) —C(O)—C 1-6 alkyl, (h) —C(O)—C 1-6 alkenyl, (i) —C(O)—C 1-6 alkynyl, (j) —C(O)—C 3-10 saturated, unsaturated, or aromatic carbocycle, and (k) —C(O)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (c)-(k) optionally is substituted with one or more moieties selected from: (aa) H, (bb) F, (cc) Cl, (dd) Br, (ee) I, (ff) CN, (gg) 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 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:
(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 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:
(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 nitrogen, oxygen, and sulfur,
wherein any of (w)-(aa) optionally is substituted with one or more moieties selected from 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 at each occurrence, independently is selected from:
(a) H, (b) F, (c) Cl, (d) Br, (e) I, (f) CN, (g) NO 2 , (h) OR 8 , (i) —S(O) p R 8 , (j) —C(O)R 8 , (k) —C(O)OR 8 , (l) —OC(O)R 8 , (m) —C(O)NR 8 R 8 , (n) —OC(O)NR 8 R 8 , (o) —C(═NR 8 )R 8 , (p) —C(R 8 )(R 8 )OR 8 , (q) —C(R 8 ) 2 OC(O)R 8 , (r) —C(R 8 )(OR 8 )(CH 2 ) r NR 8 R 8 , (s) —NR 8 R 8 , (t) —NR 8 OR 8 , (u) —NR 8 C(O)R 8 , (v) —NR 8 C(O)OR 8 , (w) —NR 8 C(O)NR 8 R 8 , (x) —NR 8 S(O) p R 8 , (y) —C(OR 8 )(OR 8 )R 8 , (z) —C(R 8 ) 2 NR 8 R 8 , (aa) —C(S)NR 8 R 8 , (bb) —NR 8 C(S)R 8 , (cc) —OC(S)NR 8 R 8 , (dd) —NR 8 C(S)OR 8 , (ee) —NR 8 C(S)NR 8 R 8 , (ff) —SC(O)R 8 , (gg) —N 3 , (hh) —Si(R 13 ) 3 , (ii) a C 1-8 alkyl group, (jj) a C 2-8 alkenyl group, (kk) a C 2-8 alkynyl group, (ll) a C 3-10 saturated, unsaturated, or aromatic carbocycle, and (mm) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, wherein (ii)-(mm) optionally are substituted with one or more R 5 groups;
R 12 is selected from:
(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 , (l) a C 3-10 saturated, unsaturated, or aromatic carbocycle, (m) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from -nitrogen, oxygen, and sulfur, (n) a —(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 nitrogen, oxygen, and sulfur,
wherein (a)-(d) and (l)-(o) optionally are substituted with one or more R 5 groups;
R 13 at each occurrence, is independently selected from (a) —C 1-6 alkyl and (b) —O—(C 1-6 alkyl);
R 14 at each occurrence is independently selected from:
(a) H, (b) F, (c) Cl, (d) Br, (e) I, (l) CN, (g) NO 2 , (h) OR 8 , (i) —S(O) p R 8 , (j) —C(O)R 8 , (k) —C(O)OR 8 , (l) —OC(O)R 8 , (m) —C(O)NR 8 R 8 , (n) —OC(O)NR 8 R 8 , (o) —C(═NR 8 )R 8 , (p) —C(R 8 )(R 8 )OR 8 , (q) —C(R 8 ) 2 OC(O)R 8 , (r) —C(R 8 )(OR 8 )(CH 2 ) r NR 8 R 8 , (s) —NR 8 R 8 , (t) —NR 8 OR 8 , (u) —NR 8 C(O)R 8 , (v) —NR 8 C(O)OR 8 , (w) —NR 8 C(O)NR 8 R 8 , (x) —NR 8 S(O) p R 8 , (y) —C(OR 8 )(OR 8 )R 8 , (z) —C(R 8 ) 2 NR 8 R 8 , (aa) —C(S)NR 8 R 8 , (bb) —NR 8 C(S)R 8 , (cc) —OC(S)NR 8 R 8 , (dd) —NR 8 C(S)OR 8 , (ee) —NR 8 C(S)NR 8 R 8 , (ff) —SC(O)R 8 , (gg) —N 3 , (hh) —Si(R 13 ) 3 , (ii) a C 1-8 alkyl group, (jj) a C 2-8 alkenyl group, (kk) a C 2-8 alkynyl group, (ll) a C 3-10 saturated, unsaturated, or aromatic carbocycle, and (mm) a 3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur, wherein (ii)-(mm) optionally are substituted with one or more R 5 groups;
alternatively, two R 14 groups are taken together to form (a) ═O, (b) ═S, (c) ═NR 8 , (e) ═NOR 8 ;
R 15 is C 1-6 alkyl, optionally substituted with from 1 to 13 fluorine atoms;
n at each occurrence is 0, 1, 2, 3, or 4;
p at each occurrence is 0, 1, or 2;
r at each occurrence is 0, 1, or 2;
t at each occurrence is 0, 1, or 2;
and u at each occurrence is 1, 2, 3, or 4.
2. The compound according to claim 1 having the structure:
or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
3. The compound according to claim 1 having the structure:
or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
4. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein R 15 is C 1-3 alkyl, optionally substituted with from 1 to 7 fluorines.
5. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein R 15 is C 1-2 alkyl, optionally substituted with from 1 to 5 fluorines.
6. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein R 15 is selected from —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 .
7. The compound according to claim 6 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein R 15 is —CH 3 .
8. The compound according to claim 1 having the structure:
or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
9. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein n is 1 or 2.
10. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein n is 1.
11. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein R 11 is F.
12. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein n is 0.
13. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein A is selected from: (a) a C 1-6 alkyl group, (b) a C 2-6 alkenyl group, (c) a C 2-6 alkynyl group, (d) a C 3-12 saturated, unsaturated, or aromatic carbocycle, (e) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more nitrogen, oxygen or sulfur atoms, (f) —CF 3 , (g) —NR 6 (CR 6 R 6 ) t R 9 , (h) —OR 9 , (i) —S(CR 6 R 6 ) t R 9 , (j) —C(O)(CR 6 R 6 ) t R 9 , (k) —OC(O)(CR 6 R 6 ) t R 9 , (l) —OC(O)O(CR 6 R 6 ) t R 9 , (m) —SC(O)(CR 6 R 6 ) t R 9 , (n) —C(O)O(CR 6 R 6 ) t R 9 , (o) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (p) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (q) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (r) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (s) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (t) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (u) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (v) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (w) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (x) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (y) —NR 6 R 6 , (z) —SR 6 , (aa) —S(O)R 6 , and (bb) —NR 6 C(O)R 6 , wherein (a)-(e) optionally are substituted with one or more R 14 groups.
14. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein A is selected from: (a) a C 1-6 alkyl group, (b) a C 2-6 alkenyl group, (c) a C 2-6 alkynyl group, (d) a C 3-12 saturated, unsaturated, or aromatic carbocycle, (e) a 3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more nitrogen, oxygen or sulfur atoms,
wherein (a)-(e) optionally are substituted with one or more R 14 groups.
15. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein A is selected from (a) —NR 6 (CR 6 R 6 ) t R 9 , (b) —OR 9 , (c) —S(CR 6 R 6 ) t R 9 , (d) —C(O)(CR 6 R 6 ) t R 9 , (e) —OC(O)(CR 6 R 6 ) t R 9 , (f) —OC(O)O(CR 6 R 6 ) t R 9 , (g) —SC(O)(CR 6 R 6 ) t R 9 , (h) —C(O)O(CR 6 R 6 ) t R 9 , (i) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (j) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (k) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (l) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (m) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (n) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (o) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (p) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (q) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (r) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (s) —NR 6 R 6 , (t) —SR 6 , (u) —S(O)R 6 , and (v) —NR 6 C(O)R 6 .
16. The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein T is
wherein:
M is selected from:
(a) —C(O)—, (b) —CH(—OR 114 )—, (c) —NR 114 —CH 2 —, (d) (e) —CH(NR 114 R 114 )—, (f) —C(═NNR 114 R 114 )—, (g) —NR 114 —C(O)—, (h) —C(O)NR 114 —, (i) —C(═NR 114 )—, (j) —CR 115 R 115 —, and (k) —C(═NOR 127 )—;
R 100 is selected from (a) H, (b) F, (c) Cl, (d) Br, (e) —SR 114 , and (f) C 1-6 alkyl, wherein (f) optionally is substituted with one or more R 115 groups;
R 101 is selected from:
(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 (a) H, (b) F, (c) Cl, (d) Br, (e) —SR 114 , (f) C 1-6 alkyl, wherein (f) optionally is substituted with one or more R 115 groups;
R 103 is selected from:
(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 with the carbon to which they are attached form (a) a carbonyl group or (b) a 3-7 membered saturated, unsaturated or aromatic carbocyclic or heterocyclic ring which can optionally be substituted with one or more R 114 groups; 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 with the carbons to which they are attached form a 3-membered saturated, unsaturated or aromatic carbocyclic or heterocyclic ring which can optionally be substituted with one or more R 114 groups;
R 104 is selected from:
(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 ;
K is selected from:
(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 (n) —S(O) p —;
alternatively, R 103 and R 104 , taken together with the atoms to which they are bonded, form:
wherein R 135 and R 136 are selected from (a) hydrogen, (b) C 1-6 alkyl, (c) C 2-6 alkenyl, (d) C 2-6 alkynyl, (d) C 3-14 saturated, unsaturated or aromatic carbocycle, (e) 3-14 membered saturated, unsaturated or aromatic heterocycle containing one or more oxygen, nitrogen, or sulfur atoms, (f) F, (g) Br, (h) I, (i) OH, and (j) —N 3 , wherein (b) through (e) are optionally substituted with one or more R 117 ;
alternatively, R 135 and R 136 taken together form ═O, ═S, ═NR 114 , ═NOR 114 , ═NR 114 , and ═N—NR 114 R 114 ;
wherein V is selected from (a) —(C 1 -C 4 -alkyl)-, (b) —(C 4 -alkenyl)-, (c) O, (d) S, and (e) NR 114 , wherein (a) and (b) are optionally further substituted with one or more R 117 ;
R 105 is selected from:
(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 with the carbon to which they are attached 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:
wherein in the preceding structure the dotted line indicates an optional double bond,
i) R 130 is —OH or R 114 ,
ii) R 131 is —OH or R 114 ,
iii) alternatively, R 130 and R 131 taken 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;
iv) alternatively, R 130 and the carbon to which it is attached or R 131 and the carbon to which it is attached are each independently —C(═O)—;
alternatively, R 105 , R 132 and M, taken together with the atoms to which they are attached, form:
R 106 is selected from:
(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:
(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, R 105 , R 106 , and R 133 taken together with the atoms to which they are attached form:
alternatively, M, R 105 , and R 106 taken together with the atoms to which they are attached form:
wherein in the preceding structure the dotted line indicates an optional double bond,
wherein J 1 and J 2 are selected from hydrogen, Cl, F, Br, I, OH, —C 1-6 alkyl, and —O(C 1-6 alkyl) or taken together form ═O, ═S and ═NR 114 , ═NOR 114 , ═NR 114 , and ═N—NR 114 R 114 ;
alternatively, M and R 104 taken together with the atoms to which they are attached form:
wherein U is selected from (a) —(C 4 -alkyl)- and (b) —(C 4 -alkenyl)-, wherein (a) and (b) are optionally further substituted with one or more R 117 ;
alternatively, M and R 105 are taken together with the atoms to which they are attached to form:
R 107 is selected from:
(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 (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:
(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 H, OH, and OR 114 ;
R 114 , at each occurrence, independently is selected from:
(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 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 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 nitrogen, oxygen, and sulfur, (q) —C(O)NR 116 R 116 , (r) —NR 116 CO—C2-6 alkyl, (s) —NR 116 CO—C 6-10 saturated, unsaturated, or aromatic carbocycle, and (t) —NR 116 C(O)-3-12 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur
wherein any of (b)-(t) 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 O, S(O) p , N, and NR 118 ;
R 115 is selected from:
(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 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:
(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 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:
(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 , (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) 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 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 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:
(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 116 , (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 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:
(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 -nitrogen, oxygen, and sulfur, (g) —C(O)—C 1-6 alkyl, (h) —C(O)—C 1-6 alkenyl, (i) —C(O)—C 1-6 alkynyl, (j) —C(O)—C 3-10 saturated, unsaturated, or aromatic carbocycle, and (k) —C(O)-3-10 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, and sulfur,
wherein any of (b)-(k) optionally is substituted with one or more moieties selected from: (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 -aryl, substituted aryl, heteroaryl, substituted heteroaryl, F, Cl, Br, I, CN, NO 2 , and OH;
R 119 , at each occurrence, independently is selected from:
(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 -nitrogen, oxygen, and sulfur;
R 120 , at each occurrence, independently is selected from:
(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 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 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 -nitrogen, oxygen, and sulfur,
wherein any of (w)-(aa) optionally is substituted with one or more moieties selected from: 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:
(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 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 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 can optionally be substituted with one or more R 114 groups;
R 132 , R 133 , and R 134 are each independently selected from: (a) H, (b) F, (c) Cl, (d) Br, (e) —OR 114 , (f) —SR 114 , (g) —NR 114 R 114 , and (h) C 1-6 alkyl, wherein (h) optionally is substituted with one or more R 115 groups;
alternatively, R 132 and R 133 taken together form a carbon-carbon double bond;
alternatively, R 133 and R 134 taken together form ═O, ═S, ═NOR 114 , ═NR 114 , and ═N—NR 114 R 114 ;
alternatively, R 105 and R 134 taken together with the carbons to which they are attached form a 3-membered ring, said ring optionally containing an oxygen or nitrogen atom, and said ring being optionally substituted with one or more R 114 groups;
alternatively, when M is a carbon moiety, R 134 and M taken together form a carbon-carbon double bond;
k, at each occurrence is 0, 1, or 2;
m, at each occurrence is 0, 1, 2, 3, 4, or 5;
n, at each occurrence is 1, 2, or 3;
p at each occurrence is 0, 1, or 2;
r at each occurrence is 0, 1, or 2;
t at each occurrence is 0, 1, or 2; and
u at each occurrence is 1, 2, 3, or 4.
17. The compound according to claim 16 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein T is selected from:
where the dotted lines indicate optional double bonds.
18. The compound according to claim 16 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein T is selected from:
19. A compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, wherein T is selected from T1 through T33:
20. A compound selected from:
Compound
No.
Structure
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
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
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
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
281
282
283
284
285
Compound
T
A
R 11
1000a
T1
H
H
1000b
T1
H
F
1000c
T2
H
H
1000d
T2
H
F
1000e
T3
H
H
1000f
T3
H
F
1000g
T4
H
H
1000h
T4
H
F
1001a
T1
CH 3 CH 2 CH 2 —
H
1001b
T1
CH 3 CH 2 CH 2 —
F
1001c
T2
CH 3 CH 2 CH 2 —
H
1001d
T2
CH 3 CH 2 CH 2 —
F
1001e
T3
CH 3 CH 2 CH 2 —
H
1001f
T3
CH 3 CH 2 CH 2 —
F
1001g
T4
CH 3 CH 2 CH 2 —
H
1001h
T4
CH 3 CH 2 CH 2 —
F
1002a
T1
CH 2 ═CHCH 2 —
H
1002b
T1
CH 2 ═CHCH 2 —
F
1002c
T2
CH 2 ═CHCH 2 —
H
1002d
T2
CH 2 ═CHCH 2 —
F
1002e
T3
CH 2 ═CHCH 2 —
H
1002f
T3
CH 2 ═CHCH 2 —
F
1002g
T4
CH 2 ═CHCH 2 —
H
1002h
T4
CH 2 ═CHCH 2 —
F
1003a
T1
HC≡CCH 2 —
H
1003b
T1
HC≡CCH 2 —
F
1003c
T2
HC≡CCH 2 —
H
1003d
T2
HC≡CCH 2 —
F
1003e
T3
HC≡CCH 2 —
H
1003f
T3
HC≡CCH 2 —
F
1003g
T4
HC≡CCH 2 —
H
1003h
T4
HC≡CCH 2 —
F
1004a
T1
H
1004b
T1
F
1004c
T2
H
1004d
T2
F
1004e
T3
H
1004f
T3
F
1004g
T4
H
1004h
T4
F
1005a
T1
H
1005b
T1
F
1005c
T2
H
1005d
T2
F
1005e
T3
H
1005f
T3
F
1005g
T4
H
1005h
T4
F
1006a
T1
H
1006b
T1
F
1006c
T2
H
1006d
T2
F
1006e
T3
H
1006f
T3
F
1006g
T4
H
1006h
T4
F
1007a
T1
H
1007b
T1
F
1007c
T2
H
1007d
T2
F
1007e
T3
H
1007f
T3
F
1007g
T4
H
1007h
T4
F
1008a
T1
H
1008b
T1
F
1008c
T2
H
1008d
T2
F
1008e
T3
H
1008f
T3
H
1008g
T4
H
1008h
T4
F
1009a
T1
H
1009b
T1
F
1009c
T2
H
1009d
T2
F
1009e
T3
H
1009f
T3
F
1009g
T4
H
1009h
T4
F
1010a
T1
H
1010b
T1
F
1010c
T2
H
1010d
T2
F
1010e
T3
H
1010f
T3
F
1010g
T4
H
1010h
T4
F
1011a
T1
H
1011b
T1
F
1011c
T2
H
1011d
T2
F
1011e
T3
H
1011f
T3
F
1011g
T4
H
1011h
T4
F
1012a
T1
H
1012b
T1
F
1012c
T2
H
1012d
T2
F
1012e
T3
H
1012f
T3
F
1012g
T4
H
1012h
T4
F
1013a
T1
H
1013b
T1
F
1013c
T2
H
1013d
T2
F
1013e
T3
H
1013f
T3
F
1013g
T4
H
1013h
T4
F
10140a
T1
H
1014b
T1
F
1014c
T2
H
1014d
T2
F
1014e
T3
H
1014f
T3
F
1014g
T4
H
1014h
T4
F
1015a
T1
H
1015b
T1
F
1015c
T2
H
1015d
T2
F
1015e
T3
H
1015f
T3
F
1015g
T4
H
1015h
T4
F
1016a
T1
HO—
H
1016b
T1
HO—
F
1016c
T2
HO—
H
1016d
T2
HO—
F
1016e
T3
HO—
H
1016f
T3
HO—
F
1016g
T4
HO—
H
1016h
T4
HO—
F
1017a
T1
HS—
H
1017b
T1
HS—
F
1017c
T2
HS—
H
1017d
T2
HS—
F
1017e
T3
HS—
H
1017f
T3
HS—
F
1017g
T4
HS—
H
1017h
T4
HS—
F
1018a
T1
F
H
1018b
T1
F
F
1018c
T2
F
H
1018d
T2
F
F
1018e
T3
F
H
1018f
T3
F
F
1018g
T4
F
H
1018h
T4
F
F
1019a
T1
Cl
H
1019b
T1
Cl
F
1019c
T2
Cl
H
1019d
T2
Cl
F
1019e
T3
Cl
H
1019f
T3
Cl
F
1019g
T4
Cl
H
1019h
T4
Cl
F
1020a
T1
Br
H
1020b
T1
Br
F
1020c
T2
Br
H
1020d
T2
Br
F
1020e
T3
Br
H
1020f
T3
Br
F
1020g
T4
Br
H
1020h
T4
Br
F
1021a
T1
I
H
1021b
T1
I
F
1021c
T2
I
H
1021d
T2
I
F
1021e
T3
I
H
1021f
T3
I
F
1021g
T4
I
H
1021h
T4
I
F
1022a
T1
F 3 C—
H
1022b
T1
F 3 C—
F
1022c
T2
F 3 C—
H
1022d
T2
F 3 C—
F
1022e
T3
F 3 C—
H
1022f
T3
F 3 C—
F
1022g
T4
F 3 C—
H
1022h
T4
F 3 C—
F
1023a
T1
NC—
H
1023b
T1
NC—
F
1023c
T2
NC—
H
1023d
T2
NC—
F
1023e
T3
NC—
H
1023f
T3
NC—
F
1023g
T4
NC—
H
1023h
T4
NC—
F
1024a
T1
N 3 —
H
1024b
T1
N 3 —
F
1024c
T2
N 3 —
H
1024d
T2
N 3 —
F
1024e
T3
N 3 —
H
1024f
T3
N 3 —
F
1024g
T4
N 3 —
H
1024h
T4
N 3 —
F
1025a
T1
NO 2 —
H
1025b
T1
NO 2 —
F
1025c
T2
NO 2 —
H
1025d
T2
NO 2 —
F
1025e
T3
NO 2 —
H
1025f
T3
NO 2 —
F
1025g
T4
NO 2 —
H
1025h
T4
NO 2 —
F
1026a
T1
(CH 3 ) 2 N—
H
1026b
T1
(CH 3 ) 2 N—
F
1026c
T2
(CH 3 ) 2 N—
H
1026d
T2
(CH 3 ) 2 N—
F
1026e
T3
(CH 3 ) 2 N—
H
1026f
T3
(CH 3 ) 2 N—
F
1026g
T4
(CH 3 ) 2 N—
H
1026h
T4
(CH 3 ) 2 N—
F
1027a
T1
CH 3 O—
H
1027b
T1
CH 3 O—
F
1027c
T2
CH 3 O—
H
1027d
T2
CH 3 O—
F
1027e
T3
CH 3 O—
H
1027f
T3
CH 3 O—
F
1027g
T4
CH 3 O—
H
1027h
T4
CH 3 O—
F
1028a
T1
CH 3 S—
H
1028b
T1
CH 3 S—
F
1028c
T2
CH 3 S—
H
1028d
T2
CH 3 S—
F
1028e
T3
CH 3 S—
H
1028f
T3
CH 3 S—
F
1028g
T4
CH 3 S—
H
1028h
T4
CH 3 S—
F
1029a
T1
CH 3 S(═O)—
H
1029b
T1
CH 3 S(═O)—
F
1029c
T2
CH 3 S(═O)—
H
1029d
T2
CH 3 S(═O)—
F
1029e
T3
CH 3 S(═O)—
H
1029f
T3
CH 3 S(═O)—
F
1029g
T4
CH 3 S(═O)—
H
1029h
T4
CH 3 S(═O)—
F
1030a
T1
CH 3 S(═O) 2 —
H
1030b
T1
CH 3 S(═O) 2 —
F
1030c
T2
CH 3 S(═O) 2 —
H
1030d
T2
CH 3 S(═O) 2 —
F
1030e
T3
CH 3 S(═O) 2 —
H
1030f
T3
CH 3 S(═O) 2 —
F
1030g
T4
CH 3 S(═O) 2 —
H
1030h
T4
CH 3 S(═O) 2 —
F
1031a
T1
HC(═O)—
H
1031b
T1
HC(═O)—
F
1031c
T2
HC(═O)—
H
1031d
T2
HC(═O)—
F
1031e
T3
HC(═O)—
H
1031f
T3
HC(═O)—
F
1031g
T4
HC(═O)—
H
1031h
T4
HC(═O)—
F
1032a
T1
CH 3 C(═O)—
H
1032b
T1
CH 3 C(═O)—
F
1032c
T2
CH 3 C(═O)—
H
1032d
T2
CH 3 C(═O)—
F
1032e
T3
CH 3 C(═O)—
H
1032f
T3
CH 3 C(═O)—
F
1032g
T4
CH 3 C(═O)—
H
1032h
T4
CH 3 C(═O)—
F
1033a
T1
CH 3 OC(═O)—
H
1033b
T1
CH 3 OC(═O)—
F
1033c
T2
CH 3 OC(═O)—
H
1033d
T2
CH 3 OC(═O)—
F
1033e
T3
CH 3 OC(═O)—
H
1033f
T3
CH 3 OC(═O)—
F
1033g
T4
CH 3 OC(═O)—
H
1033h
T4
CH 3 OC(═O)—
F
1034a
T1
CH 3 COO—
H
1034b
T1
CH 3 COO—
F
1034c
T2
CH 3 COO—
H
1034d
T2
CH 3 COO—
F
1034e
T3
CH 3 COO—
H
1034f
T3
CH 3 COO—
F
1034g
T4
CH 3 COO—
H
1034h
T4
CH 3 COO—
F
1035a
T1
CH 3 OCOO—
H
1035b
T1
CH 3 OCOO—
F
1035c
T2
CH 3 OCOO—
H
1035d
T2
CH 3 OCOO—
F
1035e
T3
CH 3 OCOO—
H
1035f
T3
CH 3 OCOO—
F
1035g
T4
CH 3 OCOO—
H
1035h
T4
CH 3 OCOO—
F
1036a
T1
CH 3 C(═O)S—
H
1036b
T1
CH 3 C(═O)S—
F
1036c
T2
CH 3 C(═O)S—
H
1036d
T2
CH 3 C(═O)S—
F
1036e
T3
CH 3 C(═O)S—
H
1036f
T3
CH 3 C(═O)S—
F
1036g
T4
CH 3 C(═O)S—
H
1036h
T4
CH 3 C(═O)S—
F
1037a
T1
CH 3 C(═O)NH—
H
1037b
T1
CH 3 C(═O)NH—
F
1037c
T2
CH 3 C(═O)NH—
H
1037d
T2
CH 3 C(═O)NH—
F
1037e
T3
CH 3 C(═O)NH—
H
1037f
T3
CH 3 C(═O)NH—
F
1037g
T4
CH 3 C(═O)NH—
H
1037h
T4
CH 3 C(═O)NH—
F
1038a
T1
CH 3 NHC(═O)—
H
1038b
T1
CH 3 NHC(═O)—
F
1038c
T2
CH 3 NHC(═O)—
H
1038d
T2
CH 3 NHC(═O)—
F
1038e
T3
CH 3 NHC(═O)—
H
1038f
T3
CH 3 NHC(═O)—
F
1038g
T4
CH 3 NHC(═O)—
H
1038h
T4
CH 3 NHC(═O)—
F
1039a
T1
CH 3 C(═NOH)—
H
1039b
T1
CH 3 C(═NOH)—
F
1039c
T2
CH 3 C(═NOH)—
H
1039d
T2
CH 3 C(═NOH)—
F
1039e
T3
CH 3 C(═NOH)—
H
1039f
T3
CH 3 C(═NOH)—
F
1039g
T4
CH 3 C(═NOH)—
H
1039h
T4
CH 3 C(═NOH)—
F
1040a
T1
CH 3 C[═N—N(CH 3 ) 2 ]—
H
1040b
T1
CH 3 C[═N—N(CH 3 ) 2 ]—
F
1040c
T2
CH 3 C[═N—N(CH 3 ) 2 ]—
H
1040d
T2
CH 3 C[═N—N(CH 3 ) 2 ]—
F
1040e
T3
CH 3 C[═N—N(CH 3 ) 2 ]—
H
1040f
T3
CH 3 C[═N—N(CH 3 ) 2 ]—
F
1040g
T4
CH 3 C[═N—N(CH 3 ) 2 ]—
H
1040h
T4
CH 3 C[═N—N(CH 3 ) 2 ]—
F
1041a
T1
H
1041b
T1
F
1041c
T2
H
1041d
T2
F
1041e
T3
H
1041f
T3
F
10410g
T4
H
1041h
T4
F
1042a
T1
CH 3 C[═N—OCH 3 ]—
H
1042b
T1
CH 3 C[═N—OCH 3 ]—
F
1042c
T2
CH 3 C[═N—OCH 3 ]—
H
1042d
T2
CH 3 C[═N—OCH 3 ]—
F
1042e
T3
CH 3 C[═N—OCH 3 ]—
H
1042f
T3
CH 3 C[═N—OCH 3 ]—
F
1042g
T4
CH 3 C[═N—OCH 3 ]—
H
1042h
T4
CH 3 C[═N—OCH 3 ]—
F
1043a
T1
CH 3 OC(═O)NH—
H
1043b
T1
CH 3 OC(═O)NH—
F
1043c
T2
CH 3 OC(═O)NH—
H
1043d
T2
CH 3 OC(═O)NH—
F
1043e
T3
CH 3 OC(═O)NH—
H
1043f
T3
CH 3 OC(═O)NH—
F
1043g
T4
CH 3 OC(═O)NH—
H
1043h
T4
CH 3 OC(═O)NH—
F
1044a
T1
CH 3 NHC(═O)O—
H
1044b
T1
CH 3 NHC(═O)O—
F
1044c
T2
CH 3 NHC(═O)O—
H
1044d
T2
CH 3 NHC(═O)O—
F
1044e
T3
CH 3 NHC(═O)O—
H
1044f
T3
CH 3 NHC(═O)O—
F
1044g
T4
CH 3 NHC(═O)O—
H
1044h
T4
CH 3 NHC(═O)O—
F
1045a
T1
CH 3 NHC(═O)NH—
H
1045b
T1
CH 3 NHC(═O)NH—
F
1045c
T2
CH 3 NHC(═O)NH—
H
1045d
T2
CH 3 NHC(═O)NH—
F
1045e
T3
CH 3 NHC(═O)NH—
H
1045f
T3
CH 3 NHC(═O)NH—
F
1045g
T4
CH 3 NHC(═O)NH—
H
1045h
T4
CH 3 NHC(═O)NH—
F
1046a
T1
CH 3 S(═O) 2 NH—
H
1046b
T1
CH 3 S(═O) 2 NH—
F
1046c
T2
CH 3 S(═O) 2 NH—
H
1046d
T2
CH 3 S(═O) 2 NH—
F
1046e
T3
CH 3 S(═O) 2 NH—
H
1046f
T3
CH 3 S(═O) 2 NH—
F
1046g
T4
CH 3 S(═O) 2 NH—
H
1046h
T4
CH 3 S(═O) 2 NH—
F
1047a
T1
CH 3 NHS(═O) 2 —
H
1047b
T1
CH 3 NHS(═O) 2 —
F
1047c
T2
CH 3 NHS(═O) 2 —
H
1047d
T2
CH 3 NHS(═O) 2 —
F
1047e
T3
CH 3 NHS(═O) 2 —
H
1047f
T3
CH 3 NHS(═O) 2 —
F
1047g
T4
CH 3 NHS(═O) 2 —
H
1047h
T4
CH 3 NHS(═O) 2 —
F
1048a
T1
NH 2 —
H
1048b
T1
NH 2 —
F
1048c
T2
NH 2 —
H
1048d
T2
NH 2 —
F
1048e
T3
NH 2 —
H
1048f
T3
NH 2 —
F
1048g
T4
NH 2 —
H
1048h
T4
NH 2 —
F
1049a
T1
(CH 3 ) 2 N—
H
1049b
T1
(CH 3 ) 2 N—
F
1049c
T2
(CH 3 ) 2 N—
H
1049d
T2
(CH 3 ) 2 N—
F
1049e
T3
(CH 3 ) 2 N—
H
1049f
T3
(CH 3 ) 2 N—
F
1049g
T4
(CH 3 ) 2 N—
H
1049h
T4
(CH 3 ) 2 N—
F
1050a
T1
(CH 3 ) 3 Si—
H
1050b
T1
(CH 3 ) 3 Si—
F
10450c
T2
(CH 3 ) 3 Si—
H
1050d
T2
(CH 3 ) 3 Si—
F
1050e
T3
(CH 3 ) 3 Si—
H
1050f
T3
(CH 3 ) 3 Si—
F
1050g
T4
(CH 3 ) 3 Si—
H
1050h
T4
(CH 3 ) 3 Si—
F
1051a
T1
(CH 3 O) 3 Si—
H
1051b
T1
(CH 3 O) 3 Si—
F
1051c
T2
(CH 3 O) 3 Si—
H
1051d
T2
(CH 3 O) 3 Si—
F
1051e
T3
(CH 3 O) 3 Si—
H
1051f
T3
(CH 3 O) 3 Si—
F
1051g
T4
(CH 3 O) 3 Si—
H
1051h
T4
(CH 3 O) 3 Si—
F
A Groups. Connection is to bond on left.
and a pharmaceutically acceptable salt, ester, or N-oxide thereof.
21. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof, and a pharmaceutically acceptable carrier.
22. A method of treating a microbial infection in a mammal comprising administering to the mammal an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or N-oxide thereof.
23. The method according to claim 22 wherein the compound is administered orally, parenterally, or topically.
24. A medical device containing a compound, or a pharmaceutically acceptable salt, ester, or N-oxide thereof, according to claim 1 .
25. The medical device according to claim 24 , wherein the device is a stent.