US2013065845A1PendingUtilityA1
Triazole Compounds and Methods of Making and Using the Same
Est. expiryAug 24, 2025(expired)· nominal 20-yr term from priority
A61P 43/00A61P 31/04A61P 31/10A61P 33/00A61P 29/00A61P 35/00A61P 31/12A61P 31/00A61P 17/00A61P 1/00C07H 17/00A61P 1/10C07H 17/08
56
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modified1 . A compound having the structure:
or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug 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) —S(O)(CR 6 R 6 ) t R 9 , (u) —S(O) 2 (CR 6 R 6 ) t R 9 (v) —C(O)(CR 6 R 6 ) t R 9 , (w) —OC(O)(CR 6 R 6 ) t R 9 , (x) —OC(O)O(CR 6 R 6 ) t R 9 , (y) —SC(O)(CR 6 R 6 ) t R 9 , (z) —C(O)O(CR 6 R 6 ) t R 9 , (aa) — NR 6 C(O)(CR 6 R 6 ) t R 9 , (bb) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (cc) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (dd) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (ee) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (ff) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (gg) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (hh) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (ii) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (jj) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (kk) —NR 6 R 6 , (ll) —NR 6 (CR 6 R 6 ) t R 9 , (mm) —SR 6 , (nn) —S(O)R 6 , (oo) —S(O) 2 R 6 , (pp) —NR 6 C(O)R 6 , (qq) —Si(R 13 ) 3 , and (rr) —C(═O)H;
wherein (a)-(e) optionally are substituted with one or more R 114 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 S , 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 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-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 C(O)OR 8 , (xx) —NR 8 C(O)NR 8 R 8 , (yy) —NR 8 S(O) r R 8 , (zz) —C(OR 8 )(OR 8 )R 8 , (ab) —C(R) 2 NR 8 R 8 , (ac) ═NR 8 , (ad) —C(S)NR 8 R 8 , (ae) —NR 8 C(S)R 8 , (af) —OC(S)NR 8 R 8 , (ag) —NR 8 C(S)OR 8 , (ah) —NR 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 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 , (l) 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 C(O)R 8 , (v) —NR 6 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)ORS, (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, (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 6 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 6 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, N-oxide, or prodrug thereof.
3 . The compound according to claim 1 having the structure:
or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof.
4 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide or prodrug 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, N-oxide or prodrug thereof, wherein R 15 is selected from —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 .
6 . The compound according to claim 1 having the structure:
or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof.
7 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein n is 1 or 2.
8 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein n is 1.
9 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein R 11 is F.
10 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein n is 0.
11 . A compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug 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) —S(O)(CR 6 R 6 ) t R 9 , (k) —S(O) 2 (CR 6 R 6 ) t R 9 , (l) —C(O)(CR 6 R 6 ) t R 9 , (m) —OC(O)(CR 6 R 6 ) t R 9 , (n) —OC(O)O(CR 6 R 6 ) t R 9 , (o) —SC(O)(CR 6 R 6 ) t R 9 , (p) —C(O)O(CR 6 R 6 ) t R 9 , (q) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (r) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (s) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (t) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (u) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (v) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (w) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (x) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (y) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (z) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (aa) —NR 6 R 6 , (bb) —NR 6 (CR 6 R 6 ) t R 9 , (cc) —SR 6 , (dd) —S(O)R 6 , (ee) —S(O) 2 R 6 , and (ff) —NR 6 C(O)R 6 , wherein (a)-(e) optionally are substituted with one or more R 14 groups.
12 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug 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 114 groups.
13 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug 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) —S(O)(CR 6 R 6 ) t R 9 , (e) —S(O) 2 (CR 6 R 6 ) t R 9 (f) —C(O)(CR 6 R 6 ) t R 9 , (g) —OC(O)(CR 6 R 6 ) t R 9 , (h) —OC(O)O(CR 6 R 6 ) t R 9 , (i) —SC(O)(CR 6 R 6 ) t R 9 , (j) —C(O)O(CR 6 R 6 ) t R 9 , (k) —NR 6 C(O)(CR 6 R 6 ) t R 9 , (l) —C(O)NR 6 (CR 6 R 6 ) t R 9 , (m) —C(═NR 6 )(CR 6 R 6 ) t R 9 , (n) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 9 , (o) —C[═NNR 6 C(O)R 6 ](CR 6 R 6 ) t R 9 , (p) —NR 6 C(O)O(CR 6 R 6 ) t R 9 , (q) —OC(O)NR 6 (CR 6 R 6 ) t R 9 , (r) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 9 , (s) —NR 6 S(O) p (CR 6 R 6 ) t R 9 , (t) —S(O) p NR 6 (CR 6 R 6 ) t R 9 , (u) —NR 6 R 6 , (v) —NR(CR 6 R 6 ) t R 9 , (w) —SR 6 , (x) —S(O)R 6 , (y) —S(O) 2 R 6 , and (z) —NR 6 C(O)R 6 .
14 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein T is
wherein:
M is selected from:
(a) —C(O)—, (b) —CH(—OR 114 )—, (c) —NR 114 —CH 2 —, (d) —CH 2 —NR 114 , (e) —CH(NR 114 R 114 )—, (f) —C(═NNR 114 R 114 )—, (g) —NR 114 —C(O)—, (h) —C(O)NR 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 (en) —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 ; or alternatively, R 135 and R 136 are taken together to form ═O, ═S, and ═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 can be taken together with the carbon to which they are attached to form a carbonyl group;
iii) alternatively, R 101 and R 109 can be taken together to 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 are taken together to form ═O, ═S and ═NR 114 , ═NOR 114 , ═NR 114 , and ═N—NR 114 R 114 , and
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 4 , (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 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 R 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 8 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 , (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 6 ) 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)(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)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 can 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, (O) 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,
wherein any of (b)-(f) optionally is substituted with one or more R 119 groups;
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 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 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 8 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 126 at each occurrence, independently is selected from:
(a) hydrogen, (b) an electron-withdrawing group, (c) aryl, (d) substituted aryl, (e) heteroaryl, (f) substituted heteroaryl, and (g) C 1-6 alkyl, optionally substituted with one or more R 115 groups;
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 are taken together to form a carbon-carbon double bond;
alternatively, R 133 and R 134 are taken together to form ═O, ═S, ═NOR 114 , ═NR 114 , and ═N—NR 114 ,R 114 ;
alternatively, R 105 and R 134 are taken together with the carbons to which they are attached to 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 are taken together to 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.
15 . The compound according to claim 14 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein T is selected from:
16 . The compound according to claim 14 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein T is selected from:
17 . The compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, wherein T is selected from T1 through T33:
18 . A compound having the structure corresponding to any of the structures listed in Table 1, Table 1A, Table 1C or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof.
19 . A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof, and a pharmaceutically acceptable carrier.
20 . A method for treating or preventing a disease state in a mammal comprising administering to a mammal in need thereof an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, N-oxide, or prodrug thereof.Cited by (0)
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