US2019322668A1PendingUtilityA1
Antimicrobial compounds and methods of making and using the same
Est. expiryApr 15, 2031(~4.8 yrs left)· nominal 20-yr term from priority
Inventors:Erin M. DuffyAshoke BhattacharjeeShili ChenZoltan F. KanyoMatthew H. ScheidemanYuanqing Tang
A61P 31/04A61P 31/06A61P 31/00A61P 17/00A61P 19/08A61P 13/02A61P 11/00C07D 487/04C07D 403/14C07D 403/12C07D 401/14C07D 239/36C07D 239/47A61K 31/519
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Claims
Abstract
The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, and reducing the risk of microbial infections in humans and animals.
Claims
exact text as granted — not AI-modified1 - 60 . (canceled)
61 . A method of treating, preventing, or reducing a microbial infection in a human or animal comprising administering to the human or animal an effective amount of a compound according to the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N; X 4 is CR 4 or N; X 5 is CR 5 or N; with the proviso that X 1 , X 2 , X 3 , X 4 , and X 5 are not all N;
Y 6 is CR 6 or N; Y 7 is CR 7 or N; Y 8 is CR 8 or N; Y 9 is CR 9 or N; Y 10 is CR 10 or N; with the proviso that Y 6 , Y 7 , Y 8 , Y 9 , and Y 10 are not all N; wherein
R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and R 10 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH 2 , (i) —OCF 3 , (j) —OCF 2 H, (k) —OCFH 2 , (l) —OCH 3 , (m) —CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) —C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 )R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) —C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ; alternatively, wherein two substituents selected from R 6 , R 7 , and R 8 are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; wherein each (a) through (b) is optionally substituted with one or more R 12 ;
each is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 ,(p) —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) C(O)OH, (u) C(O)OR 12 , (v) —N 3 , (w) NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) C 1 -C 8 alkyl, (bb) C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkenyl, (dd) haloalkyl, (ee) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 substituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 31 are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) NH 2 , (n) —NR 11 R 11 , (o) —NR 11 C(O)R 11 , —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic or (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h ,R 3i R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 NR 11 S(O) p NR 11 S(O) p NR 11 —, and NR 11 C(O)NR 11 —,
T is selected from —NR 11 R 11 , —NR 11 (C═O)OR 11 , —NR 11 (C═NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 —, (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH, (j) —OR 11 , (k) —NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR 11 C(O)R 11 , (q) —S(O) p R 11 , (r) —C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle,
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (═O)—, —(═O)NR 11 —, —S(O) p NR 11 , —NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , NR 11 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 alkyl), (w) —N 3 , (x) —NHC(O)(C 1 -C 8 alkyl), (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) C 2 -C 8 alkynyl, (ff) haloalkyl, (gg) (C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) 3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) —C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N 3 , (r) —S(O) p C 1 -C 8 alkyl, (s) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
p is 0,1, or 2; and
t is 0,1, or 2,
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
62 . (canceled)
63 . (canceled)
64 . A method of treating, preventing, or reducing the risk of a microbial infection in a human or animal comprising administering to the human or animal an effective amount of a compound according to the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N; X 4 is CR 4 or N; Xs is CR 5 or N; with the proviso that X 1 , X 2 , X 3 , X 4 , and X 5 are not all N;
Y6 is CR 6 or N; Y 7 is CR 7 or N; Y 8 is CR 8 or N; Y 9 is CR 9 or N; Yio is CR 10 or N; with the proviso that Y 6 , Y 7 , Y 8 , Y 9 , and Y 10 are not all N; wherein
R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and R 10 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH 2 , (i) —OCF 3 , (j) —OCF 2 H, (k) —OCFH 2 , (l) —OCH 3 , (m) —CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) —C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 ) t R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) —C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) -(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 6 , R 7 , and R 8 are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; wherein each (a) through (b) is optionally substituted with one or more R 12 ;
each R 11 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 , (p) —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) —C(O)OH, (u) —C(O)OR 12 , (v) —N 3 , (w) —NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) —C 1 -C 8 alkyl, (bb) —C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkenyl, (dd) -haloalkyl, (ee) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 substituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) —NH 2 , (n) —NR 11 R 11 , (o) —NR 11 C(O)R 11 , (p) —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i ,R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p —, —NR 11 S(O) p NR 11 and —NR 11 C(O)NR 11 —;
T is selected from —NR 11 R 11 , —NR 11 (C═O)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 —, (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —OR 11 , NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR11C(O)R 11 , (q) —S(O) p R 11 , (r) —C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond:
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 alkyl), (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 alkyl), (w) —N 3 , (x) —NHC(O)(C 1 -C 8 alkyl), (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) —C 2 -C 8 alkynyl, (ff) -haloalkyl, (gg) —(C 1 -C 8 alkyl)(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) —(C 1 -C 8 alkyl)(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) -3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) —C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) -haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N, (r) S(O) p C 1 -C 8 alkyl, (s) 3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle,
p is 0,1, or 2; and
t is 0,1, or 2,
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, wherein the microbial infection is selected from the group consisting of:
a skin infection, a Gram positive infection, a Gram negative infection, nosocomial pneumonia, community acquired pneumonia, postviral pneumonia, hospital acquired pneumonia/ventilator associated pneumonia, a respiratory tract infection such as chronic respiratory tract infection (CRTI), acute pelvic infection, a skin infection including an acute bacterial skin and skin structure infection (AB SSSI) and an uncomplicated skin and skin structure infection (uSSSI), a complicated intra-abdominal infection, a urinary tract infection, bacteremia, septicemia, endocarditis, an atrioventricular shunt infection, a vascular access infection, meningitis, surgical prophylaxis, a peritoneal infection, a bone infection, a joint infection, a methicillinresistant Staphylococcus aureus infection, a vancomycin-resistant Enterococci infection, a linezolid-resistant organism infection, a Bacillus anthracis infection, a Francisella tularensis infection, a Yersinia pestis infection, and tuberculosis.
65 . A method according to claim 64 , wherein the microbial infection is a Gram positive infection.
66 . A method according to claim 64 , wherein the microbial infection is a Gram negative infection.
67 . A method of treating, preventing, or reducing the risk of a microbial infection in a human or animal comprising administering to the human or animal an effective amount of a compound according to the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N; X 4 is CR 4 or N; X 5 is CR 5 or N; with the proviso that X 1 , X 2 , X 3 , X 4 , and X 5 are not all N;
Y 6 is CR 6 or N; Y 7 is CR 7 or N; Y 8 is CR 8 or N; Y 9 is CR 9 or N; Y 10 is CR 10 or N; with the proviso that Y 6 , Y 7 , Y 8 , Y 9 , and Y 10 are not all N; wherein
R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 and R 10 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH, (i) (j) —OCF 2 H, (k) —OCFH, (l) —OCH 3 , (m) —CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) —C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 ) t R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) (C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 6 , R 7 , and R 8 are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic or (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; wherein each (a) through (b) is optionally substituted with one or more R 12 ;
each R 11 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 , (p) —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) —C(O)OH, (u) —C(O)OR 12 , (v) —N 3 , (w) —NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) —C 1 -C 8 alkyl, (bb) —C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkynyl, (dd) haloalkyl, (ee) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 substituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3j , R 3k , and R 3l are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) —NH 2 , (n) —NR 11 R 11 , (o) —NR 11 C(O)R 11 , (p) —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and NR 11 C(O)NR 11 —;
T is selected from —NR 11 R 11 , —NR 11 (C═O)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —OR 11 , (k) —NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR 11 C(O)R 11 , (q) —S(O) p R 11 , (r) —C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle,
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 (w) —N 3 , (x) —NHC(O)(C 1 -C 8 (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) —C 2 -C 8 alkynyl, (ff) -haloalkyl, (gg) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) -3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) —C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) -haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N 3 , (r) —S(O) p C 1 -C 8 alkyl, (s) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
p is 0,1, or 2; and
t is 0,1, or 2,
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, wherein said infection is caused by or involves one or more microorganisms selected from: Acinetobacter spp. ( Acinetobacter baumanni ), Bacteroides distasonis, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Citrobacter koser, Clostridium clostridioforme, Clostridium perfringens, Enterobacter aerogenes, Enterobacter cloacae, Enterococcus faecalis, Enterococcus spp., Escherichia coli, Eubacterium lentum, Fusobacterium spp., Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Legionella pneumophilia, Moraxella catarrhalis, Morganella morganii, Mycoplasma spp., Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella bivia, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens, Streptococcus anginosus, Staphylococcus aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus agalactiae, Streptococcus constellatus, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus pyogenes.
68 . The method of claim 67 , wherein said infection is caused by or involves one or more of aerobic and facultative gram-positive microorganism selected from: Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp., Streptococcus agalactiae, Streptococcus pyogenes, and Staphylococcus epidermidis.
69 . The method of claim 67 , wherein said infection is caused by or involves one or more of aerobic and facultative gram-negative microorganism selected from: Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Serratia marcescens, Pseudomonas aeruginosa, Acinetobacter baumanni, Moraxella catarrhalis, Proteus mirabilis, Citrobacter koseri, Haemophilus parainfluenzae, Klebsiella oxytoca, Proteus vulgaris, Providencia rettgeri, and Providencia stuartii
70 . The method of claim 67 , wherein said infection is caused by or involves one or more of anaerobic microorganism: Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella bivia, Bacteroides vulgatus, Clostridium perfringens, and Fusobacterium spp.
71 . The method according to claim 67 , wherein the microorganism Enterococcus spp. is selected from vancomycin susceptible isolate and vancomycin resistant isolate.
72 . The method according to claim 67 , wherein the microorganism Escherichia coli is selected from extended spectrum beta-lactamase (ESBL) producing isolate and Klebsiella pneumoniae carbapenemase (KPC) producing isolate.
73 . The method according to claim 67 , wherein the microorganism Haemophilus influenzae is a beta-lactamase positive isolate.
74 . The method according to claim 67 , wherein the microorganism Klebsiella pneumoniae is selected from extended spectrum beta-lactamase (ESBL) producing isolate and Klebsiella pneumoniae carbapenemase (KPC) producing isolate.
75 . The method according to claim 67 , wherein the microorganism Klebsiella oxytoca selected from extended spectrum beta-lactamase (ESBL) producing isolate and Klebsiella pneumoniae carbapenemase (KPC) producing isolate.
76 . The method according to claim 67 , wherein the microorganism Staphylococcus aureus is selected from methicillin susceptible isolate and methicillin resistant isolate.
77 . The method according to claim 67 , wherein the microorganism Staphylococcus epidermidis is selected from methicillin susceptible isolate and methicillin resistant isolate.
78 . The method according to claim 67 , wherein the microorganism Streptococcus pneumoniae is selected from penicillin susceptible isolate and penicillin resistant isolate.
79 . The method according to claim 61 , wherein the amount of compound or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer comprises from 0.1 mg to 1500 mg.
80 . The method according to claim 79 , wherein the amount of compound or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer comprises about 25 mg, or about 50 mg, or about 75 mg, or about 100 mg, or about 125 mg, or about 150 mg, or about 175 mg, or about 200 mg, or about 225 mg, or about 250 mg, or about 275 mg, or about 300 mg, or about 325, or about 350 mg, or about 375 mg, or about 400 mg, or about 425 mg, or about 450 mg, or about 475 mg, or about 500 mg, or about 525 mg, or about 550 mg, or about 575 mg, or about 600 mg, or about 625 mg, or about 650 mg, or about 675 mg, or about 700 mg, or about 725 mg, or about 750 mg, or about 775 mg, or about 800 mg, or about 825 mg, or about 850 mg, or about 875 mg, or about 900 mg, or about 925 mg, or about 950 mg, or about 975 mg, or about 1000 mg, or about 1025 mg, or about 1050, mg, or about 1075 mg, or about 1100 mg, or about 1125 mg, or about 1150 mg, or about 1175 mg, or about 1200 mg, or about 1225 mg, or about 1250 mg, or about 1275 mg, or about 1300 mg, or about 1325 mg, or about 1350 mg, or about 1375 mg, or about 1400 mg, or about 1425 mg, or about 1450 mg, or about 1475 mg, or about 1500 mg.
81 . The method according to claim 61 wherein the compound, or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, is administered otically, ophthalmically, nasally, orally, parenterally, topically, or intravenously.
82 . (canceled)
83 . (canceled)
84 . (canceled)
85 . The method according to claim 64 wherein the compound, or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, is administered otically, ophthalmically, nasally, orally, parenterally, topically, or intravenously.
86 . The method according to claim 67 wherein the compound, or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer, is administered otically, ophthalmically, nasally, orally, parenterally, topically, or intravenously.
87 . The method according to claim 61 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
88 . The method according to claim 64 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
89 . The method according to claim 67 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
90 . The method according to claim 87 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
91 . The method according to claim 88 , wherein the compound is a compound of the
91 . The method according to claim 88 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
92 . The method according to claim 89 , wherein the compound is a compound of the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
93 . The method according to claim 61 , wherein the compound is a compound having the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, or ester of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 4 is CR 4 or N; X 5 is CR 5 or N;
R 1 , R 2 , R 4 , and R 5 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH 2 , (i) —OCF 3 , (j) —OCF 2 H, (k) —OCFH 2 , (l) —OCH 3 , (m) —CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) —C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 )R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) —C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ;
wherein:
is selected from the group consisting of:
each is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH3, (j) —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 , —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) —C(O)OH, (u) —C(O)OR 12 , (v) —N 3 , (w) —NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) —C 1 -C 8 alkyl, (bb) —C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkynyl, (dd) -haloalkyl, (ee) (C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 substituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) —NH 2 , (n) —NR 11 R 11 (o) —NR 11 C(O)R 11 , (p) —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 , —S(O) p NR 11 —, —NR 11 S(O) p ——NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
T is selected from —NR 11 R 11 , NR 11 (C═O)OR 11 , NR 11 (C═NR 11 )NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —OR 11 , (k) —NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR 11 C(O)R 11 , (q) —S(O) p R 11 , (r) 13 C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p ; —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 alkyl), (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 alkyl), (w) —N 3 , (x) —NHC(O)(C 1 -C 8 alkyl), (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) —C 2 -C 8 alkynyl, (ff) -haloalkyl, (gg) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) —(C 1 -C 8 alkyl)(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) -3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) —C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) -haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N 3 , (r) —S(O) p C 1 -C 8 alkyl, (s) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
p is 0,1, or 2; and
t is 0,1, or 2;
and wherein the nitrogen and sulfur heteroatoms in any heterocycle in the compound are unoxidized or oxidized (N→O and S(O) p , wherein p=1 or 2).
94 . The method according to claim 64 , wherein the compound is a compound having the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, or ester of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 4 is CR 4 or N; X 5 is CR 5 or N;
R 1 , R 2 , R 4 , and R 5 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH 2 , (i) —OCF 3 , (j) —OCF 2 H, (k) —OCFH 2 , (l) —OCH 3 , (m) —CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) —C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 )R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) —C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) -(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ;
wherein:
is selected from the group consisting of:
each R 11 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 , (p) —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) —C(O)OH, (u) —C(O)OR 12 , (v) —N 3 , (w) —NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) —C 1 -C 8 alkyl, (bb) —C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkynyl, (dd) -haloalkyl, (ee) (C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 substituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) —NH 2 , (n) —NR 11 R 11 (o) —NR 11 C(O)R 11 , (p) —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p NR 11 S(O) p NR 11 —, —NR 11 (O)NR 11 —;
T is selected from —NR 11 R 11 , —NR 11 (C═O)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —OR 11 , (k) —NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR 11 C(O)R 11 , (q) —S(O) p R 11 , (r) —C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , —NR 1 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —-SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 alkyl), (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 alkyl), (w) —N 3 , (x) —NHC(O)(C 1 -C 8 alkyl), (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) —C 2 -C 8 alkynyl, (ff) -haloalkyl, (gg) -(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) -(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) -3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) −C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) -haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N 3 , (r) —S(O) p C 1 -C 8 alkyl, (s) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
p is 0, 1, or 2; and
t is 0, 1, or 2;
and wherein the nitrogen and sulfur heteroatoms in any heterocycle in the compound are unoxidized or oxidized (N→O and S(O) p , wherein p=1 or 2).
95 . The method according to claim 67 , wherein the compound is a compound having the formula:
or a tautomer thereof, or a pharmaceutically acceptable salt, or ester of said compound or tautomer, wherein
X 1 is CR 1 or N; X 2 is CR 2 or N; X 4 is CR 4 or N; X 5 is CR 5 or N;
R 1 , R 2 , R 4 , and R 5 are each independently selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CF 2 H, (h) —CFH 2 , (i) —OCF 3 , (j) —OCF 2 H, (k) —OCFH 2 , (l) —OCH 3 , (m) CN, (n) —N 3 , (o) —NO 2 , (p) —NR 11 R 11 , (q) —NR 11 C(O)R 11 , (r) C(O)NR 11 R 11 , (s) —OR 11 , (t) —COH, (u) —CO(C 1 -C 8 alkyl), (v) —COR 11 , (w) —NR 11 (CNR 11 )NR 11 R 11 , (x) —S(O) p R 11 , (y) —NR 11 S(O) p R 11 , (z) —SR 11 , (aa) —SCF 3 , (bb) —C(CF 3 )H—NH—CHR 11 R 11 , (cc) —COOR 11 , (dd) —(OCH 2 CH 2 ) t R 11 , (ee) —(OCH 2 CH 2 ) t OR 11 , (ff) —C 1 -C 8 alkyl, (gg) —C 2 -C 8 alkenyl, (hh) —C 2 -C 8 alkynyl, (ii) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (jj) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (kk) -haloalkyl, (ll) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (mm) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (nn) —CHR 11 —NH-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one of more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur);
wherein each (ff) through (nn) is optionally substituted with one or more R 12 ;
wherein:
is selected from the group consisting of:
each R 11 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 12 , (k) —COR 12 , (l) —CN, (m) —NO 2 , (n) —CONH 2 , (o) —CONR 12 R 12 , (p) —COCH 3 , (q) —S(O) p CH 3 , (r) —S(O) p NR 12 R 12 , (s) —SR 12 , (t) —C(O)OH, (u) —C(O)OR 12 , (v) —N 3 , (w) —NH 2 , (x) —NR 12 C(O)R 12 , (y) —NH(C 1 -C 8 alkyl), (z) —N(C 1 -C 8 alkyl) 2 , (aa) —C 1 -C 8 alkyl, (bb) —C 2 -C 8 alkenyl, (cc) —C 2 -C 8 alkynyl, (dd) -haloalkyl, (ee) (C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (ff) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (gg) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (hh) -3-14 membered saturated, unsaturated, or aromatic carbocycle, and (ii) —(C═NH)NR 12 R 12 ;
wherein each (y) through (hh) is optionally substituted with one or more R 12 ;
alternatively two R 11 sub stituents are taken together to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 3 is selected from:
wherein R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCF 2 H, (h) —OCFH 2 , (i) —OCH 3 , (j) —OR 11 , (k) —C(O)R 11 , (l) —C(O)NR 11 R 11 , (m) —NH 2 , (n) NR 11 R 11 (o) —NR 11 C(O)R 11 , (p) —S(O) p R 11 , (q) —C(O)OH, (r) —C(O)OR 11 , (s) —C 1 -C 8 alkyl, (t) —C 2 -C 8 alkenyl, (u) —C 2 -C 8 alkynyl, (v) haloalkyl, (w) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (x) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (s) through (x) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of sub stituents selected from R 3a and R 3b , R 3c and R 3d , R 3e and R 3f , R 3g and R 3h , R 3i and R 3j , and R 3k and R 3l are taken together with the carbon atom to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic, (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, wherein two substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or wherein four substituents selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i R 3j , R 3k , and R 3l on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
U is selected from —O—, —S(O) p —, —NR 11 , —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
T is selected from —NR 11 R 11 , —NR 11 (C═O)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and OR 11 ;
alternatively, one R 11 and one substituent selected from R 3a , R 3b , R 3c , R 3d , R 3e , R 3f , R 3g , R 3h , R 3i , R 3j , R 3k , and R 3l are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 9 is selected from:
wherein R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are each independently selected from (a) hydrogen, (b) halogen, (c) —CN, (d) —N 3 , (e) —NO 2 , (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —OR 11 , (k) —NH 2 , (l) —NR 11 R 11 , (m) —C(O)R 11 , (n) —C(O)OR 11 , (o) —C(O)NR 11 R 11 , (p) —NR 11 C(O)R 11 , (q) —S(O) p R 11 , (r) —C 1 -C 8 alkyl, (s) —C 2 -C 8 alkenyl, (t) —C 1 -C 8 alkynyl, (u) haloalkyl, (v) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (w) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
wherein each (r) through (w) is optionally substituted with one or more R 12 ;
alternatively, one or more pairs of substituents selected from R 9k and R 9l , R 9m and R 9n , R 9o and R 9p , R 9q and R 9r , and R 9s and R 9t are taken together with the carbon atom to which they are attached to form (a) 3-7 membered saturated or unsaturated carbocyclic, (b) 3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (c) an exo carbon-carbon double bond, (d) carbonyl group, or (e) thiocarbonyl group;
wherein each (a) through (c) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on different carbon atoms are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
alternatively, two substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a substituted or unsubstituted carbon-carbon double bond, or four substituents selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t on two adjacent carbon atoms are taken together with the bond between said adjacent carbon atoms form a carbon-carbon triple bond;
Z is selected from —O—, —S(O) p —, —NR 11 —, —(C═O)—, —NR 11 (C═O)—, —(C═O)NR 11 —, —S(O) p NR 11 —, —NR 11 S(O) p —, —NR 11 S(O) p NR 11 —, and —NR 11 C(O)NR 11 —;
W is selected from —NR 11 R 11 , —NR 11 (CO)OR 11 , —NR 11 (C═NR 11 )NR 11 R 11 , and —OR 11 ;
alternatively, one R 11 and one substituent selected from R 9k , R 9l , R 9m , R 9n , R 9o , R 9p , R 9q , R 9r , R 9s , and R 9t are taken together with the intervening atoms to which they are attached to form (a) -3-7 membered saturated or unsaturated carbocyclic or (b) -3-7 membered saturated or unsaturated heterocyclic ring containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur;
wherein each (a) through (b) is optionally substituted with one or more R 12 ;
R 12 is independently selected from (a) hydrogen, (b) halogen, (c) —OH, (d) —SH, (e) —(C 1 -C 8 alkyl)OH, (f) —OCF 3 , (g) —OCH 3 , (h) —OCF 2 H, (i) —OCFH 2 , (j) —O(C 1 -C 8 alkyl), (k) —CN, (l) —NO 2 , (m) —CONH 2 , (n) C(O)NH(C 1 -C 8 alkyl), (o) C(O)N(C 1 -C 8 alkyl) 2 , (p) —COH, (q) —COCH 3 , (r) —S(O) p CH 3 , (s) —S(O) p N(C 1 -C 8 alkyl) 2 , (t) —S(C 1 -C 8 alkyl), (u) —C(O)OH, (v) —C(O)O(C 1 -C 8 alkyl), (w) —N 3 , (x) —NHC(O)(C 1 -C 8 alkyl), (y) —N(C 1 -C 8 alkyl)C(O)(C 1 -C 8 alkyl), (z) —NH 2 , (aa) —NH(C 1 -C 8 alkyl), (bb) —N(C 1 -C 8 alkyl) 2 , (cc) —C 1 -C 8 alkyl, (dd) —C 2 -C 8 alkenyl, (ee) —C 2 -C 8 alkynyl, (ff) -haloalkyl, (gg) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (hh) —(C 1 -C 8 alkyl)-(3-14 membered saturated, unsaturated, or aromatic carbocycle), (ii) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (jj) -3-14 membered saturated, unsaturated, or aromatic carbocycle, (kk) —(C═NH)NH 2 , (ll) —C(═NH)NH 2 , (mm) —C(O)R 13 , (nn) ═O, and (oo) ═NR 13 ;
wherein each (aa) through (jj) is optionally substituted with one or more R 13 ;
R 13 is independently selected from (a) hydrogen, (b) halogen, (c) —C 1 -C 8 alkyl, (d) —C 2 -C 8 alkenyl, (e) —C 2 -C 8 alkynyl, (f) haloalkyl, (g) —OH, (h) —OC 1 -C 8 alkyl, (i) —OC 2 -C 8 alkenyl, (j) —OC 2 -C 8 alkynyl, (k) —OCF 3 , (l) —OCH 3 , (m) —OCF 2 H, (n) —OCFH 2 , (o) —NH 2 , (p) —CN, (q) —N 3 , (r) —S(O) p C 1 -C 8 alkyl, (s) -3-14 membered saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (t) -3-14 membered saturated, unsaturated, or aromatic carbocycle;
p is 0,1, or 2; and
t is 0,1, or 2;
and wherein the nitrogen and sulfur heteroatoms in any heterocycle in the compound are unoxidized or oxidized (N→O and S(O) p , wherein p=1 or 2).
96 . The method according to claim 61 , wherein the compound is a compound according to any of the compounds in Table 1, Table 2, Table 2a and Table 2aa or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
97 . The method according to claim 64 , wherein the compound is a compound according to any of the compounds in Table 1, Table 2, Table 2a and Table 2aa or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.
98 . The method according to claim 67 , wherein the compound is a compound according to any of the compounds in Table 1, Table 2, Table 2a and Table 2aa or a tautomer thereof, or a pharmaceutically acceptable salt, ester, or prodrug of said compound or tautomer.Cited by (0)
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