Antimicrobial compounds and methods of making and using the same
View Patent ↗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/or reducing the risk of microbial infections in humans and animals.
1. A compound having the formula:
wherein -G-H-J, alternatively, is selected from
wherein each H and J is independently selected,
or -G-H-J is selected from:
wherein R x is selected from CH 2 , NH, N(C 1-8 alkyl), S, or O; R y and R z are C or CH each independently substituted with one or more F, CH 3 , CF 3 , OH, and OCH 3 ; or R x , R y , and R z are each independently selected from CH 2 or CR a R b wherein R a and R b are taken together to form a C 1-5 carbocycle;
J is selected from NH 2 , NH(C 1-8 alkyl), N(C 1-8 alkyl) 2 , NHC(═O)CH 3 , NHC(═O)NH 2 , NHC(═NH)NH 2 , NHC(═NH)H;
wherein n is 0, 1, or 2;
alternatively, -G-H-J is selected from
wherein R x is selected from CH 2 , NH, N(C 1-8 alkyl), S, or O; R z is a C or CH, substituted with one or more CH 3 or R z is CR a R b wherein IV and R b are taken together to form a C 1-5 carbocycle, wherein m is 1, 2, or 3;
J is selected from NH 2 , NH(C 1-8 alkyl), N(C 1-8 alkyl) 2 , NHC(═O)CH 3 , NHC(═O)NH 2 , NHC(═NH)NH 2 , NHC(═NH)H;
C-B-A, D-E-F, and -G-H-J are chemical moieties, wherein
A is selected from the group consisting of:
(b) —(C 1-8 alkyl)-, (c) —(C 2-8 alkenyl)-, (d) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (b)-(d) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (b)-(d) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (b)-(d) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
(e) —O—, (f) —NR 6 —, (g) —S(O) p —, (h) —C(O)—, (i) —C(O)O—, (j) —OC(O)—, k) —OC(O)O—, (l) —C(O)NR 6 —, (m) —NR 6 CO—, (n) —NR 6 C(O)NR 6 —, (o) —C(═NR 6 )—, (p) —C(═NR 6 )O—, (q) —OC(═NR 6 )—, (r) —C(═NR 6 )NR 6 —, (s) —NR 6 C(═NR 6 )—, (t) —C(═S)—, (u) —C(═S)NR 6 —, (v) —NR 6 C(═S)—, (w) —C(O)S—, (x) —SC(O)—, (y) —OC(═S)—, (z) —C(═S)O—, (aa) —NR 6 (CNR 6 )NR 6 —, (bb) —CR 6 R 6 C(O)—, (cc) —C(O)NR 6 (CR 6 R 6 ) t —, (dd) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(ee) a 3-14 member saturated, unsaturated, or aromatic carbocycle, and
(ff) —(CR 6 R 6 ) t —,
wherein (dd) or (ee) is optionally substituted with one or more R 5 groups;
D is selected from the group consisting of:
(a) a single bond, (b) —(C 1-8 alkyl)-, (c) —(C 2-8 alkenyl)-, (d) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (b)-(d) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (b)-(d) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (b)-(d) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
(e) —O—, (f) —NR 6 —, (g) —S(O) p —, (h) —C(O)—, (i) —C(O)O—, (j) —OC(O)—, k) —OC(O)O—, (l) —C(O)NR 6 —, (m) —NR 6 CO—, (n) —NR 6 C(O)NR 6 —, (o) —C(═NR 6 )—, (p) —C(═NR 6 )O—, (q) —OC(═NR 6 )—, (r) —C(═NR 6 )NR 6 —, (s) —NR 6 C(═NR 6 )—, (t) —C(═S)—, (u) —C(═S)NR 6 —, (v) —NR 6 C(═S)—, (w) —C(O)S—, (x) —SC(O)—, (y) —OC(═S)—, (z) —C(═S)O—, (aa) —NR 6 (CNR 6 )NR 6 —, (bb) —CR 6 R 6 C(O)—, (cc) —C(O)NR 6 (CR 6 R 6 ) t —, (dd) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(ee) a 3-14 member saturated, unsaturated, or aromatic carbocycle, and
(ff) —(CR 6 R 6 ) t —,
wherein (dd) or (ee) is optionally substituted with one or more R 5 groups;
G is selected from the group consisting of:
(a) a single bond, (b) —(C 1-8 alkyl)-, (c) —(C 2-8 alkenyl)-, (d) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (b)-(d) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (b)-(d) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (b)-(d) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
(e) —O—, (f) —NR 6 —, (g) —S(O) p —, (h) —C(O)—, (i) —C(O)O—, (j) —OC(O)—, k) —OC(O)O—, (l) —C(O)NR 6 —, (m) —NR 6 CO—, (n) —NR 6 C(O)NR 6 —, (o) —C(═NR 6 )—, (p) —C(═NR 6 )O—, (q) —OC(═NR 6 )—, (r) —C(═NR 6 )NR 6 —, (s) —NR 6 C(═NR 6 )—, (t) —C(═S)—, (u) —C(═S)NR 6 —, (v) —NR 6 C(═S)—, (w) —C(O)S—, (x) —SC(O)—, (y) —OC(═S)—, (z) —C(═S)O—, (aa) —NR 6 (CNR 6 )NR 6 —, (bb) —CR 6 R 6 C(O)—, (cc) —C(O)NR 6 (CR 6 R 6 ) t —, (dd) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(ee) a 3-14 member saturated, unsaturated, or aromatic carbocycle, and
(ff) —(CR 6 R 6 ) t —,
wherein (dd) or (ee) is optionally substituted with one or more R 5 groups;
is independently selected from the group consisting of:
(b) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(c) a 3-14 member saturated, unsaturated, or aromatic carbocycle,
wherein (b) or (c) is optionally substituted with one or more R 5 groups;
(d) —(C 1-8 alkyl)-, (e) —(C 2-8 alkenyl)-, (f) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (d)-(f) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —C(═NR 6 )—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (d)-(f) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (d)-(f) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
and (g) —(CR 6 R 6 ) t —,
E and H are independently selected from the group consisting of:
(a) a single bond,
(b) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(c) a 3-14 member saturated, unsaturated, or aromatic carbocycle,
wherein (b) or (c) is optionally substituted with one or more R 5 groups;
(d) —(C 1-8 alkyl)-, (e) —(C 2-8 alkenyl)-, (f) —(C 2-8 , alkenyl)-, wherein
i) 0-4 carbon atoms in any of (d)-(f) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —C(═NR 6 )—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (d)-(f) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (d)-(f) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
and (g) —(CR 6 R 6 ) t —,
C, F, and J are independently selected from the group consisting of:
(a) hydrogen, (c) F, (d) Cl, (e) Br, (f) I, (g) —CF 3 , (h) —CN, (i) —N 3 (j) —NO 2 , (k) —NR 6 (CR 6 R 6 ) t R 8 , (l) —OR 8 , (m) —S(O) p (CR 6 R 6 ) t R 8 , (n) —C(O)(CR 6 R 6 ) t R 8 , (o) —OC(O)(CR 6 R 6 ) t R 8 , (p) —SC(O)(CR 6 R 6 ) t R 8 , (q) —C(O)O(CR 6 R 6 ) t R 8 , (r) —NR 6 C(O)(CR 6 R 6 ) t R 8 , (s) —C(O)NR 6 (CR 6 R 6 ) t R 8 , (t) —C(═NR 6 )(CR 6 R 6 ) t R 8 , (u) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 8 , (v) —C(═NNR 6 C(O)R 6 )(CR 6 R 6 ) t R 8 , (w) —C(═NOR 8 )(CR 6 R 6 ) t R 8 , (x) —NR 6 C(O)O(CR 6 R 6 ) t R 8 , (y) —OC(O)NR 6 (CR 6 R 6 ) t R 8 , (z) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 8 , (aa) —NR 6 S(O) p (CR 6 R 6 ) t R 8 , (bb) —S(O) p NR 6 (CR 6 R 6 ) t R 8 , (cc) —NR 6 S(O) p NR 6 (CR 6 R 6 ) t R 8 (dd) —NR 6 R 8 , (ee) —NR 6 (CR 6 R 6 )R 8 , (ff) —OH, (gg) —NR 8 R 8 , (hh) —OCH 3 , (ii) —S(O) p R 8 , (jj) —NC(O)R 8 , (kk) —NR 6 C(NR 6 )NR 6 R 8 , (ll) a C 1-8 alkyl group, (mm) a C 2-8 alkenyl group, (nn) a C 2-8 alkynyl group, (oo) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (pp) a 3-14 member saturated, unsaturated, or aromatic carbocycle, (qq) —(CR 6 R 6 ) t NR 6 (CR 6 R 6 ) t R 8 , (rr) —N[(CR 6 R 6 ) t R 8 ][C═O(CR 6 R 6 ) t R 8 ], (ss) —(CR 6 R 6 ) t N[(CR 6 R 6 ) t R 8 ][(CR 6 R 6 ) t R 8 ], (tt) —(CR 6 R 6 ) t NR 6 (C═O)(CR 6 R 6 ) t R 8 , (uu) - haloalkyl, (vv) —C(O)(CR 6 )[(CR 6 R 6 ) t R 8 ]R 8 , (ww) —(CR 6 R 6 ) t C(O)NR 8 R 8 , (xx) —(CR 6 R 6 ) t C(O)O(CR 6 R 6 ) t R 8 , (yy) —NR 6 C(O)CR 8 R 8 R 8 , (zz) —N[(CR 6 R 6 ) t R 8 ]C(O)R 8 , and (aaa) —S(O) p NR 8 R 8 ;
wherein (ll) through (pp) is optionally substituted with one or more R 7 groups;
R 5 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 R 6 , (k) —OR 8 , (l) —NR 6 (CNR 6 )NR 6 R 6 , (m) —C 1-8 alkyl, (n) —C 1-8 alkenyl, (o) —C 1-8 alkynyl, (p) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (q) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -haloalkyl, (s) —SR 6 , (t) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (u) -3-14 member saturated, unsaturated, or aromatic carbocycle; alternatively, two R 5 groups are taken together to form a carbocycle;
wherein (m) through (r) and (t) through (u) is optionally substituted with one or more R 8 ;
R 6 is selected from (a) hydrogen, (b) —C 1-8 alkyl or alternatively two R 6 groups are taken together to form a carbocycle, (c) -haloalkyl, (d) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (e) -3-14 member saturated, unsaturated, or aromatic carbocycle;
wherein (b) through (e) is optionally substituted with one or more R 8 ;
R 7 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 R 6 , (k) —OR 6 , (l) —NR 6 (CNR 6 )NR 6 R 6 , (m) —C 1-8 alkyl, (n) —C 1-8 alkenyl, (o) —C 1-8 alkynyl, (p) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (q) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -haloalkyl, (s) —NR 6 R 8 , (t) —OR 8 , (u) —(CR 6 R 6 ) t NR 6 R 8 , (v) (w) —SR 6 , (x) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (y) -3-14 member saturated, unsaturated, or aromatic carbocycle, (z) —(CR 6 R 6 ) t C(O)NR 8 R 8 , (aa) —S(O) p R 8 , (bb) —NR 6 C(O)NR 6 R 6 , (cc) —NR 6 C(O)R 6 , and (dd) —C(═NR 6 )NR 6 R 6 ;
wherein (m) through (q) and (x) through (y) are optionally substituted with one or more R 9 ;
R 8 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 R 9 , (k) —OR 9 , (l) —NR 6 (CNR 6 )NR 6 R 6 , (m) —C 1-8 alkyl, (n) —C 1-8 alkenyl, (o) —C 1-8 alkynyl, (p) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (q) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (s) -3-14 member saturated, unsaturated, or aromatic carbocycle, (t) -haloalkyl, (u) —C(O)(CR 6 R 6 ) t R 9 , (v) —SR 6 , (w) —OC(O)(CR 6 R 6 ) t R 9 , (x) NR 6 C(O)NR 6 R 9 , (y) —NR 6 C(O)R 9 , (z) —NR 6 (CNR 9 )(NR 6 R 6 ), (aa) —ONR 6 (CNR 6 )NR 6 R 6 , (bb) —C(═NR)NR 6 R 6 , (cc) —S(O) p R 9 , (dd) —(CR 6 R 6 ) t C(O)NR 6 R 9 , (ee) —(CR 6 R 6 ) t OR 9 , and (ff) —(CR 6 R 6 ) t NR 6 R 9 ;
wherein (m) through (s) is optionally substituted with one or more R 9 ;
R 9 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 R 10 , (k) —OR 6 , (l) —NR 6 (CNR 6 )NR 6 R 6 , (m) —C(O)(CR 6 R 6 ) t NR 6 R 6 , (n) —C 1-8 alkyl, (o) —C 1-8 alkenyl, (p) —C 1-8 alkynyl, (q) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (r) -3-14 member saturated, unsaturated, or aromatic carbocycle, (s) -haloalkyl, (t) —(CR 6 R 6 ) t OR 6 , (u) —O(CR 6 R 6 ) t NR 6 R 10 , (v) —C(O)R 6 , (w) —SR 6 , (x) —C(O)OR 10 , (y) —S(O) p R 6 , (z) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (aa) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (bb) —O(CR 6 R 6 ) t OR 6 , (cc) —C(═NR 6 )NR 6 N 6 , (dd) —ONR 6 R 6 ; (ee) —NR 6 C(O)NR 6 R 6 ; (ff) —O(CR 6 R 6 ) t OR 6 , (gg) —NR 6 C(O)R 6 , and (hh) —(CR 6 R 6 ) t NR 6 R 10 ;
wherein (n) through (r) and (z) through (aa) is optionally substituted with one or more R 10 ;
R 10 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 R 6 , (k) —OR 6 , (l) —NR 6 (CNR 6 )NR 6 R 6 , (m) —C(O)(CR 6 R 6 )NR 6 R 6 , (n) —C 1-8 alkyl, (o) —C 1-8 alkenyl, (p) —C 1-8 alkynyl, (q) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (r) -3-14 member saturated, unsaturated, or aromatic carbocycle, (s) -haloalkyl, (t) —(CR 6 R 6 ) t OR 6 , (u) —O(CR 6 R 6 ) t NR 6 R 6 , (v) —C(O)R 6 , (w) —SR 6 , (x) —C(O)OR 6 , (y) —S(O) p R 6 , (z) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (aa) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (bb) —O(CR 6 R 6 ) t OR 6 , (cc) —C(═NR 6 )NR 6 R 6 , (dd) —ONR 6 R 6 , (ee) —NR 6 C(O)NR 6 R 6 , (ff) —O(CR 6 R 6 ) t OR 6 , (gg) —NR 6 C(O)R 6 , and (hh) —(CR 6 R 6 ) t NR 6 R 6 ;
optionally, wherein either the group -D-E-F or the group -G-H-J is absent, but both -D-E-F and -G-H-J are not simultaneously absent;
p is 0, 1, or 2, and
t is 0, 1, 2, or 3,
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
2. The compound according to claim 1 , wherein A is selected from
(a) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and
(b) a 3-14 member saturated, unsaturated, or aromatic carbocycle,
wherein (a) or (b) is optionally substituted with one or more R 5 groups;
B is selected from (a) —(C 1-8 alkyl)-, (b) —(C 2-8 alkenyl)-, and (c) —(C 2-8 alkynyl), wherein
i) 0-4 carbon atoms in any of (a)-(c) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —C(═NR 6 )—, —S(O) p NR 6 —, and —NR 6 S(O) p NR 6 —,
ii) any of (a)-(c) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (a)-(c) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups, and
C is selected from (a) NH 2 , (b) —NHC(═NH)NH 2 and (c) hydrogen,
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
3. The compound according to claim 2 , wherein A is selected from azepanyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridinyl, cyclohexenyl, cyclohexadienyl, dihydropyridyl, furanyl, tetrahydrofuranyl, tetrahydropyridyl, azetidinyl, pyrrolidinyl, piperidinyl and piperidenyl;
wherein any of A immediately above optionally is substituted with one or more R 5 groups;
B is (a) —(C 1-8 alkyl)-, wherein
i) 0-4 carbon atoms in (a) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —S(O) p NR 6 —, and —NR 6 S(O) p NR 6 —,
ii) (a) immediately above optionally is substituted with one or more R 5 groups, and
iii) (a) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups
C is selected from (a) NH 2 , (b) —NHC(═NH)NH 2 and (c) hydrogen;
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
4. The compound according to claim 3 , wherein C-B-A- is selected from the group consisting of:
hydrogen,
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
5. The compound according to claim 1 , wherein G is selected from
(a) a single bond, (b) —(C 1-8 alkyl)-, (c) —(C 2-8 alkenyl)-, (d) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (b)-(d) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —C(═NR 6 )—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (b)-(d) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (b)-(d) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
(e) a 3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and
(f) a 3-14 member saturated, unsaturated, or aromatic carbocycle,
wherein (e) or (f) is optionally substituted with one or more R 5 groups;
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
6. The compound according to claim 1 , wherein R 5 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NH 2 , (k) —OR 6 , (l) —NHC(═NH)NH 2 , (m) —C 1-8 alkyl, (n) —C 1-8 alkenyl, (o) —C 1-8 alkynyl, (p) —(C 1-8 alkyl) -(3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (q) —(C 1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -haloalkyl, (s) —SR 6 , (t) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (u) -3-14 member saturated, unsaturated, or aromatic carbocycle; alternatively, two R 5 groups are taken together to form a carbocycle; or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
7. The compound according to claim 1 , wherein R 6 is selected from (a) hydrogen, (b) —C 1-8 alkyl or alternatively two R 6 groups are taken together to form a carbocycle, (c) -haloalkyl, (d) -3-14 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (e) -3-14 member saturated, unsaturated, or aromatic carbocycle; or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
8. The compound according to claim 5 , wherein G selected from
(a) a single bond, (b) —(C 1-8 alkyl)-, (c) —(C 2-8 alkenyl)-, (d) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (b)-(d) immediately above optionally is replaced by a moiety selected from the group consisting of —O—, —S(O) p —, —NR 6 —, —(C═O)—, —C(═NR 6 )—, —S(O) p NR 6 —, —NR 6 S(O) p —, and —NR 6 S(O) p NR 6 —,
ii) any of (b)-(d) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (b)-(d) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
wherein p is 0, 1, or 2,
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
9. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
Comp.
No.
Structure
360
362
367
371
377
378
379
380
390
391
411
426
430
447
469
or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
10. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof, and a pharmaceutically acceptable carrier.
11. A method for treating or reducing the risk of a microbial infection in a human or animal comprising administering to a human or animal in need thereof an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
12. A method of treating a microbial infection in a human or animal comprising administering to the human or animal an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof.
13. A method of treating 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 of claim 1 , or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof, 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, post-viral pneumonia, hospital acquired pneumonia/ventilator associated pneumonia, a respiratory tract infection such as CRTI (chronic respiratory tract infection), acute pelvic infection, a complicated skin and skin structure infection, a skin and soft tissue infection (SSTI) including uncomplicated skin and soft tissue infections (uSSTI)s and complicated skin and soft tissue infections, an abdominal infection, a complicated intra-abdominal infection, a urinary tract infection, bacteremia, septicemia, endocarditis, an atrio-ventricular shunt infection, a vascular access infection, meningitis, surgical prophylaxis, a peritoneal infection, a bone infection, a joint infection, a methicillin-resistant 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.
14. The method of claim 11 , wherein the compound, or a pharmaceutically acceptable salt, ester, tautomer, or prodrug thereof, is administered otically, ophthalmically, nasally, orally, parenterally, intravenously, or topically.