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 reducing the risk of microbial infections in humans and animals.
1. A compound having the formula:
wherein: -G-H-J alternatively is
wherein each H and J are independently selected,
D and E are single bonds and F is hydrogen,
C—B-A- is selected from:
-G-H-J is selected from:
wherein G is optionally substituted with one or more R 5 groups;
H is independently selected from the group consisting of:
(a) a 4, 5, or 6 member saturated or unsaturated, or 5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur,
(b) a 3, 4, 5, or 6 member saturated, unsaturated, or 6 member aromatic carbocycle,
wherein (a) or (b) is optionally substituted with one or more R 5 groups;
(c) —(C 1-8 alkyl)-, (d) —(C 2-8 alkenyl)-, (e) —(C 2-8 alkynyl)-, wherein
i) 0-4 carbon atoms in any of (c)-(e) 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 (c)-(e) immediately above optionally is substituted with one or more R 5 groups, and
iii) any of (c)-(e) immediately above optionally is substituted with —(C 1-8 alkyl)-R 5 groups;
and (f) —(CR 6 R 6 ) t —,
J is independently selected from the group consisting of:
(a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF 3 , (g) —CN, (h) —N 3 (i) —NO 2 , (j) —NR 6 (CR 6 R 6 ) t R 8 , (k) —OR 8 , (l) —S(O) p (CR 6 R 6 ) t R 8 , (m) —C(O)(CR 6 R 6 ) t R 8 , (n) —OC(O)(CR 6 R 6 ) t R 8 , (o) —SC(O)(CR 6 R 6 ) t R 8 , (p) —C(O)O(CR 6 R 6 ) t R 8 , (q) —NR 6 C(O)(CR 6 R 6 ) t R 8 , (r) —C(O)NR 6 (CR 6 R 6 ) t R 8 , (s) —C(═NR 6 )(CR 6 R 6 ) t R 8 ,(t) —C(═NNR 6 R 6 )(CR 6 R 6 ) t R 8 , (u) —C(═NNR 6 C(O)R 6 )(CR 6 R 6 ) t R 8 , (v) —C(═NOR 8 )(CR 6 R 6 ) t R 8 , (w) —NR 6 C(O)O(CR 6 R 6 ) t R 8 , (x) —OC(O)NR 6 (CR 6 R 6 ) t R 8 , (y) —NR 6 C(O)NR 6 (CR 6 R 6 ) t R 8 , (z) —NR 6 S(O) p (CR 6 R 6 ) t R 8 , (aa) —S(O) p NR 6 (CR 6 R 6 ) t R 8 , (bb) —NR 6 S(O) p NR 6 (CR 6 R 6 ) t R 8 , (cc) —NR 6 R 8 , (dd) —NR 6 (CR 6 R 6 )R 8 , (ee) —OH, (ff) —NR 8 R 8 , (gg) —OCH 3 , (hh) —S(O) p R 8 , (ii) —NC(O)R 8 , (jj) —NR 6 C(NR 6 )NR 6 R 8 , (kk) a C 1-8 alkyl group, (ll) a C 2-8 alkenyl group, (mm) a C 2-8 alkynyl group, (nn) a 4, 5, 6, 7, 8, 9 or 10 member saturated or unsaturated, or 5, 6, or 9 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (oo) a 3, 4, 5, 6, 7, 8, 9, or 10 member saturated or unsaturated, or 6 member aromatic carbocycle, (pp) —(CR 6 R 6 ) t NR 6 (CR 6 R 6 ) t R 8 , (qq) —N[(CR 6 R 6 ) t R 8 ][C═O(CR 6 R 6 ) t R 8 ], (rr) —(CR 6 R 6 ) t N[(CR 6 R 6 ) t R 8 ][(CR 6 R 6 ) t R 8 ], (ss) —(CR 6 R 6 ) t NR 6 (C═O)(CR 6 R 6 ) t R 8 , (tt) -haloalkyl, (uu) —C(O)(CR 6 )[(CR 6 R 6 ) t R 8 ]R 8 , (vv) —(CR 6 R 6 ) t C(O)NR 8 R 8 , (ww) —(CR 6 R 6 ) t C(O)O(CR 6 R 6 ) t R 8 , (xx) —NR 6 C(O)CR 8 R 8 R 8 , (yy) —N[(CR 6 R 6 ) t R 8 ]C(O)R 8 , and (zz) —S(O) p NR 8 R 8 ;
wherein (kk) through (oo) 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) -haloalkyl, (q) —SR 6 , (r) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (s) 6 member aromatic carbocycle; alternatively, two R 5 groups are taken together to form a carbocycle
wherein (m) through (p) and (r) through (s) 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) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (e) -3, 4, 5, or 6 member saturated, unsaturated, or 6 member 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)-5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (q) —(C 1-8 alkyl)-6 member aromatic carbocycle), (r) -haloalkyl, (s) —NR 6 R 8 , (t) —OR 8 , (u) —(CR 6 R 6 ) t NR 6 R 8 , (v) —CR 6 R 8 R 8 , (w) —SR 6 , (x) -5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (y) -6 member 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)-(5 or 6 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, 4,5, or 6 member saturated, 3,4,5, or 6 member unsaturated, or 6 member aromatic carbocycle), (r) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (s) -3, 4, 5, or 6 member saturated, 3, 4, 5, or 6 member unsaturated, or 6 member 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 9 )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) 5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (r) 6 member 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)-5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (aa) —(C 1-8 alkyl)-6 member 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 10 ;
wherein (n) through (r) and (z) through (aa) is optionally substituted with one or more R 10 ;
R l0 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 ) t NR 6 R 6 , (n) —C 1-8 alkyl, (o) —C 1-8 alkenyl, (p) —C 1-8 alkynyl, (q) —haloalkyl, (r) —(CR 6 R 6 ) t OR 6 , (s) —O(CR 6 R 6 ) t NR 6 R 6 , (t) —C(O)R 6 , (u) —SR 6 , (v) —C(O)OR 6 , (w) —S(O) p R 6 , (x) —O(CR 6 R 6 ) t OR 6 , (y) —C(═NR 6 )NR 6 R 6 , (z) —ONR 6 R 6 , (aa) —NR 6 C(O)NR 6 R 6 , (bb) —O(CR 6 R 6 ) t OR 6 , (cc) —NR 6 C(O)R 6 , and (dd) —(CR 6 R 6 ) t NR 6 R 6 ;
p is 0, 1, or 2, and
t is 1, 2, or 3,
or a pharmaceutically acceptable salt, ester, or tautomer thereof.
2. 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 8 , (l) —NHC(═NH)NH 2 , (m) —C 1-8 alkyl, (n) —C 1-8 alkenyl, (o) —C 1-8 alkynyl, (p) -haloalkyl, (q) —SR 6 , (r) 5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (s) 6 member aromatic carbocycle; alternatively, two R 5 groups are taken together to form a carbocycle; or a pharmaceutically acceptable salt, ester, or tautomer thereof.
3. 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)-5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (d) -3, 4, 5, or 6 member saturated, unsaturated, or 6 member aromatic carbocycle; or a pharmaceutically acceptable salt, ester, or tautomer thereof.
4. A compound having the formula:
wherein
C-B-A- is selected from:
-G-H-J is selected from:
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) -haloalkyl, (q) —SR 6 , (r) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (s) -6 member aromatic carbocycle; alternatively, two R 5 groups are taken together to form a carbocycle
wherein (m) through (p) and (r) through (s) 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) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and (e) -3, 4, 5, or 6 member saturated, unsaturated, or 6 member aromatic carbocycle;
wherein (b) through (e) is optionally substituted with one or more R 8
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)-(5 or 6 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, 4, 5, or 6 member saturated, 3, 4, 5, or 6 member unsaturated, or 6 member aromatic carbocycle), (r) -5 or 6 member saturated, unsaturated, or aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (s) -3, 4, 5, or 6 member saturated, 3, 4, 5, or 6 member unsaturated, or 6 member 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 9 )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) -5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, (r) -6 member 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)-(5 or 6 member aromatic heterocycle containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur), (aa) —(C 1-8 alkyl)-(6 member 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 l0 ;
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 ) t NR 6 R 6 , (n) —C 1-8 alkyl, (o) —C 1-8 alkenyl, (p) —C 1-8 alkynyl, (q) -haloalkyl, (r) —(CR 6 R 6 ) t OR 6 , (s) —O(CR 6 R 6 ) t NR 6 R 6 , (t) —C(O)R 6 , (u) —SR 6 , (v) —C(O)OR 6 , (w) —S(O) p R 6 , (x) —O(CR 6 R 6 ) t OR 6 , (y) —C(═NR 6 )NR 6 R 6 , (z) —ONR 6 R 6 , (aa) —NR 6 C(O)NR 6 R 6 , (bb) —O(CR 6 R 6 ) t OR 6 , (cc) —NR 6 C(O)R 6 , and (dd) —(CR 6 R 6 ) t NR 6 R 6 ;
p is0, 1, or2,
t is 1, 2, or 3, and
n is 0, 1, or 2,
or a pharmaceutically acceptable salt, ester, or tautomer thereof.
5. A compound selected from:
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or a pharmaceutically acceptable salt, ester, or tautomer thereof.
6. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, ester, or tautomer thereof, and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising a compound according to claim 5 , or a pharmaceutically acceptable salt, ester, or tautomer thereof, and a pharmaceutically acceptable carrier.