Antimicrobial compounds and methods of making and using the same

A compound having the formula:

• wherein Z is selected from the group consisting of NR4, NR4CO, or NR4CONR4,
• C—B-A-, D-E-F, and -G-H-J are chemical moieties, wherein
• D-E-F is hydrogen or halogen;
• A and G are independently selected from the group consisting of:
• (a) a single bond, (b) —(C1-8 alkyl)-, (c) —(C2-8 alkenyl)-, (d) —(C2-8 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—, —NR6—, —(C═O)—, —S(O)pNR6—, —NR6S(O)p—, and —NR6S(O)pNR6—,
• ii) any of (b)-(d) immediately above optionally is substituted with one or more R5 groups, and
• iii) any of (b)-(d) immediately above optionally is substituted with —(C1-8 alkyl)-R5 groups;
• (e) —O—, (f) —NR6—, (g) —S(O)p—, (h) —C(O)—, (i) —C(O)O—, (j) —OC(O)—, k) —OC(O)O—, (l) —C(O)NR6—, (m) —NR6CO—, (n) —NR6C(O)NR6—, (o) —C(═NR6)—, (p) —C(═NR6)O—, (q) —OC(═NR6)—, (r) —C(═NR6)NR6—, (s) —NR6C(═NR6)—, (t) —C(═S)—, (u) —C(═S)NR6—, (V) —NR6C(═S)—, (w) —C(O)S—, (x) —SC(O)—, (y) —OC(═S)—, (z) —C(═S)O—, (aa) —NR6(CNR6)NR6—, (bb) —CR6R6C(O)—, (cc) —C(O)NR6(CR6R6)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) —(CR6R6)t—,
• wherein (dd) or (ee) is optionally substituted with one or more R5 groups;
• B 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 R5 groups;
• (d) —(C1-8 alkyl)-, (e) —(C2-8 alkenyl)-, (f) —(C2-8 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—, —NR6—, —(C═O)—, —C(═NR6)—, —S(O)pNR6—, —NR6S(O)p—, and —NR6S(O)pNR6—,
• ii) any of (d)-(f) immediately above optionally is substituted with one or more R5 groups, and
• iii) any of (d)-(f) immediately above optionally is substituted with —(C1-8 alkyl)-R5 groups;
• and (g) —(CR6R6)t—,
• C and J are independently selected from the group consisting of:
• (a) hydrogen, (c) F, (d) Cl, (e) Br, (f) I, (g) —CF3, (h) —CN, (i) —N3 (j) —NO2, (k) —NR6(CR6R6)tR8, (l) —OR8, (m) —S(O)p(CR6R6)tR8, (n) —C(O)(CR6R6)tR8, (o) —OC(O)(CR6R6)tR8, (p) —SC(O)(CR6R6)tR8, (q) —C(O)O(CR6R6)tR8, (r) —NR6C(O)(CR6R6)tR8, (s) —C(O)NR6(CR6R6)tR8, (t) —C(═NR6)(CR6R6)tR8, (u) —C(═NNR6R6)(CR6R6)tR8, (v) —C(═NNR6C(O)R6)(CR6R6)tR8, (w) —C(═NOR8)(CR6R6)tR8, (x) —NR6C(O)O(CR6R6)tR8, (y) —OC(O)NR6(CR6R6)tR8, (z) —NR6C(O)NR6(CR6R6)tR8, (aa) —NR6S(O)p(CR6R6)tR8, (bb) —S(O)pNR6(CR6R6)tR8, (cc) —NR6S(O)pNR6(CR6R6)tR8, (dd) —NR6R8, (ee) —NR6(CR6R6)R8, (ff) —OH, (gg) —NR8R8, (hh) —OCH3, (ii) —S(O)pR8, (jj) —NC(O)R8, (kk) —NR6C(NR6)NR6R8, (ll) a C1-8 alkyl group, (mm) a C2-8 alkenyl group, (nn) a C2-8alkynyl 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) —(CR6R6)tNR6(CR6R6)tR8, (rr) —N[(CR6R6)tR8][C═O(CR6R6)tR8], (ss) —(CR6R6)tN[(CR6R6)tR8][(CR6R6)tR8], (tt) —(CR6R6)tNR6(C═O)(CR6R6)tR8, (uu) -haloalkyl, (vv) —C(O)(CR6)[(CR6R6)tR8]R8, (ww) —(CR6R6)tC(O)NR8R8, (xx) —(CR6R6)tC(O)O(CR6R6)tR8, (yy) —NR6C(O)CR8R8R8, (zz) —N[(CR6R6)tR8]C(O)R8, and (aaa) —S(O)pNR8R8;
• wherein (ll) through (pp) is optionally substituted with one or more R7 groups;
• R5 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF3, (g) —CN, (h) —N3 (i) —NO2, (j) —NR6R6, (k) —OR8, (l) —NR6(CNR6)NR6R6, (m) —C1-8 alkyl, (n) —C1-8 alkenyl, (o) —C1-8 alkynyl, (p) —(C1-8 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) —(C1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -haloalkyl, (s) —SR6, (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 R5 groups are taken together to form a carbocycle,
• wherein (m) through (r) and (t) through (u) is optionally substituted with one or more R8;
• R6 is selected from (a) hydrogen, (b) —C1-8 alkyl or alternatively two R6 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 R8;
• R7 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF3, (g) —CN, (h) —N3 (i) —NO2, (j) —NR6R6, (k) —OR6, (l) —NR6(CNR6)NR6R6, (m) —C1-8 alkyl, (n) —C1-8 alkenyl, (o) —C1-8 alkynyl, (p) —(C1-8 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) —(C1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (r) -haloalkyl, (s) —NR6R8, (t) —OR8, (u) —(CR6R6)tNR6R8, (v) —CR6R8R8, (w) —SR6, (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) —(CR6R6)tC(O)NR8R8, (aa) —S(O)pR8, (bb) —NR6C(O)NR6R6, (cc) —NR6C(O)R6, and (dd) —C(═NR6)NR6R6;
• wherein (m) through (q) and (x) through (y) are optionally substituted with one or more R9;
• R8 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF3, (g) —CN, (h) —N3 (i) —NO2, (j) —NR6R9, (k) —OR9, (l) —NR6(CNR6)NR6R6, (m) —C1-8 alkyl, (n) —C1-8 alkenyl, (o) —C1-8 alkynyl, (p) —(C1-8 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) —(C1-8 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)(CR6R6)tR9, (v) —SR6, (w) —OC(O)(CR6R6)tR9, (x) —NR6C(O)NR6R9, (y) —NR6C(O)R9, (z) —NR6(CNR9)(NR6R6), (aa) —ONR6(CNR6)NR6R6, (bb) —C(═NR9)NR6R6, (cc) —S(O)pR9, (dd) —(CR6R6)tC(O)NR6R9, (ee) —(CR6R6)tOR9, and (ff) —(CR6R6)tNR6R9;
• wherein (m) through (s) is optionally substituted with one or more R9;
• R9 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF3, (g) —CN, (h) —N3 (i) —NO2, (j) —NR6R10, (k) —OR6, (l) —NR6(CNR6)NR6R6, (m) —C(O)(CR6R6)tNR6R6, (n) —C1-8 alkyl, (o) —C1-8 alkenyl, (p) —C1-8 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) —(CR6R6)tOR6, (u) —O(CR6R6)tNR6R10, (v) —C(O)R6, (w) —SR6, (x) —C(O)OR10, (y) —S(O)pR6, (z) —(C1-8 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) —(C1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (bb) —O(CR6R6)tOR6, (cc) —C(═NR6)NR6R6, (dd) —ONR6R6, (ee) —NR6C(O)NR6R6, (ff) —O(CR6R6)tOR6;
• (gg) —NR6C(O)R6, and (hh) —(CR6R6)tNR6R10;
• wherein (n) through (r) and (z) through (aa) is optionally substituted with one or more R10;
• R10 is selected from (a) hydrogen, (b) F, (c) Cl, (d) Br, (e) I, (f) —CF3, (g) —CN, (h) —N3 (i) —NO2, (j) —NR6R6, (k) —OR6, (l) —NR6(CNR6)NR6R6, (m) —C(O)(CR6R6)NR6R6, (n) —C1-8 alkyl, (o) —C1-8 alkenyl, (p) —C1-8 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) —(CR6R6)tOR6, (u) —O(CR6R6)tNR6R6, (v) —C(O)R6, (w) —SR6, (x) —C(O)OR6, (y) —S(O)pR6, (z) —(C1-8 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) —(C1-8 alkyl)-(3-14 member saturated, unsaturated, or aromatic carbocycle), (bb) —O(CR6R6)tOR6, (cc) —C(═NR6)NR6R6, (dd) —ONR6R6, (ee) —NR6C(O)NR6R6, (ff) —O(CR6R6)tOR6, (gg) —NR6C(O)R6, and (hh) —(CR6R6)tNR6R6;
• p is 0, 1, or 2, and
• t is 0, 1, 2, or 3,
• or a pharmaceutically acceptable salt or tautomer thereof.