Antimicrobial Compounds And Methods Of Making And Using The Same

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 Rx is selected from CH2, NH, N(C1-8 alkyl), S, or O;
• Ry and Rz are C or CH each independently substituted with one or more F, CH3, CF3, OH, and OCH3;
• or Rx, Ry, and Rz are each independently selected from CH2 or CRaRb wherein Ra and Rb are taken together to form a C1-5 carbocycle;
• J is selected from NH2, NH(C1-8 alkyl), N(C1-8 alkyl)2, NHC(═O)CH3, NHC(═O)NH2, NHC(═NH)NH2, NHC(═NH)H;
• wherein n is 0, 1, or 2;
• alternatively, -G-H-J is selected from
• wherein Rx is selected from CH2, NH, N(C1-8 alkyl), S, or O;
• Rz is a C or CH, substituted with one or more CH3 or Rz is CRaRb wherein Ra and Rb are taken together to form a C1-5 carbocycle,
• wherein m is 1, 2, or 3;
• J is selected from NH2, NH(C1-8 alkyl), N(C1-8 alkyl)2, NHC(═O)CH3, NHC(═O)NH2, NHC(═NH)NH2, NHC(═NH)H;
• C-B-A-, -D-E-F, and -G-H-J are chemical moieties, wherein
• A, D 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, 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 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, F, 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)NR6(CR6R6)tR8, (dd) —NR6R8, (ee) —NR6(CR6R6)R8, (f) —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)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)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;
• 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.