Antimicrobial Gel Formulations

A formulation comprising:

• a compound of Formula (I)
• A-C(R1R2)R(CH2)nC(R3R4)—Y—Z (I)
• or a derivative thereof, wherein
• A is hydrogen, HalNH— or Hal2N—, wherein Hal is a halogen selected from the group consisting of chloro, bromo and iodo;
• R1 is hydrogen or an optionally substituted group selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, haloalkyl, aryl, heteroaryl and heterocycloalkyl and —COOH;
• R2 is hydrogen or an optionally substituted group selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, haloalkyl, aryl, heteroaryl and heterocycloalkyl, or R1 and R2 together with the carbon atom to which they attach form an optionally substituted cycloalkyl or heterocycloalkyl group;
• R is a carbon-carbon single bond or a divalent cycloalkylene radical with three to six carbon atoms,
• n is 0 or an integer from 1 to 13;
• R3 and R4 are each independently selected from the group consisting of hydrogen, fluoro, —NH2, —NHHal, NHal2, and an optionally substituted group selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl and heterocycloalkyl groups;
• Y is selected from a group consisting of a single bond, —O—, —CF2—, —CHF—, —C(═O)—, —C(═O)O—, —OC(═O)—, —C(═O)NRa—, —NRaC(═O)—, P(═O)(ORb)O—, —OP(═O)(ORb)—, —P(═O)(ORb)NRc—, —NRcP(═O)(ORb)—, —S(═O)2, —S(═O)2O—, —OS(═O)2—, —S(═O)2NRd—, —NRdS(═O)2—, or heteroarylene wherein Ra, Rb, Rc and Rd are each independently selected from the group consisting of hydrogen, and optionally substituted alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl and heterocycloalkyl;
• a divalent (C1-18)alkylene group in which, optionally, one or two methylene groups are replaced with a mono- or di-substituted methylene group;
• and a divalent (C1-18)heteroalkylene group wherein the divalent (C1-18)heteroalkylene group is a divalent (C1-18)alkylene group in which, optionally, one or two methylene groups are replaced with 1 or 2 —NR′—, —O—, —S—, —S(═O)—, >C═O, —C(═O)O—, —OC(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)NR′—, —NR′C(═O)—, —S(═O)2—, —S(═O)2NR′—, —S(═O)2NH—, —NR′S(═O)2— or —NHS(═O)2— group, wherein R′ is selected from the group consisting of hydrogen, Cl, Br, and optionally substituted alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl, heterocycloalkyl, (C1-5)alkylNHC(═O)—, (C1-5)alkoxyC(═O)—, RaRbNC(═O)—, (C1-5)alkylC(═O)—, (C6-10)arylC(—O)— and (C6-10)arYl(C1-4)alkylC(═O)— wherein Ra and Rb are each independently hydrogen, (C1-5)alkyl, (C3-6)cycloalkyl, (C1-5)alkylNHC(═O)—, (C1-5)alkylC(═O)—, (C6-14)aryl, (C6-10)aryl(C1-4)alkyl, heteroaryl comprising 4 to 10 ring atoms with at least one heteroatom selected from O, S and N in the ring, or heterocycloalkyl(C1-4)alkyl, the heterocycloalkyl group containing 2-10 carbon atoms and 1 to 4 heteroatoms selected from N, O or S;
• Z is selected from the group consisting of hydrogen, —CO2H, —CONH2, —SO3H, —SO2NH2, —P(═O)(OH)2, —B(OH)2, —[X(R5)(R6)R7]Q, —S(═O)2NRcRd, —S(═O)2NHC(═O)Re, S(═O)2OC(═O)NRcRd, —S(═O)2NRcC(═O)NRcRd and —S(═O)2(N═)C(OH)NRcRd wherein Rc and Rd are each independently hydrogen or is independently selected from the group consisting of (C1-5)alkyl, (C3-6)cycloalkyl, (C1-5)alkylNHC(═O)—, (C1-5)alkylC(═O)—, (C6-10)arylC(═O)—, (C6-10)arYl(C1-4)alkylC(═O)—, (C6-14)aryl, (C6-10)aryl(C1-4)alkyl, heteroaryl comprising 4 to 10 ring atoms with at least one heteroatom selected from O, S and N in the ring, and heterocycloalkyl containing 2-10 carbon atoms and 1 to 4 heteroatoms selected from N, O or S, and Re is hydrogen or is selected from the group consisting of (C1-5)alkyl, (C3-6)cycloalkyl, (C6-14)aryl, (C6-10)aryl(C1-4)alkyl, heteroaryl comprising 4 to 10 ring atoms with at least one heteroatom selected from O, S and N in the ring, and heterocycloalkyl containing 2-10 carbon atoms and 1 to 4 heteroatoms selected from N, O or S;
• or a salt, an amine oxide thereof, or a derivative or a bioisostere or a prodrug thereof;
• X is selected from the group consisting of N, P, and S;
• Q is a counterion or is absent;
• R5 and R6 are each independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl and heterocycloalkyl, each of which may be optionally substituted;
• or R5 and R6 together with the X atom to which they are attached form heterocycloalkyl group, which may be optionally substituted;
• and
• R7 is alkyl, aryl, cycloalkyl, heteroalkyl, heteroaryl or heterocycloalkyl, each of which may be optionally substituted, and may further be O when X is N, with the proviso that R7 is absent when X is S;
• with the proviso that if R is a divalent cycloalkylene radical, n will not exceed the integer 11;
• wherein the compound is dispersed in a water-swellable polymer comprising poly acrylic acid;
• and wherein the compound is 90% stable for at least 30 days at about 25° C.