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1. A method of treating a microbial infection in an animal in need thereof, said method comprising systemically administering to the animal an effective amount of a pharmaceutical composition comprising an amphiphilic oligomer of Formula II:
R1-[-x-A1-x-y-A2-y-]m-R2 (II) or an acceptable salt or solvate thereof, wherein: x is NR8, —N(R8)N(R8)—, or —C(R7R7′)NR8—, and y is C═O;
wherein R8 is hydrogen; R7 and R7′are independently hydrogen or alkyl, or R7 and R7′together are —(CH2)p—, wherein p is 4 to 8; Al and A2 are independently o-, m-, or p-phenylene or one of A1 and A2 is o-, m-, or p-phenylene and the other of A1 and A2 is heteroarylene, wherein A1 is substituted with one or more polar (PL) groups and is optionally substituted with one or more non-polar (NPL) groups and A2 is independently optionally substituted with one or more polar (PL) groups, one or more non-polar (NPL) groups, or a combination of one or more polar (PL) groups and one or more non-polar (NPL) groups; R1 is
(i) hydrogen, a polar group (PL), or a non-polar group (NPL), and R2 is -x-A1-x-R1, wherein A1 is as defined above; or(ii) hydrogen, a polar group (PL), or a non-polar group (NPL), and R2 is -x-A′-x -R1, wherein A′ is arylene or heteroarylene and is optionally substituted with one or more polar (PL) groups, one or more non-polar (NPL) groups, or a combination of one or more polar (PL) groups and one or more non-polar (NPL) groups;(iii) -y-A2-y-R2, and R2 is hydrogen, a polar group (PL), or a non-polar group (NPL); or(iv) -y-A′ and R2 is -x-A′, wherein A′ is aryl or heteroaryl and is optionally substituted with one or more polar (PL) groups, one or more non-polar (NPL) groups, or a combination of one or more polar (PL) groups and one or more non-polar (NPL) groups; or(V) R1 and R2 are independently a polar group (PL) Or a non-polar group (NPL); or(vi) R1 and R2 together form a single bond; NPL is a nonpolar group independently selected from the group consisting of —B(OR4)2 and —(NR3′)q1NPL—UNPL—(CH2)pNPL—(NR3″)q2NPL—R4′, wherein:
R3, R3′, and R3″ are independently selected from the group consisting of hydrogen, alkyl, and alkoxy;R4 and R4′are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups;UNPL is absent or selected from the group consisting of O, S, S(═O), S(═O)2, NR3, —C(═O)—, —C(═O)—N═N—NR3—, —C(═O)—NR3—N═N—, —N═N—NR3—, —C(═N—N(R3)2)—, —C(═NR3)—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O)2O—, —R3O—, —R3S—, —S—C═N— and —C(═O)—NR3—O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations;the —(CH2)pNPL- alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated;pNPL is 0 to 8;q1NPL and q2NPL are independently 0, 1 or 2; PL is a polar group selected from the group consisting of halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR5′)q1PL —UPL—(CH2)pPL—(NR5′)q2pL—V, wherein:
R5, R5′, and R5″are independently selected from the group consisting of hydrogen, alkyl, and alkoxy;UPL is absent or selected from the group consisting of O, S, S(═O), S(═O)2, NR5, —C(═O)—, —C(═O)—N═N—NR5—, —C(═O)—NR5—N═N—, —N═N—NR5—, —C(N═N(R5)2)—, —C(═NR5)—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O)2O—, —R5O—, —R5S—, —S—C═N—and —C(═O)—NR5—O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations;V is selected from the group consisting of nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH2)pNH2 wherein p is 1 to 4, —N(CH2CH2NH2)2, diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH2)pNH2 wherein p is 1 to 4, —N(CH2CH2NH2)2, amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl;the —(CH2)pPL— alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated;pPL is 0 to 8;q1PL and q2PL are independently 0, 1 or 2; and m is 1, 2 or 3; and a pharmaceutically acceptable carrier or diluent. |
