Cyclic peptide antifungal agents

Abstract

Provided are pharmaceutical formulations, and methods of inhibiting fungal and parasitic activity using a compound of formula I: ##STR1## wherein: R.sup.z1 is hydrogen, --CH.sub.2 OH, --CHOHCH.sub.3 or --CHOHCH.sub.2 C(O)NH.sub.2 ; R.sup.z2 is hydrogen, --CH.sub.2 OH or --CHOHCH.sub.3 ; R.sup.z3 is hydrogen or methyl; R.sup.x1 is hydrogen, hydroxy or O--R.sup.x1' ; R.sup.x1' is C.sub.1 -C.sub.6 alkyl, benzyl, --(CH.sub.2).sub.2 Si(CH.sub.3).sub.3, --CH.sub.2 CH.dbd.CH.sub.2, --CH.sub.2 CHOHCH.sub.2 OH, --(CH.sub.2).sub.a COOH, --(CH.sub.2).sub.b NR.sup.w1 R.sup.w2, --(CH.sub.2).sub.c POR.sup.w3 R.sup.w4 or --[(CH.sub.2).sub.2 O].sub.d --(C.sub.1 -C.sub.6)alkyl; a, b and c are independently 1, 2, 3, 4, 5 or 6; R.sup.w1 and R.sup.w2 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or R.sup.w1 and R.sup.w2 combine to form --CH.sub.2 (CH.sub.2).sub.e CH.sub.2 --; R.sup.w3 and R.sup.w4 are independently hydroxy, or C.sub.1 -C.sub.6 alkoxy; d is 1 or 2; e is 1, 2 or 3; R.sup.x2, R.sup.y1, R.sup.y2, R.sup.y3 and R.sup.y4 are independently hydroxy or hydrogen; R.sup.0 is hydroxy, --OP(O)(OH).sub.2 or a group of the formulae: ##STR2## R.sup.1 is C.sub.1 -C.sub.6 alkyl, phenyl, p-halo-phenyl, p-nitrophenyl, benzyl, p-halo-benzyl or p-nitro-benzyl; R.sup.2 is ##STR3## R.sup.3 is ##STR4## R.sup.3a, R.sup.3b, R.sup.3c and R.sup.3d are independently hydrogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 alkoxy, C.sub.1 -C.sub.12 alkylthio, halo, --O--(CH.sub.2).sub.m --[O--(CH.sub.2).sub.n ].sub.p --O--(C.sub.1 -C.sub.12 alkyl) or --O--(CH.sub.2).sub.q --X--R.sup.4 ; m is 2, 3 or 4; n is 2, 3 or 4; p is 0 or 1; q is 2, 3 or 4; X is pyrrolidino, piperidino or piperazino; and R.sup.4 is hydrogen, C.sub.1 -C.sub.12 alkyl, C.sub.3 -C.sub.12 cycloalkyl, benzyl or C.sub.3 -C.sub.12 cycloalkylmethyl; with the proviso that at least one of R.sup.z1 and R.sup.z2 must be hydrogen; or a pharmaceutically acceptable salt thereof.

Dependencies are inferred from the claim text.