Cyclic peptide antifungal agents

A compound of the formula ( 1):

• ##STR251## wherein R' is hydrogen, methyl or NH.sub.2 C(O)CH.sub.2 --;
• R" and R'" are independently methyl or hydrogen;
• R and R.sup.y are independently hydroxy or hydrogen;
• R.sub.1 is hydroxy, hydrogen, or hydroxysulfonyloxy;
• R.sub.7 is hydroxy, hydrogen, or hydroxysulfonyloxy;
• and
• R.sub.2 is an acyl group represented by the formula ##STR252## wherein:
• Z is --O--, --C.tbd.C--, --CH.dbd.CH--, --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --, or a carbon to carbon bond;
• A) R.sub.4 is hydrogen, C.sub.2 -C.sub.12 alkynyl, C.sub.2 -C.sub.12 substituted alkynyl, C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.10 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalkyl, C.sub.1 -C.sub.12 alkoxy, C.sub.3 -C.sub.12 cycloalkoxy, naphthyl, pyridyl, thienyl, benzothienyl, quinolyl or phenyl;
• or
• B) R.sub.4 is phenyl substituted by amino, C.sub.1 -C.sub.12 alkylthio, halogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 substituted alkyl, C.sub.2 -C.sub.12 substituted alkenyl, C.sub.2 -C.sub.12 substituted alkynyl, C.sub.1 -C.sub.12 alkoxy, trifluoromethyl, phenyl, substituted phenyl, phenyl substituted with a polyoxa-alkyl group represented by the formula
• --O--(CH.sub.2).sub.m --[O--(CH.sub.2).sub.n ].sub.p --O--(C.sub.1 -C.sub.12 alkyl)
• wherein m and n are integers of from 2 to 4, and p is 0 or 1;
• or
• C) R.sub.4 is phenyl substituted with C.sub.1 -C.sub.6 alkoxy substituted by fluoro, bromo, chloro or iodo;
• or
• D) R.sub.4 is C.sub.1 -C.sub.12 alkoxy substituted with C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.12 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalkyl, C.sub.2 -C.sub.12 alkynyl, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, C.sub.1 -C.sub.12 alkanoylamino, phenyl substituted with a polyoxa-alkyl group represented by the formula
• --O--(CH.sub.2).sub.m --[O--(CH.sub.2).sub.n ].sub.p --O--(C.sub.1 -C.sub.12 alkyl)
• wherein m, n and p are as defined above;
• or
• E) R.sub.4 is C.sub.1 -C.sub.12 alkoxy substituted with a group of the formula ##STR253## wherein R.sub.8 is C.sub.1 -C.sub.6 alkoxy optionally substituted with phenyl;
• or
• F) R.sub.4 is a group represented by the formula
• --O--(CH.sub.2).sub.p' --W--R.sub.5
• wherein p' is an integer of from 2 to 4;
• W is pyrrolidino, piperidino or piperazino, and R.sub.5 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;
• or
• G) R.sub.4 is a group represented by the formula
• --Y--R.sub.6
• wherein
• Y is --C.tbd.C-- or --CH.dbd.CH--;
• and
• R.sub.6 is C.sub.1 -C.sub.12 alkyl, C.sub.1 -C.sub.12 substituted alkyl;
• C.sub.3 -C.sub.12 cycloalkyl, C.sub.7 -C.sub.10 bicycloalkyl, C.sub.7 -C.sub.14 tricycloalkyl, phenyl, C.sub.3 -C.sub.12 cycloalkenyl, naphthyl, benzothiazolyl, thienyl, indanyl, fluorenyl, phenyl substituted by amino, C.sub.1 -C.sub.12 alkylthio, halogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 alkoxy, trifluoromethyl, --O--(CH.sub.2).sub.p' --W--R.sub.5, or C.sub.1 -C.sub.6 alkoxy substituted by fluoro, bromo, iodo or chloro;
• or
• R.sub.6 is phenyl substituted by a polyoxa-alkyl group represented by the formula
• --O--(CH.sub.2).sub.m --[O--CH.sub.2).sub.n ].sub.p --O--(C.sub.1 -C.sub.12 alkyl)
• wherein m, n and p are as defined above;
• or a pharmaceutically acceptable salt thereof;
• with the proviso that when
• R' is methyl or NH.sub.2 C(O)CH.sub.2 --;
• R" is methyl;
• R'" is methyl;
• R.sup.y is hydroxy;
• and
• either a) or b)
• a) R.sub.1 is hydroxysulfonyloxy and R.sub.7 is hydroxy, or hydroxysulfonyloxy;
• b) R.sub.1 is hydrogen or hydroxysulfonyloxy and R.sub.7 is hydroxysulfonyloxy;
• R.sub.2 is not ##STR254## wherein Z is a carbon to carbon bond or --O-- and R.sub.4 is hydrogen or C.sub.1 -C.sub.12 alkoxy.