Macrocyclic difluorostatone derivatives useful as antiviral agents

A compound of the formula:

• ##STR30## and the stereoisomers, hydrates, and pharmaceutically acceptable salts thereof wherein
• P.sub.2 is C.sub.1-6 alkyl, cyclopentyl, hydroxy C.sub.1-6 alkyl, phenyl, benzyl or 3-tetrahydrofuryl;
• P.sub.3 is selected from the group consisting of hydrogen, --CH.sub.3, --CH(CH.sub.3).sub.2, --CH.sub.2 CH(CH.sub.3).sub.2, --CH(CH.sub.3)(CH.sub.2 CH.sub.3), --CH.sub.2 SH, --CH.sub.2 CH.sub.2 SCH.sub.3, --CH.sub.2 OH, --CH(CH.sub.3)OH, --CH.sub.2 (CH.sub.2).sub.3 NH.sub.2, --CH.sub.2 (CH.sub.2).sub.2 NHC(.dbd.NH)NH.sub.2, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CONH.sub.2, benzyl, ##STR31## R.sub.1 is hydrogen, C.sub.1-15 alkyl, hydroxy C.sub.1-15 alkyl, CH([(CH.sub.2).sub.d -O--CH.sub.2 ].sub.f -R.sub.7).sub.2, CH.sub.2 Si(CH.sub.3).sub.2 (R.sub.8), PDL, --(C.sub.1-6 alkylene)--OR.sub.4, CH(Y)(Z), ##STR32## wherein PDL is --(CH.sub.2).sub.a -2-, 3- or 4-pyridyl;
• Y is hydroxy C.sub.1-15 alkyl, C.sub.1-6 alkyl or (CH.sub.2).sub.e -C.sub.6 H.sub.4 -(V).sub.e' ;
• Z is (CH.sub.2).sub.d -O--CHO, C.sub.1-6 alkylene-O-(CH.sub.2).sub.d -(O--CH.sub.2 --CH.sub.2).sub.e -O--C.sub.1-6 alkyl, CHO, CO.sub.2 R.sub.4, CONHR.sub.4, (CH.sub.2).sub.d -O--(CH.sub.2).sub.d' -R.sub.5, (CH.sub.2).sub.e -OR.sub.4 or ##STR33## wherein V is OR.sub.4 or hydroxy C.sub.1-6 alkylene;
• provided that d'=2 when R.sub.5 is piperazinyl, substituted piperazinyl, piperidyl or morpholinyl;
• R.sub.2 is as defined for R.sub.1 with the proviso that R.sub.2 is other than hydrogen when R.sub.1 is hydrogen, or R.sub.1 and R.sub.2 taken together with the nitrogen atom to which they are attached are selected from the group consisting of;
• ##STR34## R.sub.4 is hydrogen, C.sub.1-6 alkyl, phenyl or benzyl;
• R.sub.5 is piperazinyl, substituted piperazinyl, piperidyl, morpholinyl, pyridyl, pyrazinyl, pyrimidinyl or phenyl, wherein substituted piperazinyl is piperazinyl substituted on one nitrogen atom thereof with CHO, C(O)NHR.sub.4, C.sub.1-4 alkyl or CO.sub.2 R.sub.4 ;
• R.sub.7 is pyrimidyl, pyridyl, pyrazinyl or phenyl;
• R.sub.8 is C.sub.1-6 alkylene, hydroxy C.sub.1-6 alkyl or C.sub.1-6 alkyl;
• a is zero, 1, 2 or 3;
• b is zero or 1;
• d and d' are each independently 1 or 2;
• e and e' are each independently zero, 1 or 2;
• f is zero or one;
• and
• x is 1, 2, 3, or 4.