| abstract |
in which R 1 is hydrogen, lower alkyl, acylamino,n wherein R 4 is hydrogen, lower alkyl, aryl or heteroaryl, R 5 is hydrogen or an hydroxy protecting group, and R 8 is halogen, , -SR 9 (wherein R 9 is lower alkyl, hydrogen or an -S protecting group), or the groupn in which one of R 10 and R 11 is an -N protecting group and the other is chosen from hydrogen, lower alkyl, aryl, aralkyl and acyl, or R 10 and R 11 are independently chosen from hydrogen, lower alkyl, aralkyl, aryl and acyl with the proviso that when one is hydrogen the other is acyl,n R 2 is lower alkyl, aryl, aralkyl, aminoalkyl, N-protected amino alkyl, hydroxyalkyl, O-protected hydroxyalkyl, thioalkyl, thioaryl, thioheteroaryl, an optionally esterfied a-amino acid residue, an optionally esterfied a-(N protected) amino acid residue or an optionally esterfied alkylcarboxy group; R 3 is nitrile, tetrazolyl, or -COOR 6 wherein R 6 is hydrogen, the radical C(Hal) 3 -Alk in which Hal is halogen and Alk represents an alkylene radical, lower alkyl, aryl, an allylic group, a metabolisable ester group, or a carboxy protecting group; X and Z are independently sulfur, oxygen, the radical =NR 7 in which R 7 is hydrogen, acyl, lower alkyl; aryl, or an N-protecting group, or -(CH 2 ) n - in which n is 1 or 2; subject to the following provisos:n (i) Z and X cannot simultaneously be(̵CH 2 )̵ n in which n is 1 or 2; (ii) when X is S, Z is O or =NR 7 ; (iii) when X is O, Z is O, S or =NR 7 ; (iv) when X is -CH 2 -, Z is =NR 7 ; except that when R 7 is H or lower alkyl and R 2 is lower alkyl then R 1 cannot be acylamino; (v) when X is (̵CH 2 )̵ 2 , Z is =N R7 ; and the pharmaceutically acceptable salts. Compounds of formula 1 are antibacterial agents which can be incorporated into pharmaceutical compositions or used as intermediates in the preparation of such agents. |