Hybrid antitumor compounds containing a cyclic enediyne and a DNA-binder

Claim 1

compound having the formula D--(OCH.sub.2).sub.m --O--(CH.sub.2).sub.n --Ar--Y--CONH--B wherein D is a radical of the formula ##STR22## wherein is a double bond, a single bond, or an epoxy; one of R x or R y is hydrogen and the other is hydrogen or hydroxy; or R x and R y together is an oxo group; R w is hydrogen, --C(O) R s , --C(O)NR t R u or --C(O)OR v ; R z is hydrogen, hydroxy, --OC(O)R s , --OC(O)NR t R u or --OC(O)OR v ; R s is hydrogen, C 1-8 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, C 7-14 aralkyl or quinoxalyl; R t and R u are independently hydrogen, C 1-8 alkyl, amino-substituted C 1-8 alkyl, C 3-6 cycloalkyl, C 6-10 aryl, C 7-14 aralkyl, pyridyl or quinoxalyl; R v is C 1-8 alkyl, halo-substituted C 1-8 alkyl, C 3-6 cycloalkyl, C 6-10 aryl or C 7-14 aralkyl; B is a radical of the formula ##STR23## wherein T, U, V and W are independently CH or N; p is 1 or 2; and Z is a group selected from --CH(CH 3 )CO 2 R; --CH (CH 3 )CONHCH(CH 3 )CO 2 R; --(CH 2 ) 2 C(NH)NH 2 ; --(CH 2 ) 2 C(O)NH 2 ; --(CH 2 ) q NR 1 R 2 ; and acridine-9-(1,4-phenylenediamine) radical of the formula ##STR24## wherein R is hydrogen or lower alkyl; q is 2 or 3; R 1 and R 2 are independently H, lower alkyl, hydroxy lower alkyl, or amino lower alkyl; n is 0 and m is 1, or n is 1 and m is 0 or 1; Ar is an aromatic residue selected from the group consisting of phenyl, naphthyl, pyridyl, quinolinyl and indolyl; and Y is a direct bond, --CH 2 -- or CH═CH; or a pharmaceutically acceptable salt thereof.