Targeted forms of methyltrithio antitumor agents

A carrier-drug conjugate of the formula ##STR22## prepared from a compound of formula CH.sub.3 SSS-W wherein CH.sub.3 SSS-W is an antitumor antibiotic designated as LL-E33288.alpha..sub.1.sup.Br, .alpha..sub.1.sup.I, .alpha..sub.2.sup.Br, .alpha..sub.3.sup.Br, .alpha..sub.3.sup.I, .alpha..sub.4.sup.Br, .beta..sub.1.sup.Br, B.sub.1.sup.I, .beta..sub.2.sup.Br, .beta..sub.2.sup.I, .gamma..sub.1.sup.Br, .gamma..sub.1.sup.I, .delta..sub.1.sup.I, the iodo or bromo pseudoaglycones, their dihydro or N-acyl counterparts, BBM-1675, FR-900405, FR-900406, PD 114759, PD 115028, CL-1577A, CL-1577B, CL-1577D, CL-1577E, CL-1724 or their N-acetyl counterparts comprising:

• reacting CH.sub.3 SSS-W with a compound of general formula A-Sp-SH, wherein Sp is a straight or branched-chain divalent or trivalent (C.sub.1 -C.sub.18) radical, divalent or trivalent aryl or heteroaryl radical, divalent or trivalent (C.sub.3 -C.sub.18) cycloalkyl or heterocycloalkyl radical, divalent or trivalent aryl-or heteroaryl-alkyl (C.sub.1 -C.sub.18) radical, divalent or trivalent cycloalkyl- or heterocycloalkyl-alkyl (C.sub.1 -C.sub.18) radical or divalent or trivalent (C.sub.2 -C.sub.18) unsaturated alkyl radical, wherein if Sp is a trivalent radical, it can be additionally substituted by amino, alkylamino, arylamino, heteroarylamino, carboxyl, lower alkoxy, hydroxy, thiol, or lower alkylthio groups;
• and Q is, or can be subsequently converted to, halogen, amino, alkylamino, carboxyl, carboxaldehyde, hydroxy, tiol, .alpha.-haloacetyloxy, lower alkyldicarboxyl, --CONHNH.sub.2, --NHCONHNH.sub.2, --NHCSNHNH.sub.2, --ONH.sub.2, --CON.sub.3, ##STR23## to produce an intermediate of formula Q-Sp-SS-W, wherein Q, Sp, and W are as hereinbefore defined,
• reacting Q-Sp-SS-W with a molecule of the formula Tu-(Y).sub.n wherein the carrier Tu is defined as a mono- or polyclonal antibody, its fragments, its chemically or genetically manipulated counterparts, or growth factors or steroids;
• Y is a side-chain amino, carboxy, or thiol group of a protein, an aldehyde derived from glycoprotein carbohydrate residues, or an amidoalkylathio group;
• and n is an integer of from 1 to 100, to produce a compound of the formula:
• ##STR24## wherein Tu, Y, Sp, W, and n are as hereinbefore defined, and Z is formed from covalent reaction of the groups Q and Y directly or after subsequent reduction, and Z is --CONH--, --CONHN.dbd.CH--, --CONHNHCH.sub.2 --, --NHCONHN.dbd.CH--, --NHCONHNHCH.sub.2, --NHCSNHN.dbd.CH--, --NHCSNHNHCH.sub.2 --, --OH.dbd.CH--, --NH--, --NHCH.sub.2 --, --N.dbd.CH--, --CO.sub.2 --, --NHCH.sub.2 CO.sub.2 --, --SS--, ##STR25## and m is 0.1 to 15.