Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
AssigneeAmerican Cyanamid Company
InventorsWilliam J. McGahren, Martin L. Sassiver, George A. Ellestad
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Abstract
This disclosure describes disulfide analogs of the family of antibacterial and antitumor agents known collectively as the LL-E33288 complex.
Claims33
A substituted disulfide of formula Q--Sp--SS--W, prepared from a compound of formula CH.sub.3 SSS--W and designated as L-E33288.alpha..sub.1 -Br, .alpha..sub.1 -I, .alpha..sub.2 -Br, .alpha..sub.2 -I, .alpha..sub.3 -Br, .alpha..sub.3 -I, .alpha..sub.4 -Br, .beta..sub.1 -Br, .beta..sub.1 -I, .beta..sub.2 -Br, .beta..sub.2 -I, .gamma..sub.1 -Br, .gamma..sub.1 -I, .delta..sub.1 -I, the iodo or bromo pseudoaglycones, their dihydro or N-acyl counterparts, BBM-1675, FR-900405, FR-900406, PD114759, PD115028, CL-1577A, CL-1577B, CL-1577D, CL-1577E, CL-1724, or their N-acetyl counterparts, wherein ##STR14## R.sub.5 is CH.sub.3, C.sub.2 H.sub.5, or (CH.sub.3).sub.2 CH;
- R.sub.8 is OH and R.sub.9 is H, or R.sub.8 and R.sub.9 together is a carbonyl group;
- X is an iodine or bromine atom;
- R.sub.5, is a hydrogen or the group RCO, wherein R is hydrogen, CH.sub.3 or a mono-substituted C.sub.6 -C.sub.11 aryl group;
- Sp is a straight or branched-chain divalent or trivalent (C.sub.1 -C.sub.18) radical, divalent or trivalent (C.sub.6 -C.sub.11) aryl or heteroaryl radical, divalent or trivalent cyclo-alkyl (C.sub.3 -C.sub.18) radical, divalent or trivalent (C.sub.6 -C.sub.11)aryl- or heteroaryl-alkyl (C.sub.4 -C.sub.18) radical, divalent or trivalent (C.sub.3 -C.sub.18) cycloalkyl-alkyl (C.sub.4 -C.sub.18) radical, or divalent or trivalent (C.sub.2 -C.sub.18) unsaturated alkyl radical, wherein heteroaryl is (4-methyl-coumarinyl-7-yl)amino;
- and wherein if Sp is a trivalent radical, it can be additionally substituted by amino, C.sub.1 -C.sub.10 alkylamino, C.sub.6 -C.sub.11 arylamino, heteroarylamino, carboxyl, lower alkoxy, hydroxy, thiol, or lower alkylthio groups;
- Q is hydrogen, halogen, amino, C.sub.1 -C.sub.10 alkylamino, C.sub.1 -C.sub.10 dialkylamino, piperidino, pyrrolidino, piperazino, carboxyl, carboxaldehyde, lower alkoxy, hydroxy, thiol, lower alkyldicarboxyl, --CONHNH.sub.2, --NHCONHNH.sub.2, --CSNHNH.sub.2, --NHCSNHNH.sub.2, or --ONH.sub.2 ;
- with the proviso that when Sp is ethylidine, Q cannot be hydrogen.
The ethyl disulfide of LL-E33288.gamma..sub.1 -I having the structure ##STR21##
The propyl disulfide of LL-E33288.gamma..sub.1 -I having:
- a) a proton magnetic resonance spectrum as shown in FIG. XXII;
- and
- b) a mass spectrum as shown in FIG. XXIII having the structure ##STR22##
The 1-methyl-1-propyl disulfide of LL-E33288.gamma..sub.1 -I having the structure ##STR23##
The t-butyl disulfide of LL-E33288.gamma..sub.1 -1 having the structure ##STR24##
The 3-mercaptoproprionyl hydrazide disulfide of LL-E33288.gamma..sub.1 -I having the structure ##STR25##
The 3-mercaptobutyryl hydrazide disulfide of LL-E33288.alpha..sub.3 -I having the structure ##STR26##
The 3-mercaptoisovaleryl hydrazide disulfide of N-acetyl LL-E33288.gamma..sub.1 -I having the structure ##STR27##
The p-mercaptodihydrocinnamyl hydrazide disulfide of N-acetyl LL-E33288.gamma..sub.1 -I having the structure ##STR28##
The compound LL-E33288.gamma..sub.2 -I having:
- a) ultraviolet spectrum as shown in FIG. XVIII;
- b) a proton magnetic resonance spectrum as shown in FIG. XIX;
- c) an infrared spectrum as shown in FIG. XX;
- d) a mass spectrum as shown in FIG. XXI;
- and
- e) having the structure ##STR29##
The compound LL-E33288.gamma..sub.2 -Br having the structure ##STR30##
Dependencies are inferred from the claim text.