Golfomycin derivatives: fused ring cyclodecadiyne derivatives having DNA-cleaving properties and antitumor activity
AssigneeScripps Clinic and Research Foundation
InventorsGolfo Skokotas, Kyriacos C. Nicolaou
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Abstract
5-Hydroxy-benzo-(1',2')-cyclodeca-2,7-diyne-1-one and derivatives thereof and related fused ring diyneone macrocyclic compounds are disclosed. The compounds possess DNA-cleaving, antibiotic and tumor growth-inhibiting properties. Methods of making and using the same are also disclosed.
Claims31
A compound having the structural formula ##STR6## wherein W together with the carbon atoms bonded to the depicted vinylene group is an aromatic monocyclic ring or bicyclic fused ring system that includes five or six atoms in the ring containing the depicted vinylene group;
- and
- Y is selected from the group consisting of hydrogen, PO.sub.3 M.sub.2, C.sub.1 -C.sub.6 acyl and benzoyl, where M is selected from the group consisting of hydrogen, ammonium and an alkali metal ion.
A compound having the structural formula ##STR7## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and are selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, perfluoromethyl, perfluoromethoxy, hydroxyl, C.sub.1 -C.sub.6 acyloxy, benzyloxy, nitro, halo and amino having the formula NR.sup.5 R.sup.6 wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl, C.sub.1 -C.sub.6 acyl and benzoyl, and R.sup.6 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl and benzyl, or NR.sup.5 R.sup.6 together form a 5- or 6-membered ring, or
- R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 together with the depicted benzo ring form a fused bicyclic aromatic ring system;
- and
- Y is selected from the group consisting of hydrogen, PO.sub.3 M.sub.2, C.sub.1 -C.sub.6 acyl and benzoyl, where M is selected from the group consisting of hydrogen, ammonium and an alkali metal ion.
Golfomycin A, a compound having the structural formula ##STR8##
Golfomycin B.
Naphthyl golfomycin, having the structural formula ##STR9##
A pharmaceutical composition comprising a pharmaceutically acceptable carrier having dispersed therein a DNA-cleaving amount of a compound having the structural formula ##STR10## wherein W together with the carbon atoms bonded to the depicted vinylene group is an aromatic monocyclic ring or a bicyclic fused ring system that includes five or six atoms in the ring containing the depicted vinylene group;
- and
- Y is selected from the group consisting of hydrogen, PO.sub.3 M.sub.2, C.sub.1 -C.sub.6 acyl and benzoyl, where M is selected from the group consisting of hydrogen, ammonium and an alkali metal ion.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier having dispersed therein a DNA-cleaving amount of a compound having the structural formula ##STR11## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and are selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, perfluoromethyl, perfluoromethoxy, hydroxyl, C.sub.1 -C.sub.6 acyloxy, benzyloxy, nitro, halo and amino having the formula NR.sup.5 R.sup.6 wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl, C.sub.1 -C.sub.6 acyl and benzoyl, and R.sup.6 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl and benzyl, or NR.sup.5 R.sup.6 together form a 5- or 6-membered ring, or
- R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 together with the depicted benzo ring from a fused bicyclic aromatic ring system;
- and
- Y is selected from the group consisting of hydrogen, PO.sub.3 M.sub.2, C.sub.1 -C.sub.6 acyl and benzoyl, where M is selected from the group consisting of hydrogen, ammonium and an alkali metal ion.
A compound having the structural formula ##STR12## wherein Y is selected from the group consisting of hydrogen, PO.sub.3 M.sub.2, C.sub.1 -C.sub.6 acyl and benzoyl, where M is selected from the group consisting of hydrogen, ammonium, and an alkali metal ion.
Dependencies are inferred from the claim text.