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OwnerDonald R Phillips, Susanne M. Cutts +2inventors
InventorsDonald R Phillips, Susanne M. Cutts, Ada Raphaell, Abraham Nudelman
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A method of treating cancer, comprising the step of administering to a subject in need thereof an effective amount of a compound or compounds which increase or supplement the intracellular levels of endogenous aldehyde, prior to, together with, or subsequent to the administration of a therapeutically-effective amount of a chemotherapeutic agent such as anthracyclines and anthracenediones, wherein the efficacy of the chemotherapeutic agent is enhanced relative to the efficacy of the chemotherapeutic agent alone. The compound may be an aldehyde-releasing compound (preferably formaldehyde), including known aldehyde-releasing compounds and two new classes of aldehyde-releasing compounds. One new class of aldehyde-releasing compounds of formula (II) release more than one equivalent of aldehyde Z-(L-M1-CHR-M2)x (II) wherein x is an integer of 2 or more Z is a direct bond or a linking group of valency x; L is either a direct bond or a spacer group R is H or C1-4 alkyl, alkenyl or alkynyl; M1 is a decomposable or hydrolysable group; and M2 is a second decomposable or hydrolysable group. Another new class of aldehyde-releasing compounds include a radical based on an inhibitor of an aldehyde detoxifying agent, such as buthionine sulphoximine or crotonaldehyde.
A method of treating cancer, comprising the step of administration to a subject in need thereof an effective amount of an aldehyde-releasing compound selected from:
A method of preferentially forming a chemotherapeutic agent-DNA adduct, comprising the step of administering to a subject in need thereof an effective amount of an aldehyde-releasing compound selected from:
A method as claimed in claim 232, wherein, in formula II, Z′ is an optionally substituted cyclic alkylene, an optionally substituted cyclic alkenylene, an optionally substituted cyclic alkynylene, an optionally Substituted heterocyclic group, an optionally substituted aryl or an optionally substituted heteroaryl.
A pharmaceutical composition comprising:
A pharmaceutical composition comprising one or more aldehyde-releasing compounds selected from;
Use of an aldehyde-releasing compound selected from;
A method of treating cancer comprising the steps of:
An aldehyde-releasing compound of formula (II):
A compound which includes the aldehyde-releasing compound of formula (XI):
An aldehyde-releasing compound including a radical based on an inhibitor of an aldehyde detoxifying agent, which aldehyde releasing compound releases said inhibitor and an aldehyde on hydrolysis or decomposition in situ.
An aldehyde-releasing compound of the formula (IV):
A method of treating anthracycline or anthracyclinedione-resistant cancer cells, comprising the step of administering to a subject in need thereof an effective amount of an aldehyde-releasing compound which, upon hydrolysis by esterases, releases one or more equivalents of aldehyde,
Dependencies are inferred from the claim text.