US 2010/0144779 A1 · Marine Alkalod Makaluvamines and Derivatives Thereof

Abstract

The present disclosure provides compounds based on the marine alkaloid makaluvamine. Described are compounds of the general formula (I) and (II). Also described are pharmaceutical compositions comprising one or more of the compounds of the general formula (I) and (II). The compounds and pharmaceutical compositions described inhibit the growth of several cancer lines, induce apoptosis and cell cycle arrest, display topoisomerase II inhibitory activity and modulate the activity and/or expression of key proteins involved in the regulation of cell growth. Methods of treatment and prevention using the compounds and pharmaceutical compositions described are also provided.

Claims61

Dependent claims

A compound having the following structural formula

wherein
R1 is selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heterocyclylalkyl;
R2 and R3 are each independently selected from H or substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heterocyclylalkyl;
L is selected from a substituted or unsubstituted alkyl of 2-15 carbon atoms in length or a substituted or unsubstituted alkynyl of 2-15 carbon atoms in length;
M and N are each independently selected from a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl;
A=1;
B and C are each independently selected from 0 or 1, or a pharmaceutically acceptable salt thereof;
and
R1 is selected from:

6 more elements

A compound having the following structural formula

Wherein
R1 is selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heterocyclylalkyl;
R2 and R3 are each independently selected from H or substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted heterocyclylalkyl;
L, M and N are each independently selected from a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl;
A=1;
and
B and C are each independently selected from 0 or 1, or a pharmaceutically acceptable salt thereof;
provided that when R1 is selected from straight chain alkyl of 1-10 carbon atoms, furan, thiopene, napthyl, pyridyl, phenyl, mono-substituted phenyl or di-substituted phenyl (where the substitutions include the following:
a straight chain alkyl of 1-4 carbon atoms, trifluoromethyl, nitro, an O-alkyl of 1-4 carbon atoms, hydroxyl, F, Cl, Br, NRxRx, where Rx is a straight chain alkyl from 1-4 carbon atoms, or CO2Rx),
L is not CH2;
and further provided that when L is a substituted or unsubstituted alkyl or alkenyl of 2 carbon atoms in length, the R1 is not
where R14 is F, Cl, Br, NO2, straight chain alkyl of 1 to 4 carbons, O-alkyl of 1 to 4 carbons or trifluoromethyl.

9 more elements

Dependencies are inferred from the claim text.

Marine Alkalod Makaluvamines and Derivatives Thereof

Life of this patent

Marine Alkalod Makaluvamines and Derivatives Thereof

Life of this patent

Abstract

Claims61