Use of colchinol derivatives as vascular damaging agents
First Claim
1. A method for the treatment of a disease where inappropriate angiogenesis occurs in a warm-blooded animal comprising administering to said animal a compound of the formula whereinR1, R2, R3 and R6 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, alkanoyl, PO3H2;
- X is carbonyl (CO), thiocarbonyl (CS), methylene (CH2) or a group CHR4;
R4 is OH, O-alkyl or NR8R9;
R5 and R7 are each independently H, alkyl, halogen, hydroxy, alkoxy, nitro or amino;
R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and
R9 is H, alkyl or cycloalkyl;
and the pharmaceutically acceptable salts, solvates and hydrates thereof.
1 Assignment
0 Petitions
Accused Products
Abstract
Colchinol derivatives of formula
wherein
R1, R2, R3 and R6 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, alkanoyl, PO3H2; X is carbonyl (CO), thiocarbonyl (CS), methylene (CH2) or a group CHR4; R4 is OH, O-alkyl or NR8R9; R5 and R7 are each independently H, alkyl, halogen, hydroxy, alkoxy, nitro or amino; R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and R9 is H, alkyl or cycloalkyl; and the pharmaceutically acceptable salts, solvates, and hydrates thereof have been found to be useful for treatment of diseases involving angiogenesis. Some of these compounds are novel. Particularly preferred are those compounds in which R6 is PO3H2.
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Citations
16 Claims
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1. A method for the treatment of a disease where inappropriate angiogenesis occurs in a warm-blooded animal comprising administering to said animal a compound of the formula
wherein R1, R2, R3 and R6 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, alkanoyl, PO3H2; -
X is carbonyl (CO), thiocarbonyl (CS), methylene (CH2) or a group CHR4;
R4 is OH, O-alkyl or NR8R9;
R5 and R7 are each independently H, alkyl, halogen, hydroxy, alkoxy, nitro or amino;
R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and
R9 is H, alkyl or cycloalkyl;
and the pharmaceutically acceptable salts, solvates and hydrates thereof. - View Dependent Claims (2, 3, 4, 5, 6)
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7. A compound of the formula
wherein R1, R2, R3 and R6 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, alkanoyl or PO3H2, provided that at least one of R1, R2, R3 and R6 is PO3H2; -
X is carbonyl (CO), thiocarbonyl (CS), methylene (CH2) or a group CHR4;
R4 is OH, O-alkyl or NR8R9;
R5 and R7 are each independently H, alkyl, halogen, hydroxy, alkoxy, nitro or amino;
R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and
R9 is H, alkyl or cycloalkyl;
and pharmaceutically acceptable salts, solvates, and hydrates thereof. - View Dependent Claims (8, 9)
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10. A compound of the formula
wherein R1, R2 and R3 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, alkanoyl, or PO3H2; -
R6 is PO3H2;
R4 is H or NR8R9;
R5 and R7 are each independently H, alkyl, halogen, alkoxy, nitro or amino;
R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkyaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and
R9 is H, alkyl or cycloalkyl;
and pharmaceutically acceptable salts, solvates and hydrates thereof. - View Dependent Claims (13, 14, 16)
wherein R1, R2, R3, R4, R5, R6 and R7 are as defined in claim 10 or 11.
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11. A compound of the formula
wherein R1, R2 and R3 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, alkanoyl or PO3H2; -
R6 is H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl or PO3H2;
R4 is H or NR8R9;
R5 and R7 are each independently H, alkyl, halogen, nitro or amino;
R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulphonyl, arylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl or arylaminosulphonyl; and
R9 is H, alkyl or cycloalkyl;
with the proviso that, when R1, R2 and R3 are all methyl groups and R4 is hydrogen, acetylamino, acetylmethylamino, amino, methylamino or dimethylamino then R6 is not hydrogen, methyl, hydroxyethyl, or acetoxyethyl;
and pharmaceutically acceptable salts, solvates and hydrates thereof. - View Dependent Claims (12)
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15. The compound N-acetylcolchinol-O-phosphate, or a salt, solvate or hydrate thereof.
Specification