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US 2004/0171602 A1Published application
Novel metallotexaphyrin derivatives
AssigneePharmacyclics, Inc.
InventorsTarak D. Mody, Joshua Galanter
Life of this patent
Estimating the term…
Abstract
Novel derivatives of metallotexaphyrins are prepared by modifying the apical ligands associated with the central metal component of a metallotexaphyrin.
Claims42
A compound of the Formula:
- 6
- wherein:
- M is a monovalent, divalent, trivalent, or tetravalent metal cation;
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1, R2, R3, R4, R6, R7, R8, and R9, are independently chosen from the group consisting of hydrogen, halogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted haloalkyl;
- alkylalkoxy, nitro, acyl, optionally substituted alkoxy, saccharide, optionally substituted amino, carboxyl, optionally substituted carboxyalkyl, optionally substituted carboxyamide, optionally substituted carboxyamidealkyl, optionally substituted heterocycle, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted heterocycloalkylalkyl;
- and a group —X-Y, in which X is a covalent bond or a linker and Y is a catalytic group, a chemotherapeutic agent, or a site-directing molecule, and;
- R5, R10, R11, and R12 are independently hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted alkoxy, optionally substituted carboxyalkyl, or optionally substituted carboxyamidealkyl;
- with the proviso that the halogen is other than iodide and the haloalkyl is other than iodoalkyl.
7 more elements
A compound of Formula I
- 7
- wherein:
- M is selected from Gd(III), Mn(III), Mn(III) and Lu(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A method for treating a disease or condition in a mammal resulting from the presence of neoplastic tissue, neovascularization, or an atheroma, which method comprises:
- (a) administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I
- 8
- wherein:
- M is selected from Gd(III), Mn(III), Mn(III) and Lu(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3;
- and
- (b) treating the area in proximity to the neoplastic tissue with a therapeutic energy means or with a chemotherapeutic agent;
- or
- (c) treating the area in proximity to the neovascularization or atheroma with a therapeutic energy means.
13 more elements
A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of Formula I
- 9
- wherein:
- M is selected from Gd(III), Mn(II), Mn(III) and Lu(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, and R11 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of Formula I
- 10
- wherein:
- M reprsents Gd(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of Formula I
- 11
- wherein:
- M represents Lu(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A method for treating a disease or condition in a mammal resulting from the presence of neoplastic tissue, neovascularization, or an atheroma, which method comprises:
- (a) administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I
- 12
- wherein:
- M represents Gd(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3;
- and
- (b) treating the area in proximity to the neoplastic tissue with a therapeutic energy means or with a chemotherapeutic agent;
- or
- (c) treating the area in proximity to the neovascularization or atheroma with a therapeutic energy means.
13 more elements
A method for treating a disease or condition in a mammal resulting from the presence of neoplastic tissue, neovascularization, or an atheroma, which method comprises:
- (a) administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I
- 13
- wherein:
- M represents Lu(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3;
- and
- (b) treating the area in proximity to the neoplastic tissue with a therapeutic energy means or with a chemotherapeutic agent;
- or
- (c) treating the area in proximity to the neovascularization or atheroma with a therapeutic energy means.
13 more elements
A compound of Formula I
- 14
- wherein:
- M represents Gd(III);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A compound of Formula I
- 15
- wherein:
- M represents Lu(II);
- AL is an apical ligand derived from a group consisting of gluconic acid, phosphoric acid, glucoronic acid, lactic acid, pyruvic acid, and p-toluene sulfonic acid;
- n is 1 when M is a divalent cation, or n is 2 when M is a trivalent cation;
- R1 represents —CH2CH2CH2OH;
- R2 and R3 represent —CH2CH3;
- R4 represents —CH3;
- R5, R6, R9, R10, R11, and R12 represent H;
- and
- R7 and R8 represent —O(CH2CH2O)3CH3.
8 more elements
A process for preparing a metallotexaphyrin having the formula:
- (T-M)n+(AL−)n
- wherein:
- T is a texaphyrin;
- M is a divalent or trivalent metal cation constrained within the binding cavity of the texaphyrin;
- AL is an apical ligand;
- and
- n is an integer of 1-5;
- comprising:
- (a) contacting an apical ligand (AL)H with a quarternary amine resin;
- (b) contacting the resin complex produced in step a) with a metallotexaphyrin of the formula:
- (T-M)n+(AL1−)n
- in which T and M are as defined above;
- (AL1) represents a displaceable apical ligand;
- and
- n is an integer of 1-5.
12 more elements
A process for preparing a metallotexaphyrin having the formula:
- (T-M)n+(AL−)n
- wherein:
- T is a texaphyrin;
- M is a divalent or trivalent metal cation constrained within the binding cavity of the texaphyrin;
- AL is an apical ligand;
- and
- n is an integer of 1-5;
- comprising:
- contacting a metallotexaphyrin of the formula:
- (T-M)n+(AL1−)n
- in which T and M are as defined above;
- (AL1) represents a displaceable apical ligand;
- and
- n is an integer of 1-5;
- with an excess of an apical ligand (AL)H;
- at a temperature of 20-100° C.
13 more elements
Dependencies are inferred from the claim text.