Compounds and compositions for the treatment or prevention of pathological conditions associated with excess fibrin deposition and/or thrombus formation
AssigneeCereno Scientific AB
InventorsNiklas Bergh, Jonas Faijerson Säljö, Sverker Jern
Life of this patent
Estimating the term…
Abstract
There is herein provided an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, as described in the description, for use in treating or preventing a pathological condition associated with excess fibrin deposition and/or thrombus formation, wherein said treatment comprises treating a patient with an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, in a specific manner, and formulations for use or designed for use in such treatments.
Claims22
A method of in treating or reducing the risk of developing a pathological condition associated with excess fibrin deposition and/or thrombus formation, the method comprising administering to a patient in need thereof at least one dose of an HDAC inhibitor, or a pharmaceutically acceptable salt thereof such that the maximum plasma concentration (Cmax) of the HDAC inhibitor, or a salt and/or metabolite thereof, in the patient occurs during a time period that is from four hours before to one hour after the maximum plasma concentration (Cmax) of PAI-1 in the patient,
- wherein the HDAC inhibitor is a compound selected from the list consisting of:
- (a) N-hydroxy-N′-phenyl-octanediamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (b) {6-[(diethylamino) methyl]-naphthalen-2-yl}methyl[4-(hydroxycarbamoyl)phenyl]carbamate or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (c) (2E)-3-[3-(anilinosulfonyl)phenyl]-N-hydroxy-acrylamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (d) (E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)-ethylamino]methyl]phenyl]prop-2-enamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (e) 3-(dimethylaminomethyl)-N-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (f) N-hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (g) (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (h) N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- and
- (i) CXD101 or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
(canceled)
A method of treating or reducing the risk of developing a pathological condition associated with excess fibrin deposition and/or thrombus formation in a patient, wherein said treatment comprises:
- (i) monitoring the plasma concentration of PAI-1 in the patient in order to determine the time at, or time period during which, the maximum plasma concentration of PAI-1 occurs;
- and
- (ii) administering at least one dose of the HDAC inhibitor, or a pharmaceutically acceptable salt thereof, to the patient such that at the time when the patient experiences the maximum plasma concentration of PAI-1, the patient has a plasma concentration of the HDAC inhibitor, or a salt and/or metabolite thereof, that is within the therapeutic window for the relevant HDAC inhibitor,
- wherein the HDAC inhibitor is a compound selected from the list consisting of:
- (a) N-hydroxy-N′-phenyl-octanediamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (b) {6-[(diethylamino) methyl]-naphthalen-2-yl}methyl[4-(hydroxycarbamoyl)phenyl]carbamate or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (c) (2E)-3-[3-(anilinosulfonyl)phenyl]-N-hydroxy-acrylamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (d) (E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (e) 3-(dimethylaminomethyl)-N-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (f) N-hydroxy-2-(4-((((1-methyl-1H-indol-3-yl)methyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (g) (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- (h) N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof;
- and
- (i) CXD101 or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
(canceled)
22-27. (canceled)
Dependencies are inferred from the claim text.