Methods of treatment
AssigneeIntra-Cellular Therapies, Inc.
InventorsPeng Li, Robert Davis
Life of this patent
Estimating the term…
Abstract
The disclosure relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) useful for the treatment of certain cancers or tumors, such as colon cancer. In another embodiment, the disclosure relates to the use of inhibitors of PDE1 and an optional antitumor agent for the treatment of certain cancers or tumors.
Claims12
A method of treating colon cancer or colorectal cancer comprising administering a pharmaceutically acceptable amount of a PDE1 inhibitor to a subject in need thereof, wherein the PDE1 inhibitor is a compound of Formula Ia
- wherein
- (i) R2 and R5 are independently H or hydroxy and R3 and R4 together form a tri- or tetra-methylene bridge;
- or R2 and R3 are each methyl and R4 and R5 are each H;
- or R2, R4 and R5 are H and R3 is isopropyl;
- (ii) R6 is (optionally halo-substituted) phenylamino, (optionally halo-substituted) benzylamino, C1-4alkyl, or C1-4alkyl sulfide;
- (iii) R10 is C1-4alkyl, methylcarbonyl, hydroxyethyl, carboxylic acid, sulfonamide, (optionally halo- or hydroxy-substituted) phenyl, (optionally halo- or hydroxy-substituted) pyridyl, or thiadiazolyl;
- and
- X and Y are independently C or N,
- in free, pharmaceutically acceptable salt or prodrug form, including its enantiomers, diastereoisomers and racemates.
A method of inhibiting the proliferation, migration and/or invasion of cancerous or tumorous cells in the colon comprising administering a pharmaceutically acceptable amount of a PDE1 inhibitor to a subject in need thereof, wherein the PDE1 inhibitor is a compound of formula Ia
- wherein
- (i) R2 and R5 are independently H or hydroxy and R3 and R4 together form a tri- or tetra-methylene bridge;
- or R2 and R3 are each methyl and R4 and R5 are each H;
- or R2, R4 and R5 are H and R3 is isopropyl;
- (ii) R6 is (optionally halo-substituted) phenylamino, (optionally halo-substituted) benzylamino, C1-4alkyl, or C1-4alkyl sulfide;
- (iii) R10 is C1-4alkyl, methylcarbonyl, hydroxyethyl, carboxylic acid, sulfonamide, (optionally halo- or hydroxy-substituted) phenyl, (optionally halo- or hydroxy-substituted) pyridyl, or thiadiazolyl;
- and
- X and Y are independently C or N,
- in free, pharmaceutically acceptable salt or prodrug form, including its enantiomers, diastereoisomers and racemates.
A method of treating colon cancer or colorectal cancer comprising administering a pharmaceutically acceptable amount of a PDE1 inhibitor and a checkpoint inhibitor to a subject in need thereof, wherein the PDE1 inhibitor is a compound of formula Ia
- wherein
- (i) R2 and R5 are independently H or hydroxy and R3 and R4 together form a tri- or tetra-methylene bridge;
- or R2 and R3 are each methyl and R4 and R5 are each H;
- or R2, R4 and R5 are H and R3 is isopropyl;
- (ii) R6 is (optionally halo-substituted) phenylamino, (optionally halo-substituted) benzylamino, C1-4alkyl, or C1-4alkyl sulfide;
- (iii) R10 is C1-4alkyl, methylcarbonyl, hydroxyethyl, carboxylic acid, sulfonamide, (optionally halo- or hydroxy-substituted) phenyl, (optionally halo- or hydroxy-substituted) pyridyl, or thiadiazolyl;
- and
- X and Y are independently C or N,
- in free, pharmaceutically acceptable salt or prodrug form, including its enantiomers, diastereoisomers and racemates.
Dependencies are inferred from the claim text.