IP Library › Granted Patent US 12,636,287
Granted Patent B2
US 12,636,287 · App. 17/059,160 · Granted May 26, 2026

Organic compounds

Inventors: Lawrence P. Wennogle (Hillsborough, NJ); Joseph Hendrick (New York, NY); Robert Davis (San Diego, CA)
Assignee: INTRA-CELLULAR THERAPIES, INC.
A61K31/519A61P35/00
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Quick Facts
Patent No.
US 12,636,287
App. No.
17/059,160
Granted
May 26, 2026
Kind
B2
Abstract

The disclosure relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) useful for the treatment of certain cancers or tumors, such as gliomas. In another embodiment, the disclosure relates to the combination of inhibitors of PDE1 and an antitumor agent for the treatment of certain cancers or tumors, such as gliomas.

Claims (50)

1 . A method of treating a condition selected from a cancer or tumor comprising administering a pharmaceutically acceptable amount of a PDE1 inhibitor to a subject in need thereof, wherein the PDE1 inhibitor is a compound selected from:

(A) Formula II:

wherein

(i) X is methylene;

(ii) Y is phenylene;

(iii) Z is pyridyl optionally substituted with halo;

(iv) R 4 is H and R 5 is phenyl optionally substituted with halo in free or pharmaceutically acceptable salt form;

(B) Formula 1a:

wherein

(i) R 2 and R 3 are each methyl and R 4 and R 5 are each H;

(ii) R 6 is (optionally halo-substituted) phenylamino;

(iii) R 10 is methylcarbonyl or (optionally halo-substituted) pyridyl; and

X and Y are both C,

in free or pharmaceutically acceptable salt form,

and wherein the cancer or tumor is a glioma, osteosarcoma, melanoma, leukemia, or neuroblastoma.

2 . The method according to claim 1 , wherein the PDE1 inhibitor is selected from any of the following

in free or pharmaceutically acceptable salt form.

3 . The method according to claim 1 , wherein the condition is a glioma.

4 . The method according to claim 1 , wherein the condition is glioblastoma multiforme.

5 . A method of inhibiting the proliferation, migration and/or invasion of a cancer or tumor comprising administering a pharmaceutically acceptable amount of a PDE1 inhibitor to a subject in need thereof, wherein the PDE1 inhibitor is a compound selected from:

(A) Formula II:

wherein

(i) X is methylene;

(ii) Y is phenylene;

(iii) Z is pyridyl optionally substituted with halo

(iv) R 4 is H and R 5 is phenyl optionally substituted with halo in free or pharmaceutically acceptable salt form;

(B) Formula 1a:

wherein

(i) R 2 and R 3 are each methyl and R 4 and R 5 are each H;

(ii) R 6 is (optionally halo-substituted) phenylamino;

(iii) R 10 is methylcarbonyl or (optionally halo-substituted) pyridyl; and

X and Y are both C,

in free or pharmaceutically acceptable salt form,

and wherein the cancer or tumor is a glioma, osteosarcoma, melanoma, leukemia, or neuroblastoma.

6 . The method according to claim 5 , wherein the PDE1 inhibitor is selected from any of the following

in free or pharmaceutically acceptable salt form.

7 . The method according to claim 5 , wherein the condition is a glioma.

8 . The method according to claim 7 , wherein the condition is glioblastoma multiforme.

9 . The method according to claim 1 , wherein the PDE1 inhibitor is

in free or pharmaceutically acceptable salt form.

10 . The method according to claim 1 , wherein the PDE1 inhibitor is,

free or pharmaceutically acceptable salt form.

11 . The method according to claim 1 , wherein the PDE1 inhibitor is

in free or pharmaceutically acceptable salt form.

12 . The method according to claim 5 , wherein the PDE1 inhibitor is

in free or pharmaceutically acceptable salt form.

13 . The method according to claim 5 , wherein the PDE1 inhibitor is

free or pharmaceutically acceptable salt form.

14 . The method according to claim 5 , wherein the PDE1 inhibitor is

in free or pharmaceutically acceptable salt form.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 14, 2023
From: WENNOGLE, LAWRENCE P.; HENDRICK, JOSEPH; DAVIS, ROBERT
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 063326/0948 →
Continuity (3)
Provisional Application 62688641 · Jun 22, 2018
Provisional Application 62676638 · May 25, 2018
Related Publication 20210205310A1 · Jul 8, 2021
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