IP Library › Granted Patent US 12,280,065
Granted Patent B2
US 12,280,065 · App. 17/605,750 · Granted Apr 22, 2025

Pharmaceutical compounds and therapeutic methods

Inventors: Spencer David Kimball (New Brunswick, NJ); Darren R. Carpizo (New Brunswick, NJ); John A. Gilleran (New Brunswick, NJ)
Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
A61K31/555A61K31/282A61K31/337A61K31/437A61K31/4745A61K31/475A61K31/506A61K31/5545A61K31/704A61K31/7068A61K38/14A61P35/00C07F3/06
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Quick Facts
Patent No.
US 12,280,065
App. No.
17/605,750
Granted
Apr 22, 2025
Kind
B2
Abstract

The invention provides a complex comprising Zn2+ and a compound of formula (I): or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt thereof that is useful for treating cancer, as well as compositions and kits comprising such complexes.

Claims (33)

1. A complex comprising Zn 2+ and a compound of formula (I):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex, wherein:

R 1 is morpholinomethyl, 2-morpholinoethyl, or (C 1 -C 6 )alkyl that is substituted with (C 1 -C 6 )alkoxy that is substituted with one or more groups independently selected from (C 1 -C 6 )alkoxy, halo, cyano, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkanoyloxy, (C 2 -C 6 )alkoxycarbonyl, and —N(R a ) 2 ;

R 2 is selected from the group consisting of H, phenyl, heteroaryl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, and (C 3 -C 6 )cycloalkyl, wherein any phenyl, heteroaryl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, and (C 3 -C 6 )cycloalkyl is optionally substituted with one or more groups independently selected from halo, —N(R b ) 2 , (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkanoyloxy, (C 2 -C 6 )alkoxycarbonyl, (C 2 -C 6 )alkylaminocarbonyl, and (C 2 -C 6 )alkanoylamino;

R 3 and R 4 are each independently selected from H, (C 1 -C 6 )alkyl, piperidinyl, or piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl; or R 3 and each R 4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, 8, or 9 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;

Y is S, O, or Se;

each R a is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkylaminocarbonyl and (C 1 -C 6 )alkoxycarbonyl, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkylaminocarbonyl, is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 )cycloalkyl, and (C 1 -C 6 )alkoxy; or two Rª taken together with the nitrogen to which they are attached form an azetidino, pyrrolidino, piperidino, or morpholino ring; and

each R b is independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkylaminocarbonyl and (C 1 -C 6 )alkoxycarbonyl, wherein any (C 1 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkoxycarbonyl, and (C 1 -C 6 )alkylaminocarbonyl, is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 )cycloalkyl, and (C 1 -C 6 )alkoxy; or two R a taken together with the nitrogen to which they are attached form an azetidino, pyrrolidino, piperidino, or morpholino ring.

2. The complex of claim 1 , which comprises a compound of formula (Ia):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex.

3. The complex of claim 1 , which comprises a compound of formula (Ib):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex.

4. The complex of claim 1 , which comprises a compound of formula (Ih):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex.

5. The complex of claim 1 , which comprises a compound of formula (Im):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex.

6. The complex of claim 1 , wherein R 1 is morpholinomethyl.

7. The complex of claim 1 , wherein R 1 is (C 1 -C 6 )alkyl that is substituted with (C 1 -C 6 )alkoxy that is substituted with one or more groups independently selected from (C 1 -C 6 )alkoxy, halo, cyano, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkanoyloxy, (C 2 -C 6 )alkoxycarbonyl, and —N(R a ) 2 .

8. The complex of claim 1 , wherein R 1 is (C 1 -C 6 )alkyl that is substituted with (C 1 -C 6 )alkoxy that is substituted with (C 1 -C 6 )alkoxy.

9. The complex of claim 1 , wherein R 1 is methyl that is substituted with (C 1 -C 6 )alkoxy that is substituted with (C 1 -C 6 )alkoxy.

10. The complex of claim 1 , wherein R 1 is methyl that is substituted with ethoxy that is substituted with (C 1 -C 6 )alkoxy.

11. The complex of claim 1 , wherein the compound and the Zn 2+ are present in a ratio of about 2:1.

12. The complex of claim 1 , which is a complex of formula:

13. The complex of claim 1 , which is a complex of formula:

14. The complex of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:

and

or an ion or poly-ion thereof, or a salt of said complex.

15. A pharmaceutical composition, comprising a complex of claim 1 or a solvate thereof, and a pharmaceutically acceptable carrier.

16. A method of treating cancer in an animal comprising administering a complex of claim 1 to the animal.

17. The method of claim 16 , further comprising administering a chemotherapeutic agent to the animal.

18. The method of claim 17 wherein the chemotherapeutic agent is selected from the group consisting of: Actinomycin, All-trans retinoic acid, Azacitidine, Azathioprine, Bleomycin, Bortezomib, Carboplatin, Capecitabine, Cisplatin, Chlorambucil, Cyclophosphamide, Cytarabine, Daunorubicin, Docetaxel, Doxifluridine, Doxorubicin, Epirubicin, Epothilone, Etoposide, Fluorouracil, Gemcitabine, Hydroxyurea, Idarubicin, Imatinib, Irinotecan, Mechlorethamine, Mercaptopurine, Methotrexate, Mitoxantrone, Oxaliplatin, Paclitaxel, Pemetrexed, Teniposide, Tioguanine, Topotecan, Valrubicin, Vemurafenib, Vinblastine, Vincristine, Vindesine, and Vinorelbine.

19. A compound selected from the group consisting of:

or an ion or poly-ion thereof, or a salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2023
From: KIMBALL, SPENCER D.; CARPIZO, DARREN R.; GILLERAN, JOHN A.
To: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Reel/Frame 064125/0616 →
Continuity (2)
Provisional Application 62837717 · Apr 23, 2019
Related Publication 20220096492A1 · Mar 31, 2022
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Cited By (1)
US 12,734,240