3-(5-substituted-4-oxoquinazolin-3(4H)-yl)-3-deutero-piperidine-2,6-dione derivatives and compositions comprising and methods of using the same

• US 10,202,316 B2
• Filed: 12/15/2016
• Issued: 02/12/2019
• Est. Priority Date: 01/14/2013
• Status: Active Grant

• Current Assignee: Salarius Pharmaceuticals, Inc.
• Original Assignee: Deuterx, Llc
• Inventors: DeWitt, Sheila
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US15/379,908
• Publication Number:
  US 20170158579A1
• Time in Patent Office: 789 Days
• CPC Class Codes: A61K 31/515 Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07B 59/002 : Heterocyclic compounds
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides 3-deuterium-enriched 3-(5-substituted-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-diones, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same, such as in the treatment of cancer, an immune-related disease, or an inflammatory disease.

Claims

1. A method for treating a disorder selected from the group consisting of angiogenesis and multiple myeloma, comprising administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of Formula IIIb in order to treat the disorder, wherein Formula IIIb is represented by:

2. The method of claim 1, wherein the disorder is angiogenesis.

3. The method of claim 1, wherein the disorder is multiple myeloma.

4. The method of claim 1, wherein the abundance of deuterium in Z is at least 80%.

5. The method of claim 1, wherein the abundance of deuterium in Z is at least 90%.

6. The method of claim 1, wherein the abundance of deuterium in Z is at least 95%.

7. The method of claim 1, wherein the deuterium-enriched compound is represented by:

8. The method of claim 7, wherein the abundance of deuterium in Z is at least 90%.

9. The method of claim 7, wherein the abundance of deuterium in Z is at least 95%.

10. The method of claim 9, wherein the compound has an enantiomeric excess of at least 95%.

11. The method of claim 2, wherein the deuterium-enriched compound is represented by:

12. The method of claim 11, wherein the abundance of deuterium in Z is at least 90%.

13. The method of claim 11, wherein the abundance of deuterium in Z is at least 95%.

14. The method of claim 13, wherein the compound has an enantiomeric excess of at least 95%.

15. The method of claim 3, wherein the deuterium-enriched compound is represented by:

16. The method of claim 15, wherein the abundance of deuterium in Z is at least 90%.

17. The method of claim 15, wherein the abundance of deuterium in Z is at least 95%.

18. The method of claim 17, wherein the compound has an enantiomeric excess of at least 95%.