Selective HDAC3 inhibitors

• US 9,562,013 B2
• Filed: 06/29/2015
• Issued: 02/07/2017
• Est. Priority Date: 02/01/2013
• Status: Active Grant

• Current Assignee: Regenacy Pharmaceuticals LLC
• Original Assignee: Acetylon Pharmaceuticals, Inc. (Bristol-Myers Squibb Company)
• Inventors: van Duzer, John H., Mazitschek, Ralph
• Primary Examiner(s): Shterengarts, Samantha
• Application Number:
  US14/753,913
• Publication Number:
  US 20150299130A1
• Time in Patent Office: 589 Days
• Field of Search: 514/234.5, 514/253.06, 514/418, 514/394, 514/249, 514/253.05
• US Class Current: 1/1
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• 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 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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: C07D 209/34 in position 2
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 215/54 attached in position 3
• CPC Class Codes: C07D 217/26 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 235/06 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
• CPC Class Codes: C07D 235/08 : Radicals containing only hydrogen and carbon atoms
• CPC Class Codes: C07D 241/44 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

Provided herein are HDAC3 inhibitors, as well as methods of treatment comprising administering these compounds to a subject in need thereof.

Claims

1. A method of treating cancer, a neurodegenerative disease, or a metabolic disease, in a subject comprising administering to the subject a compound selected from

2. The method of claim 1, wherein the cancer is a hematologic malignancy.

3. The method of claim 2, wherein the hematologic malignancy is a leukemia or lymphoma.

4. The method of claim 3, wherein the leukemia is acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute monocytic leukemia (AML), or acute promyelocytic leukemia (APL).

5. The method of claim 3, wherein the lymphoma is Hodgkin'"'"'s lymphoma or Non-Hodgkin'"'"'s lymphoma.

6. The method of claim 1, wherein the cancer is a solid tumor.

7. The method of claim 6, wherein the solid tumor is a brain tumor, neuroblastoma, retinoblastoma, Wilm'"'"'s tumor, bone tumors, soft-tissue sarcomas, head cancer, neck cancer, gastric cancer, prostate cancer, bladder cancer, renal cancer, cancer of the uterus, ovarian cancer, testicular cancer, colon cancer, lung cancer, or breast cancer.

8. The method of claim 1, wherein the cancer is gastric cancer, prostate cancer, or colorectal cancer.

9. The method of claim 1, wherein the neurodegenerative disease is Huntington'"'"'s disease, Friedrich'"'"'s ataxia, myotonic dystrophy, Parkinson'"'"'s disease, spinocerebellar ataxia, Kennedy'"'"'s disease, amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, or Alzheimer'"'"'s disease.

10. The method of claim 1, wherein the metabolic disease is type 2 diabetes.

11. The method of claim 1, wherein the subject is a human.