1375465-91-0

Usage

Uses

Used in Pharmaceutical Industry:
2-(1-Phenyl-cyclopropylamino)-pyrimidine-5-carboxylic acid hydroxyamide is used as a therapeutic agent for targeting histone deacetylase 6 (HDAC6) due to its high selectivity and potency (IC50 = 1.7 nM). It modulates the acetylation of α-tubulin in the mouse brain, which is associated with anxiolytic and antidepressant-like activities when administered at a dose of 50 mg/kg.
Used in Neurological Applications:
In a mouse model of peripheral neuropathy induced by vincristine, 2-(1-Phenyl-cyclopropylamino)-pyrimidine-5-carboxylic acid hydroxyamide (100 mg/kg in the diet) is used to attenuate decreases in caudal nerve sensory nerve action potential (SNAP) amplitude and increases in hind paw mechanical hypersensitivity, demonstrating its potential in treating neuropathic pain and nerve damage.
Used in Hepatobiliary Applications:
2-(1-Phenyl-cyclopropylamino)-pyrimidine-5-carboxylic acid hydroxyamide is used to decrease hepatorenal cystogenesis in a rat model of polycystic liver disease when administered at a dose of 30 mg/kg, indicating its potential in treating liver-related diseases and conditions.
Used in Drug Development:
The compound is also used in the development of novel drug delivery systems to enhance its applications and efficacy against various diseases, including cancer and neurological disorders. This involves the use of organic and metallic nanoparticles as carriers for improved delivery, bioavailability, and therapeutic outcomes.

Upstream product

• 89793-12-4 ethyl 2-chloropyrimidine-5-carboxylate 
• 100-47-0 benzonitrile 
• 41049-53-0 1-phenylcyclopropylamine 
• 1598426-03-9 ethyl 2-((1-phenylcyclopropyl)amino)pyrimidine-5-carboxylate 
• 73930-39-9 1-phenylcyclopropane-1-amine hydrochloride 

Relevant academic research and scientific papers

HDAC INHIBITORS, ALONE OR IN COMBINATION WITH BTK INHIBITORS, FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA

Disclosed are histone deacetylase (HDAC) inhibitors, or combinations comprising an HDAC inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of chronic lymphocytic leukemia in a subject in need thereof. Also provided herein are methods for treating chronic lymphocytic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC inhibitor, or a combination comprising an HDAC inhibitor and a BTK inhibitor. Other related methods are disclosed.

METHODS OF USE AND PHARMACEUTICAL COMBINATIONS OF HDAC INHIBITORS WITH BET INHIBITORS

The disclosure relates to pharmaceutical combinations comprising an HDAC6 selective inhibitor and a BET inhibitor for the treatment of cancer in a subject in need thereof. Also provided herein are methods for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of an HDAC6 selective inhibitor and a BET inhibitor.

HDAC INHIBITORS FOR THE TREATMENT OF DIABETIC PERIPHERAL NEUROPATHY

The invention relates to HDAC inhibitors for use in the treatment of diabetic peripheral neuropathy in a subject in need thereof. Also provided herein are methods for treating diabetic peripheral neuropathy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC inhibitor.

INCREASING EXPRESSION OF INTERFERON REGULATED GENES WITH COMBINATONS OF HISTONE DEACETYLASE INHIBITORS AND IMMUNOMODULATORY DRUGS

Provided herein is a combination comprising an HDAC inhibitor and an IMiD for increasing interferon regulated gene expression or decreasing c-MYC gene expression in a cancer cell or tumor in a subject in need thereof. Increasing interferon regulated gene expression may result in increased recognition of tumors by innate or adaptive immune system and an increase in programmed cell death (apoptosis) gene expression, increasing apoptosis in cancer cells and tumors. The cells can be multiple myeloma cells or diffuse large B-cell lymphoma cells. Also provided are methods for treating myelodysplastic syndromes/acute myeloid leukemia (MDS/AML) or pathogen infections in a subject in need thereof comprising administering to the subject an effective amount of HDAC inhibitor and an IMiD. The HDAC inhibitor can be an HDAC6-selective inhibitor.

TREATMENT OF LEUKEMIA WITH HISTONE DEACETYLASE INHIBITORS

Provided herein are combinations comprising an HDAC inhibitor and azacitidine for the treatment of leukemia in a subject in need thereof. Provided herein are combinations comprising an HDAC inhibitor and azacitidine for the treatment of acute myelogenous leukemia in a subject in need thereof. Also provided herein are methods for treating leukemia in a subject in need thereof, comprising administering to the subject an effective amount of the above combination or an HDAC inhibitor, as well as methods for treating acute myelogenous leukemia in a subject in need thereof, comprising administering to the subject an effective amount of the above combination or an HDAC inhibitor.

PYRIMIDINE HYDROXY AMIDE COMPOUNDS FOR TREATING PERIPHERAL NEUROPATHY

The invention relates to HDAC inhibitors for the treatment of peripheral neuropathy in a subject in need thereof. Also provided herein are methods for treating peripheral neuropathy in a subject in need thereof comprising administering to the subject a th

COMBINATIONS OF HISTONE DEACETYLASE INHIBITORS AND BENDAMUSTINE FOR USE IN THE TREATMENT OF LYMPHOMA

The invention relates to pharmaceutical combinations comprising an HDAC inhibitor and bendamustine; pharmaceutical compositions comprising the same; and methods of using such combinations and compositions for treating lymphoma in a subject in need thereof.

HISTONE DEACETYLASE 6 (HDAC6) BIOMARKERS IN MULTIPLE MYELOMA

The invention relates to histone deacetylase (HDAC) biomarkers in multiple myeloma. Specifically, the biomarkers are drug specific, histone deacetylase (HDAC) or HDAC6 biomarker RNAs for multiple myeloma. The invention also relates to a kit for determining the treatment efficiency of a HDAC6 inhibitor, and a kit for identifying a histone deacetylase 6 (HDAC6) inhibitor. The invention further relates to a method for monitoring treatment efficiency of an HDAC inhibitor in a subject.

COMBINATIONS OF HISTONE DEACETYLASE INHIBITORS AND EITHER HER2 INHIBITORS OR PI3K INHIBITORS

The invention relates to combinations comprising an HDAC inhibitor and a Her2 inhibitor for the treatrent of breast cancer in a subject in need thereof. The invention also relates to combinations comprising an HDAC inhibitor and a PI3K inhibitor for the treatment of breast cancer in a subject in need thereof. Also provided herein are methods for treating breast cancer in a subject in need thereof comprising administering to the subject an effective amount of one of the above combinations. Further provided are methods for inhibiting migration and/or invasion of a breast cancer cell in a subject by administering to the subject a HDAC6 specific inhibitor.

COMBINATIONS OF HISTONE DEACETYLASE INHIBITORS AND IMMUNOMODULATORY DRUGS

The invention relates to combinations comprising an HDAC inhibitor and an immunomodulatory drug for the treatment of multiple myeloma in a subject in need thereof. The combinations may, optionally, further comprise an anti-inflammatory agent, such as dexamethasone. Also provided herein are methods for treating multiple myeloma in a subject in need thereof comprising administering to the subject an effective amount of one of the above combinations.