Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism

A technology for hypometabolism and neurons, applied in chemical treatment to inactivate enzymes, nervous system diseases, medical preparations containing active ingredients, etc., can solve problems such as inability to slow down and treatment.

Inactive Publication Date: 2010-08-04
ACCERA INC
View PDF22 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, current treatments for Alzheimer's disease do little to slow or do little to treat the disease

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism
  • Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism
  • Inhibitors of acetyl-COA carboxylase for treatment of neuronal hypometabolism

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0200] In one embodiment, suitable ACC inhibitors are one or more of a class of compounds for the treatment or prevention of cognitive function loss caused by neuronal hypometabolism, which includes the drug combination described in US Patent No. 4,908,385 things. US Patent No. 4,903,385 is specifically incorporated herein by reference in its entirety and the following general formulas, all species and methods for their preparation are also specifically incorporated by reference. The compounds are useful for treating, preventing, inhibiting or alleviating diseases associated with neuronal hypometabolism, such as age-associated memory impairment (AAMI), mild cognitive impairment (MCI), Alzheimer's disease, Parkinson's disease, Reedreich's ataxia (FRDA), GLUT1-deficiency epilepsy, dwarfism and Rabson-Mendenhall syndrome, coronary artery bypass graft (CABG) dementia, anesthesia-induced memory loss, Huntington's disease, etc. , including at least one α-halogenated dicarboxylic ac...

Embodiment 1

[0206] Pharmacokinetic (PK) studies in mice

[0207] Objective: To determine blood levels of ketone bodies at different time points after oral (po) and intraperitoneal (ip) administration of TOFA in mice

[0208] Animals: 6-7 week old 75I CR male mice were used. Each mouse weighs 20-30 g.

[0209] General Study Design: Animals (housed 3 / cage) were acclimatized for at least 3 days prior to dosing. Mice were given a single po dose (0.5 mg / kg-5 mg / kg) of compound or a single ip dose (1 mg / kg). Mice were anesthetized for blood sampling at 0.5, 1, 2 and 3 hours. Whole blood (-0.4 mls) was collected by cardiac puncture and heparin sodium (Heparin Na, 1:9 ratio) anticoagulant was collected. Blood was centrifuged at 13,000 rpm for 8 minutes to separate plasma. Plasma was transferred to pre-labeled color-coded Eppendorf tubes and frozen at -70°C. Animals were observed for signs of toxicity and clinical observations were recorded. Plasma levels of β-hydroxybutyrate (BHB) were det...

Embodiment 2

[0216] Use of ACC Inhibitors in Elevating Serum Ketone Levels in a Rat Model

[0217] Sprague-Dawley rats were fed a standard commercial rat diet. After a 15-day acclimatization period, the rats in both groups were fed an ACC inhibitor such as 5-(tetradecyloxy)-2-furan-carboxylic acid (TOFA) or CP-610431 at 1-50 mg / kg / day. experimental diet. The control group maintained the standard diet.

[0218] The weight of each rat was determined daily. Urine samples were collected daily and analyzed for 3-hydroxybutyrate by enzymatic assay. After 5 days on the experimental diet, rats were euthanized and blood samples were collected and analyzed for 3-hydroxybutyrate, acetoacetate and acetone by standard enzymatic techniques.

[0219] Concentrations of ketone bodies in rat plasma collected at the time of euthanasia were determined enzymatically. The control group is expected to exhibit normal concentrations of 3-hydroxybutyrate and acetoacetate of about 0.02-0.07 mM. Rats fed an ACC...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

This invention relates to methods of using inhibitors of the enzyme acetyl-CoA carboxylase (ACC) for the treatment, prevention, inhibition or alleviation of diseases associated with neuronal hypometabolism and / or loss of cognitive function caused by reduced neuronal metabolism such as, for example, Age Associated Memory Impairment (AAMI), Mild Cognitive Impairment (MCI), Alzheimer's disease, Parkinson's disease, Friedreich's Ataxia (FRDA), GLUT1-deficient Epilepsy, Leprechaunism and Rabson-Mendenhall Syndrome, Coronary Arterial Bypass Graft (CABG) dementia, anesthesia induced memory loss, Huntington's disease and many others.

Description

field of invention [0001] The present invention relates to the field of therapeutic agents for the treatment of Alzheimer's disease, mild cognitive impairment and other diseases related to neuronal metabolic decline, including Parkinson's disease, Huntington's disease and epilepsy. Background of the invention [0002] Many diseases are associated with neuronal hypoglucose metabolism and there is a need to treat these disorders. The compounds of the present invention are useful in the treatment of these disorders. [0003] Alzheimer's disease (AD) is a progressive neurodegenerative disorder that mainly affects the elderly. In 1984, Blass and Zemcov (Blass and Zemcov 1984) proposed that AD results from a decreased metabolic rate in a subpopulation of cholinergic neurons. However, it has become clear that AD is not limited to the cholinergic system, but involves many types of transmission systems and several discrete brain regions. Decreased metabolic rate appears to correla...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K31/35C07K7/06C07D407/04C12N9/99
CPCA61K31/35G01N2800/52A61P25/08A61P25/14A61P25/16A61P25/28A61P43/00
Inventor S·T·汉德森
Owner ACCERA INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com