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

Pfkfb3 inhibitors and their uses

A C3-C8, -O-C3-C8 technology, applied in the field of PFKFB3 inhibitors and their uses, can solve problems such as reduction and unclear inhibitory effect

Pending Publication Date: 2021-09-14
GERO PTE LTD
View PDF48 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has been reported that 3PO (3-(3-pyridyl)-1-(4-pyridyl)-2-propen-1-one) and ACT-PFK-158 ((E)-1-(pyridin-4-yl )-3-(7-(trifluoromethyl)quinolin-2-yl)prop-2-en-1-one) inhibits PFKFB3, reduces the intracellular concentration of Fru-2,6-BP, and reduces glucose uptake , and reduces the growth of tumor-forming tumors in vivo, however, the inhibitory effect of PFKFB3 on 3PO is unclear based on conflicting studies

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
  • Pfkfb3 inhibitors and their uses
  • Pfkfb3 inhibitors and their uses
  • Pfkfb3 inhibitors and their uses

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[1203] Compound preparation

[1204] The compounds used in the reactions described herein are prepared according to known organic synthesis techniques starting from commercially available chemicals and / or compounds described in the chemical literature. "Commercially available chemicals" are obtained from standard commercial sources. The following non-exhaustive and non-exclusive commercial list of commercial suppliers is provided by way of example and reference only, and compounds useful in the present invention may be obtained from other suppliers: Acros Organics (Gill, Belgium), Aldrich Chemical (Milwaukee, WI, including Acros Organics ( Gill, Belgium), Aldrich Chemical (Milwaukee, Wisconsin including SigmaChemical and Fluka), Alfa Aesar (Heysham, UK), Alfa Chemistry (Holtsville, New York), Angene International Limited (London, UK), Apin Chemicals Ltd. (Milton, UK (Milton Park)), Apollo Scientific Ltd (Stockport, UK), Ark Pharm, Inc. (Libertyville, Israel), AuroraFine Chemi...

Embodiment 1

[1859] Example 1: 2-(2-Methoxybiphenyl-4-yl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid

[1860]

[1861] 129. 2-(2-Methoxybiphenyl-4-yl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid was synthesized as described in Synthetic Process K Preparation from trimellitic anhydride and 2-methoxy-[1,1'-biphenyl]-4-amine; MS m / z: (M+H) + for C 22 h 15 NO 5 Calculated: 374.36; detected: 374.14. LC / MS retention time: 2.53 minutes.

Embodiment 2

[1862] Example 2: 1,3-dioxo-2-[3-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]-2,3-dihydro-1H- Isoindole-5-carboxylic acid

[1863]

[1864] 130. 1,3-Dioxo-2-[3-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]-2,3-dihydro-1H-isoindol Indole-5-carboxylic acid was prepared from trimellitic anhydride and crude 3-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-amine (interm. 18) as described in Synthetic Step K; MS m / z:(M+H) + for C 22 h 13 N 5 o 4 Calculated value: 412.38; detected value: 412.26. LC / MS retention time: 2.19 minutes.

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 disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and / or PFKFB4 has beneficial effect as well as neuroprotection.

Description

Background technique [0001] Even under normoxic conditions, cancer cells display a preference for glycolysis over oxidative phosphorylation. Cancer cells benefit from elevated glycolytic flux to meet their high energy demands for rapid growth and proliferation. This finding is being used clinically as a diagnostic tool for solid tumors, whereby 2-deoxy-2-[ 18 F] Uptake of fluoroglucose. In recent years, glycolysis has attracted considerable attention due to its relationship with cancer, and enzymes in the glycolytic pathway have been developed as potential targets for therapeutic intervention. Small molecule inhibitors have been identified, for example, against glucose transporters, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hexokinase II, and hypoxia-inducible factor 1-alpha (HIF1-alpha). Inhibition of glycolysis (eg, by 2-deoxy-D-glucose, bromopyruvate, lonidamine, phloretin, WZB117) has been shown to promote cell death. However, direct targeting of glycolytic enz...

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
IPC IPC(8): C07D209/44C07D401/10C07D401/14C07D401/04C07D403/10C07D403/14C07D403/04C07D405/10C07D213/16C07D409/04C07D205/04C07D207/06C07D233/06C07D277/18C07D249/06C07D333/10A61K31/166A61K31/4035A61K31/415A61K31/4192C07C233/75A61K31/44A61P25/00A61P35/00
CPCA61P25/00A61P35/00C07D205/04C07D249/06C07D277/18C07D401/04C07D401/14C07D403/04C07D403/10C07D403/14C07D409/04A61K45/06A61K38/00C07D209/48C07D413/14C07D209/34C07D403/12C07D405/14C07D233/58C07D213/75C07D207/12C07D471/08C07D211/14C07D333/38C07D409/12C07C233/81C07C237/40C07C235/56C07C2601/14C07C381/10A61K9/0019A61K31/337A61K31/704A61K31/454A61K31/502A61K31/422A61K31/381A61K31/194A61K31/404A61K31/7105A61K31/713A61K31/415A61K2300/00C07B2200/05C07D209/46C07D409/14
Inventor P·O·费迪切夫K·格林曼C·志-聪M·N·霍林E·G·格曼捷夫T·V·叶德科娃A·V·卡杜什金T·V·佩尔科夫D·V·希绍夫J·P·博拉诺斯-赫尔南德兹K·A·扎库尔达娃O·A·伯莫斯特罗娃
Owner GERO PTE LTD
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