Direct ampk activator compounds in combination with indirect ampk activator compounds, compositions, methods and uses thereof

A compound and activator technology, applied in the field of direct AMPK activator and indirect AMPK activator, direct AMPK activator compound, can solve unsatisfied problems of natural compounds and combinations

Pending Publication Date: 2022-07-15
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] The present invention addresses the apparent unmet need for new natural compounds and combinations of AMPK-activating compounds having the advantages described above

Method used

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  • Direct ampk activator compounds in combination with indirect ampk activator compounds, compositions, methods and uses thereof
  • Direct ampk activator compounds in combination with indirect ampk activator compounds, compositions, methods and uses thereof
  • Direct ampk activator compounds in combination with indirect ampk activator compounds, compositions, methods and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0523] Combinations of the present invention

[0524] The present invention relates to combinations of direct AMPK activators and indirect AMPK activators for activating AMPK.

[0525] The direct AMPK activators of the present invention act by binding to the ADaM binding site at the interface between the alpha-subunit of AMPK and the beta-subunit of AMPK. Indirect AMPK activators work by indirectly altering the nucleotide state of the cell by reducing ATP and increasing AMP / ADP in the cell, thereby activating AMPK via the gamma-subunit.

[0526] Compounds of the present invention

[0527] Direct AMPK activator compounds of general formula I as described herein have the structure shown below

[0528]

[0529] wherein R1, R2, R3, R4, R5, R6, R7 and R8 are each independently: H; CH 3 ;CH 2 OH;CHO;COOH;OH;OCH 3 ;CO-(CH 2 ) 2 -CH 3 ;O-CO-CH 3 ; Halogen; O-glycosides; C-glycosides; Acylated O-glycosides; Acylated C-glycosides; Sulfated O-glycosides; Sulfated C-glycosi...

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Abstract

The present invention relates to a combination of a direct AMPK activator and an indirect AMPK activator for activating AMPK. In particular, the present invention provides a combination of a benzocoumarin of formula I as a direct AMPK activator and a urolithin of formula VII as an indirect AMPK activator.

Description

Background technique [0001] AMP-activated protein kinase (AMPK) is an evolutionarily conserved master regulator of energy homeostasis, coordinating metabolic pathways to balance nutrient supply with energy demand. AMPK is considered a key drug target against increasingly prevalent metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disease. [0002] AMPK activity is present in all tissues, including liver, kidney, muscle, lung and brain (PMID: 10698692). Structurally, AMPK is a heterotrimeric complex consisting of a catalytic subunit (α) and two regulatory subunits (β and γ). The AMPK complex is evolutionarily conserved and is also found in yeast and plants. Mammalian AMPK is composed of subunits of different isoforms: α1, α2, β1, β2, γ1, γ2 and γ3 (PMID: 11746230), resulting in 12 possible heterotrimeric combinations. The α2 isoform is predominantly found in skeletal and cardiac AMPK; both the α1 and α2 isoforms are found in hepatic AMPK; whereas in adi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P1/16A61P3/04A61P3/10A61P9/00A61P9/12A61P11/00A61P35/00
CPCA61K31/352A61P1/16A61P3/04A61P3/10A61P9/00A61P9/12A61P11/00A61P35/00A61K2300/00A23L33/10A61K31/366
Inventor M·桑德斯Y·拉蒂诺D·M·巴伦坂本圭
Owner SOC DES PROD NESTLE SA
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