Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2. / Hansen, Anders Højgaard; Christensen, Henriette B.; Pandey, Sunil K.; Sergeev, Eugenia; Valentini, Alice; Dunlop, Julia; Dedeo, Domonkos; Fratta, Simone; Hudson, Brian D.; Milligan, Graeme; Ulven, Trond; Ulven, Elisabeth Rexen.
I: ChemMedChem, Bind 16, Nr. 21, 2021, s. 3326-3341.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2
AU - Hansen, Anders Højgaard
AU - Christensen, Henriette B.
AU - Pandey, Sunil K.
AU - Sergeev, Eugenia
AU - Valentini, Alice
AU - Dunlop, Julia
AU - Dedeo, Domonkos
AU - Fratta, Simone
AU - Hudson, Brian D.
AU - Milligan, Graeme
AU - Ulven, Trond
AU - Ulven, Elisabeth Rexen
PY - 2021
Y1 - 2021
N2 - Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.
AB - Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.
KW - FFA2
KW - GPCR
KW - GPR43
KW - inflammation
KW - short-chain fatty acids
U2 - 10.1002/cmdc.202100356
DO - 10.1002/cmdc.202100356
M3 - Journal article
C2 - 34288488
VL - 16
SP - 3326
EP - 3341
JO - Farmaco
JF - Farmaco
SN - 1860-7179
IS - 21
ER -
ID: 276322295