Sulfonamides as GPR40- and GPR120-agonists
AssigneeDompé Farmaceutici S.P.A.
InventorsMaria De Pizzol, Anna Sirico, Mara Zippoli, Gianluca Bianchini, Andrea Beccari, Andrea Aramini, Chiara Rossana Maria Liberati
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Abstract
The invention relates to compounds acting as agonists of G-protein coupled receptor 120 (GPR120) and/or 40 (GPR40), and having formula (I): Said compounds are useful in the treatment of diseases or disorders modulated by GPR120 and/or GPR40 such as diabetes (particularly type 2 diabetes), impaired oral glucose tolerance, insulin resistance, obesity, obesity related disorders, metabolic syndrome, dyslipidemia, elevated LDL, elevated triglycerides, obesity induced inflammation, osteoporosis and obesity related cardiovascular disorders.
Claims15
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- A is a mono or di-carbocyclic residue, optionally partially or totally unsaturated, comprising carbon atoms and optionally one or more heteroatoms selected from N, S and O;
- R1, R2, and R3 are independently selected from the group consisting of —H, -halogen, —CF3, —CN, —CH2CN, —OMe, —OCF3, —OH, phenyl, —OPh, —OCH2Ph, —OCH2OMe, —OCH2CN—NO2, —NR′R″, linear or branched C1-C6 alkyl, —O(CH2)p—S(O)2Me and a five-membered ring heterocycle;
- wherein R′ and R″ are independently —H or C1-C4 alkyl;
- wherein phenyl and the five-membered ring heterocycle are independently unsubstituted or substituted with a group selected from the group consisting of linear or branched C1-C4 alkyl, halogen, —OMe and —OH;
- p is 1 to 4;
- X is —CH2 or —C(O);
- n is 0, 1 or 2;
- R4 is —Y—C(O)OH, wherein Y is a straight chain C4-C18 hydrocarbon, saturated or unsaturated;
- and
- R4 is in position meta or para on the aromatic ring;
- wherein when A is phenyl, n is 0, and Y is a C4 hydrocarbon, at least one of said R1, R2, R3 is not hydrogen;
- wherein when A is phenyl, n is 0, Y is a C4 hydrocarbon, and R1 and R2 are hydrogen, R3 is not Cl in position para on the aromatic ring.
Dependencies are inferred from the claim text.