4068-73-9Relevant academic research and scientific papers
Discovery and Optimization of a Series of Benzofuran Selective ERAP1 Inhibitors: Biochemical and in Silico Studies
Deddouche-Grass, Safia,Andouche, Cyrielle,B?renz, Felix,Halter, Célia,Hohwald, Arnaud,Lebrun, Louison,Membré, Nathalie,Morales, Renaud,Muzet, Nicolas,Poirot, Matthieu,Reynaud, Morgane,Roujean, Véronique,Weber, Fabienne,Zimmermann, André,Heng, Rama,Basse, Nicolas
, p. 1137 - 1142 (2021)
ERAP1 is a key aminopeptidase involved in peptide trimming before major histocompatibility complex (MHC) presentation. A single nucleotide polymorphism (SNP) in the ERAP1 gene can lead to impaired trimming activity and affect ERAP1 function. ERAP1 genetic variations have been linked to an increased susceptibility to cancer and autoimmune disease. Here, we report the discovery of novel ERAP1 inhibitors using a high throughput screening approach. Due to ERAP1 broad substrate specificity, the hit finding strategy included testing inhibitors with a range of biochemical assays. Based on the hit potency, selectivity, and in vitro absorption, distribution, metabolism, excretion, and toxicity, the benzofuran series was selected. Fifteen derivatives were designed and synthesized, the compound potency was improved to the nanomolar range, and the structure-activity relationship supported by modeling studies.
BENZO-FUSED HETEROCYCLIC DERIVATIVES USEFUL AS AGONISTS OF GPR120
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Paragraph 0401; 0789, (2014/09/30)
The present invention is directed to benzo-fused heterocyclic derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by GPR120. More particularly, the compounds of the present invention are agonists of GPR120, useful in the treatment of, such as for example, Type II diabetes mellitus.
