1104083-23-9Relevant articles and documents
Design and synthesis of cyanamides as potent and selective N-acylethanolamine acid amidase inhibitors
Malamas, Michael S.,Farah, Shrouq I.,Lamani, Manjunath,Pelekoudas, Dimitrios N.,Perry, Nicholas Thomas,Rajarshi, Girija,Miyabe, Christina Yume,Chandrashekhar, Honrao,West, Jay,Pavlopoulos, Spiro,Makriyannis, Alexandros
, (2020)
N-acylethanolamine acid amidase (NAAA) inhibition represents an exciting novel approach to treat inflammation and pain. NAAA is a cysteine amidase which preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-α (PPAR-α), which is a key regulator of inflammation and pain. Thus, blocking the degradation of PEA with NAAA inhibitors results in augmentation of the PEA/PPAR-α signaling pathway and regulation of inflammatory and pain processes. We have prepared a new series of NAAA inhibitors exploring the azetidine-nitrile (cyanamide) pharmacophore that led to the discovery of highly potent and selective compounds. Key analogs demonstrated single-digit nanomolar potency for hNAAA and showed >100-fold selectivity against serine hydrolases FAAH, MGL and ABHD6, and cysteine protease cathepsin K. Additionally, we have identified potent and selective dual NAAA-FAAH inhibitors to investigate a potential synergism between two distinct anti-inflammatory molecular pathways, the PEA/PPAR-α anti-inflammatory signaling pathway,1–4 and the cannabinoid receptors CB1 and CB2 pathways which are known for their antiinflammatory and antinociceptive properties.5–8 Our ligand design strategy followed a traditional structure–activity relationship (SAR) approach and was supported by molecular modeling studies of reported X-ray structures of hNAAA. Several inhibitors were evaluated in stability assays and demonstrated very good plasma stability (t1/2 > 2 h; human and rodents). The disclosed cyanamides represent promising new pharmacological tools to investigate the potential role of NAAA inhibitors and dual NAAA-FAAH inhibitors as therapeutic agents for the treatment of inflammation and pain.
As the NS4B inhibitor benzofuran analogs (by machine translation)
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Paragraph 0386; 0388; 0389; 0390; 0391, (2016/10/31)
The present invention discloses a kind of as NS4B benzofuran analogue inhibitors, in particular to the formula (I) below or a pharmaceutically acceptable salt thereof. (by machine translation)
SUBSTITUTED IMIDAZO[1,2-a]PYRIDINE COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TrkA) INHIBITORS
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, (2016/01/15)
The present application relates to a series of substituted imidazo[1,2-a]pyridine compounds of formula (I), pharmaceutically acceptable salts, pharmaceutically acceptable solvates or stereoisomers thereof, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
