1104083-23-9Relevant academic research and scientific papers
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.
TARGETING COMPOUNDS
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Paragraph 0274, (2019/07/19)
The disclosure provides, at least in part, liver, intestine and/or kidney-targeting compounds and their use in treating liver, intestine and/or kidney disorders, such as non-alcoholic steatohepatitis, alcoholic steatohepatitis, hepatocellular carcinoma, liver cirrhosis, and hepatitis B; and/or chronic kidney disease, glomerular disease such as IGA nephropathy, lupus nephritis, or polycystic kidney disease. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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 HETEROCYCLIC COMPOUNDS AS TROPOMYOSIN RECEPTOR KINASE A (TRKA) INHIBITORS
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, (2015/02/05)
The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.
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.
N-ACYLETHANOLAMINE HYDROLYZING ACID AMIDASE (NAAA) INHIBITORS AND THEIR USE THEREOF
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Paragraph 0304, (2015/12/08)
A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA). The present technology is directed to compounds, compositions, and methods to inhibit N-acylethanolamine hydrolyzing acid amidase and to treat N-acylethanolamine hydrolyzing acid amidase mediated conditions in a subject.
5,7-SUBSTITUTED-IMIDAZO[1,2-C]PYRIMIDINES
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Paragraph 00397, (2013/04/25)
Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R1, R2, R3, R4, R5, R6, X1 and X2 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.
Pyrrolopyrazine Kinase Inhibitors
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Page/Page column 91, (2011/10/10)
The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables n, p, q, Q, X, X′ and Y are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.
HEPATITIS C INHIBITOR COMPOUNDS
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Page/Page column 52, (2011/06/23)
Compounds of Formula (I) wherein R1, R2, R3, R4 and R5 are defined herein, maintain good activity against NS3 proteases containing clinically relevant genotype 1a R155K and genotype 1b D168V resistance mutations. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.
SEROTONIN RECEPTOR MODULATORS
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Page/Page column 151, (2010/07/10)
The biphenyic compounds of formula (I) are serotonin modulators useful in the treatment of serotonin-mediated diseases.
