1039982-77-8Relevant academic research and scientific papers
Discovery of isoquinolinone indole acetic acids as antagonists of chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) for the treatment of allergic inflammatory diseases
Kaila, Neelu,Follows, Bruce,Leung, Louis,Thomason, Jennifer,Huang, Adrian,Moretto, Alessandro,Janz, Kristin,Lowe, Michael,Mansour, Tarek S.,Hubeau, Cedric,Page, Karen,Morgan, Paul,Fish, Susan,Xu, Xin,Williams, Cara,Saiah, Eddine
, p. 1299 - 1322 (2014/03/21)
Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. H
Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5 antagonists
Wu, Lingyun,Lu, Kai,Packiarajan, Mathivanan,Jubian, Vrej,Chandrasena, Gamini,Wolinsky, Toni C.,Walker, Mary W.
scheme or table, p. 2167 - 2171 (2012/04/18)
A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor.
Diazine indole acetic acids as potent, selective, and orally bioavailable antagonists of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2) for the treatment of allergic inflammatory diseases
Kaila, Neelu,Huang, Adrian,Moretto, Alessandro,Follows, Bruce,Janz, Kristin,Lowe, Michael,Thomason, Jennifer,Mansour, Tarek S.,Hubeau, Cedric,Page, Karen,Morgan, Paul,Fish, Susan,Xu, Xin,Williams, Cara,Saiah, Eddine
experimental part, p. 5088 - 5109 (2012/08/28)
New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.
INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS
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Page/Page column 37, (2011/05/08)
Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.
