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 was written by 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. And the article was included in Journal of Medicinal Chemistry in 2012.Recommanded Product: 19017-52-8 This article mentions the following:
New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit I had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type I 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. III 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. In the experiment, the researchers used many compounds, for example, 2-(5-Chloro-2-methyl-1H-indol-3-yl)acetic acid (cas: 19017-52-8Recommanded Product: 19017-52-8).
2-(5-Chloro-2-methyl-1H-indol-3-yl)acetic acid (cas: 19017-52-8) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Recommanded Product: 19017-52-8
Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles