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ID: ALA1155060
Journal: Bioorg Med Chem Lett
Title: Discovery of brain penetrant, soluble, pyrazole amide EP1 receptor antagonists.
Authors: Hall A, Billinton A, Bristow AK, Brown SH, Chowdhury A, Cutler L, Giblin GM, Goldsmith P, Hayhow TG, Kilford IR, Naylor A, Passingham B, Rawlings DA.
Abstract: We describe the discovery of a series of pyrazole amide EP(1) receptor antagonists with good aqueous solubility and CNS penetration. In order to achieve solubility we investigated the incorporation of a basic group in the region of the molecule previously occupied by a carboxylic acid, which was known to be a key element of the pharmacophore. This study led to the identification of compounds such as 4h, 4j and 10b which demonstrated brain-to-blood ratios of 0.8:1-2.0:1 in addition to good solubility and metabolic stability.
CiteXplore: 18571922