{"entity": "publication", "iuid": "36c71a4fd05b423a9ff82550c4965755", "timestamp": "2026-08-22T06:57:54.256Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/36c71a4fd05b423a9ff82550c4965755.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/36c71a4fd05b423a9ff82550c4965755"}}, "title": "Angiotensin II AT2 receptor ligands with phenylthiazole scaffolds.", "authors": [{"family": "Gopalan", "given": "Greeshma", "initials": "G"}, {"family": "Palo-Nieto", "given": "Carlos", "initials": "C"}, {"family": "Petersen", "given": "Nadia N", "initials": "NN"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}, {"family": "Larhed", "given": "Mats", "initials": "M"}], "type": "journal article", "published": "2022-07-01", "journal": {"title": "Bioorg. Med. Chem.", "issn": "1464-3391", "volume": "65", "pages": "116790", "issn-l": "0968-0896"}, "abstract": "The syntheses and the AT1R and AT2R binding data of a series of new small molecule ligands are reported. These ligands comprise a phenylthiazole scaffold rather than the biphenyl or phenylthiophene scaffolds found in essentially all of the previously described ligands originating from the nonselective AT1R/AT2R ligand L-162,313 and the AT2R selective agonist C21, the latter now in Phase II/III clinical trials. A phenylthiazole rather than the phenylthiophene scaffold that is present in the AT2R selective agonist C21 and in the AT2R selective antagonist C38 had a deleterious effect on the affinity to AT2R. Nevertheless, a significant improvement could be accomplished by introduction of a small bulky alkyl group in the 2-position of the imidazole ring attached through a methylene group bridge to the phenylthiazole scaffold. Hence, a combination of a 2-tert-butyl or a 2-isopropyl group and a butoxycarbonyl furnished potent AT2R selective ligands. Furthermore, a high affinity ligand derived from L-162,313 and exhibiting a > 35 fold selectivity for AT1R was identified (10). The ligand 21 with the 2-tert-butyl group and \u223c 35 fold selectivity for AT2R, demonstrated high stability in human, rat and mouse liver microsomes and a very attractive profile with regard to the inhibition of common drug-metabolizing CYP enzymes. Thus, very low levels of inhibition of CYP 3A (5%), 2D6 (12%), 2C8 (26%), 2C9 (23%) and 2B6 (24%) were observed with the 2-tert-butyl derivative comprising the methoxycarbonyl sulfonamide function, levels that are significantly lower than those obtained with C21 under the same experimental conditions.", "doi": "10.1016/j.bmc.2022.116790", "pmid": "35550979", "labels": [], "xrefs": [{"db": "pii", "key": "S0968-0896(22)00182-1"}], "notes": [], "created": "2026-08-20T06:43:49.541Z", "modified": "2026-08-20T06:43:49.589Z"}