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However, clinical use of approved CaSR\u2010targeting drugs such as cinacalcet is limited due to adverse side effects including hypocalcaemia, nausea and vomiting, and in some instances, a lack of efficacy. The CaSR agonist and positive allosteric modulator (ago\u2010PAM), AC265347, is chemically distinct from clinically\u2010approved CaSR PAMs. AC265347 potently suppressed parathyroid hormone (PTH) release in rats with a lower propensity to cause hypocalcaemia compared to cinacalcet and may therefore offer benefits over current CaSR PAMs. Here we report a structure activity relationship (SAR) study seeking to optimise AC265347 as a drug candidate and disclose the discovery of AC265347\u2010like compounds with diverse pharmacology and improved physicochemical and drug\u2010like properties.<\/jats:p>","DOI":"10.1002\/cmdc.202100368","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T22:01:04Z","timestamp":1625263264000},"page":"3451-3462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of AC265347\u2010Inspired Calcium\u2010Sensing Receptor Ago\u2010Positive Allosteric 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