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REV-ERBalpha has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBalpha agonists based on GSK4112 (1) for potency, selectivity, and bioavailability.(1) Potent REV-ERBalpha agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRalpha. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing.
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Reference：
Thiazole | C3H4267NS – PubChem,
Thiazole | chemical compound | Britannica