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Updated: Sep 27, 2026

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
Published on: July 28, 2014
Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin
Philip A Carpino1, Bruce A Lefker, Steven M Toler
1Pfizer Global Research and Development, Groton Labs, MS8220-3004, Eastern Point Rd, CT 06340, Groton, USA. philip_a_carpino@groton.pfizer.com
Abstract:
Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a K(i)=7 nM, rat pituicyte EC(50)=3 nM) and the des-methyl analogue 5c (hGHS-R1a K(i)=17 nM, rat pituicyte EC(50)=3 nM), increased plasma GH levels in an anesthesized rat model, with ED(50) values less than 0.05 mg/kg iv. Capromorelin showed enhanced intestinal absorption in rodent models and exhibited superior pharmacokinetic properties, including high bioavailabilities in two animal species [F(rat)=65%, F(dog)=44%]. This short-duration GHS was orally active in canine models and was selected as a development candidate for the treatment of musculoskeletal frailty in elderly adults.
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