title: Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries.
abstract: Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.
authors: Pfizer Worldwide Research & Development, Eastern Point Road, Groton, CT 06340, United States. allyn.t.londregan@pfizer.com
authors: Allyn T
authors: AT
authors: Londregan
authors: David W
authors: DW
authors: Piotrowski
authors: Kentaro
authors: K
authors: Futatsugi
authors: Joseph S
authors: JS
authors: Warmus
authors: Markus
authors: M
authors: Boehm
authors: Philip A
authors: PA
authors: Carpino
authors: Janice E
authors: JE
authors: Chin
authors: Ann M
authors: AM
authors: Janssen
authors: Nicole S
authors: NS
authors: Roush
authors: Joanne
authors: J
authors: Buxton
authors: Terri
authors: T
authors: Hinchey
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; C473772:GPBAR1 protein, human; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; C031280:pyrazole