Related Experiment Video
Updated: Jul 13, 2026

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Non-steroidal glucocorticoid agonists: the discovery of aryl pyrazoles as A-ring mimetics
Margaret Clackers1, Diane M Coe, Derek A Demaine
1Medicines Research Centre, riCEDD, GlaxoSmithKline, Stevenage, UK.
Abstract:
Starting from an established series of non-steroidal glucocorticoid receptor (GR) agonists, a large array was designed where a metabolically labile benzoxazinone moiety was replaced. Initial hits bound to GR but lacked agonist activity. Following two further iterations, potent GR agonists were discovered with 20D1E1 having NFkappaB agonism pIC(50) 8.8 (103%). Other analogues such as 23D1E1 display a dissociated profile (NFkappaB pIC(50) 8.1 (103%), MMTV pEC(50) 7.02 (36%)). The tetrahydronaphthalene moiety can also be replaced with substituted aryls such as 24E1 and 25E1.
Related Concept Videos
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
Five-Membered Heterocyclic Aromatic Compounds: Overview
