The discovery of indole-derived long acting β2-adrenoceptor agonists for the treatment of asthma and COPD

A Selective Pharmacophore Model for β2-Adrenoceptor Agonists

“…Based on the published literature, we selected a series of potent and selective β 2 -agonists ( Figure 1 ) to generate a pharmacophore model. These compounds were taken from different literature sources [ 10 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], and the activity values were measured in various systems. In addition, due to limited structural diversity, qualitative HipHop pharmacophore modeling was performed based on the collected β 2 -agonists.…”

A novel triazine-aryl-bis-indole derivative inhibits both phosphodiesterase IV and expression of cell adhesion molecules

“…The indole and its various derivatives such as bis-indoles and octahydro indoles seem to be potent biologically active compounds 10,11 . Importantly, indole derivatives have also shown to act as long acting β2-adrenoceptor agonists similar to to salmeterol 19 . These indole derivatives have been found to have anti-cancer, anti-oxidant, antiinflammatory and antimicrobial activities 18 .…”

“…18 Importantly, indole derivatives have also shown to act as long acting b2adrenoceptor agonists similar to salmeterol. 19 Since, bis-indoles have been found to exist in various nutritional components such as cruciferous vegetables 18,20,21 it is likely that bis-indoles may be highly bioavailable and safer. The natural and unnatural analogs of bis-indole derivatives have potent anticancer activities.…”

Lead Generation Approaches Delivering Inhaled β 2 ‐Adrenoreceptor Agonist Drug Candidates

“…The starting point for their program was an indole-containing hit that was identified following a high-throughput screening campaign and led to 16 after some fol low-up work (Figure 20.7 -Ar and R have not been disclosed; β 2 EC 50 0.74 nM versus 0.07 nM for salmeterol) [28]. Separation of the diastereosiomers, intro duction of the dimethoxybenzyl amide, and the saligenin head group led to ana log 17 that was potent at β 2 AR and selective over β 1 AR (β 2 EC 50 0.058 nM; β 1 /β 2 20.2 Lead Generation Exercises to Discover β 2 AR Agonist Clinical Candidates 4035).…”