Table 1. Potency and Intrinsic Activity at the Human β2AR.
compd no. | R1 | R2 | R3 | β2 potency pEC50a | IAb |
---|---|---|---|---|---|
1 | H | nBu | phenethyl | 8.8 | 0.9 |
2 | H | -(CH2)2NEt2 | phenethyl | 8.1 | 0.9 |
3 | OH | -(CH2)2NEt2 | phenethyl | 8.4 | 1.0 |
4 | OH | -(CH2)2NEt2 | 3-chlorophenethyl | 8.4 | 0.9 |
5 | H | -(CH2)2NMe2 | phenethyl | 8.2 | 1.0 |
6 | H | -(CH2)3NH2 | phenethyl | 6.5 | 0.5 |
7 | H | -(CH2)3NMe2 | phenethyl | 7.8 | 1.0 |
8 | H | -(CH2)3N(Me)iPr | 3-chlorophenethyl | 8.3 | 0.8 |
9 | H | -(CH2)3N(Me)Et | 3-chlorophenethyl | 8.0 | 0.8 |
10 | H | -(CH2)3N(Me)cyPr | 3-chlorophenethyl | 8.1 | 0.8 |
11 | H | -(CH2)2-piperidin-1-yl | 3-chlorophenethyl | 7.9 | 0.7 |
12 | H | -(CH2)2NEt2 | 2-(naphthalen-1-yl)ethyl | 8.2 | 0.8 |
13 | H | -(CH2)2NEt2 | 2-(naphthalen-2-yl)ethyl | 8.0 | 0.5 |
14 | H | -(CH2)2NEt2 | 3-fluorophenethyl | 8.1 | 0.8 |
15 | H | -(CH2)2NEt2 | 3-methoxyphenethyl | 8.1 | 0.6 |
16 | H | -(CH2)2NEt2 | 3-chlorophenethyl | 8.2 | 0.7 |
β2AR agonism was performed in H292 cells (bronchial epithelial cell line) expressing the human β2 adrenergic receptor. Functional activity was determined by measuring accumulation of intracellular cAMP using AlphaScreen. The compounds were incubated for 1 h at 22 °C.
IA (Intrinsic activity) measured relative to formoterol (pEC50 8.6, IA = 1).