Table 1. SAR of Aromatic Substitution, h/rTRPA1 IC50 [nM] Potency, for Compounds 15, 16, and 24a–h.
compounda | R1 | R2 | R3 | hTRPA1 IC50 [nM] | rTRPA1 IC50 [nM] |
---|---|---|---|---|---|
15 | H | H | NO2 | 14 | 1370 |
(rac)-16 | H | H | F | 36 | 1560 |
eutomer 16a | H | H | F | 33 | 860 |
16b | H | H | F | >25 000 | >25 000 |
24a | H | H | Cl | 340 | 11 500 |
24b | H | H | CN | 390 | 7570 |
24c | H | H | Me | 1270 | >12 500 |
24d | H | H | OMe | >125 00 | >12 500 |
24e | H | H | –C(O)NHEt | >12 500 | >12 500 |
24f | H | F | H | 750 | 3800 |
24g | H | CN | H | 5550 | 13 000 |
24h | F | H | F | 1000 | >10 000 |
Compounds are diastereomeric mixtures unless stated otherwise (#4, ratio >10:1 cis/trans).