Antagonist activity of β-lactams 1a–d and analogue 9d at rTRPM8 channels in microfluorometry assays and patch-clamp experiments
| Compound | R | Configuration | Ca2+ microfluorometry | Patch clamp | ||
|---|---|---|---|---|---|---|
| IC50 (µM) | 95% confidence intervals | IC50 (µM) | 95% confidence intervals | |||
| 1a | OtBu | 3S,4S,2'S | 1.06 ± 1.21 | 0.72 to 1.55 | 0.97 ± 1.56 | 0.38 to 2.45 |
| 1b | OtBu | 3S,4S,2'R | 0.72 ± 0.12 | 0.64 to 0.80 | 1.21 ± 0.4 | 0.82 to 1.72 |
| 1c | OtBu | 3R,4R,2'S | 4.48 ± 0.80 | 3.62 to 5.56 | 2.94 ± 0.75 | 2.27 to 3.69 |
| 1d | OtBu | 3R,4R,2'R | 5.02 ± 1.50 | 3.76 to 6.77 | 3.34 ± 0.8 | 2.40 to 5.52 |
| 9d | NHiBu | 3R,4R,2'R | 0.41 ± 0.10 | 0.36 to 0.46 | 0.90 ± 1.25 | 0.57 to 1.42 |
| AMTB | NA | ND | 7.3 ± 1.5 | 8.82 to 7.85 | ND | ND |
ND: no determined; NA: not applicable; AMTB: N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)benzamide hydrochloride; IC50: concentration exerting a half-maximal inhibition; rTRPM8: rat transient receptor potential melastatin channel, subtype 8; R: substituent at the 4-position; OtBu: tert-butyl ester; NHiBu: N-isobutyl amide