Antagonist activity of N-benzoylated derivatives 11a–16a in rTRPM8 channels (Ca2+ microfluorometry assay). Activation is induced by 100 µM menthol
| Compound | R | aTPSA, (A2) | cLogP | IC50 (µM) | 95% confidential intervals |
|---|---|---|---|---|---|
| 1a | NA | 49.85 | 9.88 | 1.06 ± 1.21 | 0.72 to 1.55 |
| 2a | NA | 58.64 | 7.63 | 3.06 ± 1.25 | 2.67 to 3.51 |
| 11a | H | 75.71 | 7.01 | 2.49 ± 1.45 | 1.10 to 5.66 |
| 12a | Ph | 75.71 | 8.90 | 1.14 ± 1.53 | 0.46 to 2.80 |
| 13a | F | 75.71 | 7.36 | 2.30 ± 1.29 | 1.34 to 3.95 |
| 14a | OMe | 84.94 | 7.29 | 3.21 ± 1.30 | 1.85 to 5.57 |
| 15a | OAc | 102.01 | 6.64 | 9.73 ± 1.28 | 5.74 to 16.48 |
| 16a | N(Me)2 | 78.95 | 7.37 | 2.54 ± 1.33 | 1.40 to 4.60 |
| AMTB | NA | ND | ND | 7.3 ± 1.5 | 8.82 to 7.85 |
a Calculated with ChemDraw 22.2.0. TPSA: total polar surface area; IC50: concentration exerting a half-maximal inhibition; rTRPM8: rat transient receptor potential melastatin, subtype 8; R: substituent at the benzoyl moeity; cLogP: logarithm of the partition coefficient between n-octanol and water; ND: no data; NA: not applicable