Table 1. In Vitro Metabolic Stability of Psilocybin and Twenty-Eight Novel Prodrug Derivatives (NPDs) upon Exposure to Human Serum and Human S9 and Microsomal Fractions.
|
in vitro Half-life (T1/2) [min] |
||||||
|---|---|---|---|---|---|---|
| NPDa | (aq) | liver S9 fraction | liver microsomes | intestine S9 fraction | intestine microsomes | serum |
| PCB | ∞ | ∞ | ∞ | ∞ | 195.0 | ∞ |
| ES01 | ∞ | 21.0 | 17.0 | 132.0 | 315.0 | 1.0 |
| ES02 | ∞ | 3.0 | 1.0 | 104.0 | 62.0 | 1.0 |
| ES03 | 85.0 | 1.0 | 1.0 | 56.0 | 32.0 | 0.7 |
| ES04 | ∞ | 529.0 | 390.0 | ∞ | 113.0 | ∞ |
| ES05 | ∞ | 39.0 | 87.0 | 69.0 | 71.0 | 19.0 |
| ES06 | ∞ | ∞ | 241.0 | 445.0 | 621.0 | 101.0 |
| ES07 | 80.0 | 16.0 | 5.0 | 72.0 | 60.0 | 0.8 |
| ES08 | ∞ | 15.0 | 25.0 | 16.0 | 11.0 | ∞ |
| ES09 | ∞ | 3.0 | 2.0 | 2.0 | 2.0 | 49.0 |
| ES10 | ∞ | 33.0 | 22.0 | ∞ | ∞ | 33.0 |
| C01 | ∞ | 22.0 | 52.0 | 16.0 | 13.0 | 0.8 |
| C02 | ∞ | ∞ | 113.0 | 529.0 | 211.0 | ∞ |
| C03 | ∞ | 9.0 | 4.0 | 327.0 | 271.0 | 3.0 |
| C04 | ∞ | ∞ | 277.0 | 221.0 | 150.0 | 182.0 |
| C05 | 18.0 | 49.0 | 31.0 | 24.0 | 24.0 | 26.0 |
| T01 | ∞ | 5.0 | 6.0 | 50.0 | 71.0 | 14.0 |
| T02 | 6.0 | 7.0 | 9.0 | 24.0 | 13.0 | 32.0 |
| ET01 | ∞ | 60.0 | 27.0 | 64.0 | 50.0 | ∞ |
| EE01 | ∞ | 4.0 | 3.0 | 241.0 | 74.0 | 2.0 |
| EE02 | ∞ | 5.0 | 4.0 | 39.0 | 112.0 | 3.0 |
| EE03 | 145.0 | 16.0 | 13.0 | 52.0 | 22.0 | 0.8 |
| EC01 | ∞ | 293.0 | 104.0 | 266.0 | 894.0 | 3.0 |
| SE01 | ∞ | 191.0 | 347.0 | ∞ | ∞ | ∞ |
| SE02 | ∞ | 96.0 | 104.0 | 57.0 | 27.0 | ∞ |
| SE03 | ∞ | 391.0 | 229.0 | ∞ | ∞ | ∞ |
| P02 | ∞ | 96.0 | 43.0 | 52.0 | 28.0 | ∞ |
| P03 | ∞ | ∞ | ∞ | ∞ | ∞ | ∞ |
| PA01 | 10.0 | 26.0 | 22.0 | 39.0 | 29.0 | 145.0 |
a
ES = ester; C = carbonate; T = thiocarbonate; ET = ether; EE = ether-esters; EC = ether-carbonate; SE = silyl-ether; P = phosphate; PA = phosphoramidate; PCB = psilocybin; (Aq) indicates that the assay was conducted in aqueous buffer only, minus any biological fraction; and “∞” indicates that compound is stable over the 120-min incubation period.