Metabolites identified in mouse, rat, dog, and human samples collected after administration of a single intravenous dose of PR-104
For proposed structures, see Fig. 5. Relative abundance (++, ≥10%; +, <10%; −, not detected) was estimated from absorbance at 370 nm, or for M22 and M23 from the MS signal.
| Met ID | Name | λmax* | m/z | Halide Isotope | Biotransformation | Mouse† | Rat† | Dog‡ | Human† |
|---|---|---|---|---|---|---|---|---|---|
| PR-104 | 370 | 579 | Br | ++/++ | ++/++ | ++ | ++/− | ||
| PR-104A | 370 | 499 | Br | Hydrolysis | ++/++ | ++/++ | ++ | ++/+ | |
| M1 | PR-104G | 370 | 675 | Br | O-Glucuronidation | +/+ | +/− | ++ | ++/++ |
| M2 | 376 | 726 | GSH conjugate (Br displacement) | ++/+ | ++/+ | ++ | −/− | ||
| M3 | 376 | 540 | CySH conjugate (Br displacement) | ++/++ | ++/− | ++ | ++/++ | ||
| M4 | 376 | 716 | CySH conjugate/O-glucuronidation | −/− | −/− | − | −/+ | ||
| M5 | 376 | 582 | NAC conjugate (Br displacement) | +/− | +/− | − | −/− | ||
| M6 | 380 | 710 | Br | GSH conjugate (OMs displacement) | +/− | +/− | − | −/− | |
| M7 | 380 | 524 | Br | CySH conjugate (OMs displacement) | +/− | +/− | − | −/− | |
| M8 | PR-104S1 | 355 | 393 | Oxidative N-dealkylation | ++/++ | ++/++ | − | +/+ | |
| M9 | 355 | 569 | Oxidative N-dealkylation/O-glucuronidation | −/− | −/− | − | −/+ | ||
| M10 | PR-104S2 | 355 | 377 | Br | Oxidative N-dealkylation | +/− | +/− | − | −/− |
| M11 | 360 | 604 | Oxidative N-dealkylation/GSH conjugate | ++/− | +/− | − | −/− | ||
| M12 | 360 | 418 | Oxidative N-dealkylation/CySH conjugate | ++/++ | +/− | − | −/− | ||
| M13 | 360 | 460 | Oxidative N-dealkylation/NAC conjugation | −/++ | −/++ | − | −/− | ||
| M14 | 380 | 403 | Br | Intramolecular alkylation | +/− | +/− | − | − | |
| M15 | 365 | 297 | Intramolecular alkylation/oxidative N-dealkylation | −/+ | −/+ | − | − | ||
| M16 | 345 | 630 | Intramolecular alkylation/GSH conjugate | −/+ | − | − | − | ||
| M17 | 345 | 444 | Intramolecular alkylation/CySH conjugate | −/++ | −/+ | − | −/++ | ||
| M18 | 345 | 486 | Intramolecular alkylation/NAC conjugate | −/+ | −/+ | − | −/+ | ||
| M19 | 380 | 421 | Br | Hydrolysis | +/+ | +/+ | − | −/− | |
| M20 | 370 | 455 | Cl | Nucleophilic displacement | +/+ | +/+ | − | −/− | |
| M21 | 370 | 373 | Oxidation/hydrolysis | −/− | −/++ | − | −/− | ||
| M22 | PR-104H | 240 | 485 | Br | Nitroreduction | +/− | +/− | + | ++/− |
| M23 | PR-104M | 240 | 469 | Br | Nitroreduction | ++/− | ++/− | + | +/− |