Table 1: Half-lives (t1/2) of triazene prodrugs (17a-17g) in PBS buffer, 80% human plasma and in the presence of tyrosinase (100 U/mL) at 37C.

 

Compound

R

R

t1/2

7.4 buffer* (h)

80% human plasma* (h)

Tyrosinase** (min)

17a

CH3CO

H

a

b

13.0

17b

CO2Et

H

a

71.5

12.9

17c

CN

H

a

b

11.8

17d

Me

H

364

b

18.2

17e

CH3CO

OH

15.1

9.30

9.9

17f

CO2Et

OH

20.8

14.7

6.1

17g

Me

OH

b

5.66

8.4

 

*substrate concentration 10-5 M; ** substrate concentration 5 x 10-5 M.

aStable for 15 days; bStable for 2 days.