1,2-Dihydro-3,1-benzoxazin-4-one and 4-H-1,2-dihydro-pyrido-[2,3-d]-[1,3]-oxazin-4-one derivatives as potential prodrugs. Part II: Hydrolysis.
The kinetics of the spontaneous hydrolysis of the potential prodrugs 1a-1f, 2a-2g, and 3a-3e in methanol-buffer mixtures (3:7) at various pH-values was studied and a simple analytical uv-spectroscopic method was developed. The results show that most of the new potential prodrugs were very quickly reconverted to their parent drugs under these conditions. All of the potential prodrugs are very sensitive between pH 4.0 and 8.0, with half lives less than 50 min at 20 degrees C, except for compounds 1f, 2f, and 3d. Compounds 1b and 1c are so sensitive that they reconverted to their parent drug during the mixing of the stock solution and the buffer-methanol-mixture.
Schwenker
G
G
Pharmazeutisch-chemisches Institut, Universität Heidelberg.
Chen
J B
JB
D006868:Hydrolysis; D007700:Kinetics; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
D010078:Oxazines; D011355:Prodrugs; D011725:Pyridines