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.

1,2-Dihydro-3,1-benzoxazin-4-one and 4H-1,2-dihydro-pyrido-[2,3-d]- [1,3]-oxazin-4-one derivatives as potential prodrugs. Part III: Permeability through excised human skin in vitro.

The percutaneous permeation characteristics of 6 potential prodrugs 2-7 in comparison with their parent drug mefenamic acid (1) in vitro using excised human skin were studied. The results show that all potential prodrugs tested were at least 2.0 times as effective as mefenamic acid; compounds 2 and 7 permeated almost 5 times as quickly as mefenamic acid through excised human skin. The relations between the permeation behaviour, the RM values and the melting points were interpreted.

[5-Acyloxydioxolanones as prodrugs of non-steroidal anti-inflammatory agents. 1]. / 5-Acyloxydioxolanone als Prodrugs nichtsteroidaler Antirheumatika, 1. Mitt.

The derivatissation of various acidic non-steroidal anti-inflammatory drugs to 5-acyloxy-1,3-dioxolan-4-ones is described. The synthesis of the title compounds is achieved by reaction of 5-bromo-1,3-dioxolan-4-ones with the salts of the carbonic acids.