Pliva-lachema A.s.

Vrije Universiteit Brussel

Interuniversitair Microelektronica Centrum (imec)

Plus Chemicals Sa

Petr Dobrovolny

Pierre Wambacq

Gerd Vandersteen

Yves Rolain

The method of manufacturing of 7-ethyl-10-hydroxycamptothecin of formula I characterized in that 7-ethyl-1,2,6,7-tetrahydrocampotothecin of formula IV is oxidized with an oxidizing agent selected from the group comprising iodosobenzene, an ester of iodosobenzene, sodium periodate, potassium periodate, potassium peroxodisulfate and ammonium peroxodisulfate, in a solvent formed by a saturated aliphatic monocarboxylic add containing 1 to 3 carbon atoms, and in the presence of water.

Method of manufacturing of 7-ethyl-10-hydroxycamptothecin

The method of manufacturing of 7-ethyl-10-hydroxycamptothecin of formula I characterized in that 7-ethyl-1,2,6,7-tetrahydrocampotothecin of formula IV is oxidized with an oxidizing agent selected from the group comprising iodosobenzene, an ester of iodosobenzene, sodium periodate, potassium periodate, potassium peroxodisulfate and ammonium peroxodisulfate, in a solvent formed by a saturated aliphatic monocarboxylic acid containing 1 to 3 carbon atoms, and in the presence of water.

The invention relates to the method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin by condensation of 7-ethyl-10-hydroxycamptothecin with 1-chlorocarbonyl-4-piperidinopiperidine hydrochloride in a polar aprotic solvent in the presence of 4-dimethylaminopyridine.

Method of manufacturing of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]- carbonyloxy- camptothecin

Simulation methods and simulators are presented which operate on a computer under software control. Said computer simulation methods and simulators are specially suited for simulating digital circuits and mixed analog digital circuits. The methods enable efficient simulation, meaning resulting in a fast simulation while still obtaining accurate results. With fast simulation is meant that the simulation can be completed in a short simulation time. Accurate means that the signals obtained or determined by simulation are good approximations of the signals that would be measured when the circuit, which representation is under simulation, is actually running in real world. Indeed the simulation methods and the related simulation apparatus or simulator exploits a representation of a circuit.

Growing community of inventors

Trebic, Czechia

Petr Dobrovolny