The evaluation of new drugs with new mechanisms of action to treat pathological pain, especially rheumatoid and osteoarthritis, neuropathic pain and cancer pain is one of the most intense areas of development of new analgesics today. Different combinations of opioids and COX-2 inhibitors could be of interest for treatment of severe acute and chronic pain. This data confirms, that the idea of unifying of elements of opioids and NSAID's in one molecule could be both harmonious and efficacous. Noncondensed biheterocyclic piperidine derivatives are synthesized starting from compounds, which strangely are not described in literature – from 1-(2-phenethyl)-4-hydrazinopiperidines which were obtained starting from corresponding 1-(2-phenethyl)-piperidine-4-one. 1-(2-Phenethyl)-piperidines-4-one was condensed with acetyl- or benzoylhydrazine, obtained hydrazone was be reduced to corresponding hydrazide which after hydrolysis gave the expected 1-(2-phenethyl)-4-hydrazinopiperidine. The same scheme was implemented to obtain 1-benzyl- and 1-methylhydrazinopiperidines. The obtained hydrazines have been used in heterocyclization reactions with a variety of 1,3- dicarbonyl compounds for the synthesis of targeted derivatives. An interesting observation has been made during this work. Simultaneously with “normal” condensation with formation of pyrazolones-5 an “abnormal” cyclization with formation of 5-ethoxypyrazoles takes place.

This heterocyclization reactions contain many possibilities for creation of a wide diversity of noncondensed pyrazolopiperidines, which are being evaluated by biological screening.

Supported by grants from the US Public Health Service, National Institute of Drug Abuse