Remedy Against Narcotic Dependence
Theoretical Development, Synthesis and Experimental Investigation of Novel Narcotic Dependence Remedies
Tech Area / Field
- CHE-SYN/Basic and Synthetic Chemistry/Chemistry
3 Approved without Funding
State Research Institute of Organic Chemistry and Technology, Russia, Moscow
- INEOS (Organo-Element Compounds), Russia, Moscow\nFederal State Institution “National Research Centre on Addictions of Russian Federation Ministry of Public Health”, Russia, Moscow
- Universität Innsbruck / Institute of Pharmacy, Austria, Innsbruck\nWake Forest University, USA, Winston-Salem
Project summaryThe development of remedies for narcotic dependence is presently among most relevant medical and social problems.
Only two “pure” opiate antagonists – naloxon and naltrexon – having the polycyclic structure of morphine and differing only in substituents at the nitrogen atom (N-allyl in the case of naloxon, and N-cyclopropylmethyl 14-oxynordihydromorphinones in the case of naltrexon) are currently applied in medical practice. The chemical synthesis of the mentioned preparations is complicated and involves the use of natural raw materials (tebaine).
The methodology of the search for novel medical products is based on modern concept of the interaction of ligands with opiate receptors; implies the use of new efficient software and up-to-date equipment which allow successfully solving chemical and biological problems. The synthesis of most active chemical compounds – opiate antagonists will be performed in the series of substituted benzomorphanes and 4-arylpiperidines.
The fact that among benzomorphanes and 4-arylpiperidines there is known a number of compounds – highly efficient “pure” opiate antagonists – is a precondition for successful solution of the problem.
The choice of the mentioned classes of compounds is conditioned by consecutive simplification of the morphine structure and passage from rigid frame molecular structure to more labile 4-phenylpiperidine structure.
In the framework of the Project it is proposed to elaborate in-principal new schemes of chemical synthesis which would allow the preparation of not yet described benzomorphanes and 4-arylpiperidines with different pharmacophore substituents, to establish the structure of novel compounds using modern analytical approaches and to examine their biological activity.
Deepened search for opiate antagonists among substituted benzomorphanes and 4-phenylpiperidines is anticipated to result in the creation of more efficient medical preparations exhibiting minimum by-effect.
The main object of the Project is to develop efficient remedies for narcotic dependence, acute overdosage of barbiturates, alcohol and benzodiazepines, as well as in the therapy of different kinds of shocks.
The Project comprises 4 tasks
Task 1. To analyze the literature; to carry out computer studies of the properties of molecules – opiate receptor ligands for the purpose of establishing “molecular descriptor – affinity to receptor – agonistic/antagonistic properties of the ligand” relationships.
Task 2. To contemplate different schemes of synthesis of novel structures.
Task 3. To perform experimental elaboration of the synthesis schemes selected.
Task 4. To examine the biological activity of the novel compounds.
Practical result of the Project implementation will consist in synthesizing novel compounds of the series of substituted benzomorphanes and 4-arylpiperidines which will be subjected to preclinical trials for the purpose of their application as efficient remedies for narcotic dependence, overdosage of barbiturates, alcohol and benzodiazepine, as well as therapy of different kinds of shocks.
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