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Cardiac and Antitumor Drugs

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Synthesis and study of properties of cardiac and antitumor drugs using the methods developed at producing weapons of mass destruction.

Tech Area / Field

  • MED-DRG/Drug Discovery/Medicine
  • BIO-CHM/Biochemistry/Biotechnology

Status
8 Project completed

Registration date
02.12.1993

Completion date
22.11.1998

Senior Project Manager
Kondratenkov Yu B

Leading Institute
Institute of Problems of Chemical Physics, Russia, Moscow reg., Chernogolovka

Collaborators

  • Medical College, USA, New York\nDeutsches Krebsforschungs Zentrum Heidelberg Stiftungsvorstand, Germany, Heidelberg

Project summary

The object of the work is the formulation of novel cardiac and antitumor drugs together with the development of the primary technology for their preparation that is applicable to the production conditions of medical preparations or the production conversion of ex plosives and propellants.

For this work the scientific potential, accumulated at the Institute of Chemical Physics in Chernogolovka, RAS, at the development of high explosives and propellants for ballistic missiles has been used.

This potential includes:

- the novels original methods for synthesizing energetic substances of various classes, containing in carbo-, heterochains or cycles various functions and substituents together with nitro- and nitrate groups;

- the methods for preparing free radicals, in particular nitroxyl ones and their application as the "labels" and "probes" to the production of polymeric binders for solid mixed propellants;

- the methods for estimating stability of components and mixed systems under the operating conditions of ammunition and the items as well as the methods for predicting the assured storage;

- the current principles and the novel ideology for developing the technological production processes for highly qualitative components with the purity required in accordance with the required conditions of ecology and safety;

- the scientific highly skilled, staff who possesses the most current techniques in the world science with large theoretical knowledge and experience in the experimental work.

From the investigations, carried out previously at the Institute of Chemical Physics in Chernogolovka, the opportunity of creating the drugs with high cardiac and anti tumor activity and lower tonicity has been found.

The Project involves the following Marks:

1) in the field of synthesis:

- the preparation. of nitrates of polyatomic and polyfunctional alcohols, whose molecule's include the fragments of known physiologically active compounds – vitamins, amino acids derivative's of phosphoric acid;
- the preparation of novel aminonitroxyl platinum complexes (including mixed-ligands), which are as effective as cisplatin, but less toxic;


2) in the field of properties:

- the study of stability of inpidual compounds and mined systems obtained, containing these compounds, by kinetic methods;
- the primary screening of the novel compounds and the estimation of the most promising ones;


3) in the field of technology:

- the study of explosion hazard of the single stages and operations in the technology of the nitration process and the development of explosion proof technology for preparing novel and perspective compounds, which will be included into the large scale production for preclinic and clinic trials.


Expected Results:

1. The development of novel physiologically active substances containing in a molecule the nitrate groups which may serve as for the drugs. These drugs are more effective in treating heart failure and angina pectiris than available ones but have less toxicity and other non-desirable effects.

2. The development of novel compounds from the group of platinum-nitroxyl complexes - cisplatin analogs - possessing high antitumor activity with markedly less general and specific toxicity.

3. The most promising platinum-nitroxyl complexes may be suggested to the Pharmacological Committee of the Ministry of Health to receive an authorization for the phase I clinical trials depending on the results of preclinical testing. The clinical trials usually are conducted at the Oncological Scientific Center of RAMS (Moscow), the Prof. N.N.Petrov Institute of Oncology of the Ministry of Health (Sankt-Petersburg) and other institutions.

4. The development of technology for preparing cardiac active nitrate substances, that is explosion proof in the stage of introducing the nitrate group into a molecule by various nitrating system's.

5. The development of the accelerated aging method for the quick determination of stability and assured storage of the inpidual medical substances and the drugs on their basis.


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