Mitochondria and their free radicals play a prominent role in the development of heart failure (Nat. Rev. Cardiol. 2015, 12, 6-8), however, there is no medicine that can protect patients through mitochondrium. A lot of scientific work emphasises the role of mitochondrium in the process of cell death caused by oxidative stress in the cardiovascular system (PubMed approx. 1500 publications), and the most prestigious journals also consider the role of mitochondrium in the development of heart failure and enlargement (Nat Med). 2016, 22, 175-82;Nature2016, 529, 216-20). Participants in the proposal with 50 publications (38 of which. Q1) in the above area, most of which were made in cooperation between groups. On the other hand, the severe negative effect of mitochondrium damage in well-known sepsis/septic shock, such as mitochondrial “damage-associated molecular patterns” (DAPM(s)), which contribute significantly to death. However, there is no good protection against the above processes. Preliminary results show that inhibition of mitochondrial permeability transition (MPT) cyclofiline D in exterminated animals significantly protects against mortality and inhibits many inflammation-related processes. Thus, the development of small molecules that inhibit these processes can be an effective way of protecting against septic shock. Indirectly, the inhibition of the PARP-1 enzyme and our previous work with mitochondrial protection show this through modification of signal transmission processes (J. Biol. Chem.2005, 280, 35767-75; It’s Free Radic. It’s Biol. Med.2010, 49, 1978-88. PARP-1/2, the molecules that activate mitochondrium fusion and MPT inhibitors are being developed in the present tender. These have a protective effect on our preliminary results, suggesting that our commitments will be successfully completed. From chemical synthesis (including analytical, structure testing methods), recombinant protein production, in vitro assays, cell culture model systems to complete mRNA profile sequencing. We aim to detect the biological/mitochondrial effects of our new compounds through ‘Pathway’ analysis and animal testing. For the most potent compounds, animal evidence is also used to show potential therapeutic areas of action. The interdisciplinary team included organic chemists, analysts, biochemists — with significant drug development experience — the team involved in the production of recombinant proteins, the team dealing with the genetic background of diseases and researchers from the Cardiological Clinic with great animal testing experience. This broad scientific background ensures that the tasks undertaken are carried out at the highest possible level. On the other hand, we also examine the mutations of our target targets in the diseases we study (inflammatory and cardiovascular diseases) in order to demonstrate the importance of the above target molecules in the development of diseases from the human side. With the close cooperation of the above research groups within the framework of this project, a multidisciplinary strategic workshop will be created, which can be successfully included in the national and international applications of the following years, and can become the defining centre of the Hungarian scientific life. Researchers from the Institute of Chemistry of PTE TTK, the Institute of Organic and Pharmaceutical Chemistry of ÁOK and the Institute of Chemistry of the University of Pannonia basically wish to base successful biochemistry-medical research with two approaches. A) We realise the high-efficiency synthesis of known families of compounds by ‘blending’ conventional and modern homogeneous methods of analytic chemistry. B) We plan the synthesis of new target compounds with the help of high-efficiency, transition metal catalysed synthetic processes that have been unavailable by using the existing methods. A1) Some polycyclic compounds not yet tested but already available (pyrrolo(3,4-b)benzo(1,5)thiazepine, pirrolo(3,4-b)quinoline, benzimidazo(2,1-b)pyrrolo(3,4-e)(1,3(thiazin, pirrolo)3,4-b(pyridine, pyrrolo[3‘,4’:3,4]pyrido[1,2-a]quinazoline skeletons) and synthesis by new palladium catalysed homogenic reactions. A2) Further selective modification of 4-carboxamidobenzidazole derivatives is carried out and new methods are being developed for the direct development of the amido group. The introduction of flow chemical methods (e.g. catalytic hydrogenation, cross-connection reactions) would be helpful in the synthesis of this family of compounds. A3) We implement the integration of new functional groups (fluoro, difluoromethyl, trifluoromethyl) into the aromatic ring(s) by means of homogeneous catalysis. A4) Hybrids (conjugates) of compounds with known effect (e.g. mexiletin) formed with nitroxides are produced using the above mentioned switching methods. A5) Clots on palladium catalysed reactions