Ivars KALVINSH

Professor Ivars KALVINS Director , Head of the Department of Medicinal Chemistry Latvian Institute of Organic Synthesis, Aizkraukles iela 21, Riga, LV-1006 Latvia Phone: +371 551822, +371 7553233 Fax: +371 550338 E-mail: [email protected]

Born: June 2, 1947, Riga, Latvia.

Interests:

• New physiologically active substances for CNS, cardiovascular and malignant diseases
• Chemistry of heterocyclic compounds and amino acid analogues
• Action of new medicines: biochemical mechanisms
• Immunochemistry.

Originator of antiischaemic drug mildronate and anticancer immunostimulator leakadine.

Languages: Latvian, English, German, and Russian

Education

• University of Latvia (Faculty of Chemistry), 1969
• Dr. chem. (Candidate of Science in former USSR, Ph.D. in Western countries), Latvian Academy of Sciences, Riga, 1976
  • Thesis: "Methods of Synthesis of Functionalized 1-H and 1-NH2-Aziridines".
• Dr. habil. chem. (Doctor of Science in former USSR), Leningrad (Saint-Peterburg) University, Russia, 1988
  • Thesis "Synthesis and Investigation of Aziridin-, Thiiran- Hydrazinocarboxylic Acids as Physiologically Active Analogues of Natural Amino Acids".

Experience

Latvian Institute of Organic Synthesis:

• Engineer, 1969 -1970
• Senior Engineer, 1970 - 1971
• Head of Research group, 1971- 1985
• Head of Laboratory of Medicinal Chemistry, since 1986
• Vice-director (for science), 1987-2004
• Director, since 2004
• Head, Department of Medicinal Chemistry, since 1992
• Professor (Chemistry), since 1994

Abroad:

• Postdoctoral studies, Institute of Organic Chemistry, University of Munich (BRD), 1979-1980
• Institute of Organic Chemistry, University Goettingen (BRD), 1994

Honours and Awards

• Corresponding Member, Latvian Academy of Sciences, 1994
• Full Member, Latvian Academy of Sciences, 1994
• Honorary Academician, Ukrainian Medical Stomatological Academy, 2006
• Latvian SSR State Prize for Science and Technology,  1988
• D.H. Grindel Medal for merits in the synthesis and investigations of drugs (company " Grindex", Latvia), 1996
• S.Hillers Medal for contribution to the development of medicinal preparations (Latvian Institute of Organic Synthesis), 1997
• Oswald Schmiedeberg Medal (Tartu University, Tartu, Estonia), 2001
• Gustav Vanags' Prize of  Latvian Academy of Sciences for series of publications "Synthesis and investigation of bioactive low-molecular NO-inductors and donors", 2003
• Paul Walden's Medal for outstanding contribution to the development of medicinal chemistry in Latvia and series of works devoted to the development of a new approach in the creation of medicaments", 2003
• St.George Medal awarded by International rating Academy "Golden Fortune" in collaboration with the ortodox church of the Ukraine for the succesful co-operation between Latvia and Ukraine, 2004
• The Solomons Hillers Prize  for outstanding achievments in biomedicine and the design of new medications (a cycle of investigations "Synthesis, development and introduction into practice of a cycloprotector with an original mechanism of action Mildronate) , 2005 
• Certificate and Golden Medal  of World Intellectual Property Organisation (WIPO) for long-term and highly productive work as inventor, 2005
• The Three Stars Order of the Republic of Latvia, 2006
• The Award of the Cabinet of Ministers, Republic of Latvia, 2006

Professional Activities and Memberships

• President , Latvian Chemical Society, 1994 - 2000
• Member of Council, Latvian Agency of Medicines, 1994 - 2002
• Member of Senate, Latvian Academy of Sciences, since 1994
• Member of Habilitation and Promotion Council, Latvian Institute of Organic Synthesis, 1991 - 1998
• Member, Editorial Board for Latvian Journal of Chemistry, since 1996
• Member, Editorial Board for Proceedings of the Estonian Academy of Sciences, since 1998
• Member, Editorial Board for Molecules, since 2003
• Head of Library Council, Latvian Academy of Sciences, since 1998
• Member of Advisory Convent , Faculty of Material Sciences and Applied Chemistry, Riga Technical University, since 2000
• Member of Steering Committee, company "Olainpharm", since 2003
• Member of American Chemical Society 

Courses

• Medicinal Chemistry, Riga Technical University, since 1996

Recent/Representative Publications

Total number of publications - > 590,  including 277 patents.

• I.Kalvinsh, K.H. Metten, R.Brückner. A novel pathway to alkenyl(trifluoro methanesulfonates). Application to the conversion of sugar lactones into versatile chirons. - Heterocycles, 1995, vol. 40, N 2, pp. 939-952.
• R.Vegners, I.Shestakova, I.Kalvinsh, R.M.Ezzell, P.A.Janmey. Use of a gel-forming dipeptide derivative as a carrier for antigen presentation. - J.Pept. Sci., 1995, vol. 1, pp. 371-378
• L.Fisera, R.Huisgen, I.Kalvinsh, E.Langhals, X.Li, et.al. New thione chemistry. - Pure Appl. Chem., 1996, vol. 68, N 4, pp. 789-798.
• P.Trapencieris, I.Kalvins, E.Kupce, E.Lukevics. Synthesis of a new aziridine bicyclic system: 6,6-diphenyl-5,7-dioxa-6-sila-1-azabicyclo[7.1.0]decane. - J. Chem. Res., 1996, pp. 142-143.
• A.Jirgensons, I.Kums, V.Kauss, I.Kalvins. A convenient reagent for N-hydroxylation. - Synth. Commun., 1997, vol. 27, N 2, pp. 315-322.
• R.Huisgen, I.Kalwinsh, J.R.Moran, H. Nöth, J.Rapp. An unorthodox pathway to the 1,2-dithiin system. - Liebigs Ann./Recueil, 1997, pp. 1677-1684.
• O.Pugovics, V.Kauss, I.Kalvins, M.R.Gold. The synthesis of (3,5-di-tert-butyl-4-hydroxyphenyl)methyl-(3-pyridylalkyl)ethers via 1-(3,5-di-tert-butyl-4-hydroxyphenyl)methyl pyridinium salts. - Synth.Commun., 1998, vol. 28, N 12, pp.2227-2236.
• G.Veinberg, I.Shestakova, N.Grigan, D.Musel, I.Kanepe, I.Domrachova, I.Grigoryeva, O.Zharkova, I.Turovskis, I.Kalvinsh, A.Strakovs, E.Lukevics. New biological properties of tert-butyl cepalosporanate sulfones. - Eur. J. Med. Chem., 1998, vol. 33, N 10, pp. 755-762.
• R.Huisgen, I.Kalvinsch, X.Li, G.Mloston. 1,3-Dipolar cycloadditions, 116: The formation of 1,3-dithiolanes from aromatic thioketones and diazomethane. - The mechanism of the Schonberg reaction. - Eur. J. Org. Chem., 2000, pp. 1685-1694.
• A.Jirgensons, V.Kauss, I.Kalvinsh, M.R.Gold, W.Danysz, C.G.Parsons, G.Quack. Synthesis and structure-affinity relationshiops of 1,3,5- alkylsubstituted cyclohexylamines binding at NMDA receptor PCP site. - Eur. J. Med. Chem., 2000, vol. 35, pp. 1-11.
• I.Starchenkov, P.Trapencieris, V.Kauss, G.Jas, I.Kalvinsh. A convenient synthesis of 5ß-cholestan-26-oic and 5ß-cholestan-26,27-dioic acids. - Steroids, 2000, vol.65, pp. 143-147.
• G.Veinberg, M.Vorona, I.Shestakova, I.Kanepe, O.Zharkova, R.Mezapuke, I.Turovskis, I.Kalvinsh, E.Lukevics. Synthesis and antitumor activity of selected 7-alkylidene substituted cephems - Bioorg. Med. Chem., 2000, vol. 8, N 5, pp. 1033-1040.
• M.Dambrova, L.Baumane, A.Kiuru, I.Kalvinsh, J.E.S.Wikberg. N-Hydroxyguanidine compound 1-(3,4-dimethoxy-2-chlorobenzylideneamino)-3-hydroxyguanidine iInhibits the xantine oxidase mediated generation of superoxide radical . - Arch. Biochem. Biophys, 2000, vol. 377, N 1, pp. 101-108.
• A.Lorenzen, Ch.Stanek, H.Lang , V.Andrianov, I. Kalvinsh , U.Schwabe. Characterization of a G protein-coupled receptor for nicotinic acid. - Molecular Pharmacology, 2001,vol. 59, N 2, pp. 349-357.
• M.Dambrova, E.Liepinsh, I.Kalvinsh. Mildronate: cardioprotective action through carnitine-lowering effect. - Trends Cardiovasc. Med., 2002, vol. 12, N 6, pp. 275-279.
• M.Dambrova, O. Kirjanova, L. Baumane, E. Liepinsh, L. Zvejniece, R.Muceniece, I.Kalvinsh, J.E.S.Wikberg. EPR investigation of /in vivo/ inhibitory effect of guanidine compounds on Nitric Oxide production in rat tissues. - Journal of Physiology and Pharmacology, 2003, vol 54, N 3, pp. 339-347.
• M.Dambrova,  E.Liepinsh, O.Kirjanova, O. Gorshkova , V.Kozlowski, S.Chlopicki ,  S.Uhlen, I.Liepina , R.Petrovska , I.Kalvinsh . The  methylester of gamma- butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation . - N-S Arch. Pharmacol., 2003, vol. 11, N10, pp.
• P. Prusi, M.Dambrova,  V.Andrianov, E.Rozhkov , V.Semenikhina , I.Piskunova , E.Ongwae,  T.Lunstedt, I.Kalvinsh, J.E.S.Wikberg.  Synthesis and quantitative structure-activity relationship of hydrazones of N-amino-N’-hydroxyguanidine as electron acceptors for xantine oxidase. -  J.Med.Chem.,   2004, vol. 47, pp.  3105-3110.
• D.Katkevica, P.Trapencieris , A.Boman, I.Kalvins , T.Lundstedt. The Nenitzescu reaction: an initial screening of experimental conditions for improvement of the yield of a model reaction. -  J.Chemometrics, 2004, vol. 18, pp.183-187. (www.interscience.wiley.com. DOI: 10.1002/cem.863).
• P.W.Finn, M.Bandara, Ch.Butcher, A.Finn, R.Hollinshead,N.Khan, N.Law, S.Murthy, R.Romero, C.Watkins, V.Andrianov, R.M.Bokaldere, K.Dikovska, V.Gailite, E.Loza, I.Piskunova, I.Stachenkov, M.Vorona,  I.Kalvinsh.  Novel sulfonamide derivatives as inhibitors of histone deacetylase. - Helvetica Chimica Acta, 2005, vol. 88, pp. 1630-1643.
• N.Sjakste, A.Gutcaits , I.Kalvinsh. Mildronate: an antiischemic drug for neurological indications. - CNS Drug Reviews, 2005, vol. 11, N 2, pp.151-168.
• Sesti C., Simkhovich B.Z., Kalvinsh I., Kloner R.A. Mildronate, a Novel FAtty Acid Oxidation Inhibitor and Antoanginal Agent, Reduces Myocardial Infarct Size Without Affecting Hemodynamics. - J.Cardiovasc.Pharmacol., 2006, vol. 47, N 3,  pp. 493-499.
• Sjakste N., Kalvinsh I. Mildronate: an Antiischemic Drug with Multiple Indications. - Pharmacologyonline, 2006,  1: 1-18  .
• Kalvinsh I., Gutcaits A., Bagdoniene L., Labeikyte D., Trapencieris P., Sjakste N. Hypothetical gamma-butyrobetaine esterase-dependent signal transduction system: possible link to mildronate. -  Medical Hypotheses and Research, 2006, vol.3, N 3, pp.  803-812. (also available online at www.journal-MHR.com.)
• Chipens G., Ievina N., Kalvinsh I.   Exons and introns of globin genes originated from repetitive nucleic acids. - Latv. J. Chem.,  2006, N 3, pp. 256-262.

Research Projects

• I.Kalvins (Head of Project). Synthesis of hypolipidemic agents and parcial agonists and antagonists of NMDA receptors for the evaluation of new medicines. Latvian Council of Science (1993-1996).
• I.Kalvins (Head of Project). Synthesis and investigation of carbocyclic amines. Latvian Council of Science (1997-2000).
• I.Kalvins (Head of the Latvian Part of Project). Baltic cancer cell collection. European Community (1994-1996).
• I.Kalvins (Head of the Latvian Part of Project). The novel pathways to synthesis of mitosenes. NATO Communication (1994-1997).
• I.Kalvins (Head of Project). Synthesis of polyfunctional alkoxyphenyldiazene oxides. TAIHO Foundation (1995-1996).
• I.Kalvins (Head of the Latvian Part of Project). Development of rational drug design methods for G-protein coupled receptors. Royal Academy of Sweden (1994-1997).
• I.Kalvins (Head of Project). Synthesis of steric hindered substituted cycloalkylamines for nicotinic acethylcholine pharmacophore model investigations. Latvian Council of Science (2001 - 2004).
• I.Kalvins (Head of Project). Stereoselective synthesis of aryl-, alkynyl- and alkenyl- cyclohexanamines and their application. Latvian Council of Science (2005 - ).
• I.Kalvins (Head of Project). Synthesis of functionalized indoles in the development of novel nonsteroidal anti-inflammatory drugs. Latvian Council of Science (2005 - ).
• I.Kalvins (Head of Project).Synthetic analogs of native inhibitors of Zn containing metalloproteases. Latvian Council of Science (2005 - ).
• I.Kalvins (Head of Project). Original medicines and biocorrectors: design, transport forms and mechanisms of action. Latvian State Research Program (2005 - ).
• I.Kalvins (Head of Project). Network of support for development of SMEs in high-tech industries. PHARE 2003 ESK Project (2005 - ).
• I.Kalvins (Head of Project). Research on sustainable development of Latvian chemical and pharmaceutical industries (2006 - ).

Last update 07.02.2007