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 67551822, +371 67553233 Fax: +371 67550338 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
• Investigation   of biochemical mechanisms of action of new medicines:
• Immunochemistry.

Inventor of anti-ischemic drug Mildronate and anti-cancer immunostimulator Leakadine, Mildronate GX, new Mildronate-containing pharmaceutical compositions, as well as drug candidates under clinical trials Belinostat and Neramexane.

More than 650 papers published, including about 300 patents.

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
• Member of European Academy of Sciences and Arts, 2012
• 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
• The Grand Medal of the Latvian Academy of Sciences for creation of new competitive medicinal preparations and strenghtening of innovative orientation in the Latvian Institute of Organic Synthesis, 2009

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
• Editor-in-Chief, journal "Chemistry of Heterocyclic Compounds"(Rus), since 2010
• Head of Library Council, Latvian Academy of Sciences,  1998 - 2010
• Head of Promotion Council in Pharmacie, Riga Stradins University, since 2007
• Head of Board, Latvian Inovators Union, since 2009
• Chairman of Board of the Latvian Fund Taiho, since 2009
• Head of Association of Latvian State Research Institutes, 2009
• Head of the Union of Latvian Scientists
• Chairman of Board,  Association « Baltic Institute of Research, Technology and Innovation » (BIRTI), 2013
• Member of Advisory Convent , Faculty of Material Sciences and Applied Chemistry, Riga Technical University, since 2000
• Member of Advisory Convent , Riga Stradins University, since 2008
• Chairman of Advisory Convent , Liepaja University, 2013

Courses

• Medicinal Chemistry, Riga Technical University, since 1996

Recent/Representative Publications

Total number of publications - > 650,  including about 300 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.
• Strumf B., Hermane E., Kalvinsh I., Trapencieris P. Unnatural amino acids. 3. Aziridinyl ketones from esters and amides of aziridine-2-carboxylic acids. - Chem. Heterocycl. Comp. (Engl.Ed.), 2007, vol. 43, N 2, pp. 169-174.
• Habarova O., Andrianov V., Kalvinsh I., Lundstedt T., Boman A., Trapencieris P. Synthesis, structure and isomerization of t-butylpyrrole aldehydes / Template for SYNLETT and SYNTHESIS, ThiemeStuttgart, New York, 2007-03-01, P. 1-2.
• Muceniece R., Zvejniece L., Vilskersts R., Liepinsh E., Baumane L., Kalvinsh I., Wikberg J.E., Dambrova M. Functional evaluation of THIQ, a melanocortin 4 receptor agonists, in models of food intake and inflammation . -  Basic&Clinical Pharmacology and Toxicology, 2007, vol.101. N 6, pp.393-464.
• Pupure J., Fernandes M.A., Santos M.S., Moreno A.J., Kalvinsh I., Klusa V., Oliveira C.R. Mitohondria as the target for mildronate's protective effects inazidothymidine (AZT)-induced toxicity of isolated rat liver mitohondria. - Cell Biochem. Funct., 2008, vol. 26, N 5, pp. 620-631.
• Dambrova M., Zvejniece L., Liepinsh E., Cirule H., Zharkova O., Veinberg G., Kalvinsh I. Comparative pharmacological activity of optical isomers of phenibut. - Eur. J. Pharmacol., 2008, vol. 583, N 1, pp.128-134.
• Dambrova M., Cirule H., Svalbe B., Zvejniece L., Pugovichs O., Zorenko T., Kalvinsh I., Liepinsh E., Belozertseva I. Effect of inhibiting carnitine biosynthesis on male rat sexual performance. - Physiol. Behav., 2008, vol. 95,  N 3, pp.341-347.
• E. Liepinsh, R. Vilskersts, L. Zvejniece, B. Svalbe, E. Skapare, J. Kuka; H. Cirule, S. Grinberga, I. Kalvinsh, M. Dambrova. Protective effects of mildronate in an experimental model of type 2 diabetes in Goto-Kakizaki rats - Brit. J. Pharmacol. 2009, 157(8), 1549-1556.
• V. Andrianov, V. Gailite, D. Lola, E. Loza, V. Semenikhina, I. Kalvinsh, P. Finn, K. Dumong Petersen, J.W.A. Ritchie, N. Khan, A. Tumber, L.S. Collins., S.M. Vadlamudi, F. Bjorkling, M. Sehested. Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR - European Journal of Medicinal Chemistry, 2009, Vol.44, P. 1067-1085.
• M.K. Christensen, K.D. Erichsen, Ch. Trojel-Hansen, J. Tjornelund, S.J. Nielsen, K. Frydenvang, T.N. Johansen, B. Nielsen, M. Sehested, P.B. Jensen, M. Ikaunieks, A. Zaichenko, E. Loza, I. Kalvinsh, F. Bjoerkling. Synthesis and Antitumor Effect in Vitro and in Vivo of Substituted 1,3-Dihydroindole-2-ones - J.Med.Chem. 2010, Okt 14;53(19):7140-7145.
• L. Zvejniece, B. Svalbe, M. Makrecka, E. Liepinsh, I. Kalvinsh, M. Dambrova. Mildronate exerts acute anticonvulsant and antihypnotic efects - Behavioural Pharmacology 2010, 21(5&6), 548-555.
• E. Rostoka, L.Baumane, S. Isajevs, A. Line, M. Dzintare, D.Svirina, J. Sharipova, K.Silina, I.Kalvinsh, N. Sjakste. Effects of Kaemferol and Miricitin on inducible nitric oxide synthase expression and nitric oxide production in rats. - Basic&Clinical Pharmacology and Toxicology, 2010, vol.106, N 6, pp.461-466.
• J. Kuka, R. Vilskersts, H. Cirule, M. Makrecka, O. Pugovics, I. Kalvinsh, M. Dambrova, E. Liepinsh. The Cardioprotective Effect of Mildronate is Diminished after Co-Treatment with L-Carnitine. - J. Cardiovasc. Pharmacol. Ther. 2012, 17(2), 215-222.
• M. Christensen, K. Erichsen, U. Olesen, J. Tjørnelund, P. Fristrup, A. Thougaard, S. Nielsen, M. Sehested, P. Jensen, E. Loza, I. Kalvinsh, A.Garten, W. Kiess, F. Bjorkling. "Nicotinamide phosphoribosyltransferase inhibitors, design, preparation and Structure-Activity Relatioship" - Journal of Medicinal Chemistry 2013, 56, 9071-9088.

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 - 2008).
• I.Kalvins (Head of Project). Synthesis of functionalized indoles in the development of novel nonsteroidal anti-inflammatory drugs. Latvian Council of Science (2005 - 2008).
• I.Kalvins (Head of Project). Synthetic analogs of native inhibitors of Zn containing metalloproteases. Latvian Council of Science (2005 - 2008).
• I.Kalvins (Head of Project). Original medicines and biocorrectors: design, transport forms and mechanisms of action. Latvian State Research Program (2005 - 2009).
• I.Kalvins (Head of Project). Network of support for development of SMEs in high-tech industries. PHARE 2003 ESK Project (2005 - 2006).
• I.Kalvins (Head of Project). Research on sustainable development of Latvian chemical and pharmaceutical industries (2006 - 2008).
• Latvian State Research Program "A new prevention, therapy, diagnostic tools and techniques, the development of biomedical technologies to improve public health" project groups „Cardiovascular and metabolic disease" co-manager (2010 - 2013)
• Market-oriented research project (doctoral thesis work ) „Pharmacological regulation of glucose transporters and NO production in animals with experimental diabetes" leader (2012 - 2013)
• Coordinator of EU 7th Framework Programme project  "Strengthening the research and innovation capacities of the Latvian Institute of Organic Synthesis, the leading Baltic regional centre for drug discovery" (InnovaBalt, Grant Agreement Nr.: 316149). (2013 -    )

   

Last update 21.02.2014