Dr. Ron Bihovsky
Key Synthesis LLC
804 Primrose Lane
Wynnewood, PA 19096
Phone: (610) 357-3281
E-mail: RBihovsky@KeySynthesis.com
Web Page: www.KeySynthesis.com

Specialties:

Dr. Ron Bihovsky is the founder of Key Synthesis LLC, an organic chemistry laboratory located in the Philadelphia, Pennsylvania metropolitan area. Key Synthesis is fully equipped to conduct custom organic synthesis, contract medicinal chemistry research and process research for the pharmaceutical and biotechnology industries. Dr. Bihovsky performs chemical research and consults for the pharmaceutical and biotechnology industries. He has served as a chemistry consultant and expert witness for intellectual property law firms and has testified at high-profile pharmaceutical patent litigation trials.

Services and Expertise:

Dr. Ron Bihovsky, an organic, pharmaceutical and medicinal chemist, has 25 years of experience in the pharmaceutical industry, where he worked on numerous classes of small molecules ranging from heterocycles to peptide mimetics. Before working in industry, Dr. Bihovsky conducted research on total synthesis of natural products as a professor of organic chemistry at SUNY Stony Brook. He has taught graduate courses in medicinal chemistry and organic synthesis. He has authored 50 publications and is an inventor on 15 US patents and numerous international patents. He serves as chairman of Chemical Consultants Network.

Dr. Bihovsky earned a Ph.D. in organic chemistry from the University of California, Berkeley, and was an NIH postdoctoral fellow at the University of Wisconsin, Madison.


Publications:
(Note: Ron Bihovsky previously worked and published under the names Ron Bates and Hans A. Bates)

M. Tao,* C. H. Park, R. Bihovsky, G. J. Wells, J. Husten, M. A. Ator, R. L. Hudkins, "Synthesis and Structure-Activity Relationships of Novel Poly(ADP-ribose)Polymerase-1 Inhibitors." Bioorg. Med. Chem. Lett. 16, 938-942 (2006).


G. W. Wells,* R. Bihovsky, R. L. Hudkins, M. A. Ator, and J. Husten, "Synthesis and Structure-Activity Relationships of Novel Pyrrolocarbazole Lactam Analogs as Potent and Cell-Permeable Inhibitors of Poly(ADP-ribose)polymerase-1 (PARP-1)."  Bioorg. Med. Chem. Lett. 16, 1151-1155 (2006)


R. Bihovsky, M. Tao, J. P. Mallamo, and G. Wells,* "1,2-Benzothiazine 1,1-Dioxide α-Ketoamide Analogues as Potent Calpain I Inhibitors."  Bioorg. Med. Chem. Lett. 14, 1035-1038 (2004). 


S. J. Miknyoczki, S. Jones-Bolin, S. Pritchard, K. Hunter, H. Zhao, W. Wan, M. Ator, R. Bihovsky, R. Hudkins, S. Chatterjee, A. Klein-Szanto, C. Dionne, and B. Ruggeri,  "Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly(ADP-ribose) polymerase inhibitor."  Mol. Cancer Ther. 2, 371-382 (2003).


G. J. Wells, M. Tao, K. A. Josef, and R. Bihovsky,* "1,2-Benzothiazine 1,1-dioxide P2- P3 Peptide Mimetic Aldehyde Calpain I Inhibitors." J. Med. Chem. 44, 3488-3503 (2001).


K. A. Josef,* F. W. Kauer, and R. Bihovsky, "Potent a-Ketohydroxamate Inhibitors of Recombinant Human Calpain I." Bioorg. Med. Chem. Lett. 11, 2615-2617 (2001). 


S. Chatterjee,* D. Dunn, M. Tao, G. Wells, Z.-Q. Gu, R. Bihovsky, M. A. Ator, R. Siman, and J. P. Mallamo, "P2-Achiral, P'-Extended a-Ketoamide Inhibitors of Calpain." Bioorg. Med. Chem. Lett. 9, 2371-2374 (1999).


G. J. Wells* and R. Bihovsky, "Calpain Inhibitors as Potential Treatment for Stroke and Other Neurodegenerative Diseases.  Recent Trends and Developments." Expert Opin. Ther. Patents 8, 1707-1727 (1998).


M. Tao,* R. Bihovsky, G. J. Wells, and J. P. Mallamo, "Novel Peptidyl Phosphorous Derivatives as Inhibitors of Human Calpain I." J. Med. Chem. 41, 3912-3916 (1998).


S. Chatterjee,* Z.-Q. Gu, D. Dunn, M. Tao, K. Josef, R. Tripathy, R. Bihovsky, S. E. Senadhi, T. M. O'Kane, B. A. McKenna, S. Mallya, M. A. Ator, D. Bozyczko-Coyne, R. Siman, and J. P. Mallamo, "D-Amino Acid Containing High Affinity Inhibitors of Recombinant Human Calpain I." J. Med. Chem. 41, 2663-2666 (1998).


S. Chatterjee,* M. A. Ator, D. Bozyczko-Coyne, K. Josef, G. Wells, R. Tripathy, M. Iqbal, R. Bihovsky, S. Mallya, S. E. Senadhi, T. M. O'Kane, B. A. McKenna, R. Siman, and J. P. Mallamo,  "Synthesis and Biological Activity of a Series of Potent Fluoromethyl Ketone Inhibitors of Recombinant Human Calpain I." J. Med. Chem. 40, 3820-3828 (1997).


R. Bihovsky* and M. A. Ator, "Calpains:  Their Role in Pathology, and New Therapeutic Opportunities."  Investigational Drugs Weekly Highlights, 22-25, May, 1997.


M. Iqbal, P. Messina, B. Freed, M. Das, S. Chatterjee, R. Tripathy, M. Tao, K. A. Josef, B. Dembofsky, D. Dunn, E. Griffith, R. Siman, S. E. Senadhi, W. Biazzo, D. Bozyczko-Coyne, S. L. Meyer, M. A. Ator, and R. Bihovsky*, "Subsite Requirements for Peptide Aldehyde Inhibitors of human Calpain I." Bioorg. Med. Chem. Lett., 7, 539-544 (1997).


M. Tao*, R. Bihovsky, and J. C. Kauer "Inhibition of Calpain by Peptidyl Heterocycles." Bioorg. Med. Chem. Lett., 6, 3009-3012 (1996).


R. Bihovsky*, and I. Pendrak, "Synthesis of Cystamidin A (Pyrrole-3-propanamide), a Reported Calpain Inhibitor." Bioorg. Med. Chem. Lett., 6, 1541-1542 (1996).


S. Chatterjee*, K. Josef, G. Wells, M. Iqbal, R. Bihovsky, J. P. Mallamo, M. Ator, D. Bozyczko-Coyne, S. Mallya, S. Senadhi, and R. Siman "Potent Fluoromethyl Ketone Inhibitors of Recombinant Human Calpain I."  Bioorg. Med. Chem. Lett., 6, 1237-1240 (1996).


S. L. Meyer*, D. Bozyczko-Coyne, S. K. Mallya, C. M. Spais, R. Bihovsky, J. K. Kawooya, D. M. Lang, R. W. Scott, and R. Siman "Biologically Active Monomeric and Heterodimeric Recombinant Human Calpain I Produced Using the Baculovirus Expression System". Biochem. J. 314, 511-519 (1996).


R. Bihovsky*, B. Levinson, R. Loewi, P. W. Erhardt, and M. Polokoff, "Hydroxamic Acids as Potent inhibitors of Endothelin Converting Enzyme,"  J. Med. Chem. 38, 2119-2129 (1995).


R. Bihovsky*, J. C. Powers, C.-M. Kam, R. Walton, and R. Loewi, "Further Evidence for the Importance of Free Carboxylate in Epoxysuccinate Inhibitors of Thiol Proteases," J. Enzyme Inhib.  7, 15-25 (1993).


R. Bihovsky*, "Reactions of a,ß-Epoxy Carbonyl Compounds with Methanethiolate: Regioselectivity and Rate,"J. Org. Chem., 57, 1029-1031 (1992).


R. Bihovsky*, "Applications of Cyclic a-Haloethers and Unsaturated Oxonium Ions to Natural Product Synthesis: Carbon-Carbon Bond Formation," Trends in Organic Chemistry, 3, 1-6 (1992).


R. Mohan*, Y. L. Chou, R. Bihovsky, W. C. Lumma, Jr. P. Erhardt, and K. Shaw, "Synthesis and Biological Activity of Angiotensin II Analogs Containing a Val-His Replacement, ValY[CH(CONH2)NH]His," J. Med. Chem., 34, 2402-2410, (1991).


S. Rosenblum and R. Bihovsky*, "Synthesis of the Papulacandin C-Arylglucosylspiroketal Nucleus," J. Amer. Chem. Soc., 112, 2746-2748 (1990).


R. Bihovsky* and V. Bodepudi, "Synthesis of (+)-Biotin:  Efficient Resolution of Key Intermediates," Tetrahedron, 46, 7667-7676, (1990).


R. Bihovsky*, M. U. Kumar, S. Ding, and A. Goyal, "Oxonium Ions in Organic Synthesis: Condensation of 2,3-Dihydrofuran and 3,4-Dihydro-2H-pyran with 1,3-Dicarbonyl Compounds," J. Org. Chem., 54, 4291-4293 (1989).


R. Bihovsky*, C. Selick, and I. Giusti, "Synthesis of C-Glucosides by Reactions of Glucosyl Halides with Oranocuprates," J. Org. Chem., 53, 4026-4031 (1988).


H. Bates*, K. Bagheri, and P. Vertino, "Effect of pH on the Regioselectivity of Pictet‑Spengler Reactions of 3‑Hydroxyphenethylamines with Formaldehyde and Acetaldehyde," J. Org. Chem. 51, 3061-3063 (1986).


H. Bates*, J. Farina, and M. Tong, "An Approach to Pseudomonic Acids from Acetylenic Precursors:  Synthesis of 2‑(Hydroxymethyl)‑3‑butyn‑1‑ol," J. Org. Chem., 51, 2637-2641 (1986).


H. Bates* and S. Rosenblum, "Nucleophilic Displacements on an a‑Chlorothioether by Organocuprates:  A Novel Synthesis of Desoxybiotin," J. Org. Chem., 51, 3447-3451 (1986).


H. Bates, "Structure of Crown Gall Tumor Metabolites:  Chemical Mediators of Parasitism," Anal. New York Acad. Sci., 471, 289-290 (1986).


H. Bates*, N. Condulis, and N. Stein, "Reduction of Cyclic Ureas with Lithium Aluminum Hydride," J. Org. Chem., 51, 2228-2229 (1986).


H. Bates*, J. Magrath, and A. Kaushal, "A Direct Method for Assignment of Absolute Configurations in Crown Gall Metabolites: The Structure of Nopaline," J. Nat. Prod., 48, 598-601 (1985).


H. Bates* and J. Farina, "Oxonium Ion Electrophiles:  Synthesis of the Hypotensive Oudenone," J. Org. Chem., 50, 3843-3845 (1985).


H. Bates* and S. Rosenblum, "300 MHz1H NMR Spectra and Conformations of Biotin and Related Hexahydrothienoimidazolone Derivatives," Tetrahedron Lett., 41, 2331-2336 (1985).


H. Bates*, L. Smilowitz, and S. Rosenblum, "A Practical Stereospecific Synthesis of the Biotin Precursor (3aa,6aa)‑1,3‑Dibenzylhexahydro‑1 H‑thieno[3,4‑d]imidazol‑2(3H)‑one 1,1‑Dioxide," J. Chem. Soc., Chem. Commun., 353-354 (1985).


H. Bates* and C. Selick, "Convenient Preparation of 2,3,4,6‑Tetra‑O‑Methyl‑ a‑D‑Glucopyranosyl Bromide," J. Carbohydr. Chem., 4, 273-275 (1985).


H. Bates*, L. Smilowitz, and J. Lin, "Preparation of (3aa,6a a)‑1,3‑Dibenzylhexahydro-1H-thieno[3,4‑d]imidazol‑2(3H)‑one: A Key Biotin Intermediate," J. Org. Chem., 50, 899-901 (1985).


H. Bates* and J. Garelick, "Synthesis of Tetrahydro‑4,6,7‑Isoquinolinetriols and Tetrahydro-4,7,8-isoquinolinetriols," J. Org. Chem., 49, 4552-4557 (1984).


H. Bates*, A. Kaushal, P. Deng, and D. Sciaky, "Structure and Synthesis of Histopine, a Histidine Derivative Produced by Crown Gall Tumors," Biochemistry, 23, 3287-3290 (1984).


H. Bates* and P. Deng, "Synthesis of the Civet Constituent cis‑(6‑Methyltetrahydropyran-2-yl)acetic Acid," J. Org. Chem., 48, 4479-4481 (1983).


H. Bates, "Characterization of Tetrahydroisoquinolines Produced by Pictet‑Spengler Reactions of Norepinephrine with Formaldehyde and Acetaldehyde," J. Org. Chem., 48, 1932-1934 (1983).


H. Bates, "Decarbonylation of Tetrahydrofuran‑2‑carboxylic Acids and Tetrahydropyran-2-carboxylic Acids in Concentrated Sulfuric Acid: Formation of Oxonium Ions," J. Am. Chem. Soc., 104, 2490-2493 (1982).


H. Bates*, "Pictet‑Spengler Reactions of Epinephrine with Formaldehyde," J. Org. Chem., 46, 4931-4935 (1981).


H. Bates and C. Sih*, "Arachidonic Acid is Responsible for the Smooth Muscle‑Contracting Activity of G-Acid," Proc. Nat. Acad. Sci., 76, 2712-2714 (1979).


H. Bates and H. Rapoport*, "Synthesis of Anatoxin a via Intramolecular Cyclization of Iminium Salts," J. Am. Chem. Soc., 101, 1259-1265 (1979).


H. Bates, R. Kostriken, and H. Rapoport*, "The Occurrence of Saxitoxin and Other Toxins in Various Dinoflagellates," Toxicon, 16, 595-601 (1978).


H. Bates, R. Kostriken, and H. Rapoport*, "A Chemical Assay for Saxitoxin: Improvements and Modifications," J. Agr. Food Chem., 26, 252-254 (1978).


J. Bordner, W. Thiessen, H. Bates, and H. Rapoport*, "The Structure of a Crystalline Derivative of Saxitoxin. The Structure of Saxitoxin," J. Am. Chem. Soc., 97, 6008-6012 (1975).


H. Bates and H. Rapoport*, "A Chemical Assay for Saxitoxin, the Paralytic Shellfish Poison," J. Agr. Food Chem., 23, 237-239 (1975).


H. Ruben, H. Bates, A. Zalkin*, and D. Templeton, "2,4,4‑Triphenyl‑1,2‑diazetidine-3-one-1-carboxylic Acid, Ethyl Ester," Acta Cryst. B., 30, 1631-1633 (1974).


Patents:

K. A. Josef, J. P. Mallamo, and R. Bihovsky, "Hydroxamate-Containing Cysteine and Serine Protease Inhibitors" US Patent 7,060,683 (2006).


M. Ator, R. Bihovsky, S. Chatterjee, D. Dunn, and R. Hudkins, "Multicyclic Compounds and the use thereof as Inhibitors of PARP, VEGFR2 and MLK3 Enzymes." WO 01/85686 (2001), EP 1294725. (2003), US Patent 7,122,679 (2006).


S. Chatterjee, J. P. Mallamo, R. Bihovsky, and G. Wells, "Peptide-Containing a Ketoamide Cysteine and Serine Protease Inhibitors" US Patent 7,001,907 (2006).


S. Chatterjee, J. P. Mallamo, R. Bihovsky, and G. Wells, "Peptide-Containing a Ketoamide Cysteine and Serine Protease Inhibitors" US Patent 6,703,368 (2004).


K. A. Josef, J. P. Mallamo, and R. Bihovsky, "Hydroxamate-Containing Cysteine and Serine Protease Inhibitors" WO 00/16767 (2001), EP 1115390 (2001), US Patent 6,686,335 (2004).


M. Tao and R. Bihovsky, "Peptidyl-2-Amino-1-hydroxyalkanesulfonic Acid Cysteine Protease Inhibitors" WO 98/47523 (1998); US Patent 6,348,448 (2002).


M. Tao and R. Bihovsky, "Peptidyl-2-Amino-1-hydroxyalkanesulfonic Acid Cysteine Protease Inhibitors" US Patent 6,500,802 (2002).


S. Chatterjee, J. P. Mallamo, R. Bihovsky, and G. Wells, "Peptide-Containing a Ketoamide Cysteine and Serine Protease Inhibitors" US Patent 6,288,231 (2001).


S. Chatterjee, J. P. Mallamo, R. Bihovsky, and G. Wells, "Peptide-Containing a Ketoamide Cysteine and Serine Protease Inhibitors" WO 99/17790 (1999); US Patent 6,150,378 (2000).


R. Bihovsky, G. Wells, and M. Tao,  "Benzothiazo and Related Heterocyclic Group-Containing Cysteine and Serine Protease Inhibitors," WO 98/21186 (1998); US Patent 5,952,328 (1999).


J. P. Mallamo, R. Bihovsky, M. Tao, and G. Wells, "Phosphorous-Containing Cysteine and Serine Protease Inhibitors," WO 97/03679 (1997); US Patent 5,639,732 (1997).


J. P. Mallamo, R. Bihovsky, S. Chatterjee, and R. Tripathy, "Cysteine Protease and Serine Protease Inhibitors,"US Patent 5,658,906 (1997).


J. P. Mallamo, R. Bihovsky, S. Chatterjee, and R. Tripathy, "Cysteine Protease and Serine Protease Inhibitors," WO 96/14067 (1996); US Patent 5,498,616 (1996).


R. Bihovsky, P. Erhardt, J. Lampe, R. Mohan, and K. Shaw, "Inhibitors of the Conversion of Big Endothelin to Endothelin," WO 93/11154 (1993); US Patent 5,504,070 (1996).


H. Bates and S. Rosenblum, "Improved Synthesis of Biotin," U.S. Patent 4,656,289 (1987).