Our Expertise
The major areas of expertise applicable to medicinal chemistry and early drug discovery are:- Lead identification, including HTS follow-up
- Hit-to-Lead medicinal chemistry
- Lead optimization chemistry
- Structure based drug design and computational chemistry
- Prodrug design and prodrug strategies
- ADME and safety guidance during lead optimization
- Patent assessments and evaluations of drug discovery projects
Biography
Hans Maag, PhDHans received his education in chemistry at the Federal Institute of Technology (ETH) in his native Switzerland. Following graduate studies on the total synthesis of Vitamin B12 in the group of Albert Eschenmoser at ETH, he conducted synthetic studies on fusidic acid as a postdoctoral fellow in the group of Robert E. Ireland at CalTech. He started his industrial career at Hoffmann-LaRoche Inc. in Nutley, NJ, working as a medicinal chemist in the field of antibiotics and prostacyclins. In 1985, he moved to Syntex in Palo Alto, CA, and research on antiviral agents with a focus on anti-HIV agents. This effort expanded to prodrugs of Ganciclovir leading to the discovery and clinical development of Valganciclovir (ValcyteTM).
With the purchase of Syntex by Roche in 1995, his managerial responsibilities increased, leading to the position of VP, Chemistry, in 2001; a position he held until his retirement from Roche in June 2010. At Roche Palo Alto, he led many project teams, from early lead identification to preclinical (pre-IND) development and was involved in several therapeutic areas: CNS, immune suppression, bronchopulmonary, and genitourinary diseases as well as a renewed effort in virology. He managed outside collaborations in parallel synthesis as well as drug discovery projects with Memory Pharmaceuticals and with InterMune. Within Roche, he led a global task force on lead generation and had responsibility for the computational chemistry group in Palo Alto.
Currently, Hans is a consultant to a number of biotech companies as well as two patent law firms.
Selected Publications and Patents
PublicationsIreland R.E.; Beslin, P.; Giger, R.; Hengartner, U.; Kirst, H.A.;Maag, H. "Studies on the Total Synthesis of Steroidal Antibiotics. 2. Two Convergent Schemes for the Synthesis of Tetracyclic Intermediates", J. Org. Chem. 42, 1267-1276 (1977).
Maag, H.; Blount, J.F.; Coffen, D.L.; Steppe, T.V.; Wong, F. "Structure, Absolute Configuration, and Total Synthesis of an Acid-Catalyzed Rearrangement Product of Bicyclomycin", J. Amer. Chem. Soc. 100, 6786-6788, (1978).
Maag, H.; Rydzewski, R.M.; McRoberts, M.J.; Crawford-Ruth, D.; Verheyden, J.P.H.; Prisbe, E.J. "Synthesis and Anti-HIV Activity of 4'-Azido- and 4'-Methoxynucleosides." J. Med. Chem. 35, 1440-1451 (1992).
Maag, H.; Nelson, J.T.; Rios Steiner, J.L.; Prisbe, E.J. "Solid State and Solution Conformation of the Potent HIV Inhibitor, 4'-Azidothymidine." J. Med Chem. 37, 431- 438 (1994).
Maag, H.; Schmidt, B.; Rose S.J. "Oligodeoxynucleotide Probes with Multiple Labels Linked to the 4'-Position of Thymidine Monomers: Excellent Duplex Stability and Detection Sensitivity", Tetrahedron Lett. 35, 6449-6452 (1994).
Dillon, M.P.; Cai, H., Maag, H. “Application of the “Trimethyl Lock” to Ganciclovir, a Prodrug with Increased Bioavailability”, Bioorg. Med. Chem. Lett. 6, 1653-1656 (1996).
Salaski, E.J.; Maag, H. “GMP Synthase: Synthesis of stable Analog of the putative AMP-XMP Intermediate”, SynLett, Special Issue, 897-900, (1999).
Maag, H. "Prodrugs of Carboxylic Acids." In Prodrugs: Challenges and Rewards; Stella, V.J; Borchardt, R.T.; Hageman, M.J.; Oliyai, R.; Maag, H.; Tilley, J.W. Eds.; AAPS Press and Springer, Publishers; New York, 2007.
Maag, H. "Valganciclovir: A Prodrug of Ganciclovir." In Prodrugs: Challenges and Rewards; Stella, V.J; Borchardt, R.T.; Hageman, M.J.; Oliyai, R.; Maag, H.; Tilley, J.W. Eds.; AAPS Press and Springer, Publishers; New York, 2007.
Li, F.; Maag, H.; Alfredson, T. “Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting”, J. Pharmaceut. Sciences, 97, 1109-1134 (2007) [Volume Date 2008].
Patents
Maag, H.; Holland, G.W.; Rosen, P. (Hoffmann-LaRoche Inc.) "7-Fluoro-prostacyclin analogues - useful as thrombocyte aggregation inhibitors, gastric secretion inhibitors and hypotensives". U.S. Pat. 4'558'142; issued December 10, 1985. U.S. Pat. 4'612'380; issued September 16, 1986. U.S. Pat. 4'650'883; issued March 17, 1987. U.S. Pat. 4'665'198; issued May 12, 1987.
Maag, H.; Prisbe, E.J.; Verheyden, J.P.H. (Syntex (USA) Inc.) "2'-Deoxy-4'-azido- nucleoside(s) - useful as antibacterial, antifungal and partic. as antiviral agents in the treatment of AIDS". Europ. Pat. Appl. EP371366, published June 6, 1990. U.S. Pat. 5,449,664, issued September 12, 1995
Maag, H.; Prisbe, E.J.; Verheyden, J.P.H. (Syntex (USA) Inc.) "New 4'-azido- and 4'- methoxy-substd. nucleoside antiviral agents - have potent activity and high therapeutic
ratio, and are used for treating HIV, bacterial and fungal infections". Europ. Pat. Appl. EP457326, published November 11, 1991. U.S. Pat. 5,449,664, issued September 12, 1995
Maag, H.; Schmidt, B.; Rose S. (Syntex (USA) Inc.) "Preparation of oligonucleotides containing 4'-substituted nucleotides”. U.S. Pat. 5,446,137, issued August 29, 1995. U.S. Pat. 5,750, 343, issued May 12, 1998.
Nestor, J.J.; Womble, S.W.; Maag, H. (Hoffmann-LaRoche AG) “2-(2-Amino-1,6- dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative.” Eur. Pat. Appl. EP694,547, published January 31, 1996. U.S. Pat. 6,083,953, issued July 4, 2000.
Nestor, J.J.; Womble, S.W.; Maag, H. (Hoffmann-LaRoche AG) “Preparation of Ganciclovir derivatives as virucides”. U.S. Pat. 5,543,414, issued August 6, 1996.
Caroon, J.M., Clark, R.D., Dillon, M.P., Harris, R.H. III, Hegde, S.S., Lin, C.J.J., Maag, H., Repke, D.B. (F. Hoffman-La Roche AG, Switz.). “Preparation of piperidinylmethylamino-ethylarenes as muscarinic receptor antagonists.” PCT Int. Appl. (1999), WO 9943657 A1.
Dvorak, C.A.; Fisher, L.E.; Green, K.L.; Harris, R.N., III; Maag, H.; Prince, A.; Repke, D.B.; Stabler, R.S. (F. Hoffmann-La Roche A.-G., Switz.). “Preparation of aminoalkyllactams as muscarinic receptor antagonists.” U.S. Pat. 6,667,301, issued December 23, 2003. U.S. Pat. 7,094,778, issued August 22, 2006.
Maag, Hans; Sui, Meng; Zhao, Shu-hai. (Roche Palo Alto LLC, USA). “Preparation of substituted benzoxazinones as selective 5-HT6 antagonists for treating central nervous system diseases and gastrointestinal tract disorders.” US7141562 B2, issued November 28, 2006.
Du Bois, D.J.; Elworthy, T.R.; Maag, H.; Sahdeo, S. “Preparation of tetrazole- substituted aryl amide derivatives as modulators of nicotinic receptors”. (F. Hoffmann-La Roche AG, Switz.). PCT Int. Appl. (2009), WO2009043780 A1.
Du Bois, D.J.; Hurst, D.N.; Loughhead, D.G.; Maag, H.; Manka, J.; Smith, D.B. „Preparation of arenecarboxylic acid cyclopropylamides as positive .alpha.7 nAChR nicotinic acetylcholine receptor allosteric modulators“. (F. Hoffmann-La Roche AG, Switz.). PCT Int. Appl. (2009), WO2009043784 A1.