Profile photo of John M. Wetzel, Ph.D.

John M. Wetzel, Ph.D.

Chemistry Leadership for Drug Discovery and Development
Certificate # 943
Wetzel Chemistry Consulting, LLC
4141 Baker Rd.
Albany, OH 45710
Phone #: 1-740-698-0420

Compound design, synthesis and evaluation Intellectual property protection Chemistry, Manufacturing & Controls management Due diligence Infrastructure design and implementation Litigation consulting For more information, please visit www.wetzelconsulting.com.

How other clients have benefited:

In Drug Discovery:
—– Several chemical series were prioritized according to their potential to yield drug-like leads for an anti-cancer target
—– The binding mode, structure-activity relationships and likely sites of off-target binding were elucidated for two leading chemical series
—– Predicted off-target binding was experimentally verified for several key cross-reactivity sites

—– Testing strategies were designed and implemented for efficient prioritization of new compounds and minimization of off-target interactions
—– New analogs with improved selectivity for the desired target were identified
—– Patent applications were carefully written, Examiner concerns were addressed and patents were issued.
In Drug Development:
—– Chemistry, Manufacturing and Controls (CMC) documents were provided in support of Investigational New Drug Application (IND), New Drug Application (NDA), and postapproval change filings
—– Chemistry concerns raised by regulatory agencies were successfully addressed; one drug received U.S. marketing approval
—– Technical challenges were solved in active pharmaceutical ingredient (API) synthesis
—– API manufacturing costs were reduced
—– Toxic and environmentally hazardous chemistry was eliminated from an API synthetic process

Experience:

Wetzel Chemistry Consulting, LLC
Albany, OH,
2005-present, Principal
Lundbeck Research USA
Paramus, NJ.
2003-2005, Director, Chemistry Support Services
—– Led project teams for MCH1 antagonist discovery and Chemistry Technology Platform development.
—– Co-led the selection of an automated storage / retrieval strategy for the Lundbeck screening collection worldwide.
Synaptic Pharmaceutical Corporation
Paramus, NJ.
1990-2003, positions of increasing responsibility, culminating in Director, Department of Chemistry
—– Managed 40 FTEs, including Medicinal, Computational, Analytical and Bioanalytical Chemists.
—– Managed the outsourcing of Chemistry, Manufacturing and Controls (CMC) efforts for preclinical and clinical development of a novel anti-depressant, including chemical process development, GMP-compliant synthesis, GLP-compliant analysis and bioanalysis, and formulation. Contributed CMC section to IND filing and annual update.
—– Designed and synthesized alpha-1a adrenoceptor antagonists for treatment of benign prostatic hyperplasia.
—– Discovered the first subtype-selective alpha-1a antagonist, SNAP 5089
—– Discovered highly selective alpha-1d adrenoceptor antagonists exemplified by SNAP 8493.
—– Designed and implemented a novel strategy for the efficient characterization, purification and formatting of combinatorial libraries culminating in neat solid archive samples.
—– Developed a novel LCMS-guided HPLC purification strategy for library purification.
—– Conducted numerous HPLC separations, including enantioselective separations and high throughput library purifications, on milligram and gram scales.
—– Procured and maintained NMR, LCMS, HPLC and other instruments.
Suntory Institute for Bioorganic Research
Osaka, Japan
1988-1990, Postdoctoral Fellow
—– Explored the chemical relationship between the brown planthopper (Nilaparvata lugens) and its intracellular yeast-like symbiote through deuterium labeling and GCMS techniques.

U.S. Patents:

1. Use of Alpha1C Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu, G.; Branchek, T.A.; Wetzel, J.M.; Hartig, P.R. (1995). U.S. Patent 5,403,847.
2. Use of Alpha-1C Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu, G.; Branchek, T.A.; Wetzel, J.M.; Hartig, P.R. (1996). U.S. Patent 5,578,611.
3. Dihydropyridines and New Uses Thereof. Gluchowski, C.; Wetzel, J.M.; Chiu, G.; Marzabadi, M.R.; Wong, W.C.; Nagarathnam, D. (1998). U.S. Patent 5,767,131.
4. Use of Alpha1c Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu, G.; Branchek, T.A.; Wetzel, J.M.; Hartig, P.R. (1998). U.S. Patent 5,780,485.
5. Alpha1C Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu, G.; Branchek, T.A.; Wetzel; John M.; Hartig; Paul R. (1999) U.S. Patent 5,990,128.
6. Use of Alpha-1C Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu, G.; Branchek, T.A.; Wetzel, J.M.; Hartig, P.R. (2000) U.S. Patent 6,015,819.
7. Dihydropyridines and New Uses Thereof. Gluchowski,C.; Wetzel, J.M.; Chiu, G.; Marzabadi, M.R.; Wong, W.C.; Nagarathnam, D. (2001) U.S. Patent 6,211,198.
8. Dihydropyridines and New Uses Thereof. Gluchowski, C.; Wetzel, J.M.; Chiu, G.; Marzabadi, M.R.; Wong, W.C.; Nagarathnam, D. (2001) U.S. Patent 6,310,076.
9. Use of Alpha1C Specific Compounds to Treat Benign Prostatic Hyperplasia. Gluchowski, C.; Forray, C.C.; Chiu; G.; Branchek, T.A.; Wetzel; J.M.; Hartig; P.R. (2003). U.S. Patent 6,602,888.
10. Dihydropyridines and New Uses Thereof. Gluchowski, C.; Wetzel; J.M.; Chiu; G.; Marzabadi, M.R.; Wong, W.C.; Nagarathnam, D. (2003). U.S. Patent 6,608,086.
11. Compounds Specific for the Human Alpha1d Adrenergic Receptor and Uses Thereof. Konkel, M.; Wetzel, J.M.; Noble, S.A.; Gluchowski, C.; Craig, D.A. (2004). U.S. Patent
6,706,716.
12. Selective Melanin Concentrating Hormone-1 (MCH1) Receptor Antagonists and Uses Thereof. Marzabadi, M.R.; Wetzel, J.; DeLeon, J.E.; Lagu, B; Gluchowski, C.; Noble, S.; Nagarathnam, D. (2004). U.S. Patent 6,720,324.
13. Substituted Anilinic Piperidines as MCH Selective Antagonists. Marzabadi, M.R.; Wetzel, J.; Deleon, J.E.; Jiang, Y.; Chen, C.-A.; Lu, K. (2004). U.S. Patent 6,727,264.
14. Substituted Anilinic Piperidines as MCH Selective Antagonists. Marzabadi, M.R.; Wetzel, J.; DeLeon, J.E.; Jiang, Y.; Chen, C.-A.; Lu, K. (2006). U.S. Patent 7,067,534.
15. Use of GALR3 Receptor Antagonists for the Treatment of Depression and/or Anxiety and Compounds Useful in Such Methods. Konkel, M.; Wetzel, J.M.; Talisman, J. (2006). U.S. Patent 7,081,470.
16. Substituted Alkyl Amido Piperidines. Marzabadi, M.R.; Wetzel, J.; Chen, C.-A.; Jiang, Y.; Lu, K. (2006). U.S. Patent 7,105,544.
17. 3-Imino-2-indolones for the Treatment of Depression and/or Anxiety. Konkel, M.; Wetzel, J.M.; Talisman, J. (2007). U.S. Patent 7,166,635.
18. Substituted Alkyl Amido Piperidines. Marzabadi,M.R.; Wetzel, J.; Chen, C.-A.; Jiang, Y.; Lu, K. (2007). U.S. Patent 7,199,135.
19. Spirocyclic Piperidines as MCH1 Antagonists and Uses Thereof. Marzabadi, M.R.; Jiang, Y.; Lu, K.; Chen, C.-A.; De Leon, J.E.; Wetzel, J.M.; Andersen, K. (2008). U.S. Patent 7,335,665.
20. Use of GALR3 Antagonist for Treatment of Depression and/or Anxiety and Compounds Useful in Such Methods. Blackburn, T.P.; Konkel, M.J.; Boteju, L.W.; Talisman, I.J.; Wetzel, J.M.; Packiarajan, M.; Chen, H.; Jimenez, H. (2008). U.S. Patent 7,465,750.
21. Secondary Amino Anilinic Piperidines as MCH1 Antagonists and Uses Thereof. Marzabadi, M.R.; Jiang, Y.; Lu, K.; Chen, C.-A.; De Leon, J.E.; Wetzel, J.M. (2009). U.S. Patent 7,473,698.

Publications:

1. Mechanistic studies in the deoxygenation of pyridine N-oxide: new 1,2 elimination. Hwu, J.R.; Wetzel, J.M. (1985) Journal of Organic Chemistry 50(3), 400-2.
2. The trimethylsilyl cationic species as a bulky proton. Application to chemoselective dioxolanation. Hwu, J.R.; Wetzel, J.M. (1985) Journal of Organic Chemistry 50(20), 3946-8.
3. Calcium in liquid ammonia for the reduction of benzyl ethers. Mechanistic clues derived from chemoselectivity studies. Hwu, J.R.; Chua, V.; Schroeder, J.E.; Barrans, R.E., Jr.; Khoudary, K.P.; Wang, N.; Wetzel, J.M. (1986) Journal of Organic Chemisty 51(24), 4731-3.
4. General scope of 1,3-dioxolanation of alpha,beta-unsaturated aldehydes with 1,2-bis (trimethylsilyloxy) ethane and trimethylsilyl trifluoromethanesulfonate. Hwu, J.R.; Leu, L.C.; Robl, J.A.; Anderson, D.A.; Wetzel, J.M.. (1987) Journal of Organic Chemistry 52(2), 188-91.
5. Silicon-promoted ring contractions in the formation of carbocyclic spiro compounds. Total synthesis of (-)- solavetivone. Hwu, J.R.; Wetzel, J.M. (1992) Journal of Organic Chemistry 57 (3), 922-8.
6. Diversity in steroidogenesis of symbiotic microorganisms from planthoppers. Wetzel, J.M.; Ohnishi, M.; Fujita, T.; Nakanishi, K.; Naya, Y.; Noda, H.; Sugiura, M. (1992) Journal of Chemical Ecology 18(11), 2083-94.
7. Comparison of the electronic effect and the steric influence between the 1,1,2,2,2-pentamethyldisilanyl and the trimethylsilyl groups. Hwu, J.R.; Wetzel, J.M.; Lee, J.S.; Butcher, R.J. (1993) Journal of Organometallic Chemistry 453(1), 21-8.
8. The alpha1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha1c subtype. Forray, C.; Bard, J.A.; Wetzel, J.M.; Chiu, G.; Shapiro, E.; Tang, R.; Lepor, H.; Hartig, P.R.; Weinshank, R.L.; Branchek, T.A.; Gluchowski, C. (1994) Molecular Pharmacology 45(4), 703-8.
9. Discovery of alpha1a-adrenergic receptor antagonists based on the L-type Ca2+ channel antagonist niguldipine. Wetzel, J. M.; Miao, S.W.; Forray, C.; Borden, L.A.; Branchek, T.A.; Gluchowski, C. (1995) Journal of Medicinal Chemistry 38(10), 1579-81.
10. Fragmentation studies of ergosterol. The formation of the fragment ion at m/z 337. Kenney, P.T.M.; Wetzel, J.M. (1995) European Mass Spectrometry 1(4), 411-13.
11. Modeling and mutagenesis of the human alpha1a-adrenoceptor: orientation and function of transmembrane helix V sidechains. Wetzel, J.M.; Salon, J.A.; Tamm, J.A.; Forray, C.; Craig, D.; Nakanishi, H.; Cui, W.; Vaysse, P.J.-J.; Chiu, G.; Weinshank, R.L., Hartig, P.R., Branchek, T.A., Gluchowski, C. (1996)  receptors and Channels 4(3), 165-177.
12. Localization of mRNA and receptor binding sites for the alpha1a-adrenoceptor subtype in the rat, monkey and human urinary bladder and prostate. Walden, P.D.; Durkin, M.M.; Lepor, H.; Wetzel, J.M.; Gluchowski, C.; Gustafon, E.L. (1997) Journal of Urology (Baltimore) 157(3), 1032-1038.
13. Characterization of specific binding of [125I]L-762,459, a selective alpha1A-adrenoceptor radioligand to rat and human tissues. O’Malley, S.S.; Chen, T.B.; Francis, B.E.; Gibson, R.E.; Burns, H.D.; DiSalvo, J.; Bayne, M.L.; Wetzel, J.M.; Nagarathnam, D.; Marzabadi, M.; Gluchowski, C.; Chang, R.S.L. (1998) European Journal of Pharmacology 348(2/3), 287-295.
14. Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate. Wong, W.C.; Chiu, G.; Wetzel, J.M.; Marzabadi,M.R.; Nagarathnam, D.; Wang, D.; Fang, J.; Miao, S.W.; Hong, X.; Forray, C.; Vaysse, P.J.J.; Branchek, T.A.; Gluchowski, C.; Tang, R.; Lepor, H. (1998) Journal of Medicinal Chemistry 41(14), 2643-2650.
15. Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia. Nagarathnam, D.; Wetzel, J.M.; Miao, S.W.; Marzabadi, M.R.; Chiu, G.; Wong, W.C.; Hong, X.; Fang, J.; Forray, C.; Branchek, T.A.; Heydorn, W.E.; Chang, R.S.L.; Broten, T.; Schorn, T.W.; Gluchowski, C. (1998) Journal of Medicinal Chemistry 41(26), 5320-5333.
16. Design and synthesis of novel dihydropyridine alpha-1A antagonists. Marzabadi, M.R.; Hong, X.;  agarathnam, D.; Miao, S.; Chiu, G.; Wong, W.C.; Wetzel, J.M.; Fang, J.; Forray, C.; Chen, T.B.; O’Malley, S.S.; Chang, R.S.L.; Gluchowski, C. (1999) Bioorganic & Medicinal Chemistry Letters 9(19), 2843-2848.
17. Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 4. Structureactivity relationship in the dihydropyrimidine series. Wong, W.C.; Sun, W.; Lagu, B.; Tian, D.; Marzabadi, M.R.; Zhang, F.; Nagarathnam, D.; Miao, S.W.; Wetzel, J.M.; Peng, J.; Forray, C.; Chang, R.S.L.; Chen, T.B.; Ransom, R.; O’Malley, S.; Broten, T.P.; Kling, P.; Vyas, K.P.; Zhang, K.; Gluchowski, C. (1999) Journal of Medicinal Chemistry 42(23) 4804-4813.
18. Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 1. Structureactivity relationship in dihydropyrimidinones. Nagarathnam, D.; Miao, S. Wu; Lagu, B.; Chiu, G.; Fang, J.; Dhar, T.G. Murali; Zhang, J.; Tyagarajan, S.; Marzabadi, M.R.; Zhang, F.; Wong, W.C.; Sun, W.; Tian, D.; Wetzel, J.M.; Forray, C.; Chang, R.S.L.; Broten, T.P.; Ransom, R.W.; Schorn, T.W.; Chen, T.B.; O’Malley, S.; Kling, P.; Schneck, K.; Bendesky, R.; Harrell, C.M.; Vyas, K.P.; Gluchowski, C. (1999) Journal of Medicinal Chemistry 42(23), 4764-4777.
19. Design and synthesis of novel alpha1a adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety. Dhar, T.G.M.; Nagarathnam, D.; Marzabadi, M.R.; Lagu, B.; Wong, W.C.; Chiu, G.; Tyagarajan, S.; Miao, S.W.; Zhang, F.; Sun, W.; Tian, D.; Shen, Q.; Zhang, J.; Wetzel, J.M.; Forray, C.; Chang, R.S.L.; Broten, T.P.; Schorn, T.W.; Chen, T.B.; O’Malley, S.; Ransom, R.; Schneck, K.; Bendesky, R.; Harrell, C.M.; Vyas, K.P.; Zhang, K.; Gilbert, J.; Pettibone, D.J.; Patane, M.A.; Bock, M.G.; Freidinger, R.M.; Gluchowski, C. (1999) Journal of
Medicinal Chemistry 42 (23), 4778-4793.
20. De novo design of a novel oxazolidinone analogue as a potent and selective alpha1A adrenergic receptor antagonist with high oral bioavailability. Lagu,B.; Tian, D.; Jeon, Y.; Li, C.; Wetzel, J.M.; Nagarathnam, D.; Shen, Q.; Forray, C.; Chang, R.S.L.; Broten, T.P.; Ransom, R.W.; Chan, T.-B.; O’Malley, S.S.; Schorn, T.W.; Rodrigues, A.D.; Kassahun, K.; Pettibone, D.J.; Freidinger, R.; Gluchowski, C. (2000) Journal of Medicinal Chemistry 43(15), 2775-2778.
21. Determination of the relative and absolute stereochemistry of a potent and alpha1Aselective adrenoceptor antagonist. Lagu, B.; Wetzel, J. M.; Forray, C.; Patane, M.A.; Bock, M.G.
(2000) Bioorganic & Medicinal Chemistry Letters 10(24), 2705-2707.
22. Identification and characterization of two G protein-coupled receptors for neuropeptide FF. Bonini, J.A.; Jones, K.A.; Adham, N.; Forray, C.; Artymyshyn, R.; Durkin, M.M.; Smith, K.E.; Tamm, J.A.; Boteju, L.W.; Lakhlani, P.P.; Raddatz, R.; Yao, W.-J.; Ogozalek, K.L.; Boyle, N.; Kouranova, E.V.; Quan, Y.; Vaysse, P.J.; Wetzel, J.M.; Branchek, T.A.; Gerald, C.; Borowsky, B. (2000) Journal of Biological Chemistry 275(50), 39324-39331.
23. Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin- 1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists. Konkel, M.J.; Wetzel, J.M.; Cahir, M.; Craig, D.A.; Noble, S.A.; Gluchowski, C. (2005) Journal of Medicinal Chemistry 48(8), 3076-3079.
24. Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH1) Antagonists Part 1. The Discovery of Arylacetamides as Viable Replacements for the Dihydropyrimidinone Moiety of an HTS Hit. Jiang, Y.; Chen, C.-A.; Lu, K.; Daniewska, I.; De Leon, J.; Kong, R.; Forray, C.; Li, B.; Hegde, L.G.; Wolinsky, T.D.; Craig, D.A.; Wetzel, J.M.; Andersen, K.; Marzabadi, M. (2007) Journal of Medicinal Chemistry 50(16), 3870-3882.

25. Synthesis and SAR Investigations for Novel Melanin-Concentrating Hormone 1 Receptor (MCH1) Antagonists Part 2: A Hybrid Strategy Combining Key Fragments of HTS Hits. Chen, C.-A.; Jiang, Y.; Lu, K.; Daniewska, I.; Mazza, C.G.; Negron, L.; Forray, C.; Parola, T.; Li, B.; Hegde, L.G.; Wolinsky, T.D.; Craig, D.A.; Kong, R.; Wetzel, J.M.; Andersen, K.; Marzabadi, M. (2007) Journal of Medicinal Chemistry 50(16), 3883-3890.