From Undergraduate Research at Washington State University
1. A. R. Martin, A. P. Parulkar, D. J. Gusseck, L. J. Anderson, G. L. Grunewald and A. I. White, "Substituted Tetralins I: Synthesis and Analgesic Activities of Some 2-Aminotetralins," J.Pharm.Sci., 58, 340–347 (1969).
From Graduate Research at the University of Wisconsin
2. H. E. Zimmerman and G. L. Grunewald, "The Chemistry of Barrelene. II. A Remarkable Transformation to Naphthalene Derivatives," J.Amer.Chem.Soc., 86, 1434–1436 (1964).
3. H. E. Zimmerman and G. L. Grunewald, "The Chemistry of Barrelene. III. A Unique Photoisomerization to Semibullvalene," J.Amer.Chem.Soc., 88, 183–184 (1966).
4. H. E. Zimmerman, G. L. Grunewald and R. M. Paufler, "α–Pyrone," Org. Syn., 46, 101–104 (1966).
5. H. E. Zimmerman, G. L. Grunewald, R. M. Paufler and M. A. Sherwin, "Synthesis and Physical Properties of Barrelene, A Unique Mobius-like Molecule," J.Amer.Chem.Soc., 91, 2330–2338 (1969).
6. H. E. Zimmerman, R. W. Binkley, R. S. Givens, G. L. Grunewald and M. A. Sherwin, "The Barrelene to Semibullvalene Transformation. Correlation of Excited-State Potential Energy Surfaces with Reactivity. Mechanistic and Exploratory Organic Photochemistry. XLIV," J.Amer.Chem.Soc., 91, 3316–3323 (1969).
From Research at the University of Kansas
7. G. L. Grunewald, A. M. Warner, S. J. Hays, R. H. Bussell and M. K. Seals, "Medicinal Chemistry of [10]Annulenes and Related Compounds. 1. 11-Azatricyclo[4.4.1.0 1,6]undecane, 11-Azatricyclo-[4.4.1.01,6 ]undeca-3,8-diene, and 11-Azabicyclo[4.4.1]undeca-1,3,5,7,9-pentaene as Antiviral Agents," J.Med.Chem., 15, 747–750 (1972).
8. G. L. Grunewald and A. M. Warner, "Medicinal Chemistry of [10]-Annulenes and Related Compounds. 2. N-(2-Chloroethyl) Derivatives of 11-Azatricyclo[4.4.1.0 1,6]undecane, 11-Azatricyclo[4.4.1.0 1,6]undeca-3,8-diene, and 11-Azabicyclo[4.4.1]undeca-1,3,5,7,9-pentaene," J.Med.. Chem., 15, 1192–1194 (1972).
9. G. L. Grunewald, I. M. Uwaydah, R. E. Christoffersen and D. Spangler, "ab initio and Semi-Empirical Molecular Orbital Calculations on 1,6-Methano[10]annulene," Tetrahedron Lett., 933–936 (1975).
10. G. L. Grunewald, J. M. Grindel, W. C. Vincek and R. T. Borchardt, "Importance of the Aromatic Ring in Adrenergic Amines. Nonaromatic Analogs of Phenylethanolamine as Substrates for Phenylethanolamine N-Methyltransferase," Mol. Pharmacol., 11, 694–699 (1975).
11. G. L. Grunewald and J. M. Grindel, "Synthesis of Carbomethoxycyclooctatetraene," Org. Photochem. Syn., 2, 20–22 (1976).
12. G. L. Grunewald, J. A. Ruth, T. R. Kroboth, B. V. Kamdar, P. N. Patil and K. N. Salman, "Conformationally Defined Adrenergic Agents. I. Potentiation of Norepinephrine in Rat Vas Deferens by endo- and exo-2-Aminobenzobicyclo[2.2.2]octene, Conformationally Defined Analogs of Amphetamine," J.Pharm.Sci., 65, 920–925 (1976).
13. G. L. Grunewald, J. M. Grindel, P. N. Patil and K. N. Salman, "Importance of the Aromatic Ring in Adrenergic Amines. 2. Synthesis and Adrenergic Activity of Some Non-aromatic Six- and Eight-membered Ring Analogs of ß -Phenylethanolamine," J.Med.Chem., 19, 10–16 (1976).
14. K. H. Kim and G. L. Grunewald, "A Rapid, Convenient, High Yield Procedure for the Regeneration of 2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) from the Corresponding Hydroquinone (DDHQ)," Org. Prep. Proced. Int., 8, 141–143 (1976).
15. V. D. Warner, J. D. Musto, J. N. Sane, K. H. Kim and G. L. Grunewald, "Quantitative Structure-Activity Relationships for 5-Substituted-8-Hydroxyquinolines as Inhibitors of Dental Plaque," J.Med.Chem., 20, 92–96 (1977).
16. R. T. Borchardt , W. C. Vincek and G. L . Grunewald, "A Liquid Chromatographic Assay for Phenylethanolamine N-Methyltransferase," Anal. Biochem., 82, 149–157 (1977).
17. R. M. Bartholow, L. E. Eiden, J. A. Ruth, G. L. Grunewald, J. Siebert and C. O. Rutledge, "Conformationally Defined Adrenergic Agents. II. The Effect of endo- and exo-2-Aminobenzobicyclo-[2.2.2]octene, Conformationally Defined Amphetamine Analogs, on the Uptake and Release of Central Catecholamines," J. Pharmacol. Exp. Ther.202, 532–543 (1977).
18. J. A. Ruth, G. L. Grunewald and C. O. Rutledge, "Conformationally Defined Adrenergic Agents. III. Importance of Compartmentation in the Release of Norepinephrine from Rat Atria by endo- and exo-2-Methylaminobenzobicyclo[2.2.2]octene, Conformationally Defined Analogs of Methamphetamine," J. Pharmacol. Exp. Ther., 204, 615–624 (1978).
19. D. E. Walters, G. L. Grunewald, M. Staples, J. Rodgers, J. R. Ruble and B. Lee, "(±)-9-exo-Amino-5,6,7,8-tetrahydro-5,8-methano-9H-benzocyclohepten-8-ol Hydrochloride," Acta Crystallogr., B34, 947–949 (1978).
20. G. L. Grunewald and W. J. Brouillette, "An Ethoxycarbonyl Migration from an Amide Nitrogen to Oxygen," J.Org.Chem., 43, 1839–1841 (1978).
21. G. L. Grunewald, D. E. Walters, D. L. Flynn, S. D. Atwood, M. W. Creese, B. A. Frenz and J. M. Troup, "(±)-2-exo- and endo-Methylamino-1,2,3,4-tetrahydro-1,4-ethanonapthalene Hydrochloride," Acta Crystallogr., B34, 3462–3465 (1978).
22. G. L. Grunewald, D. E. Walters and T. R. Kroboth, "Synthesis of Bridgehead Hydroxyl-Substituted Benzobicyclo[3.2.1]octenes and -octadienes via an Acyloin Rearrangement in the Benzobicyclo[2.2.2]octene Ring System," J.Org.Chem., 43, 3478–3481 (1978).
23. G. L. Grunewald and D. P. Davis, "A New Convenient Synthesis of Bridgehead Substituted Norbornenes," J.Org.Chem., 43, 3074–3076 (1978).
24. V. D. Warner, D. M. Lynch, K. H. Kim and G. L. Grunewald, "The Quantitative Structure-Activity Relationships for Biguanides, Carbamimidates, and Bisbiguanides as Inhibitors of Streptococcus mutans No. 6715," J.Med.Chem., 22, 359–366 (1979).
25. G. L. Grunewald, T. J. Reitz, J. A. Ruth, S. Vollmer, L. E. Eiden and C. O. Rutledge, "The Inhibition of Neuronal Uptake of 3H-Biogenic Amines into Rat Cerebral Cortex by Partially and Fully Saturated Derivatives of Imipramine and Desipramine. Importance of the Aromatic Ring in Adrenergic Amines. 3.," Biochem. Pharmacol., 28, 417–421 (1979).
26. W. J. Brouillette, E. E. Smissman and G. L. Grunewald, "N-Acylcarbamates as Intermediates in Synthetic Approaches to a Bicyclic Trimethylene-bridged 2,4-Oxazolidinedione and Hydantoin," J.Org.Chem., 44, 839–843 (1979).
27. G. L. Grunewald, W. C. Vincek, D. P. Davis and R. T. Borchardt, "Some New Inhibitors of Epinephrine Biosynthesis. Importance of the Aromatic Ring in Adrenergic Amines. 4.," in "Catecholamines: Basic and Clinical Frontiers," edited by E. Usdin, I. J. Kopin and J. Barchas ( Pergamon Press, New York), 1979, pp. 189–191.
28. G. L. Grunewald, M. W. Creese and D. E. Walters, "Application of CNDO/2 Calculations and X-ray Crystallographic Analysis to the Design of Conformationally-Defined Analogs of Methamphetamine," in "Computer-Assisted Drug Design," R. C. Olson and R. E. Christoffersen, eds., American Chemical Society Symposium Series: American Chemical Society, Washington, D. C., Vol. 112, Ch. 21, 439–487 (1979).
29. G. L. Grunewald, W. J. Brouillette and J. A. Finney, "Synthesis of α-Hydroxyamides via the Cyanosilylation of Aromatic Ketones," Tetrahedron Lett., 21, 1219–1220 (1980).
30. G. L. Grunewald, T. J. Reitz, A. Hallett, C. O. Rutledge, S. Vollmer, J. M. Archuleta III and J. A. Ruth, "Pronounced Pharmacological Differences Arising from Minor Structural Changes in Conformationally Defined Amphetamine Analogues. Comparative Evaluation of endo- and exo-2-Amino- and 2-Methylaminobenzobicyclo[2.2.1]heptene and Benzobicyclo[2.2.2]octene Analogues. Conformationally Defined Adrenergic Agents. 4.," J.Med.Chem., 23, 614–620 (1980).
31. G. L. Grunewald, S. H. Kuttab, M. A. Pleiss, J. B. Mangold and P. Soine, "Conformationally Defined Aromatic Amino Acids. Synthesis and Stereochemistry of 2-endo- and exo-Amino-1,2,3,4-tetrahydro-1,4-ethanonapthalene-2-carboxylic Acids (2-endo- and exo-Aminobenzobicyclo[2.2.2]-octene-2-carboxylic Acids)," J.Med.Chem., 23, 754–758 (1980).
32. W. C. Vincek, C. S. Aldrich, R. T. Borchardt and G. L. Grunewald, "Non-aromatic Analogues of Phenylethanolamine as Inhibitors of Phenylethanolamine N-Methyltransferase: the Role of Hydrophobic and Steric Interactions. Importance of the Aromatic Ring in Adrenergic Amines. 5.," J.Med.Chem., 24, 7–12 (1981).
33. D. P. Davis, R. T. Borchardt and G. L. Grunewald, "Non-aromatic Analogues of Phenylethanolamine as Inhibitors of Phenylethanolamine N-Methyltransferase: the Role of π-Electronic and Steric Interactions. Importance of the Aromatic Ring in Adrenergic Amines. 6.," J.Med.Chem., 24, 12–16 (1981).
34. G. L. Grunewald and M. F. Rafferty, "Stereochemical Aspects of Binding of Aromatic and Non-aromatic Substrates and Inhibitors to Phenylethanolamine N-Methyltransferase," in "Function and Regulation of Monoamine Enzymes: Basic and Clinical Aspects." edited by E. Usdin, N. Weiner and M. B. H. Youdim (Macmillan and Company, New York), 1981, pp. 691–699.
35. G. L. Grunewald and M. W. Creese, "Fenfluramine, (±)-N-Ethyl-m-(trifluoromethyl)amphetamine Hydrochloride," Acta Crystallogr., B37, 1790–1793 (1981).
36. G. L. Grunewald, R. T. Borchardt, M. F. Rafferty and P. Krass, "Conformational Preferences of Amphetamine Analogues for Inhibition of Phenylethanolamine N-Methyltransferase. Conformationally Defined Adrenergic Agents. 5.," Mol.Pharmacol., 20, 377–381 (1981).
37. C. B. Brouillette, W. J. Brouillette, G. L. Grunewald, C. L. Cole, J. R. Ruble and B. K. Lee, "1-Ethoxycarbonyl-3-hydroxy-3-phenyl-2-piperidone," Cryst. Struct. Commun., 10, 1239–1243 (1981).
38. N. Liang, R. E. Tessel, R. T. Borchardt and G. L. Grunewald, "The Use of Phenylethanolamine N-Methyltransferase Inhibitors in Elucidating the Role of Brain Epinephrine in the Control of Cardiovascular Function," in "The Biochemistry of S-Adenosylmethionine and Related Compounds," edited by R. T. Borchardt, C. R. Creveling and E. Usdin (Macmillan and Company, London), 1982, pp. 457–460.
39. G. L. Grunewald and M. F. Rafferty, "Conformational Aspects of Binding of Substrates and Inhibitors of Phenylethanolamine N-Methyltransferase (PNMT)," in "The Biochemistry of S-Adenosylmethionine and Related Compounds," edited by R. T. Borchardt, C. R. Creveling and E. Usdin (Macmillan and Company, London), 1982, pp. 453–456.
40. M. F. Rafferty and G. L. Grunewald, "The Remarkable Substrate Activity for Phenylethanolamine N-Methyltransferase of Some Conformationally-Defined Phenylethylamines Lacking a Side Chain Hydroxyl Group. Conformationally-Defined Adrenergic Agents. 6.," Mol.Pharmacol., 22, 127–132 (1982).
41. G. L. Grunewald, M. A. Pleiss and M. F. Rafferty, "Conformational Preferences of Dopamine Analogues for Inhibition of Norepinephrine N-Methyltransferase. Conformationally Defined Adrenergic Agents. 7.," Life Sciences,31, 993–1000 (1982).
42. M. F. Rafferty, D. S. Wilson, J. A. Monn, P. Krass, R. T. Borchardt and G. L. Grunewald, "Comparison of the Stereoselectivity of Norepinephrine N-Methyltransferase for Aromatic versus Non-aromatic Substrates and Inhibitors. The Importance of the Aromatic Ring in Adrenergic Amines. 7.," J.Med.Chem., 25, 1198–1204 (1982).
43. G. L. Grunewald, J. A. Monn, M. F. Rafferty, R. T. Borchardt and P. Krass, "Probes of the Active Site of Norepinephrine N-Methyltransferase: The Effect of Hydrophobic and Hydrophilic Interactions on Side Chain Binding of Amphetamine and α-Methylbenzylamine," J.Med.Chem., 25, 1248–1250 (1982).
44. M. F. Rafferty, P. Krass, R. T. Borchardt and G. L. Grunewald, "2-(Aminomethyl)-trans-2-decalols as Inhibitors of Norepinephrine N-Methyltransferase. Importance of the Aromatic Ring in Adrenergic Amines. 8.," J.Med.Chem., 25, 1250–1252 (1982).
45. M. F. Rafferty, R. T. Borchardt and G. L. Grunewald, "Directional Probes of the Hydrophobic Component of the Aromatic Ring Binding Site of Norepinephrine N-Methyltransferase," J.Med.Chem., 25, 1204–1208 (1982).
46. N. Y. Liang, R. T. Borchardt, J. C. Choi, R. E. Tessel and G. L. Grunewald, "Effects of Phenylethanolamine N-Methyltransferase Inhibitors on Rat Brain Catecholamine Levels and Body Temperature," Res. Commun. Chem. Pathol. Pharmacol., 37, 445–452 (1982).
47. N. Y. Liang, R. E. Tessel, G. L. Grunewald and R. T. Borchardt, "Inhibitors of Phenylethanolamine N-Methyltransferase. 1. Effects of 2-Cyclooctyl-2-Hydroxyethylamine on Rat Brain and Adrenal Catecholamine Content and Blood Pressure," J. Pharmacol. Exp. Ther., 223, 375–381 (1982).
48. N. Y. Liang, R. E. Tessel, G. L. Grunewald and R. T. Borchardt, "Inhibitors of Phenylethanolamine N-Methyltransferase. 2. Comparison of Nonaromatic Analogues of Phenylethanolamines, 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (SKF-64139) and 2,3-Dichloro- α-methylbenzylamine: Effects on Rat Brain and Adrenal Catecholamine Content and Blood Pressure," J.Pharmacol. Exp. Ther., 223, 382–387 (1982).
49. T. J. Reitz, G. L. Grunewald, C. H. Park and B. K. Lee, "6-Nitrobenzonorbornen-2-one," Cryst. Struct. Commun., 11, 1659–1662 (1982).
50. M. W. Creese and G. L. Grunewald, "Conformational Energies of Fenfluramine: Graphical Representation of Energy as a Function of Four Conformational Variables," J.Amer.Chem.Soc., 105, 2463–2469 (1983).
51. G. L. Grunewald, V. M. Paradkar, B. Pazhenchevsky, M. A. Pleiss, D. J. Sall, W. L. Seibel and T. J. Reitz, "Synthesis of Conformationally-Defined Analogues of Norfenfluramine. A Highly Stereospecific Synthesis of Amines from Alcohols in the Benzobicyclo[2.2.1]heptene System," J.Org.Chem., 48, 2321–2327 (1983).
52. T. J. Reitz and G. L. Grunewald, "Carbon-13 Nuclear Magnetic Resonance Examination of Benzonorbornene Derivatives. Assignment of Site of Aromatic Ring Substitution in Benzonorbornen-2-ones," Org.Magn. Reson., 21, 596–601 (1983).
53. M. A. Pleiss and G. L. Grunewald, "An Extension of the f-Fragment Method for the Calculation of Hydrophobic Constants (log P) of Conformationally Defined Systems," J.Med.Chem., 26, 1760–1764 (1983).
54. W. J. Brouillette and G. L. Grunewald, "Synthesis and Anticonvulsant Activity of Some Substituted Lactams and Amides," J.Med.Chem., 27, 202–206 (1984).
55. G. L. Grunewald, M. A. Pleiss, C. L. Gatchell, R. Pazhenchevsky, and M. F. Rafferty, "Gas Chromatographic Quantitation of Underivatized Amines in the Determination of Their Octanol-0.1 N NaOH Partition Coefficients by the Shake-Flask Method," J.Chromatogr., 292, 319–331 (1984).
56. N. Y. Liang, A. Chandra, R. E. Tessel, G. L. Grunewald and R. T. Borchardt, "Inhibitors of Phenylethanolamine N-Methyltransferase: Effects on Brain Catecholamine Content and Blood Pressure in DOCA-Salt Hypertensive Rats," Res. Commun. Chem. Pathol. Pharmacol., 46, 319–329 (1984).
57. G. L. Grunewald and M. W. Creese, "Conformational Analysis of Nisoxetine and Fluoxetine, Selective Inhibitors of Norepinephrine and Serotonin Reuptake. Are Conformational Differences an Explanation of Neurotransmitter Selectivity?," Drug Design Delivery, 1, 23–37 (1986).
58. G. L. Grunewald, H. Arrington, W. J. Bartlett, T. J. Reitz and D. J. Sall, "Binding Requirements of Phenolic Phenylethylamines in the Benzonorbornene Skeleton at the Active Site of Phenylethanolamine N-Methyltransferase (PNMT)," J.Med.Chem., 29, 1972–1982 (1986).
59. G. L. Grunewald, D. J. Sall and J. A. Monn, "A Computer Graphics Model of the Active Site of Phenylethanolamine N-Methyltransferase and its Use in the Design of Selective Inhibitors," in "QSAR in Drug Design and Toxicology: Proceedings of the 6th European Symposium on Quantitative Structure-Activity Relationships," edited by J.-B. Hadzi and Borka Jerman-Blazic (Elsevier, Amsterdam), 1987, pp. 118–120; [Pharmacochem. Libr., 10, 118–120 (1987)].
60. T. M. Creese, G. L. Grunewald and M. W. Creese, "The Energy Well Connection Graph: A Use of Curvilinear Coordinates to Achieve Dimension Reduction for Graph Representation of Molecular Conformation Energy Data," Theor. Chim. Acta,71, 75–88 (1987).
61. G. L. Grunewald, Q. Ye and F. Takusagawa, "Structures of Two Isomeric Phenylethanolamine Analogs Containing the Benzobicyclo[3.2.1]octane Skeleton," Acta Crystallogr., Sect. C: Cryst. Struct. Commun., C43, 2418–2420 (1987).
62. G. L. Grunewald, K. M. Markovich and D. J. Sall, "Binding Orientation of Amphetamine and Norfenfluramine Analogues in the Benzonorbornene and Benzobicyclo[3.2.1]octane Ring Systems at the Active Site of Phenylethanolamine N-Methyltransferase (PNMT)," J.Med.Chem., 30, 2191–2208 (1987).
63. D. J. Sall and G. L. Grunewald, "Inhibition of Phenylethanolamine N-Methyltransferase (PNMT) by Aromatic Hydroxy-substituted 1,2,3,4-Tetrahydroisoquinolines: Further Studies on the Hydrophilic Pocket of the Aromatic Ring Binding Region of the Active Site," J.Med.Chem., 30, 2208–2216 (1987).
64. G. L. Grunewald, A. E. Carter, D. J. Sall and J. A. Monn, "Conformational Preference for the Binding of Bi-Aryl Substrates and Inhibitors to the Active Site of Phenylethanolamine N-Methyltransferase (PNMT)," J.Med.Chem., 31, 60–65 (1988).
65. G. L. Grunewald, Q. Ye, L. Kieffer and J. A. Monn, "Conformational Requirements of Substrates for Activity with Phenylethanolamine N-Methyltransferase (PNMT)," J.Med.Chem., 31, 169–171 (1988).
66. G. L. Grunewald, J. A. Monn and D. J. Sall, "Approaches to the Design of Selective Inhibitors of Phenylethanolamine N-Methyltransferase (PNMT). Development of an Active Site Model for PNMT," in "Proceedings of the International Symposium on Brain Epinephrine," edited by J. Stolk, D. U’Prichard and K. Fuxe (Oxford Press, London), 1988, pp. 117–140.
67. G. L. Grunewald, D. J. Sall and J. A. Monn, "Conformational and Steric Aspects of the Inhibition of Phenylethanolamine N-Methyltransferase (PNMT) by Benzylamines," J.Med.Chem., 31, 433–444 (1988).
68. G. L. Grunewald, D. J. Sall and J. A. Monn, "Synthesis and Evaluation of 3-Substituted Analogues of 1,2,3,4-Tetrahydroisoquinoline as Inhibitors of Phenylethanolamine N-Methyltransferase (PNMT)," J.Med.Chem., 31, 824–830 (1988).
69. G. L. Grunewald, M. W. Creese and H. J. R. Weintraub, "Conformational Preferences in Alkylbenzenes and Aryl-alkylamines: A Comparative Study Using CAMSEQ, MM2 and Molecular Dynamics Methods," J. Comput. Chem., 9, 315–326 (1988).
70. T. Högberg, S. Ross, P. Ström, G. L. Grunewald, M. W. Creese and J. D. Bunce, "Homoallylic Amines Related to Zimeldine. A Comparative Study on Neuronal Serotonin and Norepinephrine Reuptake Based on Conformational Analysis," J.Med.Chem., 31, 913–919 (1988).
71. G. L. Grunewald and Q. Ye, "Synthesis of Benzobicyclo[3.2.1]octanes Involving Inversion of Configuration via an N to O Acetyl Migration," J. Org. Chem., 53, 4021–4026 (1988).
72. W. J. Brouillette, G. B. Brown, T. M. DeLorey, S. S. Shirali and G. L. Grunewald, "Synthesis and Anticonvulsant Activities of 2,4-Oxazolidinediones with 5-Phenyl Substituents. Attempted Correlation with Binding to the Voltage-Dependent Sodium Channel," J. Med. Chem., 31, 2218–2221 (1988).
73. G. L. Grunewald and Q. Ye, "Stereochemical Aspects of Phenylethanolamine Analogues as Substrates of Phenylethanolamine N-Methyltransferase," J. Med. Chem., 31, 1984–1986 (1988).
74. S. M. Knepper, G. L. Grunewald and C. O. Rutledge, "Inhibition of Norepinephrine Transport into Synaptic Vesicles by Amphetamine Analogs," J. Pharmacol. Exp. Ther., 247, 487–494 (1988).
75. Q. Ye and G. L. Grunewald, "Conformationally Restricted and Conformationally Defined Tyramine Analogues as Inhibitors of Phenylethanolamine N-Methyltransferase," J. Med. Chem., 32, 478–486 (1989).
76. G. L. Grunewald, Q. Ye, D. J. Sall, K. R. Criscione and B. Wise, "Conformational and Steric Aspects of Phenylethanolamine and Phenylethylamine Analogues as Substrates or Inhibitors of Phenylethanolamine N-Methyltransferase," Mol. Pharmacol., 35, 93–97 (1989).
77. W. J. Brouillette, G. L. Grunewald, G. B. Brown, T. M. DeLorey, M. S. Akhtar, and G. Liang, "Sodium Channel Binding and Anticonvulsant Activities for the Enantiomers of a Bicyclic 2,4-Oxazolidinedione and Monocyclic Models, " J. Med. Chem., 32, 1577–1580 (1989).
78. G. L. Grunewald, A. J. Kolar, M. S. S. Palanki, V. M. Paradkar, T. J. Reitz and D. J. Sall, "One-step Synthesis of Trifluoromethyl- and of Methoxy-substituted Benzyne Precursors," Org. Prep. Proced. Int.,22, 747–753 (1990).
79. G. L. Grunewald, M. S. S. Palanki and F. Takusagawa, "Structures of exo-2-Formamido-1,4-epoxy-1,2,3,4-tetrahydro-8-trifluoromethylnaphthalene and exo-2-Formamido-1,4-epoxy-1,2,3,4-tetrahydro-6-trifluoromethylnaphthalene," Acta Crystallogr., Sect. C: Cryst. Struct. Commun., C47, 771–775 (1991).
80. G. L. Grunewald and V. M. Paradkar, "A Regioselective Synthesis of 8,9-Dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (LY134046), a Potent Phenylethanolamine N-Methyltransferase Inhibitor," Bioorg. Med. Chem. Lett., 1, 59–60 (1991).
81. G. L. Grunewald, V. M. Paradkar, D. M. Stillions and F. Ching, "A New Procedure for Regioselective Synthesis of 8,9-Dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine (LY134046) and its 3-Methyl Analogue as Inhibitors of Phenylethanolamine N-Methyltransferase (PNMT)," J. Heterocyclic Chem., 28, 1587–1592 (1991).
82. G. L. Grunewald, M. S. S. Palanki and D. Vander Velde, "Use of Transferred Nuclear Overhauser Effects to Determine the Conformation of 1-(3,4-Dichlorophenyl)-2-aminopropane When Bound to the Active Site of Phenylethanolamine N-Methyltransferase (PNMT)," Bioorg. Med. Chem. Lett., 2, 1681–1684 (1992).
83. G. L. Grunewald, N. Skjærbæk and J. A. Monn, "An Active Site Model of Phenylethanolamine N-Methyltransferase Using CoMFA," in Trends in QSAR and Molecular Modelling ’92, C. G. Wermuth, Editor (ESCOM Science Publishers B. V., Leiden), 1993, pp. 513–516.
84. G. I. Georg, S. R. Gollapudi, G. L. Grunewald, C. W. Gunn, R. H. Himes, B. K. Rao, X.-Z. Liang, Y. W. Mirhom, L. A. Mitscher, D. G. Vander Velde, and Q.-M. Ye, "A Reinvestigation of the Taxol Content of Himalayan Taxus wallichiana Zucc. and a Revision of the Structure of Brevifoliol," Bioorg. Med. Chem. Lett., 3, 1345–1348 (1993).
85. R.-S. Tsai, P.-A. Carrupt, B. Testa, N. E. Tayar, G. L. Grunewald and A. F. Casy, "Influence of Stereochemical Factors on the Partition Coefficient of Diastereomers in a Biphasic Octan-1-ol/water System," J. Chem. Res. (S), 298-299 (1993); J. Chem. Res. (M), 1901–1909 (1993).
86. D. G. Vander Velde, G. I. Georg, G. L. Grunewald, C. W. Gunn and L. A. Mitscher, ""Hydrophobic Collapse" of Taxol and Taxotere Solution Conformations in Mixtures of Water and Organic Solvent," J. Am. Chem. Soc., 115, 11650–11651 (1993).
87. K.-H. A. Czaplinski and G. L. Grunewald, "A Comparative Molecular Field Analysis Derived Model of the Binding of Taxol Analogues to Microtubules," Bioorg. Med. Chem. Lett., 4, 2211–2216 (1994).
88. G. L. Grunewald and V. H. Dahanukar, "Synthesis of 3-Alkyl-8-substituted- and 4-Hydroxy-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazepines," J. Heterocyclic Chem., 31, 1609–1617 (1994).
89. G. C. B. Harriman, R. K. Jalluri, G. L. Grunewald, D. G. Vander Velde, G. I. Georg and R. H. Himes, "The Chemistry of the Taxane Diterpene: Stereoselective Synthesis of 10-Deacetoxy-11,12-epoxypaclitaxel," Tetrahedron Lett., 36, 8909–8912 (1995).
90. G. L. Grunewald, V. H. Dahanukar, P. Ching and K. R. Criscione, “Effect of Ring Size or an Additional Heteroatom on the Potency and Selectivity of Bicyclic Benzylamine-Type Inhibitors of the Enzyme Phenylethanolamine N-Methyltransferase,” J. Med. Chem., 39, 3539–3546 (1996).
91. J. M. Caine, I. G. Macreadie, G. L. Grunewald and M. J. McLeish, “Recombinant Human Phenylethanolamine N-methyltransferase: Overproduction in E. coli, Purification and Characterisation,” Protein Expression & Purification, 8, 160–166 (1996).
92. S. F. Victory, D. G. Vander Velde, R.K. Jalluri, G. L. Grunewald and G. I. Georg, “Relative Stereochemistry and Solution Conformation of the Novel Paclitaxel-like Antimitotic Agent Epothilone A,” Bioorg. Med. Chem. Lett., 6, 893–898 (1996).
93. W.-J. Cho and G. L. Grunewald, "Design and Stereoselective Synthesis of Conformationally Constrained Analogues of Zimeldine," Arch. Pharm. Res., 19, 168–170 (1996).
94. G. L. Grunewald, V. H. Dahanukar, T. M. Caldwell and K. R. Criscione, "Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Towards Inhibition of Phenylethanolamine N-Methyltransferase vs. the α
2-Adrenoceptor," J. Med. Chem., 40, 3997–4005 (1997).
95. G. L. Grunewald, V. H. Dahanukar, R. K. Jalluri and K. R. Criscione, "Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure-Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities Toward Phenylethanolamine N-Methyltransferase and the α
2-Adrenoceptor," J. Med. Chem., 42, 118–134 (1999).
96. G. L. Grunewald, T. M. Caldwell, Q. Li and K. R. Criscione, "1,3-Dimethyl-7-substituted-1,2,3,4-tetrahydroisoquinolines as Probes for the Binding Orientation of Tetrahydroisoquinoline at the Active Site of Phenylethanolamine N-Methyltransferase," Bioorg. Med. Chem., 7, 869–880 (1999).
97. G. L. Grunewald, T. M. Caldwell, V. H. Dahanukar, R. K. Jalluri and K. R. Criscione, "Comparative Molecular Field Analysis (CoMFA) Models of Phenylethanolamine N-Methyltransferase (PNMT) and the α
2-Adrenoceptor: The Development of New, Highly Selective Inhibitors of PNMT," Bioorg. Med. Chem. Lett., 9, 481–486 (1999).
98. G. L. Grunewald, V. H. Dahanukar, B. Teoh and K. R. Criscione, "3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines Display Remarkable Potency and Selectivity as Inhibitors of Phenylethanolamine N-Methyltransferase versus the α
2-Adrenoceptor," J. Med. Chem., 42, 1982–1990 (1999).
99. G. L. Grunewald, T. M. Caldwell, Q. Li and K. R. Criscione, "Synthesis and Evaluation of 3-Trifluoromethyl-7-substituted-1,2,3,4-tetrahydroisoquinolines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α
2-Adrenoceptor," J. Med. Chem., 42, 3315–3323 (1999).
100. G. L. Grunewald, T. M. Caldwell, Q. Li, M. Slavica, R. T. Borchardt, W. Wang and K. R. Criscione, "Synthesis and Biochemical Evaluation of 3-Fluoromethyl-1,2,3,4-tetrahydroisoquinolines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α
2-Adrenoceptor," J. Med. Chem., 42, 3588–3601 (1999).
101. G. L. Grunewald, T. M. Caldwell, Q. Li, V. H. Dahanukar, B. McNeil and K. R. Criscione, "Enantiospecific Synthesis of 3-Fluoromethyl-, 3-Hydroxymethyl-, and 3-Chloromethyl-1,2,3,4-tetrahydroisoquinolines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α
2-Adrenoceptor," J. Med. Chem., 42, 4351–4361 (1999).
102. T. C. Boge, M. Hepperle, D. G. Vander Velde, C. W. Gunn, G. L. Grunewald and G. I. Georg, "The Oxetane Conformational Lock of Paclitaxel: The Structural Analysis of D-Secopaclitaxel," Bioorg. Med. Chem. Lett., 9, 3041–3046 (1999).
103. G. L. Grunewald, M. J. McLeish, and K. R. Criscione. "Phenylethanolamine N-Methyltransferase Kinetics: Bovine versus Recombinant Human Enzyme," Bioorg. Med. Chem. Lett., 11, 1579–1582 (2001).
104. G. L. Grunewald, V. H. Dahanukar, and K. R. Criscione. "Effect of a 3-Alkyl-, 4-Hydroxy- and/or 8-Aromatic-substituent on the Phenylethanolamine N-Methyltransferase Inhibitory Potency and α
2-Adrenoceptor Affinity of 2,3,4,5-Tetrahydro-1H-2-benzazepines," Bioorg. Med. Chem., 9, 1957–1965 (2001).
105. G. L. Grunewald, T. M. Caldwell, Q. Li, and K. R. Criscione. "Synthesis and Evaluation of 4-Fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as Selective Inhibitors of Phenylethanolamine N-Methyltransferase versus the α
2-Adrenoceptor," J. Med. Chem., 44, 2849–2856 (2001).
106. J. L. Martin, J. Begun, M. J. McLeish, J. M. Caine, and G. L. Grunewald. “Getting the Adrenaline Going: Crystal Structure of the Adrenaline-Synthesizing Enzyme PNMT,” Structure, 9,977–985 (2001).
107. J. Begun, M. J. McLeish, J. M. Caine, E. Palant, G. L. Grunewald and J. L. Martin. “Crystallization of PNMT, the Adrenaline-synthesizing Enzyme, is Critically Dependent on a High Protein Concentration,” Acta Cryst., D58, 314–315 (2002).
108. Lankin, D. C.; Grunewald, G. L.; Romero, F. A.; Oren, I.; Snyder, J. P. “The NH—FC Dipole Orientation Effect for Pendent Exocyclic CH 2F,” Org. Lett., 4, 3557–3560 (2002).
109. Stone, E. A.; Grunewald, G. L.; Lin, Y.; Ahsan, R.; Rosengarten, H.; Kramer, H. K.; Quartermain, D. “Role of Epinephrine Stimulation of CNS α1-Adrenoceptors in Motor Activity in Mice,” Synapse, 49, 1, 67–76 (2003).
110. McMillan, F. M.; Archbold, J.; McLeish, M. J.; Caine, J. M.; Criscione, K. R.; Grunewald, G. L.; Martin, J. L. “Molecular Recognition of Sub-micromolar Inhibitors by the Adrenaline Synthesising Enzyme PNMT,” J. Med. Chem., 47, 37–44 (2004).
111. Wu, Q.; Criscione, K. R.; Grunewald, G. L.; McLeish, M. J. “Phenylethanolamine N-Methyltransferase Inhibition: Re-evaluation of Kinetic Data,” Bioorg. Med. Chem. Lett., 14, 4217–4220 (2004).
112. Romero, F. A.; Vodonick, S. M.; Criscione, K. R.; McLeish, M. J.; Grunewald, G. L. “Inhibitors of Phenylethanolamine N-Methyltransferase That Are Predicted to Penetrate the Blood-Brain Barrier: Design, Synthesis and Evaluation of 3-Fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines That Possess Low Affinity toward the α
2-Adrenoceptor,” J. Med. Chem., 47, 4483–4493, (2004).
113. Grunewald, G. L.; Romero, F. A.; Criscione, K. R. “Nanomolar Inhibitors of CNS Epinephrine Biosynthesis: (R)-(+)-3-Fluoromethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines as Potent and Highly Selective Inhibitors of Phenylethanolamine N-Methyltransferase,” J. Med. Chem., 48, 1806–1812, (2005).
114. Grunewald, G. L.; Romero, F. A.; Criscione, K. R. “3-Hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline Inhibitors of Phenylethanolamine N-Methyltransferase that Display Remarkable Potency and Selectivity,” J. Med. Chem., 48, 134–140 (2005).
115. Grunewald, G. L.; Romero, F. A.; Seim, M. R.; Criscione, K. R. Deupree, J. D.; Spackman, C. C.; Bylund, D. B. “Exploring the Active Site of Phenylethanolamine N-Methyltransferase with 3-Hydroxyethyl- and 3-Hydroxypropyl-7-substituted-1,2,3,4-tetrahydrisoquinolines,” Bioorg. Med. Chem. Lett., 15, 1143–1147 (2005).
116. Grunewald, G. L.; Romero, F. A.; Chieu, A. D.; Fincham, K. J.; Bhat, S. R.; Criscione, K. R. “Exploring the Active Site of Phenylethanolamine N-Methyltransferase: 3-Alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline Inhibitors,” Bioorg. Med. Chem., 13, 1261–1273 (2005).
117. Gee, C. L.; Nourse, A.; Hsin, A-Y.; Wu, Q.; Tyndall, J. D.; Grunewald, G. L.; McLeish, M. J.; Martin, J. L. “Disulfide-Linked Dimers of Human Adrenaline Synthesizing Enzyme PNMT are Catalytically Active.” Biochim. Biophys. Acta , 1750, 82–92 (2005).
118. Grunewald, G. L.; Lu, Jian; Criscione, K. R.; Okoro, C. “Inhibitors of Phenylethanolamine N-Methyl¬transferase Devoid of α
2-Adrenoceptor Affinity.” Bioorg. Med. Chem. Lett., 15, 5319–5323 (2005).
119. Wu, Q.; Gee, C. L.; Lin, F.; Tyndall, J. D.; Martin, J. L.; Grunewald, G. L.; McLeish, M. J. “Structural, Mutagenic, And Kinetic Analysis of the Binding of Substrates and Inhibitors of Human Phenylethanolamine N-Methyltransferase.” J. Med. Chem., 48, 7243–7252 (2005).
120. Gee, C. L.; Tyndall, J. D. A.; Grunewald, G. L.; Wu, Q.; McLeish, M. J.; Martin, J. L. “Mode of Binding of Methyl Acceptor Substrates to the Adrenaline-Synthesizing Enzyme Phenylethanolamine N-Methyltransferase: Implications for Catalysis.” Biochemistry, 44, 16875–16885 (2005).
121. Grunewald, G. L.; Seim, M. R.; Lu, J.; Criscione, K. R. “Application of the Goldilocks Effect to the Design of Potent and Selective Inhibitors of Phenylethanolamine N-Methyltransferase: Balancing pKa and Steric Effects in the Optimization of 3-Methyl-1,2,3,4-tetrahydroisoquinoline Inhibitors by β-Fluorination.” J. Med. Chem. 49, 2939–2952 (2006).
122. Grunewald, G. L.; Seim, M. R.; Regier, R. C.; Martin, J. L.; Gee, C. L.; Drinkwater, N.; Criscione, K. R. “Comparison of the Binding of 3-Fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with Their Isosteric Sulfonamides to the Active Site of Phenylethanolamine N-Methyltransferase.” J. Med. Chem. 49, 5424–5433 (2006).
123. Grunewald, G. L.; Seim, M. R.; Regier, R. C.; Criscione, K. R. “Exploring the Active Site of Phenylethanolamine N-Methyltransferase with 1,2,3,4-Tetrahydrobenz[h]isoquinoline Inhibitors.” Bioorg. Med. Chem. 15, 1298–1310 (2007).
For More Information, Please Contact:
Dr. Gary Grunewald
1251 Wescoe Hall Dr.
4060a Malott Hall
Tel: 785-864-4497
FAX: 785-864-5326
Email:
ggrunewald@ku.edu
