Drug Design

  • John J. Baldwin


The discovery of drugs depends on a number of interdependent factors, including insight, serendipity, and persistence. A common characteristic of the successful program is a clearly delineated strategy based on quantitative pharmacological assays. The particular problem chosen often will influence this strategy and dictate the type of approach; that is, either a rational or an empirical one. Depending on this selection, the synthetic targets then will either be derived from drug design concepts for the former or developed around systematic variation of a lead compound for the latter.


Angiotensin Converting Enzyme Drug Discovery Drug Design Drug Research Cross Term 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abeles, R. H. and Maycock, A. L. (1976) Suicide enzyme inactivators. Acc. Chew. Res. 9, 313–319.CrossRefGoogle Scholar
  2. Albers-Schonberg, G„ Arison, B. H., Chabala, J. C., Douglas, A. W., Eskola, P., Fisher, M. H., Lusi, A., Mrozik, H., Smith, J. L., and Tolman, R. L. (1981) Avermectins. Structure determination. J. Am. Chem. Soc. 103, 4216–4221.Google Scholar
  3. Albert, A. (1971) Relations between molecular structure 6501 and biological activity: Stages in the evolution of current concepts. Attn. Rev. Pharmacol. 11, 13–36.CrossRefGoogle Scholar
  4. Albert, A. (1982) The long search for valid structure-action relationships in drugs. J.Med. Chem. 25, 1–5.PubMedCrossRefGoogle Scholar
  5. Alberts, A. W., Chen., Kuron, G., Hunt, V., Huff, H., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H., Harris, E., Patchett, A., Monaghan, R., Currie, S., Stapley, E., Albers-Schonberg, G., Hensens, O., Hirshfield, J., Hoogsteen, K., Liesch, J., and Springer, J. (1980) Mevinolin: A highly potent competitive inhibitor of hydroxymethvlglutaryl-coenzyme A reductase and a cholesterol- lowering agent. Proc. Natl. Acad. Sci. USA 77, 3957–3961.PubMedCrossRefGoogle Scholar
  6. Anand, N. (1983) Molecules with restricted conformational mobility—an approach to drug design. Proc. Indian Natn. Sci. Acad. 49, A, 233–255.Google Scholar
  7. Andrews, P. R. and Winkler, D. A. (1984) The Design and Medicinal Applications of Transition State Analogues, in Drug Design: Fact or Fantasy? ( Jolles, G. and Wooldridge, K. R. H., eds.) Academic, New York.Google Scholar
  8. Ariens, E. J. (1971) A General Introduction to the Field of Drug Design, in Drug Design vol. I (Ariens, E.)., ed.) Academic, New York.Google Scholar
  9. Ariens, E. J. (1980) Design of Safer Chemicals, in Drug Design vol. IX ( Ariens, E. J., ed.) Academic, New York.Google Scholar
  10. Ariens, E. J. and Simonis, A. M. (1982) Optimalization of Pharmacokinetics—An Essential Aspect of Drug Development—by “Metabolic Stabilization,” in Strategy in Drug Research (Keverling Buisman, J. A., ed.) Elsevier, Amsterdam.Google Scholar
  11. Austel, V. (1982) A manual method for systematic drug design. Eur. J. Med. Chem. 17, 9–16.Google Scholar
  12. Austel, V. (1984) Design of test series in medicinal chemistry. Drugs of the Future 9, 349–365.Google Scholar
  13. Austel, V. and Kutter, E. (1981) The theory of sets as a tool in systematic drug design. Arzneimittelforsch. /Drug Res 31, 130–135.Google Scholar
  14. Baker, D.J., Beddell, C. R., Champness, J. N., Goodford, P.J., Norrington, F. E. A., Smith, D. R., and Stammers, D. K. (1981) The binding of trimethoprim to bacterial dihydrofolate reductase. FEBS Lett. 126, 49–52.PubMedCrossRefGoogle Scholar
  15. Baldwin, J. J., Lumma, W. C., Lundell, G. F., Ponticello, G. S., Raab, A. W., Engelhardt, E. L., Hirschmann, R., Sweet, C. S., and Scriabine, A. (1979) Symbiotic approach to drug design: Anti-hypertensive β-adrenergic blocking agents. J. Med. Chern. 22, 1284–1290.CrossRefGoogle Scholar
  16. Bodor, N. (1982) Soft drugs: Strategies for Design of Safer Drugs, in Strategy in Drug Research ( Keverling Buisman, J. A., ed.) Elsevier, Amsterdam.Google Scholar
  17. Bodor, N. (1984a) Novel Approaches to the Design of Safer Drugs: Soft Drugs and Site-Specific Chemical Delivery Systems, in Advances in Drug Research vol. 13 (Testa, B., ed.) Academic, New York.Google Scholar
  18. Bodor, N. (1984b) Soft drugs: Principles and methods for the design of safe drugs. Med. Res. Rev. 4, 449–469.PubMedCrossRefGoogle Scholar
  19. Boger, J. (1983) Renin Inhibitors. Design of Angiotensinogen Transition- State Analogs Containing Statine, in Peptides: Structure and Function ( Hruby, V. J. and Rich, D. H„ eds.) Pierce Chemical Company, Rockford, Illinois.Google Scholar
  20. Boger, J., Lohr, N. S„ Ulm, E. H., Poe, M., Blaine, E. H., Fanelli, G. M., Lin, T. Y„ Payne, L. S., Schorn, T. YV., LaMont, B. I., Vassil, T. C., Stabilito, I. I., Veber, D. F., Rich, D. H., and Bopari, A. S. (1983) Novel renin inhibitors containing the amino-acid statine. Nature 303, 81–84.PubMedCrossRefGoogle Scholar
  21. Brugger, W. E. and Jurs, P. C. (1977) Extraction of important molecular features of musk compounds using pattern recognition techniques. J. Agric. Food Chem. 25, 1158–1164.PubMedCrossRefGoogle Scholar
  22. Burchall, J. J. and Hitchings, G. H. (1965) Inhibitor binding analysis of dihydrofolate reductases from various species. Mol. Pharmacol. 1, 126–136.PubMedGoogle Scholar
  23. Burger, A. (1970) Hallucinogenic Agents, in Medicinal Chemistry 3rd ed. ( Burger, A., ed.) Wiley-Interscience, New York.Google Scholar
  24. Burger, A. (1983) A Guide to the Chemical Basis of Drug Design. Wiley, New York.Google Scholar
  25. Bustard, T. M. (1974) Optimization of alkyl modifications by Fibonacci search. J. Med. Chem. 17, 777–778.PubMedCrossRefGoogle Scholar
  26. Cannon, J. G., Lee, T., Goldman, D., Long, J. P., Flynn, J. R., Verimer, T., Costall, B., and Naylor, R. J. (1980) Congeners of the β conformer of dopamine derived from cis- and tras-octahydrobenzo(f)quinoline and trans-octahydrobenzo(g) quinoline. J. Med. Chem. 23, 1–5.PubMedCrossRefGoogle Scholar
  27. Cha, S., Agarwal, R. P., and Parks, R. E., Jr. (1975) Tight-binding inhibitors. II. Non-steady state nature of inhibition of milk xanthine oxidase by allopurinol and alloxanthine and of human erythrocytic adenosine deaminase by coformycin. Biochem. Pharmacol. 24, 2187–2197.Google Scholar
  28. Charton, M. (1983) The Upsilon Steric Parameter-Definition and Determination, in Steric Effects in Drug Design (Charton, M. and Motoc, I., eds.) Springer-Verlag, New York.Google Scholar
  29. Charton, M. and Motoc, I. (1983) Introduction, in Steric Effects in Drug Design ( Charton, M. and Motoc, I., eds.) Springer-Verlag, New York.Google Scholar
  30. Chou, J. T. and Jurs, P. C. (1979) Computer-assisted computation of partition coefficients from molecular structures using fragment constants. J. Chem. Inf. Comput. Sci. 19, 172–178.CrossRefGoogle Scholar
  31. Cohen, N. C. (1983) Towards the rational design of new leads in drug research. TIPS 503–506.Google Scholar
  32. Conover, L. H. (1971) Discovery of drugs from microbiological sources. Adv. Chem. Ser. 108, 33–80.CrossRefGoogle Scholar
  33. Cromartie, T. H. and Walsh, C. (1975) Mechanistic studies on the rat kidney flavoenzyme L-alpha-hvdroxyacid oxidase. Biochemistry 14, 3482–3489.PubMedCrossRefGoogle Scholar
  34. Curd, J., Smith, T. W., Jaton, J. C., and Haber, E. (1971) The isolation of digoxin-specific antibodv and its use in reversing the effects of digoxin. Proc. Natl. Acad. Sci. USA 68, 2401–2406.PubMedCrossRefGoogle Scholar
  35. Douglas, K. T. (1983) Transition-state analogues in drug design. Chem. Ind.. 311–315.Google Scholar
  36. Duchamp, D. J. (1979) Molecular mechanics and crystal structure analysis in drug design. ACS Symp. Ser. 112. 79–102.CrossRefGoogle Scholar
  37. Dufau, M. L„ Ryan, D. W., Baukal, A. J., and Catt, K. J. (1975) Gonadotropin receptors. Solubilization and purification by affinity chromatography. J. Biol. Chem. 250. 4822–4824.Google Scholar
  38. Dunn, W. J., Greenberg, M. J., and Callejas, S. S. (1976) Use of cluster- analysis in development of structure-activity relations for antitumor triazenes. J.Med. Chem. 19, 1299–1301.PubMedCrossRefGoogle Scholar
  39. Editorial (1981) Drug licensing or innovation. Lancet II, 788.Google Scholar
  40. Endo, A., Kuroda, M., and Tsujita, Y. (1976) ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum. J. Antibiotics 29, 1346–1348.Google Scholar
  41. Esaki, T. (1982) Quantitative drug design studies. V. Approach to lead generation by pharmacophoric pattern searching. Chem. Pharm. Bull. (Tokyo) 30. 3657–3661.Google Scholar
  42. Farnsworth, N. R. and Bingel, A. S. (1977) Problems and prospects of discovering new drugs from higher plants by pharmacological screening. New Nat. Prod. Plant Drugs Pharmacol. I, Proc. Int. Cong., 1st, 1–22.Google Scholar
  43. Foye, W. O. (1974) Principles of Medicinal Chemistry pp. 93–102. Lea & Febiger, Philadelphia.Google Scholar
  44. Free, S. M. and Wilson, J. VV. (1964) A mathematical contribution to structure-activity studies. J. Med. Chem. 7, 395–399.PubMedCrossRefGoogle Scholar
  45. Freidinger, R. M. and Veber, D. F. (1984) Design of novel cyclic hexapep- tide somatostatin analogs from a model of the bioactive conformation. ACS Symp. Ser. 251, 169–187.CrossRefGoogle Scholar
  46. Fujita, T. (1984) The Role of QSAR in Drug Design, in Drug Design: Fact or Fantasy? ( Jolles, G. and Wooldridge, K. R. H., eds.) Academic, New York.Google Scholar
  47. Gabayani, Z., Surjan, P., and Naray-Szabo, G. (1982) Application of topological molecular transforms to rational drug design. Eur. J. Med. Chem.-Chim. Ther. 17, 307–311.Google Scholar
  48. Ganellin, C. R. (1982) Cimetidine, in Chronicles of Drug Discovery vol. 1 (Bindra, J. S. and Lednicer, D., eds.) Wiley, New York.Google Scholar
  49. Goodford, P. J. (1984) Drug design by the method of receptor fit. J. Med. Chem. 27, 557–564.Google Scholar
  50. Gordon, E. M., Godfrey, J. D., Pluscec, J., VonLangen, D., and Natarajan, S. (1985) Design of peptide derived amino alcohols as transition- state analog inhibitors of angiotensin converting enzyme. Biochern. Biophys. Res. Commun. 126, 419–426.CrossRefGoogle Scholar
  51. Gross, F. (1984) Antihypertensive therapy: Modern concepts, future aspects in research. Triangle 23, 25–32.Google Scholar
  52. Gund, P. (1984) Present and future computer aids to drug design. X-Ray Crystallogr. Drug Action, Course Int. Sch. Crystallogr. 9th, 495–506.Google Scholar
  53. Haber, E. (1983) Antibodies as models for rational drug design. Biochem. Pharmacol. 32, 1967–1977.PubMedCrossRefGoogle Scholar
  54. Halberstam, M. J. (1979) Too many drugs? Forum on Medicine 2, 170–291.PubMedGoogle Scholar
  55. Hansch, C. (1974) Bioisosterism. Intrascience Chem. Rep. 8, 17–25.Google Scholar
  56. Hansch, C. (1982) Dihydrofolate reductase inhibition. A study in the use of X-ray crystallography, molecular graphics, and quantitative structure-activity relations in drug design. Drug. Intel. Clin. Pharm. 16, 391–396.Google Scholar
  57. Hansch, C. (1984) On the state of QSAR. Drug. Infor. J. 18, 115–122.Google Scholar
  58. Hansch, C. and Blaney, J. M. (1984) The New Look to QSAR, in Drug Design: Fact or Fantasy? (Jolles, G. and Wooldridge, K. K. H., eds.) Academic, New York.Google Scholar
  59. Hansch, C. and Leo, A. J. (1979) Substituent Constants for Correlation Analysis in Chemistry and Biology. Wiley, New York.Google Scholar
  60. Hansch, C., Unger, S. H., and Forsythe, A. B. (1973) Strategy in drug design. Cluster analysis as an aid in the selection of substituents. J. Med. Chem. 16, 1217–1222.PubMedCrossRefGoogle Scholar
  61. Hathway, D. E. (1982) Structure-activity considerations; a synthesis of ideas. Chem. Biol. Interact. 42. 1–26.PubMedCrossRefGoogle Scholar
  62. Henry, D. R., Jurs, P. C, and Denny, W. A. (1982) Structure-antitumor activity relationships of 9-anilinoacridines using pattern recognition. J. Med. Chem. 25, 899–908.PubMedCrossRefGoogle Scholar
  63. Hopfinger, A. J. (1984) Computational chemistry, molecular graphics and drug design. Pharm. Int. 5, 224–228.Google Scholar
  64. Jurs, P. C. (1983) Studies of relationships between molecular structure and biological activity by pattern recognition methods. Struct.-Act. Correl. Predict. Tool Toxicol. (Golberg, L., ed.) Hemisphere, Washington, DC.Google Scholar
  65. Jurs, P. C., Ham, C. L., and Brugger, W. E. (1981) Computer-assisted studies of chemical structure and olfactory quality using pattern recognition techniques. ACS Symp. Ser. 148. 143–160.CrossRefGoogle Scholar
  66. Jurs, P. C., Hasan, M. N., Henry, D. R., Stouch, T. R„ and Whalen- Pedersen, E. K. (1983) Computer-assisted studies of molecular structure and carcinogenic activity. Fund. Appl. Toxicol. 3, 343–349.CrossRefGoogle Scholar
  67. Kalman, T. I. (1981) Enzyme inhibition as a source of new drugs. Drug Dev. Res. 1, 311–328.CrossRefGoogle Scholar
  68. Kier, L. B. (1980) Molecular Connectivity as a Description of Structure for SAR Analyses, in Physical Chemical Properties of Drugs ( Yalkowskv, S. H., Sinkula, A. A., and Valvani, S. C., eds.) Dekker, New York.Google Scholar
  69. Kirschner, G. L. and Kowalski, B. R. (1979) The Application of Pattern Recognition to Drug Design, in Drug Design vol. VIII ( Ariens, E. J., ed.) Academic, New York.Google Scholar
  70. Klopman, G. and Contreras, R. (1985) Use of artificial intelligence in structure-activity correlations of anticonvulsant drugs. Mol. Pharmacol. 27, 86–93.PubMedGoogle Scholar
  71. Kohli, J. D., Goldberg, L. I., and Nand, N. (1979) 1-Aminomethyl isochromans: New vascular dopamine agents. Pharmacologist 21, 202.Google Scholar
  72. Korolkovas, A. and Burckhalter, J. H. (1976) Essentials of Medicinal Chemistry, pp. 23–26. Wiley, New York.Google Scholar
  73. Kutter, E. and Austel, V. (1981) Application of the theory of sets to drug designArzneimittelforsch. /Drug Res 31, 135–141.Google Scholar
  74. Kuyper, L. F., Roth, B„ Baccanari, D. P., Ferone, R., and Beddell, C. R. (1982) Receptor-based design of dihydrofolate-reductase inhibitors- comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogs. J. Med. Chem. 25, 1120–1122.Google Scholar
  75. Lee, H. J., Khalil. M. A., and Lee, J. W. (1984) Antedrug—a conceptual basis for safer anti-inflammatory steroids. Drugs Under Experimental and Chemical Research 10, 835–844.Google Scholar
  76. Lienhard, G. E. (1972) Transition state analogs as enzyme inhibitors. Ann. Rep. Med. Chem. 7, 249–258.CrossRefGoogle Scholar
  77. Lienhard, G. E. (1973) Enzvme catalysis and transition-state theorv. Science 180, 140–154.CrossRefGoogle Scholar
  78. Lindquist, R. N. (1975) The Design of Enzyme Inhibitors: Transition State Analogs, in Drug Design vol. V (Ariens, E., ed.) Academic, New- York.Google Scholar
  79. Marciniszyn, Hartsuck, J. A., and Tang, J. (1976) Mode of inhibition of acid proteases by pepstatin. J. Biol. Chem. 251, 7088–7094.PubMedGoogle Scholar
  80. Marshall, G. R. (1984) Computational Chemistry and Receptor Characterization, in Drug Design: Fact or Fantasy? ( Jolles, G. and Wooldridge, K. R. H., eds.) Academic, New York.Google Scholar
  81. Marshall, G. R., Barry, C. D., Bosshard, H. E., Dammkoehler, R. A., and Dunn, D. A. (1979) The conformational parameter in drug design: The active analog approach. ACS Symp. Ser. 112. 205–226.CrossRefGoogle Scholar
  82. Martin. Y. C. (1978) Quantitative Drug Design. A Critical Introduction. Dekker. New York.Google Scholar
  83. Martin, Y. C. (1979) Advances in the Methodology of Quantitative Drug Design, in Drug Design vol. VIII ( Ariens, E. J., ed.) Academic, New York.Google Scholar
  84. Martin, Y. C. (1981) A practitioner’s perspective of the role of quantitative structure-activity analvsis in medicinal chemistry. J. Med. Chem. 24, 229–237.PubMedCrossRefGoogle Scholar
  85. Martin, Y. C. (1983) Studies of relationships between structural properties and biological activity by Hansch analysis. Struct.-Act. Correl. Predict. Tool Toxicol. (Golberg, L., ed.), Hemisphere, Washington, DC.Google Scholar
  86. Martin, Y. C. and Panas, H. N. (1979) Mathematical considerations in series design. J. Med. Chem. 22, 784–791.PubMedCrossRefGoogle Scholar
  87. Martin. Y. C., Holland, J. B., Jarboe, C. H„ and Plotnikoff, N. (1974) Discriminant analysis of the relationship between physical properties and the inhibition of monoamine oxidase by aminotetralins and aminoindans. J. Med. Chem. 17, 409–416.PubMedCrossRefGoogle Scholar
  88. Maxwell, R. A. (1984) The state of the art of the science of drug discovery—an opinion. Drug Dev. Res. 4, 375–389.CrossRefGoogle Scholar
  89. Metcalf, B. W. and Jund, K. (1977) Synthesis of beta, gamma-unsaturated amino acids as potential catalytic irreversible enzyme inhibitors. Tetrahedron Lett. 3689–3692.Google Scholar
  90. Meunier, J. C., Olson, R. YV., Menez, A., Fromageot, P., Boquet, P., and Changeux, J. P. (1972) Some physical properties of the cholinergic receptor protein from Electrophorus electricus revealed by a tritiated a-toxin from Naja nigricollis venom. Biochemistry 11, 1200–1210.PubMedCrossRefGoogle Scholar
  91. Motoc, I., ed. (1983) Molecular Shape Descriptors, in Steric Effects in Drug Design ( Charton, M. and Motoc, I., eds.) Springer-Verlag, New York.Google Scholar
  92. Nicolaus, B. J. R. (1983) Symbiotic Approach to Drug Design, in Decision Making in Drug Research ( Gross, F., ed.) Raven, New York.Google Scholar
  93. Notari, R. E. (1981) Prodrug design. Pharmacol. Ther. 14, 25–53.PubMedCrossRefGoogle Scholar
  94. Oelschlager, II. (1982) Drug Biotransformation as a Source of Drug Development, in Strategy in Drug Research ( Keverling Buisman, J. A., ed.) Elsevier, Amsterdam.Google Scholar
  95. Olson, G. L., Cheung, H., Morgan, K. D., Blount, J. F., Todaro, L., Berger, L., Davidson, A. B., and Boff, E. (1981) A dopamine receptor model and its application in the design of a new class of rigid pyrrolo[2,3-g] lisoquinoline antipsychotics. J. Med. Chem. 24, 1026–1034.PubMedCrossRefGoogle Scholar
  96. Pitman, I. H. (1981) Pro-drugs of amides, imides and amines. Med. Res. Rev. 1, 189–214.PubMedCrossRefGoogle Scholar
  97. Ramiller, N. (1984) Computer-assisted studies in structure-activity relationships. Am. Lab. 78–88.Google Scholar
  98. Rando, R. R. (1977) Mechanism of irreversible inhibition of gamma-amino- butyric acid alpha-ketoglutaric acid transaminase by neurotoxin gabaculine. Biochemistry 16. 4604–4610.PubMedCrossRefGoogle Scholar
  99. Robinson, F. A. (1974) Therapeutic innovation—the end or a new beginning? Chem. Brit. 10. 129–136.Google Scholar
  100. Rose, S. L. and Jurs, P. C. (1982) Computer-assisted studies of structure activity relationships of N-nitroso compounds using pattern recognition. J. Med. Chem. 25. 769–776.PubMedCrossRefGoogle Scholar
  101. Rozenblit, A. B. (1982) Computer-Assisted Drug Design. Strategy and Algorithms, in Strategy in Drug Research ( Keverling Buisman, J. A., ed.) Elsevier, Amsterdam.Google Scholar
  102. Schmidt, P. G., Bernatowicz, M. S., and Rich. D. H. (1982) Pepstatin binding to pepsin-enzyme conformation changes monitored by nuclear magnetic resonance. Biochemistry 21, 6710–6716.PubMedCrossRefGoogle Scholar
  103. Seiler, M. P. and Markstein, R. (1984) Further characterization of structural requirements for agonists at the striatal dopamine D2 receptor and a comparison with those at the striatal dopamine D1, receptor. Mol. Pharmacol. 26, 452–457.PubMedGoogle Scholar
  104. Silverman, R. B. and Hoffman, S. J. (1984) The organic chemistry of mechanism-based enzyme inhibition: A chemical approach to drug design. Med. Res. Rev. 4, 415–447.PubMedCrossRefGoogle Scholar
  105. Silverman, R. B. and Levy, M. A. (1981) Mechanism of inactivation of gamma-aminobutyric acid alpha-ketoglutaric acid aminotransferase by 4-amino-5-halopentanoic acids. Biochemistry 20, 1197–1203.PubMedCrossRefGoogle Scholar
  106. Skala, G., Smith, C. W., Taylor, C. J. and Ludens, J. H. (1984) A conformationally constrained vasopressin analog with antidiuretic antagonistic activity. Science 226, 443–445.PubMedCrossRefGoogle Scholar
  107. Smith. T. W., Butler, V. P., Haber, E., Fozzard, H„ Marcus, F. I., Bremner, VV. F., Schulman, I. C., and Phillips, A. (1982) Treatment of life-threatening digitals intoxication with digoxin-specific Fab antibody fragments. N. Eng. J. Med. 307, 1357–1362.CrossRefGoogle Scholar
  108. Soper, T. S., Manning,. M., Marcotte, P. A., and Walsh, C. T. (1977) Inactivation of bacterial D-amino acid transaminases by olefinic amino acid-K-vinylglycine. J. Biol. Chem. 252, 1571–1575.PubMedGoogle Scholar
  109. Stark, G. R. and Bartlett, P. A. (1983) Design and use of potent, specific enzyme inhibitors. Pharmacol. Ther. 23, 45–78.PubMedCrossRefGoogle Scholar
  110. Testa, B. (1984) Drugs? Drug research? Advances in drug research? Musings of a Medicinal Chemist, in Advances in Drug Research vol. 13 Academic, New York.Google Scholar
  111. Tewksbury, D. A., Dart, R. A., and Travis, J. (1981) The amino terminal amino acid sequence of human angiotensinogen. Biochem. Biophys. Res. Commun. 99, 1311–1315.Google Scholar
  112. Thornber, C. VV. (1979) Isosterism and molecular modification in drug design. Chem. Soc. Rev. 18, 563–580.CrossRefGoogle Scholar
  113. Thorsett, E. D., Harris, E. E., Peterson, E. R., Greenlee, VV. J., Patchett. A. A., Ulm, E. H., and Vassil, T. C. (1982) Phosphorus-containing inhibitors of angiotensin converting enzyme. Proc. Natl. Acad. Sci. USA 79, 2176–2180.Google Scholar
  114. Tickle, I. J., Sibanda, B. L., Pearl, L. H., Hemmings, A. M., and Blundell, T. L. (1984) Protein crystallography, interactive computer graphics, and drug design. X-Ray Ctystallogr. Drug Action, Course Int. Sch. Crystallogr. 9th, 427–440.Google Scholar
  115. Topliss, J. G. and Edwards, R. P. (1979) Chance factors in studies of quantitative structure-activity relationships. J. Med. Chem. 22. 1238–1244.PubMedCrossRefGoogle Scholar
  116. Topliss, J. G. and Martin, Y. C. (1975) Utilization of Operational Schemes for Analog Synthesis in Drug Design, in Drug Design vol. V ( Ariens, E. J., ed.) Academic, New York.Google Scholar
  117. Tute, M. S. (1971) Principles and Practice of Hansch Analysis: A Guide to Structure-Activity Correlation for the Medicinal Chemist, in Advances in Drug Research ( Harper, N. J. and Simmonds, A. B., eds.) Academic, New York.Google Scholar
  118. Veber, D. F. (1982) Peptide analogue design based on conformation. Special Publication of the Royal Society of Chemistry 42, 309–319.Google Scholar
  119. Venter, J. C. (1982) Immobilized and insolubilized drugs, hormones, and neurotransmitters: Properties, mechanisms of action and applications. Pharmacol. Rev. 34, 153–180.PubMedGoogle Scholar
  120. Volkman, P. H., Kohli, J. D., Goldberg, L. I., Cannon, J. G., and Lee, T. (1977) Conformational requirements for dopamine-induced vasodilation. Proc. Natl. Acad. Sci. USA 74, 3602–3606.PubMedCrossRefGoogle Scholar
  121. Walsh, C. (1978) Chemical approaches to study of enzymes catalyzing redox transformations. Ann. Rev. Biochem. 47, 881–931.PubMedCrossRefGoogle Scholar
  122. Weller, H. N., Gordon, E. M., Rom, M. B., and Pluscec, J. (1984) Design of conformationally constrained angiotensin-converting enzyme inhibitors. Biochem. Biophys. Ren. Commun. 125, 82–89.CrossRefGoogle Scholar
  123. Wermuth, C. G. (1984) Designing Prodrugs and Bioprecursors, in Drug Design; Fact or Fantasy? ( Jolles, G. and Wooldridge, K. R. H., eds.) Academic, New York.Google Scholar
  124. Westwood, R. (1981) The synthesis of novel heterocyclics as one approach to drug discovery. Bull. Soc. Chim. Belg. 90, 777–780.CrossRefGoogle Scholar
  125. Wold, S. and Dunn, W. J., Ill (1983) Multivariate quantitative Structure-activity relationships (QSAR): Conditions for their applicability. J. Chem. Inf. Comput. Sci. 23, 6–13.CrossRefGoogle Scholar
  126. Wolfenden, R. (1969a) On the rate-determining step in the action of adenosine deaminase. Biochemistry 8, 2409–2415.PubMedCrossRefGoogle Scholar
  127. Wolfenden, R. (1969b) Transition state analogs for enzyme catalvsis. Nature 223, 704–705.PubMedCrossRefGoogle Scholar
  128. Wolfenden, R. (1972) Analog approaches to the structure of the transition state in enzyme reactions. Acc. Chem. Res. 5, 10–18.CrossRefGoogle Scholar
  129. Wolfenden, R. (1976) Transition-state analog inhibitors and enzyme catalysts. Ann. Rev. Biophys. Bioeng. 5, 271–306.CrossRefGoogle Scholar
  130. Wolfenden, R. (1978) Transition-State Affinity as a Basis for the Design of Enzyme Inhibitors, in Transition States of Biochemical Processes Plenum, New York.Google Scholar
  131. Wooldridge, K. R. H. (1984) The Virtues of Present Strategies for Drug Discovery, in Drug Design: Fact or Fantasy? ( Jolles, G. and VVooldridge, K. R. H., eds.) Academic, New York.Google Scholar
  132. Wootton, R., Cranfield, R., Sheppey, G. C., and Goodford, P. J. (1975) Physicochemical-activitv relationships in practice. 2. Rational selection of benzenoid substituents. J. Med. Chem. 18, 607–613.PubMedCrossRefGoogle Scholar
  133. Yuta, K. and Jurs, P. C. (1981) Computer-assisted structure-activity studies of chemical carcinogens. Aromatic amines. J. Med. Chem. 24, 241–251.PubMedCrossRefGoogle Scholar

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© The Humana Pres Inc. 1987

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  • John J. Baldwin

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