Enlistment of combinatorial techniques in drug development

Current Opinion in Drug Discovery and Development

Volumn 2, Issue 4, 1999, Pages 332-341

  Lee, S ^a  

^a Molecumetics Ltd   (United States)

Author keywords

Combinatorial library; Diversity; High throughput screening; Solid phase

Indexed keywords

HETEROCYCLIC COMPOUND; METALLOPROTEINASE INHIBITOR; NICOTINAMIDE;

ARTICLE; BIODIVERSITY; CHEMICAL ANALYSIS; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUCLEAR OVERHAUSER EFFECT; SOLID PHASE EXTRACTION; X RAY CRYSTALLOGRAPHY;

EID: 0032772517     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (107)

1. Booth S, Hermkens PH, Ottenheijm HC, Rees DC. Solidphase organic reactions III: A review of the literature Nov 96-Dec 97. Tetrahedron (1998) 54:15385-15443.
2. •A comprehensive review of solid-phase organic reactions presented in a graphical abstract format This review is the third in a series on organic reactions on solid supports.
3. Brown RC. Recent developments in solid-phase organic synthesis. J Chem Soc Perkin Trans 1 (1998) 19:3293-3320.
4. A comprehensive review of recent developments in solid-phase organic synthesis.
5. Bures MG, Martin YC. Computational methods in molecular diversity and combinatorial chemistry. Cure Opin Chem Biol (1998)2:376-380.
6. A concise review on the computational techniques used in the design of combinatorial libraries.
7. Czamik AW. Combinatorial chemistry: What is in it for analytical chemists? Anal Chem (1998) 70:378A-386A.
8. Fecik RA, Frank KE, Gentry EJ, Menon SR, Mitscher LA, Telikepalli H. The search for orally active medications through combinatorial chemistry. MedRes flev(1998) 18:149-185.
9. A review of the literature of combinatorial chemistry focused on absorption, distribution, metabolism and excretion. In particular, this review weighs the compound libraries in terms of As possible oral bioavailability.
10. Kubinyi H. Combinatorial and computational approaches In structure-based drug design. Curr Opin Drug Discov Dev (1998)1:16-27.
11. A review of the applications of structure-based ligand design methods to the rational design of combinatorial libraries.
12. Kyranos JN, Hogan JCJ. High-throughput characterization of combinatorial libraries generated by parallel synthesis. Anal Chem (1998) 70:389A-395A.
13. A review of different analytical methods employed in the characterization of the compound libraries.
14. Merritt AT. Uptake of new technology in lead optimization for drug discovery. Drug Disc Today (1998) 3:505-510.
15. Van Drie JH, Lajiness MS. Approaches to virtual library design. Drug Disc Today (1998) 3:274-283.
16. A well written review of the diversity-based and structure-based approaches to the design of virtual library design.
17. Wentworth P, Janda KD. Generating and analyzing combinatorial chemistry libraries. Curr Opin Biotechnol (1998)9:109-115.
18. Borman S. Combinatorial chemistry: Reducing time to drug discovery. Chem Eng News (1999) 8:33-48.
19. Boger DL. Combinatorial chemistry. Bioorg Med Chem Lett (1998)8:vii.
20. Ellman JA, Gallop MA. Combinatorial chemistry. Curr Opin Chem Biol (1998) 2:317-319.
21. Greenlee WJ, Desai M (Eds). Curr Opin Drug Discovery Dev, Current Drugs Ltd, London (1998) 1:1-119
22. Kubinyi H, Folkers G, Martin YC (Eds): 3D QSAR in drug design: Ligand-protein interactions and molecular similarity. Perspect Drug Discov Design, Kluwer/Escom, Amsterdam (1998):9-11.
23. Willett P (Ed). Computational Methods for the Analysis of Molecular Diversity. Perspect Drug Discov Design, Kluwer/Escom, Amsterdam (1997).
24. •A special issue devoted to the overview of computational methods and tools for molecular diversity analysis, by the leading researchers.
25. Potter T, Matter H. Random or rational design? Evaluation of diverse compound subsets from chemical structure databases. J Med Chem (1998) 41:478-488.
26. •Comprehensive and useful comparison of the performance of an optimally diverse library with a random library.
27. Ajay, Walters WP, Murcko MA. Can we learn to distinguish between 'drug-like' and 'nondrug-like' molecules? J Med Chem (1998) 41:3314-3324.
28. •Drug likeness was studied by using a set of 2-D/1-D descriptors to train neural networks, and the resulting model was found at least 3- or 4-orders of magnitude better than random methods to find drug-like compounds.
29. Sadowski J, Kubinyi H. A scoring scheme for discriminating between drugs and nondrugs. J Med Chem (1998) 41:33253329.
30. A simple method using neural network trained by drug-like and nondrug-like databases yields surprisingly good results.
31. Martin EJ, Critchlow RE. Beyond mere diversity: Tailoring combinatorial libraries for drug discovery. J Comb Chem (1999)1:32-45.
32. Protocols are described to design highly biased optimal libraries by filtering out undesirable reagents.
33. Gillet VJ, Willett P, Bradshaw J, Green DVS. Selecting combinatorial libraries to optimize diversity and physical properties. J Chem Inf Comput Sei (1999) 39:169-177.
34. •A program, SELECT, based on a genetic algorithm with a multiobjective fitness function to maximize library diversity, while keeping user-specified structural and physical properties, eg, drug-like properties, was developed for the design of libraries and its applications were demonstrated.
35. Mount J, Ruppert J, Welch W, Jain AN. IcePick: a flexible surface-based system for molecular diversity. J Mod Chem (1999)42:60-66.
36. Diversity is measured based on the 3-D molecular surface properties and distances from the equally spaced points at the spheres of 6 and 9 A with a flexible conformational search in the presence of the binding site model.
37. Brown RD, Clark DE. Genetic diversity: applications of evolutionary algorithms to combinatorial library design. ExpOpin Ther Paf (1998) 8:1447-1459.
38. Weber L. Applications of genetic algorithms in molecular diversity. CurrOpin Chem S/b/(1998) 2:381-385.
39. A good overview of the use of genetic algorithms in the design and automated synthesis of combinatorial libraries.
40. Weber L- Evolutionary combinatorial chemistry: application of genetic algorithms. Drug Disc Today (1998) 3:379-385.
41. Schneider G, Schrödl W, Wallukat G, Müller J, Nissen E, Rönspeck W, Wrede P, Kunze R. Peptide design by artificial neural networks and computer-based evolutionary search. Proc Natl Acad Sei USA (1998) 95:12179-12184.
42. De novo peptide design by evolutionary search using the trained neural networks as a fitness function was applied to generate novel peptides with substantial biological activity.
43. Stanion DT. Evaluation and use of BCUT descriptors in QSAR and QSPR studies. J Chem Inf Comput Sei (1999) 39:11 -20.
44. Stanton DT, Morris TW, Roychoudhury S, Parker CN. Application of nearest-neighbor and cluster analyses in pharmaceutical lead discovery. J Chem Inf Comput Sei (1999)39:21-27.
45. Nearest neighbor analysis was applied to design a focused library around the hit in chemical space and to achieve an improved hit rate.
46. Pearïman RS, Smith KM. Novel software tools for chemical diversity. Perspect Drug Discov Design (1998) 9-11:339-353.
47. Pearlman RS, Smith KM. Metric validation and the receptorrelevant subspace concept J Chem Inf Comput Sei (1999) 39:28-35.
48. Advantage of using low-dimensional chemistry-space metrics (BCUTs) for a cell-based clustering algorithm was examined and demonstrated for angiotensin converting enzyme (ACE) inhibitors.
49. Bôhm HJ. Prediction of binding constants of protein ligands: A fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J Comput Aided Mol Des (1998) 12:309-323.
50. Sun Y, Ewing TJ, Skillman AG, Kuntz ID. CombiDOCK: Structure-based combinatorial docking and library design. J Comput Aided Mol Des (1998) 12:597-604.
51. DOCK was modified for screening of a large library with a common scaffold. Functional groups are attached to the pre-DOCKed scaffold at several orientations and scored to find the best combination at each orientation for a faster search. It worked well for the benzodiazepine library.
52. Murray CM, Cato SJ. Design of libraries to explore receptor sites. J Chem Inf Comput Sei (1999) 39:46-50.
53. A library design method is described based on the rapid flexible fitting of compounds in large virtual libraries to the pharmacophoric centers automatically generated from a receptor binding site.
54. Böhm HJ, Banner DW, Weber L Combinatorial docking and combinatorial chemistry: design of potent non-peptide thrombin inhibitors. J Compul Aid Mol Des (1999) 13(1):51-56.
55. An account of the application of virtual screening of a library generated by a reductive amination against the thrombin active site, synthesis of top-scoring compounds, followed up by an X-ray structural analysis to compare the predicted model.
56. Lebl M, Leblova Z. Dynamic database of references in molecular diversity. httpS/www.5z.com/divinfo/spos98.html
57. Blaskovich MA, Kahn M. Solid-phase preparation of dienes. J Org Chem (1998) 63:1119-1125.
58. Preparation of a variety of functional/zed dienes on a solid support using the Stile reaction conditions.
59. Ogbu CO, Qabar MM, Boatman PD, Urban J, Meara JP, Ferguson, MD, Tulinsky J, Lum C, Babu S, Blaskovich MA, Nakanashi H, Ruan F, Cao B, Minarik R, Little T, Nelson S, Nguyen M, Gall A, Kahn M. Highly efficient and versatile synthesis of libraries of constrained beta-strand mimetics. Bioorg Med Chem Lett (1998) 8:2321 -2326.
60. •Construction of focused libraries of constrained -tum mimetics using the Diels-Alder cycloaddition reaction on solid support.
61. Boldi AM, Johnson CR, Eissa HO. Solid-phase library synthesis of triazolopyridazines via [4+2] cycloadditions. Tetrahedron Lett (1999) 40:619-622.
62. Winkler JD, Kwak YS. An approach to controlled oligomerization via iterative Diels-Alder cycloadditions on solid supports. J Org Chem (1998) 63:8634-8635.
63. Ouyang X, Armstrong RW, Murphy MM. A novel cleavage technique to generate small molecule compounds and libraries via a two-resin system. J Org Chem (1998) $3:1027-1032.
64. Hamuro Y, Scialdone MA, DeGrado WF. Resin-to-resin acyland aminoacyl-transfer reactions using oxime supports. J Am Chem Soc (1999) 121:1636-1644.
65. •Convergent solid-phase synthesis in which two fragments of a molecule are synthesized and then condensed in a resin-to-resin transfer reaction.
66. Yan B. Monitoring the progress and the yield of solidphase organic reactions directly on resin supports. Ace Chem Research (1998) 31:621-630.
67. Yan B, Gremiich H, Moss S, Coppola GM, Sun Q, Uu L. A comparison of various FTIR and FT Raman methods: applications in the reaction optimization stage of combinatorial chemistry. J Comb Chem (1999) 1:46-54.
68. Keifer PA. New methods for obtaining high-resolution NMR spectra of solid-phase synthesis resins, natural products, and solution-state combinatorial chemistry libraries. Drugs Future (1998) 23:301 -317.
69. A comprehensive review for obtaining high-resolution NMR in combinatorial and natural product chemistries.
70. Keifer PA. NMR tools for biotechnology. Curr Opin B/bfecf)/70/(1999) 10:34-41.
71. Luo Y, Ouyang X, Armstrong RW, Murphy MM. A case study of employing spectroscopic tools for monitoring reactions in the developmental stage of a combinatorial chemistry library. J Org Chem (1998) 63:8719-9722.
72. Whitehouse DL, Nelson KH, Savinov SN, Löwe RS, Austin DJ. A metathetical cycloaddition-cycloreversion approach to the formation of furan scaffold libraries. Bioorg Med Chem (1998)6:1273-1282.
73. Matthews J, Rivera RA. Solid-phase synthesis of substituted tetramic acids. J Org Chem (1998) 63:4808-4810.
74. Nefzi A, Dooley C, Ostresh JM, Houghten RA. Combinatorial chemistry: From peptides and peptidomimetics to small organic and heterocyclic compounds. Bioorg Mod Chem Lett (1998) 8:2273-2278.
75. Different examples of heterocyclic templates.
76. Boeijen A, Kruijtzer JA, ü'skamp RM. Combinatorial chemistry of hydantoins. Bioorg Med Chem Lett (1998) 8:2375-2380.
77. Vojkovsky T, Weichsel A, Patek M. Solid-phase synthesis of heterocycles containing an 1-acy!-3-oxopiperazine skeleton. J Org Chem (1998) 63:3162-3163.
78. Solid-phase synthesis of bicyclic type-l -tum using tandem Nacylinimium ion cyclization-nucleophilic addition reaction.
79. Feng Y, Wang Z, Jin S, Burgess K. SN-Ar cyclizations to form cyclic peptidomimetics of -turns. J Am Chem Soc (1998) 120:10768-10769.
80. Solid-phase synthesis of cyclic -tum mimetics utilizing solidphase SHAr macrocylization.
81. Hoekstra WJ, Poulter BL. Combinatorial chemistry techniques applied to nonpeptide integrin antagonists. Curr Med Chem (1998) 5:195-204.
82. Scicinski JJ, Barker MD, Murray PJ, Jarvie EM. The solid phase synthesis of a series of tri-substituted hydantoin ligands for the somatostatin sstS receptor. Bioorg Med Chem Lett (1998) 8:3609-3614.
83. Bums CJ, Groneberg RD, Salvino JM, McGeehan G, Condon SM, Morris R, Mom'ssette M, Mathew R, Dambrough S, Neuenschwander K, Scotese A, Djuric SW, Ullrich J, Labaudiniere R. Nanomolar inhibitors for two distinct biological target families from a single synthetic sequence: a next step in combinatorial library design? Angew Chem Int Ed Engl (1998) 37:2848-2850.
84. Construction of multiple libraries from a single synthetic sequence that recognizes members of two distinct biological target families, matrix metalloproteinases and phosphodiesterases was achieved.
85. Souers AJ, Virgilio AA, Schürer SS, Ellman JA, Kogan TP, West HE, Ankener W, Vanderslice P. Novel inhibitors of alpha 4 beta 1 integrin receptor interactions through library synthesis and screening. Bioorg Med Chem Lett (1998)8:2297-2302.
86. Synthesis and screening a 2302-membered library heterocyclic tum mimetic targeting integrin receptor.
87. Souers AJ, Virgilio AA, Rosenquist A, Fenuik W, Ellman JA. Identification of a potent heterocyclic ligand to somatostatin receptor subtype 5 by the synthesis and screening of -turn mimetic libraries. J Am Chem Soc (1999)121:1817-1825.
88. •Parallel synthesis and screening of a 172-membered focused library heterocyclic -tum mimetic targeting somatostatin receptor.
89. Brady SF, Stauffer KJ. Lumma WC, Smith GM, Ramjit HG, Lewis SD, Lucas BJ, Gardell SJ, Lyle EA, Appleby SD, Cook JJ, Holahan MA, Stranieri MT, Lynch JJ Jr, Lin JH, Chen IW, Vastag K, Naylor Olsen AM, Vacca JP: Discovery and development of the novel potent orally active thrombin inhibitor N-(9-hydroxy-9-fluorenecarboxy)prolyl trans-4aminocyclohexylmethy! amide (L-372,460): Coapplication of structure-based design and rapid multiple analogue synthesis on solid support. J Med Chem (1998) 41:401 -406.
90. Augeri DJ, O'Conner SJ, Janowick D, Szczepankiewicz B, Sullivan G, Larsen J, Kalvin D, Cohen J, Devine E, Zhang H, Cherian S, Saeed B, Ng S-C, Rosenberg S. Potent and selective non-cysteine-containing inhibitors of protein farnesyltransferase. J Med Chem (1998) 41:4288-4300.
91. Collins JL, Blanchard SG, Boswell GE, Charifson PS, Cobb JE, Henke BR, Hull-Ryde EA, Kazmierski WM, Lake DH, Leesnitzer LM, Lehmann J, Lenhard JM, Orband-Miller LA, Gray-Nunez Y, Parks DJ, Plunkett KD, Tong WQ. N-(2benzoylphenyl)-L-tyrosine PPARgamma agonists. 2. Structure-activity relationship and optimization of the pheny! alkyl ether moiety. J Med Chem (1998) 41:50375054.
92. Lee CE, Kick EK, Ellman JA. General solid-phase synthesis approach to prepare mechanism-based aspartyl protease inhibitor libraries. Identification of potent cathepsln D inhibitors. JAm Chem Soc (1998) 120:9735-9747.
93. Focused library generation to produce cathepsin D inhibitors.
94. Nicolaou KG, Winssinger N, Vourtoumis D, Ohshima T, Kim S, Pfefferkorn J, Xu JY, U T. Solid and solution-phase synthesis and biological evaluation of combinatorial sarcodictyin libraries. J Am Chem Soc (1998) 120:1081410826.
95. Library construction based on a natural product template.
96. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Bames G, LeClerc S, Meijer L, Kim S-H, Lockhart DJ, Schultz PG. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Sc/e/jce(1998) 281:533-538.
97. Discovery of selective and potent CDK2 inhibitors based on 2,6,9trisubstituted purines.
98. Tremblay MR, Poirier D. Solid-phase synthesis of phenolic steroids: Towards combinatorial libraries of estradiol derivatives. Tetrahedron Lett (1999) 40:1277-1280.
99. Rohrer SP, Birzin ET, Mosley RT, Berk SC, Hutchins SM, Shen DM, Xiong Y, Hayes EC, Parrnar RM, Poor F, Mitra SW, Degrado SJ, Shu M, Klopp JM, Cai S-J, Blake A, Chen WW, Pasternak A, Yang L, Palchett AA, Smith RG, Chapman RT, Schaeffer JM. Rapid identification of subtype-selective antagonists of the somatostatin receptor through combinatorial chemistry. Science (1998) 282:737-740.
100. Construction of solid-phase combinatorial libraries for subtypeselective agonists for each of five somatostatin receptors.
101. Eliseev AV, Nelen Ml. Use of molecular recognition to drive chemical evolution: mechanisms of an automated genetic algorithm implementation. Chem Eur J(1998) 4:825-834.
102. Dynamically equilibrated library compounds are selected and amplified as good ligand binds to target receptor and are removed as ligand-receptor complex.
103. Shapiro MJ. Wareing JR: NMR methods in combinatorial chemistry. Curr Opin Chem Biol (1998) 2:372-375.
104. A concise review of NMR methods in combinatorial chemistry: gelphase NMR, MAS NMR, Fl NMR and screening mixtures by NMR.
105. Bleicher K, Un M, Shapiro MJ, Wareing JR. Diffusion edited NMR: Screening compound mixtures by affinity NMR to detect binding ligands to Vancomycin. J Org Chem (1998) 63:8486-8490.
106. Screening of mixtures by affinity NMR to produce an edited spectrum that identifies ligand that are bound.
107. Moore JM. NMR screening in drug discovery. Curr Opin B/oteC/7HO/(1999) 10:54-58.