Molecular hashkeys: A novel method for molecular characterization and its application for predicting important pharmaceutical properties of molecules

Journal of Medicinal Chemistry

Volumn 42, Issue 10, 1999, Pages 1739-1748

  Ghuloum, Anwar M ^a   Sage, Carleton R ^a   Jain, Ajay N ^a,b  

^a MetaXen   (United States)

^b Entelos Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPRENOLOL; ATENOLOL; CIPROFLOXACIN; DIAZEPAM; FOSCARNET; LACTULOSE; MANNITOL; METOLAZONE; METOPROLOL; NORDAZEPAM; OLSALAZINE; OXAZEPAM; OXPRENOLOL; PHENAZONE; PINDOLOL; PRACTOLOL; RAFFINOSE; SALAZOSULFAPYRIDINE; SULPIRIDE; TRANEXAMIC ACID;

ARTICLE; CALCULATION; CHEMICAL STRUCTURE; DRUG STRUCTURE; INTESTINE ABSORPTION; MACHINE; MOLECULAR DYNAMICS; MOLECULAR MODEL; NERVE CELL NETWORK; PARTITION COEFFICIENT; PREDICTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; THREE DIMENSIONAL IMAGING;

DRUG DESIGN; INTESTINAL ABSORPTION; MODELS, MOLECULAR; PHARMACEUTICAL PREPARATIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033587166     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980527a     Document Type: Article

References (28)

1. Walters, W. P.; Stahl, M. T.; Murcko, M. A. Virtual Screening - an overview. Drug Discovery Today 1998, 3, 160-178.
2. Bodian, D. L.; Yamasaki, R. B.; Buswell, R. L.; Stearns, J. F.; White, J. M.; Kuntz, I. D. Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. Biochemistry 1993, 32, 2967-2978.
3. Ring, C. S.; Sun, E.; McKerrow, J. H.; Lee, G. K.; Rosenthal, P. J.; Kuntz, I. D.; Cohen, F. E. Structure-based inhibitor design by using protein models for the development of antiparasitic agents. PNAS 1993, 90, 3583-3587.
4. Rutenber, E.; Fauman, E. B.; Keenan, R. J.; Fong, S.; Furth, P. S., Demontellano, P. R. O.; Meng, E.; Kuntz, I. D.; Decamp, D. L.; Salto, R.; Rose, J. R.; Craik, C. S.; Stroud, R. M. Structure of a non-peptide inhibitor completed with HIV-1 Protease: Developing a cycle of structure-based drug design. J. Biol. Chem. 1993, 268, 15343-15346.
5. Shoichet, B. K.; Stroud, R. M.; Santi, D. V.; Kuntz, I. D.; Perry, K. M. Structure-based discovery of inhibitors of thymidylate synthase. Science 1993, 259, 1445-1450.
6. Jones, T. R.; Varney, M. D.; Webber, S. E.; Lewis, K. K.; Marzoni, G. P.; Palmer, C. L.; Kathardekar, V.; Welsh, K. M.; Webber, S.; Matthews, D. A.; Appelt, K.; Smith, W. W.; Janson, C. A.; Villafranca, J. E.; Bacquet, R. J.; Howaland, E. F.; Booth, C. L. J.; Herrmann, S. M.; Ward, R. W.; White, J.; Moomaw, E. W.; Bartlett, C. A.; Morse, C. A. Structure-based design of lipophilic quinazoline inhibitors of thymidylate synthase. J. Med. Chem. 1996, 39, 904-917.
7. Patterson, D. E.; Cramer, R. D.; Ferguson, A. M.; Clark, R. D.; Weinberger, L. E. Neighborhood Behavior: A useful concept for validation of "molecular diversity" descriptors. J. Med. Chem. 1996, 39, 3049-3059.
8. Kauvar, L. M.; Higgins, D. L.; Villar, H. O.; Sportsman, J. R.; Engqvist-Goldstein, A.; Bukar, R.; Bauer, K. E.; Dilley, H.; Rocke, D. M. Predicting ligand binding to proteins by affinity fingerprinting. Chem. Biol. 1995, 2, 107-118.
9. Briem, H.; Kuntz, I. D. Molecular similarity based on dock-generated fingerprints. J. Med. Chem. 1996, 39, 3401-3408.
10. Brown, R. D.; Martin, Y. C. The information content of 2D and 3D structural descriptors relevant to ligand-receptor binding. J. Chem. Inf. Comput. Sci. 1997, 37, 1-9.
11. Leo, A. J. Calculating log Poct from Structures. Chem. Rev. 1963, 93, 1281-1306.
12. Bodor, N.; Gabanyi, Z.; Wong, C. K. A new method for the estimation of partition coefficient. J. Am. Chem. Soc. 1989, 111, 3783-3786.
13. Moriguchi, I.; Hirono, S.; Liu, Q.; Nakagome, Y.; Matsushita, Y. Simple method of calculating octanol/water partition coefficient. Chem. Pharm. Bull. 1992, 40, 127-130.
14. Palm, K.; Stenber, P.; Luthman, K.; Artursson, P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 1997, 14, 568-571.
15. Jain, A. N.; Koile, K.; Chapman, D. Compass: Predicting Biological Activities from Molecular Surface Properties. Performance Comparisons on a Steroid Benchmark. J. Med. Chem. 1994, 37, 2315-2327.
16. Jain, A. N.; Harris, N. L.; Park, J. Y. Quantitative binding site model generation: Compass applied to multiple chemotypes targeting the 5HTla receptor. J. Med. Chem. 1995, 38, 1295-1307.
17. Comprehensive Medicinal Chemistry Database. CMC, 1997.
18. The term "hashkey" is taken from Computer Science. A hashkey is a compact numerical representation of an object that is used to solve indexing problems by storing objects using their hashkeys as memory addresses.
19. Blaney, F.; Finn, P.; Phippen, R; Wyatt, R. Molecular surface comparison: Application to drug design. J. Mol. Graph. 1993, 11, 98-105.
20. Blandon, P. A rapid method for comparing and matching the sperical parameter surfaces of molecules and other irregular objects. J. Mol. Graph. 1989, 7, 130-137.
21. Dunn, W. J.; Hopfinger, A. J.; Catana, C.; Duraiswami, C. Solution of the conformation and alignment tensors for the binding of trimethoprim and its analogues to dihydrofolate reductase: 3D-quantitative structure-activity relationship study using molecular shape analysis, 3-way partial least squares regression, and 3-way factor analysis. J. Med. Chem. 1996, 39, 4825-4832.
22. Duda, R. O.; Hart, P. E. In Pattern Classification and Scene Analysis; Duda, R. O., Hart, P. E., Eds.; John Wiley & Sons: New York, 1973.
23. MacLogP 2.0; Biobyte, 1997.
24. Rumelhart, D. E.; McClelland, J. L. Parallel Distributed Processing; The MIT Press: Cambridge, MA, 1986; Vol. 1.
25. Sutter, J. M.; Jurs, P. C. Prediction of aqueous solubility for a diverse set of heteroatom-containing organic compounds using a quantitative structure-property relationship. J. Chem. Inf. Comput. Sci. 1996, 36, 100-107.
26. Dressman, J. B.; Amidon, G. L.; Fleisher, D. Absorption potential: estimating the fraction absorbed for orally administered compounds. J. Pharm. Sci. 1985, 74, 588-589.
27. Allinger, N. L.; Yuh, Y. H.; Lii, J.-J. Molecular mechanics. The MM3 force field for hydrocarbons I. J. Am. Chem. Soc. 1989, 111, 8551-9556.
28. Rusinko, A. I.; Skell, J. M.; Balducci, R.; McGarity, C. M.; Pearlman, R. S. CONCORD: a program for the rapid generation of high quality 3D molecular structures: Tripos Associates: St. Louis, MO.