Application of Pharmacophore Models in Medicinal Chemistry

Pharmacophores and Pharmacophore Searches

Volumn , Issue , 2006, Pages 251-282

  Manetti, Fabrizio ^a   Botta, Maurizio ^a   Tafi, Andrea ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

Application of pharmacophore models; Hit identification; Lead profiling; Medicinal chemistry; Pharmacophore model for 1 AR antagonists; Pharmacophores; Rationalization of activity data of azole antifungal agents; Subtypes; Target the 1 adrenergic receptor ( 1 AR); Use of excluded volume features

Indexed keywords

ANTIFUNGAL AGENTS;

ADRENERGIC RECEPTORS; EXCLUDED VOLUME; MEDICINAL CHEMISTRY; PHARMACOPHORE MODELING; PHARMACOPHORE MODELS; PHARMACOPHORES; SUBTYPES;

PHARMACODYNAMICS;

EID: 84952938835     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/3527609164.ch12     Document Type: Chapter

References (52)

1. Chang, D. J., Chang, T.K., Yamanishi, S.S., Salazar, F.H.R., Kosaka, A.H., Khare, R., Bhakta, S., Jasper, J.R., Shieh, I.-S., Lesnick, J.D., Ford, A.P.D.W., Da-niels, D.V., Eglen, R.M., Clarke, D.E., Bach, C., Chan, H.W.Molecular cloning, genomic characterization and expression of novel human 1A-adrenoceptor iso-forms. FEBS Lett. 1998, 422, 279-283
2. Daniels, D.V., Gevel, J.R., Jasper, J.R., Kava, M.S., Lesnick, J.D., Meloy, T.D., Stepan, G., Williams, T. J., Clarke, D.E., Chang, D. J., Ford, A.P.D. W.Hu-man cloned 1A-adrenoceptor isoforms display 1L-adrenoceptor pharmacology in functional studies. Eur. J. Pharmacol. 1999, 370, 337-343.
3. de Reijke, T.M., Klarskov, P.Com-parative efficacy of two -adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symp-toms from benign prostatic enlargement. BJU Int. 2004, 6, 757-762
4. Michelotti, G.A., Schwinn, D.A.Mechanistic in-sights into the role of 1-adrenergic re-ceptors in lower urinary tract symptoms. Curr. Urol. Rep. 2004, 4, 258-266
5. Lowe, F.C.Role of the newer 1-adre-nergic receptor antagonists in the treat-ment of benign prostatic hyperplasia-re-lated lower urinary tract symptoms. Clin. Ther. 2004, 11, 1701-1713.
6. Barbaro, R., Betti, L., Botta, M., Corelli, F., Giannaccini, G., Maccari, L., Manetti, F., Strappaghetti, G., Corsano, S.Synthe-sis, biological evaluation and pharmaco-phore generation of new pyridazinone derivatives with affinity toward 1-and 2-adrenoceptors. J. Med. Chem. 2001, 44, 2118-2132.
7. Catalyst (Version 4.9), Accelrys, San Die-go, CA.
8. Accelrys, http://www.accelrys.com/sup-port/life/catalyst/hypogen.html.
9. Cheng, Y.C., Prusoff, W.H.Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (IC50)of an enzymatic reaction. Biochem. Pharma-col. 1973, 22, 3099-3108.
10. Mohamadi, F., Richards, N.G. J., Guida, W.C., Liskamp, R., Lipton, M., Caufield, C., Chang, G., Hendrickson, T., Still, W. C.Macromodel-an integrated software system for modeling organic and bioor-ganic molecules using molecular me-chanics. J. Comput. Chem. 1990, 11, 440-467.
11. Langgard, M., Bjornholm, B., Gunder-tofte, K.Pharmacophore modeling by automated methods: possibilities and limitations. In Pharmacophore Perception, Development and Use in Drug Design,Gu-ner, O.F. (ed.), IUL Biotechnology Se-ries, International University Line, La Jolla, CA, 2000, pp. 239-251.
12. De Marinis, R.M., Wise, M., Hieble, J.P., Ruffolo R.R., Jr. Structure-activity relationships for alpha-1 adrenergic re-ceptor agonists and antagonists. In The Alpha-1 Adrenergic Receptor, Ruffolo, R.R., Jr (ed.), Humana Press, Clifton, NJ, 1987, pp. 211-265
13. Montesano, F., Barlocco, D., Dal Piaz, V., Leonardi, A., Poggesi, E., Fanelli, F., De Benedetti, P.G.Isoxazolo-[3,4-d]-pyridazin-7-(6H)-ones and their corresponding 4,5-disub-stituted-3-(2H)-pyridazinone analogues as new substrates for 1-adrenoceptor se-lective antagonists: synthesis, modeling and binding studies. Bioorg. Med. Chem. 1998, 6, 925-935.
14. Betti, L., Floridi, M., Giannaccini, G., Manetti, F., Strappaghetti, G., Tafi, A., Botta, M.1-Adrenoceptor antagonists. 5. Pyridazinone-arylpiperazines. Probing the influence on affinity and selectivity of both ortho-alkoxy groups at the arylpi-perazine moiety and cyclic substituents at the pyridazinone Nucleus. Bioorg. Med. Chem. Lett. 2003, 13, 171-173.
15. Betti, L., Corelli, F., Floridi, M., Giannac-cini, G., Maccari, L., Manetti, F., Strap-paghetti, G., Botta, M.1-Adrenoceptor antagonists. 6. Structural optimization of pyridazinone-arylpiperazines. Study of the influence on affinity and selectivity of cyclic substituents at the pyridazinone ring and alkoxy groups at the arylpipera-zine moiety. J. Med. Chem. 2003, 46, 3555-3558.
16. Setoguchi, M., Sakamori, M., Takehara, S., Fukuda, T.Effects of iminodibenzyl antipsychotic drugs on cerebral dopa-mine and alpha-adrenergic receptors. Eur. J. Pharmacol. 1985, 112, 313-322.
17. Roquebert, J., Grenie, B.Alpha 2-adrenergic agonist and alpha 1-adrener-gic antagonist activity of ergotamine and dihydroergotamine in rats. Arch. Int. Pharmacodyn. Ther. 1986, 284, 30-37
18. Bonuso, S., Di Stasio, E., Marano, E., Covelli, V., Testa, N., Tetto, A., Buscaino G.A.The antimigraine effect of ergota-mine: a role for alpha-adrenergic block-ade? Acta Neurol. (Napoli) 1994, 16,1-10.
19. Giannangeli, M., Cazzolla, N., Luparini, M.R., Magnani, M., Mabilia, M., Picconi, G., Tomaselli, M., Baiocchi, L.Effect of modification of the alkylpiperazine moi-ety of trazodone on 5-HT2A and 1 recep-tor binding activity. J. Med. Chem. 1999, 42, 336-345.
20. Costa, A., Martignoni, E., Blandini, F., Petraglia, F., Genazzani, A.R., Nappi, G.Effects of etoperidone on sympathetic and pituitary-adrenal responses to di-verse stressors in humans. Clin. Neuro-pharmacol. 1993, 16, 127-138.
21. Betti, L., Botta, M., Corelli, F., Floridi, M., Fossa, P., Giannaccini, G., Manetti, F., Strappaghetti, G., Corsano, S.1-Adrenoceptor antagonists. Rational de-sign, synthesis and biological evaluation of new trazodone-like compounds. Bioorg. Med. Chem. Lett. 2002, 12, 437-440.
22. Betti, L., Botta, M., Corelli, F., Floridi, M., Giannaccini, G., Maccari, L., Manet-ti, F., Strappaghetti, G., Tafi, A., Corsa-no, S.1-Adrenoceptor antagonists. 4. Pharmacophore-based design, synthesis and biological evaluation of new imida-zo-, benzimidazo-, and indoloarylpipera-zine derivatives. J. Med. Chem. 2002, 45, 3603-3611.
23. Romeo, G., Materia, L., Manetti, F., Cag-notto, A., Mennini, T., Nicoletti, F., Bot-ta, M., Russo, F., Minneman, K.P.New pyrimido[5,4-b]indoles as ligands for 1-adrenoceptor subtypes. J. Med. Chem. 2003, 46, 2877-2894.
24. Leonardi, A., Barlocco, D., Montesano, F., Cignarella, G., Motta, G., Testa, R., Poggesi, E., Seeber, M., De Benedetti, P.G., Fanelli, F.Synthesis, screening and molecular modeling of new potent and selective antagonists at the 1d adre-nergic receptor. J. Med. Chem. 2004, 47, 1900-1918.
25. Koer, F. J., Altona, C.Conformation of non-aromatic ring compounds-84. Dipole moments and 100 MHz Fourier-transform proton magnetic resonance spectra of some substituted 3-phenylglu-taric anhydrides, a conformational analy-sis. Recl. J. R. Neth. Chem. Soc. 1974, 93/ 5, 147-151
26. Koer, F. J., Faber, D.H., Altona, C.Conformation of non-aromatic ring compounds-89. The conformation of 3-(2,6-dichlorophenyl)glutaric anhy-dride studied by dynamic proton mag-netic resonance and empirical force field calculations. Recl. J. R. Neth. Chem. Soc. 1974, 93/12, 307-311
27. Koer, F. J., Alto-na, C.Conformation of non-aromatic ring compounds-92. Carbon-13 nuclear magnetic resonance spectra of some 3-arylglutaric anhydrides. Recl. J. R. Neth. Chem. Soc. 1975, 94/6, 127-131.
28. Lopez, F. J., Arias, L., Chan, R., Clarke, D.E., Elworthy, T.R., Ford, A.P.D.W., Guzman, A., Jaime-Figueroa, S., Jasper, J.R., Morgans, D. J., Jr., Padilla, F., Per-ez-Medrano, A., Quintero, C., Romero, M., Sandoval, L., Smith, S.A., Williams, T. J., Blue, D.R. Synthesis.pharmacology and pharmakokinetics of 3-(4-aryl-pipera-zin-1-ylalkyl)-uracils as uroselective 1A-antagonists, Bioorg. Med. Chem. Lett. 2003, 13, 1873-1878.
29. Peri, S., Navarro, J.D., Amanchy, R., Kristiansen, T.Z., Jonnalagadda, C.K., Surendranath, V., Niranjan, V., Muthusa-my, B., Gandhi, T.K., Gronborg, M., Ibarrola, N., Deshpande, N., Shanker, K., Shivashankar, H.N., Rashmi, B.P., Ra-mya, M.A., Zhao, Z., Chandrika, K.N., Padma, N., Harsha, H.C., Yatish, A. J., Kavitha, M.P., Menezes, M., Choudhury, D.R., Suresh, S., Ghosh, N., Saravana, R., Chandran, S., Krishna, S., Joy, M., Anand, S.K., Madavan, V., Joseph, A., Wong, G.W., Schiemann, W.P., Constan-tinescu, S.N., Huang, L., Khosravi-Far, R., Steen, H., Tewari, M., Ghaffari, S., Blobe, G.C., Dang, C.V., Garcia, J.G., Pevsner, J., Jensen, O.N., Roepstorff, P., Deshpande, K.S., Chinnaiyan, A.M., Ha-mosh, A., Chakravarti, A., Pandey, A.Development of Human Protein Refer-ence Database as an Initial Platform for Approaching Systems Biology in Hu-mans. Genome Res. 2003, 10, 2363-2371; http://www.hprd.org/protein/00079.
30. Carrieri, A., Centeno, N.B., Rodrigo, J., Sanz, F., Carotti, A.Theoretical evidence of a salt bridge disruption as the initiating process for the 1d-adrenergic receptor activation: a molecular dynamics and docking study. Proteins 2001, 43, 382-394.
31. Romeo, G. Personal communication.
32. Greenidge, P.A., Carlsson, B., Bladh, L.-G., Gillner, M.Pharmacophores incor-porating numerous excluded volumes defined by X-ray crystallographic struc-ture in three-dimensional database searching: application to the thyroid hor-mone receptor. J. Med. Chem. 1998, 41, 2503-2512.
33. Greenidge, P.A., Merette, S.A.M., Beck, R., Dodson, G., Goodwin, C.A., Scully, M.F., Spencer, J., Weiser, J., Deadman, J. J.Generation of ligand conformations in continuum solvent consistent with protein active site topology: application to thrombin. J. Med. Chem. 2003, 46, 1293-1305.
34. Carlson, H.A., Masukawa, K.M., Rubins, K., Bushman, F.D., Jorgensen, W. J., Lins, R.D., Briggs, J.M., McCammon, J.A.Developing a pharmacophore model for HIV-1 integrase. J. Med. Chem. 2000, 43, 2100-2114.
35. Steindl, T., Langer, T. Influenza virus neuramidase inhibitors: generation and comparison of structure-based and com-mon feature pharmacophore hypotheses and their application in virtual screen-ing. J. Chem. Inf. Comput. Sci. 2004, 44, 1849-1856.
36. Bhattacharjee, A.K., Geyer, J.A., Woo-dard, C.L., Kathcart, A.K., Nichols, D.A., Prigge, S.T., Li, Z., Mott, B.T., Waters, N.C.A three-dimensional in silico phar-macophore model for inhibition of Plas-modium falciparum cyclic-dependent ki-nases and discovery of different classes of novel Pfmrk species inhibitors. J. Med. Chem. 2004, 47, 5418-5426.
37. Norinder, U. Refinement of Catalyst hypotheses using simplex algorithm. J. Comput.-Aided Mol. Des. 2000, 14, 545-557.
38. Accelrys, http://www.accelrys.com/cata-lyst/hyporefine.html.
39. Tsai, K.-C., Lin, T.-H.A ligand-based mo-lecular modeling study on some matrix metalloproteinase-1 inhibitors using sev-eral 3D QSAR techniques. J. Chem. Inf. Comput. Sci. 2004, 44, 1857-1871.
40. Tafi, A., Anastassopoulou, J., Theopha-nides, T., Botta, M., Corelli, F., Massa, S., Artico, M., Costi, R., Di Santo, R., Ragno, R.Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study. J. Med. Chem. 1996, 39, 1227-1235.
41. Tafi, A., Costi, R., Botta, M., Di Santo, R., Corelli, F., Massa, S., Ciacci, A., Man-etti, F., Artico, M.Antifungal Agents 10. New derivatives of 1-[(aryl)[4-aryl-1H-pyrrol-3-yl]methyl]-1H-imidazole, synthe-sis, anti-Candida activity, and quantitative structure-activity relationship studies. J. Med. Chem. 2002, 45, 2720-2732.
42. Liu, J., Pan, D., Tseng, Y., Hopfinger, A. J.4D-QSAR analysis of a series of antifungal P450 inhibitors and 3D-phar-macophore comparisons as a function of alignment. J. Chem. Inf. Comput. Sci. 2003, 43, 2170-2179.
43. Di Santo, R., Tafi, A., Costi, R., Botta, M., Artico, M., Corelli, F., Forte, M., Caporuscio, F., Angiolella, L., Palamara, A.T.Antifungal agents. 11. N-substituted derivatives of 1-[(aryl)[4-aryl-1H-pyrrol-3-yl]methyl]-1H-imidazole: synthesis, anti-Candida activity, and QSAR studies. J. Med. Chem. 2005, 48, 5140-5153.
44. Poulos, T.L., Howard, A. J.Crystal struc-tures of methyrapone-and phenylimida-zole-inhibited complexes of cytochrome P-450cam. Biochemistry 1987, 26, 8165-8174.
45. Yano, J.K., Koo, L.S., Shuller, D. J., Li, H., Ortiz De Montellano, P. R., Poulos, T.L.Crystal structure of a thermophilic cytochrome P450 from the archaeon Sul-folobus solfataricus. J. Biol. Chem. 2000, 275, 31086-31092.
46. Podust, L.M., Poulos, T.L., Waterman, M.R.Crystal structure of cytochrome P450 14 -sterol demethylase (CYP51) from Mycobacterium tubercolosis in com-plex with azole inhibitors. Proc. Natl. Acad. Sci. USA 2001, 98, 3068-3073.
47. Verras, A., Kuntz, I.D., Ortiz De Montel-lano, P. R.Computer-assisted design of selective imidazole inhibitors for cyto-chrome P450 enzymes. J. Med. Chem. 2004, 47, 3572-3579.
48. Upadhayaya, R.S., Sinha, N., Jain, S., Kishore, N., Chandra, R., Arora, S.K.Optically active antifungal azoles: synthe-sis and antifungal activity of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-[2-[4-arylpipera-zin-1-yl]ethyl]tetrazol-2-yl/1-yl)-1-[1,2,4]-triazol-1-yl-butan-2-ol. Bioorg. Med. Chem. 2004, 12, 2225-2238.
49. Sharma, P., Rane, N., Gurram, V.K.Synthesis and QSAR studies of pyrimi-do[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents. Bioorg. Med. Chem. Lett. 2004, 14, 4185-4190
50. Gollapudy, R., Ajmani, S., Kulkarni, A.Modeling and interaction of Aspergil-lus fumigatus lanosterol 14- demethylase 'A' with azole antifungals. Bioorg. Med. Chem. 2004, 12, 2937-2950
51. Ji, H., Zhang, W., Zhang, M., Kudo, M., Aoya-ma, Y., Yoshida, Y., Sheng, C., Song, Y., Yang, S., Zhou, Y., Lü, J., Zhu, J.Struc-ture-based de novo design, synthesis and biological evaluation of non-azole inhibi-tors specific for lanosterol 14 -demethy-lase of fungi. J. Med. Chem. 2003, 46, 474-485
52. Wiktorowicz, W., Markus-zewski, M., Krysinski, J., Kaliszan, R.Quantitative structure-activity relation-ship study of a series of imidazole deri-vatives as potential new antifungal drugs. Acta Pol. Pharm. 2002, 59, 295-306.