From nature to drug discovery: The indole scaffold as a 'privileged structure'

Mini-Reviews in Medicinal Chemistry

Volumn 9, Issue 7, 2009, Pages 782-793

  Alves, Fernando Rodrigues de Sá ^a   Barreiro, Eliezer J ^a   Fraga, Carlos Alberto Manssour ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Bioisosterism; Drug discovery; GPCR; Indole scaffold; Privileged structure

Indexed keywords

2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 5 METHOXY 3 (1,2,3,6 TETRAHYDRO 4 PYRIDYL) 1H INDOLE; ALOSETRON; ATORVASTATIN; ATYPICAL ANTIPSYCHOTIC AGENT; CANNABINOID RECEPTOR AGONIST; CELECOXIB; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDOLE; INDOMETACIN; N (3,5 DICHLORO 4 PYRIDYL) [1 (4 FLUOROBENZYL) 5 HYDROXY 3 INDOLYL]GLYOXYLIC ACID AMIDE; NARATRIPTAN; NONSTEROID ANTIINFLAMMATORY AGENT; ONDANSETRON; PHOSPHODIESTERASE INHIBITOR; PROSTAGLANDIN SYNTHASE INHIBITOR; RAMOSETRON; RIZATRIPTAN; ROFLUMILAST; ROLIPRAM; SEROTONIN 1D AGONIST; SEROTONIN 2 ANTAGONIST; SEROTONIN 3 ANTAGONIST; SERTINDOLE; SUMATRIPTAN; TADALAFIL; TROPISETRON; UNINDEXED DRUG; ZOLMITRIPTAN; BIOLOGICAL PRODUCT; CANNABINOID RECEPTOR; ENZYME INHIBITOR; INDOLE DERIVATIVE; SEROTONIN RECEPTOR;

ARTICLE; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONGESTIVE HEART FAILURE; DRUG BINDING SITE; DRUG MECHANISM; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TOLERABILITY; ENZYME ACTIVE SITE; ENZYME INHIBITION; ERECTILE DYSFUNCTION; FEVER; HUMAN; HYPERTENSION; INFLAMMATION; ISCHEMIC HEART DISEASE; MIGRAINE; NAUSEA AND VOMITING; NONHUMAN; PAIN; PULMONARY HYPERTENSION; SEROTONINERGIC SYSTEM; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; DRUG DEVELOPMENT; DRUG POTENTIATION; METABOLISM; METHODOLOGY; REVIEW;

ANIMALS; BIOLOGICAL PRODUCTS; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; INDOLES; RECEPTORS, CANNABINOID; RECEPTORS, SEROTONIN;

EID: 68849110176     PISSN: 13895575     EISSN: None     Source Type: Journal    
DOI: 10.2174/138955709788452649     Document Type: Article

References (57)

1. Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. Methods for drug discovery - development of potent, selective, orally effective cholecystokinin antagonists. J. Med. Chem., 1988, 31, 2235-46.
2. Horton, D. A.; Bourne, G. T.; Smythe, M. L. The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem. Rev., 2003, 103, 893-930.
3. Patchett, A. A.; Nargund, R.P. Privileged structures - an update. Annu. Rep. Med. Chem., 2000, 35, 289-98.
4. Duarte, C. D.; Barreiro, E. J.; Fraga, C. A. M. Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini-Rev. Med. Chem., 2007, 7, 1108-19.
5. Smith, A. L.; Stevenson, G. I.; Swain, C. J.; Castro, J. L. Traceless solid phase synthesis of 2,3-disubstituted indoles. Tetrahedron Lett., 1998, 39, 8317-20.
6. Joule, J. A.; Mills, K.; Smith, G. F. In Indoles: reactions and synthesis, Stanley Thornes: Cheltenham, 1998; pp. 305-06.
7. Krauss, G. In The Regulation of Enzyme Activity, Wiley-VCH Verlag: Weinheim, 2001, pp. 89-117.
8. Dolle, R. E. Discovery of enzyme inhibitors through combinatorial chemistry. Mol. Divers., 1997, 2, 223-36.
9. McLeish, M. J.; Kenyon, G. L. In Approaches to the Rational Design of Enzyme Inhibitors, Abraham, D. J., Ed.; John Wiley and Sons: New Jersey, 2003; Vol. 1, p. 716.
10. Blumenthal, R. S. Statins: effective antiatherosclerotic therapy. Am. Heart J., 2000, 139, 577-83.
11. Istvan, E. Statin inhibition of HMG-CoA reductase: a 3-dimensional view. Atheroscl. Suppl., 2003, 4, 3-8.
12. Deslypere, J. P. The role of HMG-CoA reductase inhibitors in the treatment of hyperlipidemia: a review of fluvastatin. Curr. Ther. Res. Clin. Exp., 1995, 56, 111-28.
13. Roth, B. D. The discovery and development of atorvastatin, a potent novel hypolipidemic agent. Prog. Med. Chem., 2002, 40, 1-22.
14. Istvan, E. S.; Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science, 2001, 292, 1160-64.
15. Smith, W.L.; DeWitt, D. L.; Garavito, R. M. Cyclooxygenases: structural, cellular, and molecular biology. Annu. Rev. Biochem., 2000, 69, 145-82.
16. Shen, T. Y.; Windholz, T. B.; Rosegay, A.; Witzel, B. E.; Wilson, A. N.; Willett, J. D.; Holtz, W. J.; Ellis, R. L.; Matzuk, A. R.; Lucas, S.; Stammer, C. H.; Holly, F. W.; Sarett, L. H.; Risley, E. A.; J. Am. Chem. Soc., 1963, 85, 488-89.
17. Hu, W.; Guo, Z.; Yi, X.; Guo, C.; Chu, F.; Cheng, G. Discovery of 2-phenyl-3-sulfonylphenyl-indole derivatives as a new class of selective COX-2 inhibitors. Bioorg. Med. Chem., 2003, 11, 5539-44.
18. Wey, S.-J.; Augustyniak, M. E.; Cochran, E. D.; Ellis, J. L.; Fang, X.; Garvey, D. S.; Janero, D. R.; Letts, L. G.; Martino, A. M.; Melim, T. L.; Murty, M. G.; Richardson, S. K.; Schroeder, J. D.; Selig, W. M.; Trocha, A. M.; Wexler, R. S.; Young, D. V.; Zemtseva, I. S.; Zifcak, B. M. Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors. J. Med. Chem., 2007, 50, 6367-82.
19. Bender, A. T.; Beavo, J. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol. Rev., 2006, 58, 488-520.
20. Jeon, Y. H.; Heo,Y.-S.; Kim, C. M.; Hyun, Y.-L.; Lee, T. G.; Ro, S.; Cho, J. M. Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell. Mol. Life Sci., 2005, 62, 1198-220.
21. Daugan, A.; Grondin, P.; Ruault, C.; Le Monnier de Gouville, A.- C.; Coste, H.; Linget, J. M.; Kirilovsky, J.; Hyafil, F.; Labaudiniere, R. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-Hexahydropyrazino[1′,2′:1,6] pyrido[3,4-b]indole-1,4-dione analogues. J. Med. Chem., 2003, 46, 4533-42.
22. Schmidt, D.; Dent, G.; Rabe, K. F. Selective phosphodiesterase inhibitors for the treatment of bronchial asthma and chronic obstructive pulmonary disease. Clin. Exp. Allergy, 1999, 29, 99-109.
23. Kuss, H.; Hoefgen, N.; Johanssen, S.; Kronbach, T.; Rundfeldt, C. In vivo efficacy in airway disease models of N-(3,5-dichloro-pyrid-4- yl)-[1-(4-fluorobenzyl)-5- hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration. J. Pharmacol. Exp. Ther., 2003, 307, 373-85.
24. Kitson, S.L. 5-hydroxytryptamine (5-HT) receptor ligands. Curr. Pharm. Des., 2007, 13, 2621-37.
25. Nichols, D. E.; Nichols, C. D. Serotonin receptors. Chem. Rev., 2008, 108, 1614-41.
26. Fink, K. B.; Göthert, M. 5-HT receptor regulation of neurotransmitter release. Pharmacol. Rev., 2007, 59, 360-417.
27. Saxena, P. R. Serotonin receptors: subtypes, functional responses and therapeutic relevance. Pharmacol. Ther., 1995, 66, 339-68.
28. Caliendo, G.; Santagada, V.; Perissutti, E.; Fiorino, F. Derivatives as 5HT1A receptor ligands - past and present. Curr. Med. Chem., 2005, 12, 1721-53.
29. Hirst, W.D.; Andree, T. H.; Aschmies, S.; Childers, W. E.; Comery, T. A.; Dawson, L. A.; Day, M.; Feingold, I. B.; Grauer, S. M.; Harrison, B. L.; Hughes, Z. A.; Kao, J.; Kelly, M. G.; Van der Lee, H.; Rosenzweig-Lipson, S.; Saab, A. L.; Smith, D. L.; Sullivan, K.; Rizzo, S. J. S.; Tio, C.; Zhang, M.-Y.; Schechter, L. E. Correlating efficacy in rodent cognition models with in vivo 5-hydroxytryptamine1A receptor occupancy by a novel antagonist, (R)-N-(2-methyl-(4-indolyl- 1-piperazinyl)ethyl)-N-(2- pyridinyl)-cyclohexane carboxamide (WAY-101405). J. Pharmacol. Exp. Ther., 2008, 325, 134-45.
30. Mantegani, S.; Brambilla, E.; Caccia, C.; Fornaretto, M. G.; Mc Arthur, R.A.; Varasi, M. Synthesis and in vitro structure-activity relationship of 13-tert- butyl-ergoline derivatives as 5-HT1A receptor ligands. Eur. J. Med. Chem., 1997, 32, 795-804.
31. Tepper, S. J.; Rapoport, A. M.; Sheftell, F. D. Mechanisms of action of the 5-HT 1B/1D receptor agonists. Arch. Neurol., 2002, 59, 1084-88.
32. Humphrey, P. P. A. The discovery and development of the triptans, a major therapeutic breakthrough. Headache, 2008, 48, 685-87.
33. Pascual, J.; Mateos, V.; Roig, C.; Sanchez-Del-Rio, M.; Jiménez, D. Marketed oral triptans in the acute treatment of migraine: a systematic review on efficacy and tolerability. Headache, 2007, 47, 1152-68.
34. Baxter, G.; Kennett, G.; Blaney, F.; Blackburn, T. Trends Pharmacol. Sci., 1995, 16, 105-10.
35. Perregaard, J.; Arnt, J.; Bogeso, K. P.; Hyttel, J.; Sanchez, C. Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1Hindoles. J. Med. Chem., 1992, 35, 1092-101.
36. Funakoshi, T.; Chaki, S.; Kawashima, N.; Suzuki, Y.; Yoshikawa, R.; Kumagai, T.; Nakazato, A.; Kameo, K.; Goto, M.; Okuyama, S. In vitro and in vivo pharmacological profile of 5-{2-[4-(6-fluoro-1H-indole-3-yl) piperidin-1-yl]ethyl}-4- (4-fluorophenyl) thiazole-2-carboxylic acid amide (NRA0562), a novel and putative atypical antipsychotic. Life Sci., 2002, 71, 1371-84.
37. Brea, J.; Castro, M.; Loza, M. I.; Masaguer, C. F.; Raviña, E.; Dezi, C.; Pastor, M.; Sanz, F.; Cabrero-Castel, A.; Galán-Rodríguez, B.; Fernández-Espejo, E.; Maldonado, R.; Robledo, P. QF2004B, a potential antipsychotic butyrophenone derivative with similar pharmacological properties to clozapine. Neuropharmacology, 2006, 51, 251-62.
38. Gyermek, L. 5-HT3 receptors: pharmacologic and therapeutic aspects. J. Clin. Pharmacol., 1995, 35, 845-55.
39. Olivier, B.; Van Wijngaarden, I.; Soudijn, W. 5-HT3 receptor antagonists and anxiety; a preclinical and clinical review. Eur. Neuropsychopharmacol., 2000, 10, 77-95.
40. Howlett, A. C.; Breivogel, C. S.; Childers, S. R.; Deadwyler, S. A.; Hampson, R. E.; Porrino, L. J. Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology, 2004, 47, 345-58.
41. Pavlopoulos, S.; Thakur, G. A.; Nikas, S. P.; Makriyannis, A. Cannabinoid receptors as therapeutic targets. Curr. Pharm. Des., 2006, 12, 1751-69.
42. Van Sickle, M. D.; Duncan, M.; Kingsley, P. J.; Mouihate, A.; Urbani, P.; Mackie, K.; Stella, N.; Makriyannis, A.; Piomelli, D.; Davison, J. S.; Marnett, L. J.; Di Marzo, V.; Pittman, Q. J.; Patel, K. D., Sharkey, K. A. Neuroscience: identification and functional characterization of brainstem cannabinoid CB2 receptors. Science, 2005, 310, 329-32.
43. Moloney, G. P.; Angus, J. A.; Robertson, A. D.; Stoermer, M. J.; Robinson, M.; Wright, C. E.; McRae, K.; Christopoulos, A. Synthesis and cannabinoid activity of 1-substituted-indole-3-oxadiazole derivatives: novel agonists for the CB1 receptor. Eur. J. Med. Chem., 2008, 43, 513-39.
44. Frost, J. M.; Dart, M. J.; Tietje, K. R.; Garrison, T. R.; Grayson, G. K.; Daza, A. V.; El-Kouhen, O. F.; Miller, L. N.; Li, L.; Yao, B. B.; Hsieh, G. C.; Pai, M.; Zhu, C. Z.; Chandran, P.; Meyer, M. D. Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity. J. Med. Chem., 2008, 51, 1904-12.
45. Shimazaki, Y.; Yajima, T.; Takani, M.; Yamauchi, O. Metal complexes involving indole rings: structures and effects of metal-indole interactions. Coord. Chem. Rev., 2009, 253, 479-92.
46. Nocek, J. M.; Zhou, J. S.; De Forest, S.; Priyadarshy, S.; Beratan, D. N.; Onuchic, J. N.; Huffman, B. M. Theory and practice of electron transfer within protein-protein complexes: application to the multidomain binding of cytochrome c by cytochrome c peroxidase. Chem. Rev., 1996, 96, 2459-89.
47. Gokel, G. W. Indole, the aromatic element of tryptophan, as a pidonor and amphiphilic headgroup. Int. Congr. Ser., 2007, 1304, 1-14.
48. Da Settimo, F.; Lucacchini, A.; Marini, A. M.; Martini, C.; Primofiore, G.; Senatore, G.; Taliani, S. Isosteric replacement of the indole nucleus by benzothiophene and benzofuran in a series of indolylglyoxylylamine derivatives with partial agonist activity at the benzodiazepine receptor. Eur. J. Med. Chem, 1996, 31, 951-56.
49. Bianucci, A. M.; Da Settimo, A.; Da Settimo, F.; Primofiore, G.; Martini, C.; Giannaccini, G.; Lucacchini, A. Benzodiazepine receptor affinity and interaction of some N-(indol-3-ylglyoxylyl)amine derivatives. J. Med. Chem, 1992, 35, 2214-20.
50. Mannhold, R.; Rekker, R. F. The hydrophobic fragmental constant approach for calculating log P in octanol/water and aliphatic hydrocarbon/ water systems. Perspect. Drug Discov. Des., 2000, 18, 1-18.
51. Thornber, C. W. Isosterism and molecular modification in drug design. Chem. Soc. Rev., 1979, 8, 563-80.
52. Lima, L. M.; Barreiro, E. J. Bioisosterism: a useful strategy for molecular modification and drug design. Curr. Med. Chem., 2005, 12, 23-49.
53. Cooper, L. C.; Chicchi, G. G.; Dinnell, K.; Elliott, J. M.; Hollingworth, G. J.; Kurtz, M. M.; Locker, K. L.; Morrison, D.; Shaw, D. E.; Tsao, K.-L.; Watt, A. P.; Williams, A. R.; Swain, C. J. 2-Aryl indole NK1 receptor antagonists: optimisation of indole substitution. Bioorg. Med. Chem. Lett., 2001, 11, 1233-36.
54. Blair, J. B.; Marona-Lewicka, D.; Kanthasamy, A.; Lucaites, V. L.; Nelson, D. L.; Nichols, D. E. Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine. J. Med. Chem., 1999, 42, 1106-11.
55. Fludzinski, P.; Evrard, D. A.; Bloomquist, W. E.; Lacefield, W. B.; Pfeifer, W.; Jones, N. D.; Deeter, J. B.; Cohen, M. L. Indazoles as indole bioisosteres: synthesis and evaluation of the tropanyl ester and amide of indazole-3-carboxylate as antagonists at the serotonin 5HT3 receptor. J. Med. Chem., 1987, 30, 1535-37.
56. Bondensgaard, K.; Ankersen, M.; Thögersen, H.; Hansen, B. S.; Wulff, B. S.; Bywater, R. P. Recognition of privileged structures by G-protein coupled receptors. J. Med. Chem., 2004, 47, 888-99.
57. Rad, R.; Mracec, M.; Mraceca, M.; Oprea, T. The privileged structures hypothesis for G protein-coupled receptors - some preliminary results. Rev. Roum. Chim., 2007, 52, 853-58.