Synthesis and evaluation of 11β-substituted 21-chloro/iodo- (17α,20E/Z)-19-norpregna-1,3,5(10),20-tetraene-3,17β-diols high-affinity ligands for the estrogen receptor

Journal of Medicinal Chemistry

Volumn 41, Issue 24, 1998, Pages 4686-4692

  Hanson, Robert N ^a   Napolitano, Elio ^b   Fiaschi, Rita ^c  

^a NORTHEASTERN UNIVERSITY   (United States)

^b SCUOLA NORMALE SUPERIORE   (Italy)

^c UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA (1 ETHENYL) 21 CHLORO (17ALPHA) 19 NORPREGNA 1,3,5(10),20 TETRAENE 3,17BETA DIOL; 11BETA (1 ETHENYL) 21 IODO (17ALPHA) 19 NORPREGNA 1,3,5(10),20 TETRAEN 3,17BETA DIOL; 11BETA (1 ETHENYL) 21 IODO (17ALPHA) 19 NORPREGNA 1,3,5(10),20 TETRAENE 3,17BETA DIOL; 11BETA METHOXY 21 CHLORO (17ALPHA) 19 NORPREGNA 1,3,5(10),20 TETRAENE 3,17BETA DIOL; 17ALPHA ETHYNYLESTRADIOL 3 ACETATE; 3 ACETOXY 11BETA (1 ETHENYL) 21 TRI N BUTYLSTANNYL (17ALPHA) 19 NORPREGNA 1,3,5(10),20 TETRAEN 17BETA OL; ESTRADIOL DERIVATIVE; ESTROGEN RECEPTOR; LIGAND; UNCLASSIFIED DRUG; VINYL DERIVATIVE; DRUG DERIVATIVE; ESTRADIOL;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYTOSOL; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; LAMB; LIGAND BINDING; NONHUMAN; RECEPTOR AFFINITY; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; ANIMAL; BINDING SITE; CHEMISTRY; FEMALE; METABOLISM; SHEEP; STEREOISOMERISM; SYNTHESIS; ULTRASTRUCTURE; UTERUS;

ANIMALS; BINDING SITES; CYTOSOL; ESTRADIOL; FEMALE; LIGANDS; RECEPTORS, ESTROGEN; SHEEP; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; UTERUS;

EID: 0032547897     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9801051     Document Type: Article

References (20)

1. Hanson, R. N.; Napolitano, E.; and Fiaschi, R. Synthesis and estrogen receptor binding of novel 11β-substituted estra-1,3,5-(10)-triene-3,17β-diols. J. Med. Chem. 1990, 33, 3155-3160.
2. Napolitano, E.; Fiaschi, R.; Hanson, R. N. Epoxidation of estra-5(10)-9(11)-diene derivatives: A convenient synthesis of 11β-vinyl estrone acetate. Gazz. Chem. Ital. 1990, 170, 323-326.
3. French, A. N.; Napolitano, E.; Van Brocklin, H. F.; Hanson, R. N.; Welch, M. J.; Katzenellenbogen, J. A. Synthesis, radiolabeling and tissue distribution of 11β-fluoroalkyl- and 11β-fluoroalkoxy-substituted estrogens: Target tissue uptake selectivity and defluorination of a homologous series of fluorine-18 labeled estrogens. Nucl. Med. Biol. 1993, 20, 31-47.
4. Hanson, R. N.; El-Wakil, H. Electrophilic destannylation: Stereospecific introduction of electrophiles at the 21-position of (17α,20E)-19-norpregna-l,3,5(10),20-tetraene-3,17β-diols. J. Org. Chem. 1987, 52, 3687-3688.
5. Napolitano, E.; Fiaschi, R; Hanson, R. N. Structure-activity relationships of estrogenic ligands: Synthesis and evaluation of (17α,20E)- and 17α,20Z)-21-halo-19-norpregna-1,3,5(10),20-tetraene-3,17β-diols. J. Med. Chem. 1991, 34, 2754-2759.
6. Napolitano, E.; Fiaschi, R.; Herman, L. W.; Hanson, R. N. Synthesis and estrogen receptor binding of (17α,20E)- and (17α,20Z)-21-phenylthio- and 21-phenylseleno-19-norpregna-1,3,5-(10),20-tetraene-3,17β-diols. Steroids 1996, 61, 384-389.
7. Hanson, R. N.; Herman, L. W.; Fiaschi, R.; Napolitano, E.: Stereochemical probes for the estrogen receptor: Synthesis and receptor binding of (17α,20E/Z)-21-phenyl-19-norpregna-1,3,5-(10),20-tetraene-3,17β- diols. Steroids 1996, 61, 718-722.
8. Anstead, G. M.; Carlson, K. E.; Katzenellenbogen, J. A. The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 1997, 62, 268-303.
9. 125I]iodo-19-norpregna-1,3,5(10)20-tetraene-3,17β-diols. J. Med. Chem. 1991, 34, 854-860.
10. Cummins, C. H. Radiolabeled steroidal estrogens in cancer research. Steroids 1993, 58, 245-259.
11. Gantchev, T. G.; Ali, H.; Van Lier, J.E.: Quantitative structure-activity relationships/comparative molecular field analysis (QSAR/ CoMFA) for receptor-binding properties of halogenated estradiol derivatives. J. Med. Chem. 1994, 37, 4164-4176.
12. Pomper, M. G.; Van Brocklin, H. F.; Thieme. A. M.; Thomas, R. D.; Kiesewetter, D. O.; Carlson, K. O.; Mathias, C. J.; Welch, M. J.; Katzenellenbogen, J. A. 11β-methoxy-, 11β-ethyl- and 17α-ethynyl-substituted 16a-fluoroestradiols. Receptor-based imaging agents with enhanced uptake efficiency and selectivity. J. Med. Chem. 1990, 33, 3143-3155.
13. Brzozowski, A. M.; Pike, A. C. W.; Dauter, Z.; Hubbard, R. E.; Bonn, R.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J.-A.; Carlquist, M. Molecular basis of agonism and antagonism in the estrogen receptor. Nature 1997, 389, 751-758.
14. Raynaud, J.-P.; Ojasoo, T.; Bouton, M. M.; Philibert, D. Receptor binding as a tool in the development of new bioactive steroids. In Drug Design; Ariens, E. J., Eds.; Academic Press: New York, 1979; Vol. III, pp 169-214.
15. Katzenellenbogen, J. A.; Johnson, J. H., Jr.; Meyers, H. M. Reagents for photoaffinity labeling of estrogen binding protein. The binding affinity of some azido and diazo derivatives of estradiol, estrone and hexestrol for the estrogen binding protein of rat uterus. Biochemistry 1973, 12, 4085-4092.
16. Katzenellenbogen, J. A., Carlsson, K. E., Johnson, J. H., Jr.; Meyers, H. M.: Estrogen photoaffinity labels II. Reversible binding and covalent attachment of photosensitive hexestrol derivatives to the uterus estrogen receptor. Biochemistry 1977, 16, 1970-1976.
17. Napolitano, E.; Fiaschi, R.; Carlsson, K. E.; Katzenellenbogen, J. A.: 11β-Substituted estradiol derivatives. Potential carbon-11 and iodine-labeled probes for the estrogen receptor. J. Med Chem. 1995, 38, 2774-2779.
18. Renaud, J.-P.; Rochel, N.; Ruff, M.; Vivat, V.; Chambon, P.; Gronemeyer, H.; Moras, D. Crystal structure of the RAR-γ ligand binding domain bound to all-trans retinoic acid. Nature 1995, 378, 681-689.
19. Wagner, R. L.; Apriletti, J. W.; McGrath, M. E.; West, B. L.; Baxter, J. D.; Fletterick, R. J.: A structural role for the hormone in the thyroid hormone receptor. Nature 1995, 378, 690-697.
20. Still, W. C., Kahn, M.; Mitra, A.: Rapid Chromatographic technique for preparative separations with moderate resolution J. Org. Chem. 1978, 43, 2923-2925.