Neighboring group participation: Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5α-reductase

Steroids

Volumn 69, Issue 7, 2004, Pages 451-460

  Wölfling, János ^a   Hackler, László ^a   Mernyák, Erzsébet ^a   Schneider, Gyula ^a   Tóth, István ^a   Szécsi, Mihály ^a   Julesz, János ^a   Sohár, Pál ^b,c   Csámpai, Antal ^b  

^a UNIVERSITY OF SZEGED   (Hungary)

^b EÖTVÖS LORÁND UNIVERSITY   (Hungary)

^c INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

Author keywords

5 Reductase; Heterocyclic steroids; In vitro inhibition; Neighboring group participation; Structure determination by IR and NMR

Indexed keywords

1 HYDROXYMETHYLPREGN 5 ENE 3BETA,20 DIOL; 17BETA [3 (N 4 BROMOPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 17BETA [3 (N 4 BROMOPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 CHLOROPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 ETHOXYPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 17BETA [3 (N 4 ETHOXYPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 ETHYLPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 17BETA [3 (N 4 ETHYLPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 FLUOROPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 METHOXYPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 17BETA [3 (N 4 METHOXYPHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 PHENYLTETRAHYDROOXACIN 2 ON 6 YL)]ANDROST 5 EN 3BETA OL; 17BETA [3 (N 4 TOLYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 17BETA [3 (N 4 TOLYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 5 EN 3BETA OL; 17BETA [3 (N PHENYL)TETRAHYDROOXACIN 2 ON 6 YL]ANDROST 4 EN 3 ONE; 3BETA ACETOXY 21 (4 TOLUENESULFONYL)OXYMETHYLPREGN 5 EN 20BETA OL; 3BETA ACETOXY 21 4 TOLUENESULFONYLOXYMETHYLPREGN 5 ENE 20BETA N PHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 EN 20BETA OL; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 BROMOPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 CHLOROPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 ETHOXYPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 ETHYLPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 FLUOROPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 METHOXYPHENYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N 4 TOLYLURETHANE; 3BETA ACETOXY 21 CHLOROMETHYLPREGN 5 ENE 20BETA N PHENYLURETHANE; 3BETA ACETOXY 21 HYDROXYMETHYLPREGN 5 EN 20ALPHA OL; 3BETA ACETOXY 21 HYDROXYMETHYLPREGN 5 EN 20BETA OL; STEROID; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SUBSTITUTION; ANALYTIC METHOD; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CYCLIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; INFRARED SPECTROSCOPY; METHANOLYSIS; OPPENAUER OXIDATION; PROTON NUCLEAR MAGNETIC RESONANCE; QUANTUM YIELD; STEREOCHEMISTRY;

ENZYME ACTIVATION; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MOLECULAR CONFORMATION; OXAZINES; STEREOISOMERISM; STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP; TESTOSTERONE 5-ALPHA-REDUCTASE;

EID: 3042775315     PISSN: 0039128X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.steroids.2004.04.003     Document Type: Article

References (27)

1. Tapolcsányi P., Wölfling J., Schneider Gy. The preparation of the four stereoisomers of 16-hydroxymethyl-5α-androstane-3β, 17-diol. Steroids. 66:2001;623-635. Part 14
2. 21scc: one enzyme with two actions: hydroxylase and lyase. J Steroid Biochem Mol Biol. 40:1991;527-532
3. 17α): potential agents for the treatment of prostate cancer. J Med Chem. 41:1998;902-912
4. 17α by abiraterone (17-(3-pyridyl)androsta-5, 16-dien-3β-ol) and related steroidal inhibitors. J Med Chem. 41:1998;5375-5381
5. Guarna A., Occiato E.G., Mechetti F., Marrucci A., Danza G., Serio M., Paoli P. 19-Nor-10-azasteroids, a new class of steroid 5α-reductase inhibitors: 2. X-ray structure, molecular modeling, conformational analysis of 19-nor-10-azasteroids and comparison with 4-azasteroids and 6-azasteroids. J Med Chem. 40:1997;3466-3477
6. 17, 20-lyase and of 5α-reductase. J Steroid Biochem Mol Biol. 42:1992;313-320
7. 17, 20-lyase). J Org Chem. 64:1999;4985-4989
8. Russel DW, Wilson JD. Steroid 5α-reductase: two genes/two enzymes. Ann Rev Biochem 1994;6325-61.
9. Normington K., Russel D.W. Tissue distribution and kinetic characterisation of rat steroid 5α-reductase isoenzymes. J Biol Chem. 267:1992;19548-19554
10. Hirsch A.F., Fujimoto G.I. Synthesis of 21-hydroxymethylprogesterone. J Org Chem. 35:1970;495-498
11. Faredin I., Toth I., Wölfling J., Schneider Gy., Mesko E. In vitro inhibitory effects o 16-methyl-substituted steroids on 5α-reductase in rat and human prostates. Steroids. 59:1994;568-571
12. Lowry O.H., Rosenbrough N.J., Farr A.L., Randall R.J. Protein measurements with the Folin phenol reagent. J Biol Chem. 193:1951;265-275
13. Scott F.L., Glick R.E., Winstein S. Amido, ureido and urethano neighbouring group participation. Experientia. 13:1957;183-185
14. Winstein S., Boschan R. The role of neighboring groups in replacement reactions. XVII. Complex neighboring groups. The benzamido group. J Am Chem Soc. 72:1950;4669-4677
15. Ponsold K., Grosse P. Ringschlußreaktionen vicinaler halogen-urethane der steroidreihe. J f prakt Chemie. 323:1981;801-818
16. Schneider G., Hackler L., Sohár P. Steroids, XXIX. Neighbouring group participation, VI. N-Arylurethane neighbouring group participation in the 16-hydroxymethylandrost-5-ene-3, 17-diol series. Acta Chim Acad Sci Hung. 111:1982;285-296
17. Hackler L., Schneider G., Sohár P. N-Arylurethane neighbouring group participation during solvolysis of 3-methoxy-17-N-phenylcarbamoyloxy-16-p- tolylsulfonyloxymethyl-estra-1, 3, 5(10)-triene stereoisomers. Tetrahedron. 42:1992;9305-9314
18. Appel R, Halstenberg M. In: Cadogan JIG, editor. Organophosphorus reagents in organic synthesis. Academic Press: New York; p. 378-424.
19. Levy GC, Nelson GL. Carbon-13 nuclear magnetic resonance for organic chemists. New York: Wiley; 1972. p. 126.
20. Holly S, Sohár P. Theoretical and technical introduction to the series (1979).In: Láng L, Prichard, WH, editors. Absorption spectra in the infrared region. Budapest: Akadémiai Kiadó; 1975. p. 94.
21. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
22. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
23. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
24. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
25. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
26. Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 180-185Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 28Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press; 1983. p. 181Sohár P. Nuclear magnetic resonance spectroscopy, vol. 1. Boca Raton, Florida: CRC Press; 1983. p. 35-38Sohár P. Nuclear magnetic resonance spectroscopy, vol. 2. Boca Raton, Florida: CRC Press;1983. p. 154-155
27. Grant D.M., Cheney B.V. Carbon-13 magnetic resonance. VII. Steric perturbation of the carbon-13 chemical shift. J Am Chem Soc. 89:1967;5315-5318