The Gif system as a tool in medicinal chemistry: The oxidation of Sch 57726 under GoAgg(III) conditions

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 11, 1997, Pages 1381-1386

  Doller, Dario ^a   Chackalamannil, Samuel ^a   Stamford, Andrew ^a   McKittrick, Brian ^a   Czarniecki, Michael ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; PHOSPHODIESTERASE INHIBITOR; SCH 57726; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG CONFORMATION; DRUG METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OXIDATION; REACTION ANALYSIS;

EID: 0030974116     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00238-2     Document Type: Article

References (15)

1. Chorghade, M. S.; Dezaro, D. A.; Hill, D. R.; Lee, E. C.; Pariza, R. J.; Andersen, J. V.; Hansen, K. T.; Dolphin, D. H. Bioorg. Med. Chem. Lett. 1994, 4, 2867, and references cited therein.
2. The Activation of Dioxygen and Homogeneous Catalytic Oxidation; Barton, D. H. R.; Martell, A. E.; Sawyer, D. T., Eds. Plenum: New York, 1993.
3. Dolphin, D. H.; Traylor, P. S.; Traylor, T. G. J. Chem. Soc., Chem. Commun. 1984, 279.
4. Barton, D. H. R.; Doller, D. Acc. Chem. Res. 1992, 25, 504.
5. Neustadt, B.; Lindo, N.; McKittrick, B. US Patent 5,393,755, 1995.
6. 50 determination was carried out utilizing PDE types I, IH, and V purified from bovine aorta, bovine heart, and bovine lung, respectively, according to: Thompson, W. J.; Brooker, G.; Appleman, M. M. Methods in Enzymol. 1974, 38, 205; Ann, H. S.; Crim, W.; Romano, M.; Sybertz, E.; Pitts, B. Biochem. Pharmacol. 1989, 38, 3331; Harrison, S. A.; Reifsnyder, D. H.; Gallis, B.; Cadd, G. G.; Beavo, J. A. Mol. Pharmacol. 1986, 29, 506; Thomas, M. K.; Francis, S. H.; Corbin, J. D. J. Biol. Chem. 1990, 265, 14964.
7. 50 determination was carried out utilizing PDE types I, IH, and V purified from bovine aorta, bovine heart, and bovine lung, respectively, according to: Thompson, W. J.; Brooker, G.; Appleman, M. M. Methods in Enzymol. 1974, 38, 205; Ann, H. S.; Crim, W.; Romano, M.; Sybertz, E.; Pitts, B. Biochem. Pharmacol. 1989, 38, 3331; Harrison, S. A.; Reifsnyder, D. H.; Gallis, B.; Cadd, G. G.; Beavo, J. A. Mol. Pharmacol. 1986, 29, 506; Thomas, M. K.; Francis, S. H.; Corbin, J. D. J. Biol. Chem. 1990, 265, 14964.
8. 50 determination was carried out utilizing PDE types I, IH, and V purified from bovine aorta, bovine heart, and bovine lung, respectively, according to: Thompson, W. J.; Brooker, G.; Appleman, M. M. Methods in Enzymol. 1974, 38, 205; Ann, H. S.; Crim, W.; Romano, M.; Sybertz, E.; Pitts, B. Biochem. Pharmacol. 1989, 38, 3331; Harrison, S. A.; Reifsnyder, D. H.; Gallis, B.; Cadd, G. G.; Beavo, J. A. Mol. Pharmacol. 1986, 29, 506; Thomas, M. K.; Francis, S. H.; Corbin, J. D. J. Biol. Chem. 1990, 265, 14964.
9. 50 determination was carried out utilizing PDE types I, IH, and V purified from bovine aorta, bovine heart, and bovine lung, respectively, according to: Thompson, W. J.; Brooker, G.; Appleman, M. M. Methods in Enzymol. 1974, 38, 205; Ann, H. S.; Crim, W.; Romano, M.; Sybertz, E.; Pitts, B. Biochem. Pharmacol. 1989, 38, 3331; Harrison, S. A.; Reifsnyder, D. H.; Gallis, B.; Cadd, G. G.; Beavo, J. A. Mol. Pharmacol. 1986, 29, 506; Thomas, M. K.; Francis, S. H.; Corbin, J. D. J. Biol. Chem. 1990, 265, 14964.
10. 2O, 0.5 mL, 0.45 mmol) added dropwise. The reaction time was ca. 60 min. After work-up, flash chromatography (60% ethyl acetate in hexanes) afforded compound II (4 mg, 2%) and recovered starting material (190 mg, 93%).
11. 2-N). FABMS 508 (M+1).
12. Ho-Sam Ahn, H.-S.; Bercovici, A.; Boykow, G.; Bronnenkant, A. Chackalamannil, S.; Chow, J.; Cleven, R.; Cook, J.; Czarniecki, M.; Domalski, C.; Fawzi, A.; Green, M.; Gündes, A.; Ho, G.; Laudicina, M.; Lindo, N.; Ma, K.; Manna, M.; McKittrick, B.; Mirzai, B.; Nechuta, T.; Neustadt, B.; Puchalski, C.; Pula, K.; Silverman, L.; Smith, E.; Stamford, A.; Tedesco, R. P.; Tsai, H.; Tulshian, D.; Vaccaro, H.; Watkins, R. W.; Weng, X.; Witkowski, J. T.; Xia, Y. and Zhang H. J. Med. Chem. Submitted for publication.
13. 3. The organic layer was purified via flash chromatography using EtOH:dichloromethane (2:98) to elute compound VIII (32 mg, 43%) whose NMR spectrum was identical with that of the product prepared in part b.
14. 6) 22.6, 25.4, 26.1, 27.7, 33.5, 34.3, 40.2, 43.4, 48.4, 48.7, 98.4, 107.1, 125.5, 125.7, 127.2, 127.4, 128.6, 128.7, 136.9, 147.5, 150.1, 151.1, 151.2, 154.2.
15. The regio- and stereochemistry of the in vivo hydroxylation process could not be established as different diastereoisomers could not be resolved under the conditions of the HPLC-MS analysis.