Unsaturated thioacetic acids as Novel mechanism - Based inhibitors of peptidylglycine α-hydroxylating monooxygenase

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 4, 1996, Pages 393-396

  Casara, P ^a   Ganzhorn, A ^a   Philippo, C ^a   Chanal, M C ^a   Danzin, C ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EQUUS CABALLUS;

ENZYME INHIBITOR; STYRYLTHIOACETIC ACID; THIOACETAMIDE DERIVATIVE; UNCLASSIFIED DRUG; UNSPECIFIC MONOOXYGENASE;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME INHIBITION; HORSE; NONHUMAN; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0029878621     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00041-8     Document Type: Article

References (25)

1. Eipper, B.A.; Stoffers, D.A.; Mains, R.E. Annu. Rev. Neurosci. 1992, 15, 57-85.
2. a) Young, S.D.; Tamburini, P.P. J. Am. Chem. Soc. 1989, 111, 1933-1934.
3. b) Katapodis, A.G.; Ping, D.; May, S.W. Biochemistry 1990, 29, 6115-6120.
4. c) Takahashi, K.; Okamoto, H.; Seino, H.; Noguchi, M. Biochem. Biophys. Res. Commun. 1990, 169, 524-530.
5. a) Bradbury, A.F.; Mistry, J.; Roos, B.A.; Smyth, D.G. Eur. J. Biochem. 1990, 189, 363-368.
6. b) Zabriskie, T.M.; Cheng, H.; Vederas, J.C. J. Am. Chem. Soc. 1992, 114, 2270-2272.
7. c) Erion, M.D.; Tan, J.; Wong, M.; Jeng, A.Y. J. Med. Chem. 1994, 37, 4430-4437.
8. d) Klinge, M.; Cheng, H.; Zabriskie, T. M.; Vederas, J.C. J. Chem. Soc., Chem. Commun. 1994, 1379-1380.
9. a) trans-styrylthioacetic acid 1 was synthesized as following: a mixture of mercaptoacetic methyl ester (13 mmoles), styrene oxide (10 mmoles) and triethylamine (14 mmoles) in methanol (20 mL) was heated under reflux for 3 hours. Usual workup and chromatography on silica gel afforded the two alcohols 1-phenyl-and 2-phenyl-2-hydroxyethyl thioacetic acid methyl ester in 23% and 57% yields, respectively. After addition of mesylchloride (5.5 mmoles) to a mixture of the secondary alcohol (5 mmoles) and DBU (15 mmoles) in dichloromethane (25 mL) at O°C, the resulting mixture was stirred at RT for 24 hours. Usual workup and chromatography on silica gel afforded trans-styrylthioacetic acid methyl ester in 12% yield. Subsequent saponification by LiOH (1 eq.) in a mixture of dioxane: water; 1:1 at RT for 2 hours, acidification and extraction give 1 in 62% yield (mp: 68-70°C).
10. b) Synthesis of cis-styrylthioacetic acid 2 was adapted from Reddy, M.V.R.; Reddy, S. Synthesis 1984, 322-323: a mixture of mercaptoacetic acid (10 mmoles), phenylacetylene (10 mmoles) and sodium hydroxyde (20 mmoles) in methanol (10 mL) was heated under reflux for 24 hours. Then, the mixture was acidified and extracted with dichloromethane, and recrystallized in diethylether: pentane to afford 2 in 84% yield (mp: 84-85°C).
11. c) Synthesis of the acetylenic sulfide 3 was adapted from Raap, R.; Micetich, R.G. Can J. Chem. 1968, 46, 1057-1063 as modified by Lalezari, I. Synthesis 1984, 660-661: to a cooled (-78°C) solution of 4-phenyl-1,2,3-thiodiazole (10 mmoles) in tetrahydrofuran (50 mL), n-butyllithium (11 mmoles) was added. The mixture was stirred at -60°C during 20 min and warmed to 0°C. Then, a solution of bromoacetic acid methyl ester (11 mmoles) in tetrahydrofuran (10 mL) was added and the resulting mixture was stirred during 4 hours. After usual workup and flash chromatography on silica gel, phenylethynylthioacetic acid methyl ester was obtained in 82% yield. Subsequent saponification by LiOH (1 eq.) in a mixture of dioxane: water; 1:1 at RT for 12 h, acidification and extraction afforded 3 (mp: 85°C).
12. c) Synthesis of the acetylenic sulfide 3 was adapted from Raap, R.; Micetich, R.G. Can J. Chem. 1968, 46, 1057-1063 as modified by Lalezari, I. Synthesis 1984, 660-661: to a cooled (-78°C) solution of 4-phenyl-1,2,3-thiodiazole (10 mmoles) in tetrahydrofuran (50 mL), n-butyllithium (11 mmoles) was added. The mixture was stirred at -60°C during 20 min and warmed to 0°C. Then, a solution of bromoacetic acid methyl ester (11 mmoles) in tetrahydrofuran (10 mL) was added and the resulting mixture was stirred during 4 hours. After usual workup and flash chromatography on silica gel, phenylethynylthioacetic acid methyl ester was obtained in 82% yield. Subsequent saponification by LiOH (1 eq.) in a mixture of dioxane: water; 1:1 at RT for 12 h, acidification and extraction afforded 3 (mp: 85°C).
13. 3), 360 MHz, δ (ppm), TSP as reference, J (Hz). 1: 7.3 (m, 5H), 6.74 (d, 1H, J=15), 6.63 (d, 1H, J=15), 3.55 (s, 2H); 2: 7.4 (m, 4H), 7.35 (d, 1H), 6.55 (d, 1H, J=10), 6.35 (d, 1H, J=10), 3.55 (s, 2H); 3: 7.72 (m, 2H), 7.60 (m, 3H), 3.95 (s, 2H); 4: 7.75 (m, 2H), 7.55 (m, 3H), 7.45 (d, 1H, J=14), 7.25 (d, 1H, J=14), 4.10 (d, 1H, JAB=10), 4.02 (d, 1H, JAB=10).
14. Katapodis, A.G.; May, S.W. Biochemistry 1990, 29, 4541-4548.
15. a) Abbot, D.J.; Colonna, S.; Stirling, C.J.M. J. Chem. Soc. Perkin. Trans.I 1976, 492-498.
16. b) Tsuchihashi, G.; Mitamura, S.; Ogura, K. Tetrahedron Lett. 1976, 855-858.
17. a) May, S.W.; Phillips, R.S. J. Am. Chem. Soc. 1980, 102, 5983-5984.
18. b) Watanabe, Y.; Iyanagi, T.; Oae, S. Tetrahedron Lett. 1980, 21, 3685-3688.
19. c) Padgette, S.R.; Wimalasena, K.; Herman, H.H.; Sirimanne, S.R.; May, S.W. Biochemistry 1985, 24, 5826-5839.
20. Bordwell, F.G.; Ji, G-Z.; Zhang, X. J. Org. Chem. 1991, 56, 5254-5256.
21. -1. Time-dependent inactivation of PHM was essentially assayed according to ref. 5.
22. Kitz, R.; Wilson, I.B. J. Biol. Chem. 1962, 237, 3245-3249.
23. M value.
24. +S-; therefore synthesis of the sulfoxidation product of 3 could be favoured (in analogy to pathway a).
25. Rhodes, C.H.; Honsinger, C. Ann. N.Y. Acad. Sci. 1993, 689, 663-666.