Thiophenesulfonamides as endothelin receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 22, 1996, Pages 2651-2656

  Raju, B ^b   Wu, Chengde ^b   Kois, Adam ^c   Verner, Erik ^d   Okun, Ilya ^a   Stavros, Fiona ^b   Chan, Ming Fai ^a  

^a ImmunoPharmaceutics Inc   (United States)

^b TEXAS BIOTECHNOLOGY CORPORATION   (United States)

^c CYTEL CORPORATION   (United States)

^d Arris Pharmaceutical Corporation   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTHELIN A RECEPTOR; ENDOTHELIN B RECEPTOR; ENDOTHELIN RECEPTOR ANTAGONIST; SULFONAMIDE; THIOPHENE DERIVATIVE;

ARTICLE; BINDING AFFINITY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; IN VITRO STUDY; MASS SPECTROMETRY; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REACTION ANALYSIS;

EID: 0000658577     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00496-9     Document Type: Article

References (22)

1. 1. Presented in part at the ACS National Meeting , Louisiana, New Orleans, April, 1996, Abstract MEDI 144.
2. 2. (a) Yanagisawa, M.; Kurihra, H.; Kimura, S.; Tomobe, Y.; Kobayashi, M.; Mitisui, Y.; Yazaki, Y.; Goto, K.; Masaki, T. Nature(London) 1988, 332, 411;
3. (b) Inoue, A.; Yanagisawa, M.; Kimura, S.; Kasuya, Y.; Miyauichi, S.; Goto, K.; Masaki, T. Proc. Natl. Acad Sci. U.S.A. 1989, 86, 2863;
4. (c) Shinmi, O.; Kimura, S.; Sawamura, T.; Sugita, Y.; Yoshizawa, T. Biochem. Biophys. Res. Commun. 1989, 164, 587.
5. 3. Wollberg, Z.; Shabo-Shina, R.; Intrator, N.; Bdolah, A.; Kochva, E.; Shavit, G.; Oron, Y.; Vidne, B. A.; Gitter, S. Toxicon 1988, 26, 525.
6. 4. (a) Arai, H.; Hori, S.; Aramori, I.; Ohkubo, H.; Nakanishi, S. Nature(London) 1990, 348, 730;
7. (b) Sakurai, T.; Yanagisawa, M.; Takuwa, Y.; Miyazaki, H.; Kimura, S.; Goto, K.; Masaki, T. Nature(London) 1990, 348, 732;
8. (c) Karne, S.; Jayawickreme, C. K.; Lerner, M. R. J. Biol. Chem. 1993, 268, 19126.
9. 5. In Endothelin receptors: From the Gene to the Human; Ruffolo Jr, R. R., Ed.; CRC Press: Florida, 1995; pp 1-271.
10. 6. For reviews see: (a) Walsh, T. F. Annu. Rep. Med. Chem. 1995, 30, 91; and references cited therein;
11. (b) Battistini, B.; Botting, R. Drugs News and Perspectives. 1995, 8, 365.
12. 7. (a) Chan, M. F.; Okun, I.; Stavros, F. D.; Hwang, E.; Wolff, M. E.; Balaji, V. N. Biochem. Biophys. Res. Commun. 1994, 201, 228.;
13. (b) Verner, E. J.; Kois, A.; Raju, B.; Wu, C.; Venktachalapathi, Y. V.; Castillo, R.; Hwang, E.; Okun, I.; Stavros, F. D.; Balaji, V. N.; Wolff, M. E.; Chan, M. F. Abstracts of Papers, 208th National Meeting of American Chemical Society, Washington, DC; American Chemical Society: Washington, DC, 1994; Abstract MEDI 215. A full account of this work has been submitted to Bioorg. Med. Chem. for publication.
14. 8. Mohamadi, F.; Spees, M.; Grindey. G. B. J. Med. Chem. 1992, 35, 3012.
15. 4, filtered and the solvent removed under reduced pressure. The residue was purified by flash column chromatography using 2% ethyl acetate in hexane as eluent to afford 3-benzylhiophene-2-sulfonyl chloride (1.2 g, 78%). (c) To a stirred solution of 3-bromothiophene (20 g, 123 mmol) in methylene chloride (50 mL) at -78 °C was added chlorosulfonic acid (50 mL, 756 mmol) dropwise over 1 h. This mixture was slowly allowed to attain ambient temperature where stirring continued for 3 h. This was then carefully poured onto ice (1500 g) and extracted with methylene chloride (4 × 100 mL). The combined organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent removed under reduced pressure. The residue was purified by flash column chromatography using 3% ethyl acetate in hexane as eluent to obtain 4-bromothiophene-2-sulfonyl chloride (1.6 g, 5%) and 3-bromothiophene-2-sulfonyl chloride (20.5 g, 64%)
16. 10. (a) Miyaura, N.; Suginome, H.; Suzuki, A. Synth. Commun. 1981, 11, 513;
17. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457
18. 11. Greene, T.W.; Wuts, P.G. In Protective Groups in Organic Synthesis; John Wiley & Sons, Inc.: New York, 1991; pp 379.
19. +.
20. 13. All sulfonamides were characterized by high resolution FAB MS analysis, high field PMR, IR. The purities of sulfonamides were determined by analytical HPLC on C18 reverse phase column (250 mm X 4.6 mm) eluting with water and acetonitrile mixture containing 0.1% TFA from 5% acetonitrile to 95% acetonitrile (Linear gradient) over 30 min period.
21. 14. Stavros, F. D.; Hasel, K. W.; Okun, I.; Baldwin, J.; Feriks, K. J. Cardivasc. Pharmacol. 1993, 22, S34; Binding assays were conducted at 24 °C.
22. 15. Chan, M. F.; Raju, B.; Kois, A.; Castillo, R. C.; Verner, E. J.; Wu, C.; Venkatachalapathi, Y. V.; Okun, I.; Wang, E.; Stavors, F. D.; Balaji, V. N. Abstracts of Papers, 209th National Meeting of American Chemical Society, Anaheim, CA; American Chemical Society: Washington, DC, 1995; Abstracts MEDI 167 and 168.