3-Chloro-4-carboxamido-6-arylpyridazines as a non-peptide class of interleukin-1β converting enzyme inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 8, 1997, Pages 1003-1006

  Dolle, Roland E ^a   Hoyer, Denton ^b   Rinker, James M ^c   Ross, Tina Morgan ^d   Schmidt, Stanley J ^e   Helaszek, Carla T ^f   Ator, Mark A ^g  

^a Sanofi Winthrop Inc   (United States)

^b PHARMACOPEIA INC   (United States)

^c NOVARTIS PHARMA AG   (Switzerland)

^d 3 Dimensional Pharmaceutical Inc   (United States)

^e JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^f Nycomed Inc   (United States)

^g Ccphalon Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALPAIN; CATHEPSIN B; CATHEPSIN L; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 1BETA CONVERTING ENZYME INHIBITOR; PYRIDAZINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

EID: 0030900525     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00145-5     Document Type: Article

References (16)

1. (a) Dinarello, C. A. Blood 1991, 77, 1627.
2. (b) Dinarello, C. A.; Wolff, S.M. N. Engl. J. Med. 1993, 328, 106.
3. (c) Dinarello, C. A. FASEB J. 1994, 8, 1314.
4. (a) Black, R. A.; Kronheim, S. R.; Sleath, P. R. FEBS Lett. 1989, 247, 386.
5. (b) Kostura, M. J.; Tocci, M. J.; Limjuco, G.; Chin, J.; Cameron, P.; Hillman, A. G.; Chartrain, N. A.; Schmidt, J. A. Proc. Nat. Acad. Sci. 1989, 86, 5227.
6. For a leading review on ICE see: Ator, M. A.; Dolle, R. E. Curr. Pharmaceutical Design 1995, 1, 191.
7. For the synthesis of these agents, see the detailed experimentals presented in: (a) Dolle, R. E. Hoyer, D.; Ross, T. M.; Rinker, J. R.; Schmidt, S. L.; Ator, M. A. Eur. Pat. Appl.: 628550 (1995).
8. (b) Lesher, G. Y.; Dickinson, W. B. US Patent: 4,590,194 (1986).
9. (c) Albright, J. D.; Envoy, F. J.; Moran, D. B. J. Heterocyclic Chem. 1978, 15, 881.
10. (a) Yanai, M.; Takeda, S.; Mitsuoka, T. Chem. Pharm. Bull. Japan 1977, 25, 1708.
11. (b) Wermurth, C.-G.; et. al. J. Med. Chem. 1989, 32, 528.
12. Protection against inactivation by increasing [S] is observed, consistent with the active-site directed reaction.
13. 4 = 4-Cl-Ph are inactive.
14. 4 = 4-Cl-Ph is inactive.
15. Hansch, C.; Leo, A. Exploring QSAR; American Chemical Society, Washington, DC, 1995.
16. 50 determinations see ref 4a. Assay for determining the second order rate constant: Dolle, R. E.; Prouty, C. P.; Prasad, C. V. C.; Cook, E.; Saha, A.; Ross, T. M.; Salvino, J. M.; Helaszek, C. T.; Ator, M. A. J. Med. Chem. 1996, 39, 2438.