Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 7, 1999, Pages 967-972

  Beck, James P ^a   Arvanitis, Argyrios G ^a   Curry, Matt A ^a   Rescinito, Joseph T ^a   Fitzgerald, Larry W ^a   Gilligan, Paul J ^a   Zaczek, Robert ^a   Trainor, George L ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOTROPIN RELEASING FACTOR ANTAGONIST; CORTICOTROPIN RELEASING FACTOR RECEPTOR; CP 1545261; PURIN 8 ONE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL LINE; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; REACTION ANALYSIS; RECEPTOR AFFINITY; RECEPTOR BLOCKING; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; TRANQUILIZING ACTIVITY;

ANTI-ANXIETY AGENTS; ANTIDEPRESSIVE AGENTS; PURINONES; RECEPTORS, CORTICOTROPIN-RELEASING HORMONE; STRUCTURE-ACTIVITY RELATIONSHIP;

ANIMALIA;

EID: 0033526094     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00108-0     Document Type: Article

References (13)

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2. 2. DeSouza, E. B.; Grigoriadis, D. E. Psychopharmacology; The Fourth Generation of Progress; Bloom, F. E.; Kupfer, D. J., Eds.; Raven: New York, NY, 1995; pp 505-517.
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5. 5. For review: Christos, T. E.; Arvanitis, A. G. Expert Opin. Ther. Pat. 1998, 8, 143.
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7. 7. Wustrow, D. J.; Capiris, T.; Rubin, R.; Knobelsdorf, J. A.; Akunne, H.; Davis, M. D.; MacKenzie, R.; Pugsley, T. A.; Zoski, K. T.; Heffner, T. G.; Wise, L. D. Bioorg. Med. Chem. Lett. 1998, 8, 2067.
8. 8. Chorvat, R. J.; Bakthavatchalam, R.; Beck, J. P.; Gilligan, P. J.; Wilde, R. G.; Cocuzza, A.; Hobbs, F. W.; Cheeseman, R. S.; Curry, M.; Rescinito, J. P.; Krenitsky, P.; Chidester, D.; Yarem, J.; Klaczkiewicz, J. D.; Hodge, C. N.; Aldrich, P. E.; Wasserman, Z. R.; Fernandez, C. H.; Zaczek, R.; Fitzgerald, L.; Huang, S. -M.; Shen, H. L.; Wong, Y. N.; Chien, B. M.; Quon, C. Y.; Arvanitis, A. J. Med. Chem. 1999, 42, in press.
9. 9. During these studies, similiar CRH-R1 receptor antagonists appeared in the patent literature: Chen, Y.L. PCT Int. Appl. WO 95/33750.
10. 10. For a comprehensive description of the isolation of cell membranes containing cloned human CRH R1 receptors and description of the CRH R1 binding assay, see reference 11.
11. 11. Arvanitis, A.; Gilligan, P. J.; Chorvat, R. J.; Cheeseman, R. S.; Christos, T. E.; Bakthavatchalam, R.; Beck, J. P.; Cocuzza, A. J.; Hobbs, F. W.; Wilde, R. G.; Arnold, C.; Chidester, D.; Curry, M.; He, L.; Hollis, A.; Klaczkiewicz, J. D.; Krenitsky, P. J.; Rescinito, J. P.; Scholfield, E.; Culp, S.; De Souza, E. B.; Fitzgerald, L.; Grigoriadis, D.; Tam, S. W.; Wong, N.; Huang, S. -M.; Shen, H.L. J. Med. Chem. 1999, 42, in press.
12. 13 afforded the desired mono-addition adduct. The remaining reaction sequence proceeded as described in Scheme 1 with Step h proceeding Step g.
13. 2, Pd/C, 50 psi, 95%).