Synthesis and SAR of 4-(1H-benzimidazole-2-carbonyl)piperidines with dual histamine H1/tachykinin NK1 receptor antagonist activity

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 22, 1997, Pages 2819-2824

  Maynard, George D ^a   Bratton, Larry D ^a   Kane, John M ^a   Burkholder, Timothy P ^a   Santiago, Braulio ^a   Stewart, Kenneth T ^a   Kudlacz, Elizabeth M ^a   Shatzer, Scott A ^a   Knippenberg, Robert W ^a   Farrell, Amy M ^a   Logan, Deborah E ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BENZIMIDAZOLE DERIVATIVE; HISTAMINE H1 RECEPTOR ANTAGONIST; NEUROKININ 1 RECEPTOR; NEUROKININ 1 RECEPTOR ANTAGONIST; PIPERIDINE DERIVATIVE;

ALLERGY; ARTICLE; BINDING AFFINITY; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

EID: 0030695112     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10097-X     Document Type: Article

References (14)

1. (a) White, M. V.; Kaliner, M. A. J. Allergy Clin. Immunol. 1992, 90, 699.
2. (b) Bousquet, J; Vignola, A. M.; Campbell, A. M.; Michel, F.-B. Int. Arch. Allergy Immunol. 1996, 110, 207
3. Woodhead, C. J. Clin. Otolaryngol. 1994, 19, 277.
4. Kudlacz, E.; Shatzer, S.; Logan, D.; Olsen, K.; Knippenberg, R.; Hsieh, L.; Esteve, H.; Maynard, G. Int. Arch. Allergy Immunol. 1997, in press.
5. Vaz, R.; Maynard, G. D.; Kudlacz, E. M.; Bratton, L. D.; Kane, J. M.; Santiago, B.; Shatzer, S. A.; Knippenberg, R. W. Bioorg. Med. Chem. Lett. 1997, accompanying paper.
6. Burkholder, T. P.; Kudlacz, E. M.; Le, T.-B.; Shatzer, S. A.; Maynard, G. D.; Knippenberg, R. W.; Webster, M. E.; Horgan, S. W. Bioorg. Med. Chem. Lett. 1996, 6, 951.
7. Kane, J. M.; Carr, A. A.; Hay, D. A.; Staeger, M. A. J. Org. Chem. 1990, 55, 1399.
8. 1 receptor antagonists and the dependence of each of these activities on the absolute configuration at the pyrrolidine 3-position will be presented in future publications covering structurally related series of compounds.
9. Maynard, G. D.; Cheng, H. C.; Kane, J. M.; Staeger, M. A. Bioorg. Med. Chem. Lett. 1993, 3, 753.
10. (a) Hughes, D. L. In Organic Reactions; Paquette, L. A., Ed.; John Wiley & Sons: New York, 1992, 42, 335.
11. (b) Mitsunobu, O. Synthesis 1981, 1.
12. For a detailed description of the biological assays used see ref 2.
13. All new compounds displayed spectra consistent with assigned structure and analytical data and are ≥95% pure by reverse-phase HPLC analysis.
14. Log P values were calculated using PCMODELS 4.41.