A nonpeptidic agonist ligand of the human C5a receptor: Synthesis, binding affinity optimization and functional characterization

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 2, 1997, Pages 213-218

  De Laszlo, S E ^a   Allen, E E ^a   Li, B ^a   Ondeyka, D ^a   Rivero, R ^a   Malkowitz, L ^a   Molineaux, C ^a   Siciliano, S J ^a   Springer, M S ^a   Greenlee, W J ^a   Mantlo, N ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT COMPONENT C5A; COMPLEMENT RECEPTOR; HYDANTOIN DERIVATIVE; LIGAND; MYELOPEROXIDASE;

ARTICLE; BINDING AFFINITY; DERIVATIZATION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; NEUTROPHIL; STRUCTURE ACTIVITY RELATION;

EID: 0031033892     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00606-3     Document Type: Article

References (17)

1. Goldstein, I. M. in Inflammation: Basic Principles and Clinical Correlates; Gallin, J. I.; Goldstein, I. M.; Snyderman, R., Eds.; Raven Press, New York, 1988; pp 55-74.
2. Hagmann, W. K.; Sindelar, R. D. Annu. Rep. Med. Chem. 1992, 27, 199.
3. Kawai, M.; Wiedeman, P. E.; Lully, J. R.; Or. Y. S. World Intelectual Property Organization: Publication WO92/12168A.
4. Mollison, K. W.; Krause, R. A.; Fey, T. A.; Miller, P. E.; Wiedeman, P. E.; Kawai, M.; Lane, B.; Luly, J. R.; Carter, G. W. FASEB J. 6:A2058, 1992.
5. Konteatis, Z. D.; Siciliano, S. J.; Van Riper, G.; Molineaux, C. J.; Pandya, S.; Fischer, P.; Rosen, H.; Mumford, R. A.; Springer, M. S. J. of Immunology 1994, 153, 4200.
6. Lanza, T. J.; Durette, P. L.; Rollins, T.; Siciliano, S.; Cianciarulo, D. N.; Kobayashi, S. V.; Caldwell, C. G; Springer, M. S.; Hagmann, W. K. J. Med.Chem. 1992, 35, 252.
7. All analogs were characterized by TLC, NMR, and FABMS.
8. Baldwin, J.; Adlington, R. M.; Godfrey, C. R. A.;Glooins, D. W.; Schofield, C. J. Tetrahedron, 1991, 47, 5835.
9. Based on: Siciliano, S. J.; Rollins, T. E. ; Springer, M. S. J. Biol. Chem. 1990, 265, 19568. Rollins, T. E.; Siciliano, S.; Spinger, M. S. J. Biol. Chem. 1988, 263, 520.
10. Based on: Siciliano, S. J.; Rollins, T. E. ; Springer, M. S. J. Biol. Chem. 1990, 265, 19568. Rollins, T. E.; Siciliano, S.; Spinger, M. S. J. Biol. Chem. 1988, 263, 520.
11. Rollins, T. E.; Springere, M. S. J. Biol. Chem. 1985, 260, 7157.
12. DeMartino, J. A.; Van Riper, G.; Siciliano, S. J.; Molineaux, C. J.; Konteatis, Z. D.; Rosen, H.; Springer, M. S. J. Biol. Chem. ; 1994, 269, 14446. Siciliano, S. J.; Rollins, R. E.; DeMartino, J.; Konteatis, A.; Malkowitz, L.; Van Riper, G.; Bondy, S.; Rosen, H.; Springer, M. S. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 1214.
13. DeMartino, J. A.; Van Riper, G.; Siciliano, S. J.; Molineaux, C. J.; Konteatis, Z. D.; Rosen, H.; Springer, M. S. J. Biol. Chem. ; 1994, 269, 14446. Siciliano, S. J.; Rollins, R. E.; DeMartino, J.; Konteatis, A.; Malkowitz, L.; Van Riper, G.; Bondy, S.; Rosen, H.; Springer, M. S. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 1214.
14. 50 (C5a) = 26% @ 30uM
15. No interaction has been found for this class of compounds with other G-protein coupled receptors following broad screening at concentrations of 1.0 mM.
16. Flanagan, K. L.; Chang, L. L.; Ashton, W. T.; Hutchins, S. M.; Malkowitz, L.; Molineaux, C.; Siciliano, S.;Springer, M. S.; Greenlee, W. J.; Mantlo, N. B. 210th ACS National Meeting, Chicago, Illinois. August 20th-24th 1995.
17. Kim, D.; Rivero, R. A.; de Laszlo, S. E.; Tran, J.; Fair, J.; Ashton, W. T.; Hutchins, S. M.; Malkowitz, L.; Molineaux, C.; Siciliano, M. S.; Springer, M. S; Greenlee, W. J.; Mantlo, N. B. 210th ACS National Meeting, Chicago, Illinois. August 20th-24th 1995.