Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists

Alexey B. Dyatkin, William J. Hoekstra, William A. Kinney, Maria Kontoyianni, Rosemary J. Santulli, Edward S. Kimball, M. Carolyn Fisher, Stephen M. Prouty, William M. Abraham, Patricia Andrade-Gordon, Dennis J. Hlasta, Wei He, Pamela J. Hornby, Bruce P. Damiano, Bruce E. Maryanoff

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The design, synthesis, and biological activity of novel α 4β1 and α4β7 integrin antagonists, containing a bridged azabicyclic nucleus, are reported. Conformational analysis of targets containing an azabicyclo[2.2.2]octane carboxylic acid and known integrin antagonists indicated that this azabicycle would be a suitable molecular scaffold. Variation of substituents on the pendant arylsulfonamide and phenylalanine groups resulted in potent α 4β1-selective and dual α4β 14β7 antagonists. Potent compounds 11i, 11h, and 14 were effective in the antigen-sensitized sheep model of asthma.

Original languageEnglish
Pages (from-to)591-596
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number3
DOIs
StatePublished - Feb 9 2004
Externally publishedYes

Fingerprint

Sulfonamides
Integrins
Azabicyclo Compounds
Amino Acids
Carboxylic Acids
Bioactivity
Phenylalanine
Scaffolds
Sheep
Asthma
Antigens

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Dyatkin, A. B., Hoekstra, W. J., Kinney, W. A., Kontoyianni, M., Santulli, R. J., Kimball, E. S., ... Maryanoff, B. E. (2004). Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists. Bioorganic and Medicinal Chemistry Letters, 14(3), 591-596. https://doi.org/10.1016/j.bmcl.2003.11.063

Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists. / Dyatkin, Alexey B.; Hoekstra, William J.; Kinney, William A.; Kontoyianni, Maria; Santulli, Rosemary J.; Kimball, Edward S.; Fisher, M. Carolyn; Prouty, Stephen M.; Abraham, William M.; Andrade-Gordon, Patricia; Hlasta, Dennis J.; He, Wei; Hornby, Pamela J.; Damiano, Bruce P.; Maryanoff, Bruce E.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 3, 09.02.2004, p. 591-596.

Research output: Contribution to journalArticle

Dyatkin, AB, Hoekstra, WJ, Kinney, WA, Kontoyianni, M, Santulli, RJ, Kimball, ES, Fisher, MC, Prouty, SM, Abraham, WM, Andrade-Gordon, P, Hlasta, DJ, He, W, Hornby, PJ, Damiano, BP & Maryanoff, BE 2004, 'Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists', Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 3, pp. 591-596. https://doi.org/10.1016/j.bmcl.2003.11.063
Dyatkin AB, Hoekstra WJ, Kinney WA, Kontoyianni M, Santulli RJ, Kimball ES et al. Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists. Bioorganic and Medicinal Chemistry Letters. 2004 Feb 9;14(3):591-596. https://doi.org/10.1016/j.bmcl.2003.11.063
Dyatkin, Alexey B. ; Hoekstra, William J. ; Kinney, William A. ; Kontoyianni, Maria ; Santulli, Rosemary J. ; Kimball, Edward S. ; Fisher, M. Carolyn ; Prouty, Stephen M. ; Abraham, William M. ; Andrade-Gordon, Patricia ; Hlasta, Dennis J. ; He, Wei ; Hornby, Pamela J. ; Damiano, Bruce P. ; Maryanoff, Bruce E. / Aza-bicyclic amino acid sulfonamides as α4β 14β7 integrin antagonists. In: Bioorganic and Medicinal Chemistry Letters. 2004 ; Vol. 14, No. 3. pp. 591-596.
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