The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I

Christopher Hulme, Kevin Moriarty, Bruce Miller, Rose Mathew, Mercy Ramanjulu, Paul Cox, John Souness, Ken M. Page, Joanne Uhl, Jeffrey Travis, Fu Chih Huang, Richard Labaudiniere, Stevan W. Djuric

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

This communication describes the synthesis and in vitro evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds described contain an indole moiety which replaces the 'rolipram- like' 3-methoxy-4-cyclopentoxy motif. Several of the compounds presented possess low nanomolar IC50's for PDEIV inhibition. In vivo activities determined from measurement of serum TNF-α levels in LPS challenged mice (mouse endotoxemia model) are also reported.

Original languageEnglish (US)
Pages (from-to)1867-1872
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume8
Issue number14
DOIs
StatePublished - Jul 21 1998
Externally publishedYes

Fingerprint

Type 4 Cyclic Nucleotide Phosphodiesterase
Phosphodiesterase 4 Inhibitors
Rolipram
Endotoxemia
Communication
Inhibitory Concentration 50
Serum
indole
In Vitro Techniques

ASJC Scopus subject areas

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

Cite this

The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I. / Hulme, Christopher; Moriarty, Kevin; Miller, Bruce; Mathew, Rose; Ramanjulu, Mercy; Cox, Paul; Souness, John; Page, Ken M.; Uhl, Joanne; Travis, Jeffrey; Huang, Fu Chih; Labaudiniere, Richard; Djuric, Stevan W.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 8, No. 14, 21.07.1998, p. 1867-1872.

Research output: Contribution to journalArticle

Hulme, C, Moriarty, K, Miller, B, Mathew, R, Ramanjulu, M, Cox, P, Souness, J, Page, KM, Uhl, J, Travis, J, Huang, FC, Labaudiniere, R & Djuric, SW 1998, 'The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I', Bioorganic and Medicinal Chemistry Letters, vol. 8, no. 14, pp. 1867-1872. https://doi.org/10.1016/S0960-894X(98)00324-2
Hulme, Christopher ; Moriarty, Kevin ; Miller, Bruce ; Mathew, Rose ; Ramanjulu, Mercy ; Cox, Paul ; Souness, John ; Page, Ken M. ; Uhl, Joanne ; Travis, Jeffrey ; Huang, Fu Chih ; Labaudiniere, Richard ; Djuric, Stevan W. / The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I. In: Bioorganic and Medicinal Chemistry Letters. 1998 ; Vol. 8, No. 14. pp. 1867-1872.
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