Orally active indole N-oxide PDE4 inhibitors

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

doi:10.1016/S0960-894X(98)00572-1

Orally active indole N-oxide PDE4 inhibitors

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

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC₅₀'s for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-α levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.

Original language	English (US)
Pages (from-to)	3053-3058
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	8
Issue number	21
DOIs	https://doi.org/10.1016/S0960-894X(98)00572-1
State	Published - Nov 1998

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0960-894X(98)00572-1

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Orally active indole N-oxide PDE4 inhibitors. / Hulme, Christopher; Mathew, Rose; Moriarty, Kevin; Miller, Bruce; Ramanjulu, Mercy; Cox, Paul; Souness, John; Page, Ken M.; Uhl, Joanne; Travis, Jeffrey; Labaudiniere, Richard; Huang, Fu Chih; Djuric, Stevan W.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 8, No. 21, 11.1998, p. 3053-3058.

Research output: Contribution to journal › Article › peer-review

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AU - Souness, John

AU - Page, Ken M.

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AU - Travis, Jeffrey

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AU - Huang, Fu Chih

AU - Djuric, Stevan W.

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Orally active indole N-oxide PDE4 inhibitors

Abstract

ASJC Scopus subject areas

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