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

12 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
Externally published	Yes

ASJC Scopus subject areas

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

Access to Document

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

Cite this

@article{7b58e3e32ea54b398b37995e19039b95,

title = "Orally active indole N-oxide PDE4 inhibitors",

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.",

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

year = "1998",

month = nov,

doi = "10.1016/S0960-894X(98)00572-1",

language = "English (US)",

volume = "8",

pages = "3053--3058",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "21",

}

TY - JOUR

T1 - Orally active indole N-oxide PDE4 inhibitors

AU - Hulme, Christopher

AU - Mathew, Rose

AU - Moriarty, Kevin

AU - Miller, Bruce

AU - Ramanjulu, Mercy

AU - Cox, Paul

AU - Souness, John

AU - Page, Ken M.

AU - Uhl, Joanne

AU - Travis, Jeffrey

AU - Labaudiniere, Richard

AU - Huang, Fu Chih

AU - Djuric, Stevan W.

PY - 1998/11

Y1 - 1998/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/17144459980

UR - https://www.scopus.com/pages/publications/17144459980#tab=citedBy

U2 - 10.1016/S0960-894X(98)00572-1

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

M3 - Article

C2 - 9873675

AN - SCOPUS:17144459980

SN - 0960-894X

VL - 8

SP - 3053

EP - 3058

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Orally active indole N-oxide PDE4 inhibitors

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this