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 - http://www.scopus.com/inward/record.url?scp=17144459980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17144459980&partnerID=8YFLogxK

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