Orally active PDE4 inhibitors with therapeutic potential

Hiroshi Ochiai; Tazumi Ohtani; Akiharu Ishida; Katuya Kishikawa; Takaaki Obata; Hisao Nakai; Masaaki Toda

doi:10.1016/j.bmcl.2003.12.018

Orally active PDE4 inhibitors with therapeutic potential

Hiroshi Ochiai, Tazumi Ohtani, Akiharu Ishida, Katuya Kishikawa, Takaaki Obata, Hisao Nakai, Masaaki Toda

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

12 Citations (Scopus)

Abstract

Based on the successful results in the clinical trial of Ariflo™, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3· 3·0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed.

Original language	English
Pages (from-to)	1323-1327
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2003.12.018
Publication status	Published - 2004 Mar 8
Externally published	Yes

Keywords

Bicyclo[3·3·0]octane
Orally active
PDE4 inhibitor
Three pharmacophores

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2003.12.018

Cite this

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title = "Orally active PDE4 inhibitors with therapeutic potential",

abstract = "Based on the successful results in the clinical trial of Ariflo{\texttrademark}, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3· 3·0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed.",

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language = "English",

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T1 - Orally active PDE4 inhibitors with therapeutic potential

AU - Ochiai, Hiroshi

AU - Ohtani, Tazumi

AU - Ishida, Akiharu

AU - Kishikawa, Katuya

AU - Obata, Takaaki

AU - Nakai, Hisao

AU - Toda, Masaaki

PY - 2004/3/8

Y1 - 2004/3/8

N2 - Based on the successful results in the clinical trial of Ariflo™, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3· 3·0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed.

AB - Based on the successful results in the clinical trial of Ariflo™, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3· 3·0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed.

KW - Bicyclo[3·3·0]octane

KW - Orally active

KW - PDE4 inhibitor

KW - Three pharmacophores

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Orally active PDE4 inhibitors with therapeutic potential

Abstract

Keywords

ASJC Scopus subject areas

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