Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors

Ikyon Kim; Jong Hwan Song; Chang Min Park; Joon Won Jeong; Hyung Rae Kim; Jin Ryul Ha; Zaesung No; Young Lan Hyun; Young Sik Cho; Nam Sook Kang; Dong Ju Jeon

doi:10.1016/j.bmcl.2009.12.070

Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors

Ikyon Kim, Jong Hwan Song, Chang Min Park, Joon Won Jeong, Hyung Rae Kim, Jin Ryul Ha, Zaesung No, Young Lan Hyun, Young Sik Cho, Nam Sook Kang, Dong Ju Jeon

Department of Pharmacy

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

59 Citations (Scopus)

Abstract

Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC₅₀ < 10 nM).

Original language	English
Pages (from-to)	922-926
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2009.12.070
Publication status	Published - 2010 Feb 1

Bibliographical note

Funding Information:
This research was supported by the Center for Biological Modulators of the 21st Century Frontier R&D program, the Ministry of Science and Technology, Korea .

All Science Journal Classification (ASJC) codes

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

Access to Document

10.1016/j.bmcl.2009.12.070

Cite this

Kim, I., Song, J. H., Park, C. M., Jeong, J. W., Kim, H. R., Ha, J. R., No, Z., Hyun, Y. L., Cho, Y. S., Sook Kang, N., & Jeon, D. J. (2010). Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors. Bioorganic and Medicinal Chemistry Letters, 20(3), 922-926. https://doi.org/10.1016/j.bmcl.2009.12.070

@article{a68831834d9443ecba7b6d67f9d1fb67,

title = "Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors",

abstract = "Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 < 10 nM).",

author = "Ikyon Kim and Song, {Jong Hwan} and Park, {Chang Min} and Jeong, {Joon Won} and Kim, {Hyung Rae} and Ha, {Jin Ryul} and Zaesung No and Hyun, {Young Lan} and Cho, {Young Sik} and {Sook Kang}, Nam and Jeon, {Dong Ju}",

note = "Funding Information: This research was supported by the Center for Biological Modulators of the 21st Century Frontier R&D program, the Ministry of Science and Technology, Korea . ",

year = "2010",

month = feb,

day = "1",

doi = "10.1016/j.bmcl.2009.12.070",

language = "English",

volume = "20",

pages = "922--926",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "3",

}

TY - JOUR

T1 - Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors

AU - Kim, Ikyon

AU - Song, Jong Hwan

AU - Park, Chang Min

AU - Jeong, Joon Won

AU - Kim, Hyung Rae

AU - Ha, Jin Ryul

AU - No, Zaesung

AU - Hyun, Young Lan

AU - Cho, Young Sik

AU - Sook Kang, Nam

AU - Jeon, Dong Ju

N1 - Funding Information: This research was supported by the Center for Biological Modulators of the 21st Century Frontier R&D program, the Ministry of Science and Technology, Korea .

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 < 10 nM).

AB - Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 < 10 nM).

UR - http://www.scopus.com/inward/record.url?scp=74349090277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74349090277&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.12.070

DO - 10.1016/j.bmcl.2009.12.070

M3 - Article

C2 - 20053559

AN - SCOPUS:74349090277

SN - 0960-894X

VL - 20

SP - 922

EP - 926

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this