3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors

Jakyung Yoo; Khac Minh Thai; Dae Kee Kim; Ju Young Lee; Hyun Ju Park

doi:10.1016/j.bmcl.2007.05.064

3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors

Jakyung Yoo, Khac Minh Thai, Dae Kee Kim, Ju Young Lee, Hyun Ju Park

Department of Pharmaceutical Sciences

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

24 Scopus citations

Abstract

Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely used oral agent for the treatment of erectile dysfunction. To develop new PDE5 inhibitors with improved therapeutic efficacy, a series of sildenafil analogues have been prepared and their in vitro PDE5 inhibitory activities were evaluated. Their IC₅₀ values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and CoMSIA gave reliable models with q² values >0.75 and r² values >0.99. The resulting CoMFA and CoMSIA models reveal a good correlation between the contour maps and the active site residues critical for the interaction with inhibitor, and nicely predict the key structural features of new analogues with improved activity and selectivity.

Original language	English
Pages (from-to)	4271-4274
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2007.05.064
State	Published - 1 Aug 2007

Bibliographical note

Funding Information:
This research was supported by a Grant (CBM2-B513-001-1-0-0) from the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Science, Republic of Korea.

Keywords

3D-QSAR modeling
PDE5 inhibitors
SK3530

Access to Document

10.1016/j.bmcl.2007.05.064

Cite this

@article{0f137b5132ff4e2cb1190cb7e2350b60,

title = "3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors",

abstract = "Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely used oral agent for the treatment of erectile dysfunction. To develop new PDE5 inhibitors with improved therapeutic efficacy, a series of sildenafil analogues have been prepared and their in vitro PDE5 inhibitory activities were evaluated. Their IC50 values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and CoMSIA gave reliable models with q2 values >0.75 and r2 values >0.99. The resulting CoMFA and CoMSIA models reveal a good correlation between the contour maps and the active site residues critical for the interaction with inhibitor, and nicely predict the key structural features of new analogues with improved activity and selectivity.",

keywords = "3D-QSAR modeling, PDE5 inhibitors, SK3530",

author = "Jakyung Yoo and Thai, {Khac Minh} and Kim, {Dae Kee} and Lee, {Ju Young} and Park, {Hyun Ju}",

note = "Funding Information: This research was supported by a Grant (CBM2-B513-001-1-0-0) from the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Science, Republic of Korea. ",

year = "2007",

month = aug,

day = "1",

doi = "10.1016/j.bmcl.2007.05.064",

language = "English",

volume = "17",

pages = "4271--4274",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "15",

}

TY - JOUR

T1 - 3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors

AU - Yoo, Jakyung

AU - Thai, Khac Minh

AU - Kim, Dae Kee

AU - Lee, Ju Young

AU - Park, Hyun Ju

N1 - Funding Information: This research was supported by a Grant (CBM2-B513-001-1-0-0) from the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Science, Republic of Korea.

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely used oral agent for the treatment of erectile dysfunction. To develop new PDE5 inhibitors with improved therapeutic efficacy, a series of sildenafil analogues have been prepared and their in vitro PDE5 inhibitory activities were evaluated. Their IC50 values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and CoMSIA gave reliable models with q2 values >0.75 and r2 values >0.99. The resulting CoMFA and CoMSIA models reveal a good correlation between the contour maps and the active site residues critical for the interaction with inhibitor, and nicely predict the key structural features of new analogues with improved activity and selectivity.

AB - Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely used oral agent for the treatment of erectile dysfunction. To develop new PDE5 inhibitors with improved therapeutic efficacy, a series of sildenafil analogues have been prepared and their in vitro PDE5 inhibitory activities were evaluated. Their IC50 values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and CoMSIA gave reliable models with q2 values >0.75 and r2 values >0.99. The resulting CoMFA and CoMSIA models reveal a good correlation between the contour maps and the active site residues critical for the interaction with inhibitor, and nicely predict the key structural features of new analogues with improved activity and selectivity.

KW - 3D-QSAR modeling

KW - PDE5 inhibitors

KW - SK3530

UR - http://www.scopus.com/inward/record.url?scp=34447121961&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2007.05.064

DO - 10.1016/j.bmcl.2007.05.064

M3 - Article

C2 - 17553682

AN - SCOPUS:34447121961

SN - 0960-894X

VL - 17

SP - 4271

EP - 4274

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5 inhibitors

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this