3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

Mohane Selvaraj Coumar; Chung Nien Chang; Chiung Tong Chen; Xin Chen; Chia Hui Chien; Ting Yueh Tsai; Jai Hong Cheng; Hsin Yi Wu; Chia Hung Han; Ssu Hui Wu; Yu Wen Huang; Tsu Hsu; Li Jen Hsu; Yu Sheng Chao; Hsing Pang Hsieh; Weir Torn Jiaang

doi:10.1016/j.bmcl.2006.12.019

3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

Mohane Selvaraj Coumar, Chung Nien Chang, Chiung Tong Chen, Xin Chen, Chia Hui Chien, Ting Yueh Tsai, Jai Hong Cheng, Hsin Yi Wu, Chia Hung Han, Ssu Hui Wu, Yu Wen Huang, Tsu Hsu, Li Jen Hsu, Yu Sheng Chao, Hsing Pang Hsieh, Weir Torn Jiaang

Center of Applied Nanomedicine

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

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Abstract

Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC₅₀ = 116 nM) has the potential for development as antidiabetic agent.

Original language	English
Pages (from-to)	1274-1279
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2006.12.019
Publication status	Published - 2007 Mar 1

All Science Journal Classification (ASJC) codes

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

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Coumar, M. S., Chang, C. N., Chen, C. T., Chen, X., Chien, C. H., Tsai, T. Y., Cheng, J. H., Wu, H. Y., Han, C. H., Wu, S. H., Huang, Y. W., Hsu, T., Hsu, L. J., Chao, Y. S., Hsieh, H. P., & Jiaang, W. T. (2007). 3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes. Bioorganic and Medicinal Chemistry Letters, 17(5), 1274-1279. https://doi.org/10.1016/j.bmcl.2006.12.019

Coumar, Mohane Selvaraj ; Chang, Chung Nien ; Chen, Chiung Tong ; Chen, Xin ; Chien, Chia Hui ; Tsai, Ting Yueh ; Cheng, Jai Hong ; Wu, Hsin Yi ; Han, Chia Hung ; Wu, Ssu Hui ; Huang, Yu Wen ; Hsu, Tsu ; Hsu, Li Jen ; Chao, Yu Sheng ; Hsieh, Hsing Pang ; Jiaang, Weir Torn. / 3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 5. pp. 1274-1279.

@article{aaedd90d45ea4f7794bafc37c65fe481,

title = "3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes",

abstract = "Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent.",

author = "Coumar, {Mohane Selvaraj} and Chang, {Chung Nien} and Chen, {Chiung Tong} and Xin Chen and Chien, {Chia Hui} and Tsai, {Ting Yueh} and Cheng, {Jai Hong} and Wu, {Hsin Yi} and Han, {Chia Hung} and Wu, {Ssu Hui} and Huang, {Yu Wen} and Tsu Hsu and Hsu, {Li Jen} and Chao, {Yu Sheng} and Hsieh, {Hsing Pang} and Jiaang, {Weir Torn}",

note = "Funding Information: The study was financially supported by National Health Research Institutes, Taiwan. ",

year = "2007",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2006.12.019",

language = "English",

volume = "17",

pages = "1274--1279",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "5",

}

Coumar, MS, Chang, CN, Chen, CT, Chen, X, Chien, CH, Tsai, TY, Cheng, JH, Wu, HY, Han, CH, Wu, SH, Huang, YW, Hsu, T, Hsu, LJ, Chao, YS, Hsieh, HP & Jiaang, WT 2007, '3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 5, pp. 1274-1279. https://doi.org/10.1016/j.bmcl.2006.12.019

3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes. / Coumar, Mohane Selvaraj; Chang, Chung Nien; Chen, Chiung Tong; Chen, Xin; Chien, Chia Hui; Tsai, Ting Yueh; Cheng, Jai Hong; Wu, Hsin Yi; Han, Chia Hung; Wu, Ssu Hui; Huang, Yu Wen; Hsu, Tsu; Hsu, Li Jen; Chao, Yu Sheng; Hsieh, Hsing Pang; Jiaang, Weir Torn.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 5, 01.03.2007, p. 1274-1279.

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

TY - JOUR

T1 - 3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

AU - Coumar, Mohane Selvaraj

AU - Chang, Chung Nien

AU - Chen, Chiung Tong

AU - Chen, Xin

AU - Chien, Chia Hui

AU - Tsai, Ting Yueh

AU - Cheng, Jai Hong

AU - Wu, Hsin Yi

AU - Han, Chia Hung

AU - Wu, Ssu Hui

AU - Huang, Yu Wen

AU - Hsu, Tsu

AU - Hsu, Li Jen

AU - Chao, Yu Sheng

AU - Hsieh, Hsing Pang

AU - Jiaang, Weir Torn

N1 - Funding Information: The study was financially supported by National Health Research Institutes, Taiwan.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent.

AB - Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent.

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UR - http://www.scopus.com/inward/citedby.url?scp=33846986803&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2006.12.019

DO - 10.1016/j.bmcl.2006.12.019

M3 - Article

C2 - 17194587

AN - SCOPUS:33846986803

VL - 17

SP - 1274

EP - 1279

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -

3-[2-((2S)-2-Cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramid e analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes

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