Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity

Mitsuhiro Arisawa; Yayoi Kasaya; Tohru Obata; Takuma Sasaki; Tomonori Nakamura; Takuya Araki; Koujirou Yamamoto; Akito Sasaki; Akihito Yamano; Mika Ito; Hiroshi Abe; Yoshihiro Ito; Satoshi Shuto

doi:10.1021/jm301084z

Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity

Mitsuhiro Arisawa, Yayoi Kasaya, Tohru Obata, Takuma Sasaki, Tomonori Nakamura, Takuya Araki, Koujirou Yamamoto, Akito Sasaki, Akihito Yamano, Mika Ito, Hiroshi Abe, Yoshihiro Ito, Satoshi Shuto

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

26 Citations (Scopus)

Abstract

We designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug resistance indicated that NSAIDS modulation of multidrug-resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.

Original language	English
Pages (from-to)	8152-8163
Number of pages	12
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	18
DOIs	https://doi.org/10.1021/jm301084z
Publication status	Published - 2012 Sept 27
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm301084z

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Arisawa, M., Kasaya, Y., Obata, T., Sasaki, T., Nakamura, T., Araki, T., Yamamoto, K., Sasaki, A., Yamano, A., Ito, M., Abe, H., Ito, Y., & Shuto, S. (2012). Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity. Journal of Medicinal Chemistry, 55(18), 8152-8163. https://doi.org/10.1021/jm301084z

Arisawa, M, Kasaya, Y, Obata, T, Sasaki, T, Nakamura, T, Araki, T, Yamamoto, K, Sasaki, A, Yamano, A, Ito, M, Abe, H, Ito, Y & Shuto, S 2012, 'Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity', Journal of Medicinal Chemistry, vol. 55, no. 18, pp. 8152-8163. https://doi.org/10.1021/jm301084z

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author = "Mitsuhiro Arisawa and Yayoi Kasaya and Tohru Obata and Takuma Sasaki and Tomonori Nakamura and Takuya Araki and Koujirou Yamamoto and Akito Sasaki and Akihito Yamano and Mika Ito and Hiroshi Abe and Yoshihiro Ito and Satoshi Shuto",

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AU - Arisawa, Mitsuhiro

AU - Kasaya, Yayoi

AU - Obata, Tohru

AU - Sasaki, Takuma

AU - Nakamura, Tomonori

AU - Araki, Takuya

AU - Yamamoto, Koujirou

AU - Sasaki, Akito

AU - Yamano, Akihito

AU - Ito, Mika

AU - Abe, Hiroshi

AU - Ito, Yoshihiro

AU - Shuto, Satoshi

PY - 2012/9/27

Y1 - 2012/9/27

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AB - We designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug resistance indicated that NSAIDS modulation of multidrug-resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.

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Design and synthesis of indomethacin analogues that inhibit P-glycoprotein and/or multidrug resistant protein without Cox inhibitory activity

Abstract

ASJC Scopus subject areas

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