Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors

Benjamin J. Ayers; Andreas F.G. Glawar; R. Fernando Martínez; Nigel Ngo; Zilei Liu; George W.J. Fleet; Terry D. Butters; Robert J. Nash; Chu Yi Yu; Mark R. Wormald; Shinpei Nakagawa; Isao Adachi; Atsushi Kato; Sarah F. Jenkinson

doi:10.1021/jo500157p

Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors

Benjamin J. Ayers^*, Andreas F.G. Glawar, R. Fernando Martínez, Nigel Ngo, Zilei Liu, George W.J. Fleet, Terry D. Butters, Robert J. Nash, Chu Yi Yu, Mark R. Wormald, Shinpei Nakagawa, Isao Adachi, Atsushi Kato, Sarah F. Jenkinson

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薬剤部

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

31 被引用数 (Scopus)

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All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N- acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.

本文言語	英語
ページ（範囲）	3398-3409
ページ数	12
ジャーナル	Journal of Organic Chemistry
巻	79
号	8
DOI	https://doi.org/10.1021/jo500157p
出版ステータス	出版済み - 2014/04/18

ASJC Scopus 主題領域

有機化学

文献へのアクセス

10.1021/jo500157p

引用スタイル

Ayers, B. J., Glawar, A. F. G., Martínez, R. F., Ngo, N., Liu, Z., Fleet, G. W. J., Butters, T. D., Nash, R. J., Yu, C. Y., Wormald, M. R., Nakagawa, S., Adachi, I., Kato, A., & Jenkinson, S. F. (2014). Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors. Journal of Organic Chemistry, 79(8), 3398-3409. https://doi.org/10.1021/jo500157p

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title = "Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors",

abstract = "All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N- acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.",

author = "Ayers, {Benjamin J.} and Glawar, {Andreas F.G.} and Mart{\'i}nez, {R. Fernando} and Nigel Ngo and Zilei Liu and Fleet, {George W.J.} and Butters, {Terry D.} and Nash, {Robert J.} and Yu, {Chu Yi} and Wormald, {Mark R.} and Shinpei Nakagawa and Isao Adachi and Atsushi Kato and Jenkinson, {Sarah F.}",

year = "2014",

month = apr,

day = "18",

doi = "10.1021/jo500157p",

language = "英語",

volume = "79",

pages = "3398--3409",

journal = "Journal of Organic Chemistry",

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TY - JOUR

T1 - Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors

AU - Ayers, Benjamin J.

AU - Glawar, Andreas F.G.

AU - Martínez, R. Fernando

AU - Ngo, Nigel

AU - Liu, Zilei

AU - Fleet, George W.J.

AU - Butters, Terry D.

AU - Nash, Robert J.

AU - Yu, Chu Yi

AU - Wormald, Mark R.

AU - Nakagawa, Shinpei

AU - Adachi, Isao

AU - Kato, Atsushi

AU - Jenkinson, Sarah F.

PY - 2014/4/18

Y1 - 2014/4/18

N2 - All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N- acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.

AB - All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of β-N- acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. β-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good α-N-acetylgalactosaminidase inhibitors.

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U2 - 10.1021/jo500157p

DO - 10.1021/jo500157p

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AN - SCOPUS:84898967445

SN - 0022-3263

VL - 79

SP - 3398

EP - 3409

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 8

ER -

Nine of 16 stereoisomeric polyhydroxylated proline amides are potent β-N-acetylhexosaminidase inhibitors

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