Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents

Isaac O. Donkor; Yasar S. Abdel-Ghany; Peter F. Kador; Tadashi Mizoguchi; Anita Bartoszko-Malik; Duane D. Miller

doi:10.1016/S0223-5234(99)80056-7

Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents

Isaac O. Donkor, Yasar S. Abdel-Ghany, Peter F. Kador, Tadashi Mizoguchi, Anita Bartoszko-Malik, Duane D. Miller

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

5 Scopus citations

Abstract

Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.

Original language	English (US)
Pages (from-to)	235-243
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	34
Issue number	3
DOIs	https://doi.org/10.1016/S0223-5234(99)80056-7
State	Published - Mar 1999
Externally published	Yes

Keywords

Aldehyde reductase
Aldose reductase
Alrestatin
Diabetic complications
Michael acceptors

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/S0223-5234(99)80056-7

Cite this

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title = "Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents",

abstract = "Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.",

keywords = "Aldehyde reductase, Aldose reductase, Alrestatin, Diabetic complications, Michael acceptors",

author = "Donkor, {Isaac O.} and Abdel-Ghany, {Yasar S.} and Kador, {Peter F.} and Tadashi Mizoguchi and Anita Bartoszko-Malik and Miller, {Duane D.}",

note = "Funding Information: The work was supported in part by NIH grant 7 R15 EY0936 to I.O.D.",

year = "1999",

month = mar,

doi = "10.1016/S0223-5234(99)80056-7",

language = "English (US)",

volume = "34",

pages = "235--243",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

number = "3",

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TY - JOUR

T1 - Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents

AU - Donkor, Isaac O.

AU - Abdel-Ghany, Yasar S.

AU - Kador, Peter F.

AU - Mizoguchi, Tadashi

AU - Bartoszko-Malik, Anita

AU - Miller, Duane D.

N1 - Funding Information: The work was supported in part by NIH grant 7 R15 EY0936 to I.O.D.

PY - 1999/3

Y1 - 1999/3

N2 - Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.

AB - Derivatives of alrestatin (1-5) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase.

KW - Aldehyde reductase

KW - Aldose reductase

KW - Alrestatin

KW - Diabetic complications

KW - Michael acceptors

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U2 - 10.1016/S0223-5234(99)80056-7

DO - 10.1016/S0223-5234(99)80056-7

M3 - Article

AN - SCOPUS:0032737043

SN - 0223-5234

VL - 34

SP - 235

EP - 243

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 3

ER -

Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents

Abstract

Keywords

ASJC Scopus subject areas

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