Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

Nada H. Saab; Isaac O. Donkor; Libaniel Rodriguez; Peter F. Kador; Duane D. Miller

doi:10.1016/S0223-5234(99)00219-6

Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

Nada H. Saab, Isaac O. Donkor, Libaniel Rodriguez, Peter F. Kador, Duane D. Miller

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

11 Scopus citations

Abstract

Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a series of N-4 substituted analogues (15-21) of the known aldose reductase inhibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC₅₀s between 0.01 and 0.19 μM. Some of the compounds are also potent affinity labels for AR. Compound 19 exhibits the highest and almost complete irreversible inhibition of AR known to date.

Original language	English (US)
Pages (from-to)	745-751
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	34
Issue number	9
DOIs	https://doi.org/10.1016/S0223-5234(99)00219-6
State	Published - Sep 1999
Externally published	Yes

Keywords

Aldose reductase
Aldose reductase inhibitors
Diabetic complication
Irreversible inhibitors
Phenylsulphonyl- nitromethane

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/S0223-5234(99)00219-6

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title = "Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase",

abstract = "Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a series of N-4 substituted analogues (15-21) of the known aldose reductase inhibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC50s between 0.01 and 0.19 μM. Some of the compounds are also potent affinity labels for AR. Compound 19 exhibits the highest and almost complete irreversible inhibition of AR known to date.",

keywords = "Aldose reductase, Aldose reductase inhibitors, Diabetic complication, Irreversible inhibitors, Phenylsulphonyl- nitromethane",

author = "Saab, {Nada H.} and Donkor, {Isaac O.} and Libaniel Rodriguez and Kador, {Peter F.} and Miller, {Duane D.}",

note = "Funding Information: This work was supported in part by NIH grant 1 R15 EY0936-02 (I.O.D). We thank Mr John Miller for running the Mass Spectra of the compounds. ",

year = "1999",

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doi = "10.1016/S0223-5234(99)00219-6",

language = "English (US)",

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TY - JOUR

T1 - Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

AU - Saab, Nada H.

AU - Donkor, Isaac O.

AU - Rodriguez, Libaniel

AU - Kador, Peter F.

AU - Miller, Duane D.

N1 - Funding Information: This work was supported in part by NIH grant 1 R15 EY0936-02 (I.O.D). We thank Mr John Miller for running the Mass Spectra of the compounds.

PY - 1999/9

Y1 - 1999/9

N2 - Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a series of N-4 substituted analogues (15-21) of the known aldose reductase inhibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC50s between 0.01 and 0.19 μM. Some of the compounds are also potent affinity labels for AR. Compound 19 exhibits the highest and almost complete irreversible inhibition of AR known to date.

AB - Aldose reductase (AR) inhibition provides a viable pharmacologically direct mode for the treatment of diabetic complications. We have synthesized a series of N-4 substituted analogues (15-21) of the known aldose reductase inhibitor phenyl-sulfonylnitromethane. The compounds are potent inhibitors of AR with IC50s between 0.01 and 0.19 μM. Some of the compounds are also potent affinity labels for AR. Compound 19 exhibits the highest and almost complete irreversible inhibition of AR known to date.

KW - Aldose reductase

KW - Aldose reductase inhibitors

KW - Diabetic complication

KW - Irreversible inhibitors

KW - Phenylsulphonyl- nitromethane

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DO - 10.1016/S0223-5234(99)00219-6

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Phenylsulfonylnitromethanes as potent irreversible inhibitors of aldose reductase

Abstract

Keywords

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