1991
DOI: 10.1021/jm00105a018
|View full text |Cite
|
Sign up to set email alerts
|

Novel, potent aldose reductase inhibitors: 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl]methyl]-1-phthalazineacetic acid (zopolrestat) and congeners

Abstract: A new working hypothesis that there is a hitherto unrecognized binding site on the aldose reductase (AR) enzyme with strong affinity for benzothiazoles was pursued for the design of novel, potent aldose reductase inhibitors (ARIs). The first application of this hypothesis led to a novel series of 3,4-dihydro-4-oxo-3-(benzothiazolylmethyl)-1-phthalazineacetic+ + + acids. The parent of this series (207) was a potent inhibitor of AR from human placenta (IC50 = 1.9 x 10(-8) M) and was orally active in preventing s… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

1
100
1
2

Year Published

1999
1999
2022
2022

Publication Types

Select...
7
2
1

Relationship

0
10

Authors

Journals

citations
Cited by 241 publications
(104 citation statements)
references
References 0 publications
1
100
1
2
Order By: Relevance
“…Epalrestat was developed in 1983 [49] and has been marketed in Japan, and recently in China and India. Tolrestat, a strong ARI and potential drug for the treatment of diabetic complications [50], was approved to several markets, but withdrawn for the reason of risk of severe liver toxicity and death.The typical carboxylic acid ARIs also include zenarestat [51], zopolrestat [52], and ponalrestat [53]. Zenarestat is a potential drug for the treatment of diabetic neuropathy, retinopathy and cataracts.…”
Section: Ar Inhibitorsmentioning
confidence: 99%
“…Epalrestat was developed in 1983 [49] and has been marketed in Japan, and recently in China and India. Tolrestat, a strong ARI and potential drug for the treatment of diabetic complications [50], was approved to several markets, but withdrawn for the reason of risk of severe liver toxicity and death.The typical carboxylic acid ARIs also include zenarestat [51], zopolrestat [52], and ponalrestat [53]. Zenarestat is a potential drug for the treatment of diabetic neuropathy, retinopathy and cataracts.…”
Section: Ar Inhibitorsmentioning
confidence: 99%
“…For example the thiazole in vitamin B serves as an electron sink, and its coenzyme form is important for the decarboxylation of -keto acids and is present in various natural products and herbicides. This important and useful structural motif has found application in drug development, as these exhibit diverse biological activities such as anti-glutamate, anti-Parkinson (Benazzouz et al, 1995), anti-microbial (Palmer et al, 1971), anthelmintic, anti-inflammatory (Haviv et al, 1988), anti-hyperlipidemic, anti-hypertension (Patt et al, 1992), and anti-oxidant properties as well as inhibition of enzymes such as acetylcholine esterase (Nagel et al, 1995), aldose reductase (Mylari et al, 1991), lipoxygenase (Hadjipavlou-Litina & Geronikaki,1998), ATPase (Sohn et al, 1999), and HCV helicase (phoon et al, 2001). Aminothiazoles are reported as a new class of adenosine receptor antagonists and ligands of estrogen receptors.…”
Section: Thiazolesmentioning
confidence: 99%
“…Tolrestat (1), which was launched in 1989, was withdrawn in 1996, principally due to its low efficacy. Of the newer compounds, zopolrestat (2) [19] and zenarestat (3) were withdrawn from clinical trials. At present, only epalrestat (4), which was developed by Ono and launched into the Japanese market in 1992, is still available [20].…”
Section: Aldose Reductase and Diabetic Complicationsmentioning
confidence: 99%