Quinazolinone cholecystokinin-B receptor ligands

Yu, Melvin J.; Thrasher, K. Jeff; McCowan, Jefferson R.; Mason, Norman R.; Mendelsohn, Laurane G.

doi:10.1021/jm00108a040

Cited by 67 publications

(35 citation statements)

References 3 publications

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“…2B) and assuming K," = K,', one obtains K," 5 8 PM. The anti-lipoxygenase activity of CAPE is thus greater than that of caffeic acid, though not as high as that of the synthetic caffeic acid derivatives described by Yu et al [14].…”

Section: Resultsmentioning

confidence: 60%

Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties

et al. 1993

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Caffeic acid phenethyl ester, an active component of propolis extract, inhibits Yipoxygenase in the micromolar concentration range. The inhibition is of an uncompetitive type, i.e. the inhibitor binds to the enzyme-substrate complex but not to the free enzyme. Caffeic acid phenethyl ester also exhibits antioxidant properties. At a concentration of 10 PM, it completely blocks production of reactive oxygen species in human neutrophils and the xanthinelxanthine oxidase system.

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Section: Resultsmentioning

confidence: 60%

Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties

et al. 1993

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“…The final compound, 72, a quinazolinone that adheres to the structural features perceived in asperlicin, was shown by the Lilly group to be an effective CCK-B receptor inhibitor (ICs0 = 9.3 nM). 157 These asperlicin derivatives represent an interesting series of potent compounds based on a peptide-derived natural product. It is believed that these antagonists are peptidomimetics in that they bind to the receptor at the normal CCK binding sites, in part because stereochemistry plays an important role in determining activity and selectivity among the different CCK-A, CCK-B, and gastrin receptors.…”

Section: ) By Chang Et Al At M E R~k L~~mentioning

confidence: 99%

Peptidomimetics derived from natural products

Wiley

Rich

1993

Medicinal Research Reviews

221

114

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Although much has been written in recent years about rational drug design, no drug has been designed de novo, that is, without using a natural substrate or inhibitor or screening lead as a starting point. Instead, as we have seen, medicinal chemists continue to depend upon serendipitous discovery of novel biological activities and novel chemical entities for structures on which to begin work. What rational drug design really means at present is rational drug discovery and rational optimization. These result from the application of modern structural and mechanistic biochemistry, and good synthetic chemistry, to obtain structures with the desired spectrum of biological activities. Traditionally, lead compounds were discovered in plant and animal extracts, and more recently in microorganisms and chemical libraries. These traditional approaches continue, but are augmented by advances in molecular biology, which now provide pure proteins in quantity for screening and structure determination, as well as for characterization by modern biophysical methods. Remarkably, x-ray and NMR methods can now provide the most important information needed to design new drugs, that is, the conformations of ligands bound to target proteins. Approaches to identifying possible ligands based only on the knowledge of the enzyme active site are being developed. Some of these, such as CAVEAT, have been recently reviewed. In spite of these impressive gains, de novo design of new drugs will not be achieved until we learn how to logically build specific inhibitors of a target enzyme knowing only the protein sequence of the enzyme or the amino acid sequence of the messenger substances. We have a long way to go, because by this very rigorous definition, even the successful design of a new nonpeptide drug beginning with enzyme-ligand NMR or x-ray structure constitutes rational optimization. However, as this article has illustrated, we have made great progress. Some of the current and futuristic approaches to drug design are shown in Fig. 8. Development of useful enzyme inhibitors, designed by knowing the enzyme catalytic mechanism or discovered by screening for natural inhibitors, is a very successful rational method. Discovery of receptor antagonists by screening protocols is also productive.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The guanidino-like function of 2[(2-hydroxyphenyl)amino]-4(3H)-quinazolinone has been associated with antihypertensive activity of this compound [40]. In addition, 3-aryl-4(3H)-quinazolinones have been reported to be cholecystokinin-B receptor ligands [41].…”

Section: M Vˆgtle and A L Marzinzikmentioning

confidence: 99%

Synthetic Approaches Towards Quinazolines, Quinazolinones and Quinazolinediones on Solid Phase

Vögtle¹,

Marzinzik²

2004

QSAR Comb. Sci.

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Full PaperQuinazolines are a pharmacologically very attractive class of compounds and have shown activity in various assays. Several successfully launched drugs are based on this scaffold. As a consequence, a more intensive exploitation in drug discovery by solid-phase syntheses of quinazoline libraries has been initiated. A diverse array of combinatorial quinazoline syntheses have been published and an increasing effort is to be expected in the near future to provide more efficient solid phase approaches towards quinazolines, quinazolinones and quinazolinediones. This review summarizes the literature published until January 2004 describing methods for synthesis and modification of these compounds on solid phase.

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Quinazolinone cholecystokinin-B receptor ligands

Cited by 67 publications

References 3 publications

Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties

Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties

Peptidomimetics derived from natural products

Synthetic Approaches Towards Quinazolines, Quinazolinones and Quinazolinediones on Solid Phase

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