ArticleJournal of medicinal chemistry2012
Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogues by cytochrome P450 3A4.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- Carboxamide: A Privileged Pharmacophore for the Development of Anti-infectious and Anti-cancer Drugs.Current topics in medicinal chemistry · 2026Review
- The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition.Biomolecules · 2024Review
- The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates.Molecules (Basel, Switzerland) · 2022Review
- Enzyme Kinetics of Oxidative Metabolism-Cytochromes P450.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Rapid kinetic methods to dissect steroidogenic cytochrome P450 reaction mechanisms.The Journal of steroid biochemistry and molecular biology · 2016Review
- Substrate Dependent Native Luminescence from Cytochromes P450 3A4, 2C9, and P450cam.The journal of physical chemistry. B · 2016Article
- Use of chemical auxiliaries to control p450 enzymes for predictable oxidations at unactivated C-h bonds of substrates.Advances in experimental medicine and biology · 2015Review
- Controlling substrate specificity and product regio- and stereo-selectivities of P450 enzymes without mutagenesis.Bioorganic & medicinal chemistry · 2014Review
- Predicting intrinsic clearance for drugs and drug candidates metabolized by aldehyde oxidase.Molecular pharmaceutics · 2013Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N-dealkylation, O-dealkylation, benzylic hydroxylation, and aromatic hydroxylation. The results demonstrated that type II binding QCA analogues were metabolically less stable (2- to 12-fold) at subsaturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation > benzylic hydroxylation> O-demethylation > aromatic hydroxylation. Finally, for the QCA analogues with aza-heteroaromatic rings, we did not detect metabolism in aza-aromatic rings (pyridine, pyrazine, pyrimidine), indicating that electronegativity of the nitrogen can change regioselectivity in CYP metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.