Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.

  title={Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.},
  author={Walter Yu and Jeffrey M. Dener and Daniel A. Dickman and Paul G. Grothaus and Yun Ling and Liang Liu and C M Havel and Kim Malesky and Tania Mahajan and Colin O'Brian and Emma J. Shelton and David Sperandio and Zhiwei Tong and Robert Yee and Joyce Mordenti},
  journal={Bioorganic \& medicinal chemistry letters},
  volume={16 15},
5 Citations
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In Vivo Metabolism in Preclinical Drug Development
Preclinical in vivo metabolism of drug candidates and prodrugs and in vitro models developed to profile human metabolism are focused on.
Microwave Mediated Dearylation of 2-Aryloxy-5-Nitropyridine
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Microsomal metabolism of N,N-diethyl-m-toluamide (DEET, DET): the extended network of metabolites.
The outcomes of this work are that previously unreported aldehydes 3b and 3c form part of the DEET network of metabolites, and the reduction of the aldeHydes 3a-c has the potential to inhibit the formation of the more highly oxidized DEET metabolites.
Metabolites of loperamide in rats.
Following intraperitoneal administration to rats of [14C]loperamide, metabolites in feces and urine were separated, and metabolites hydroxylated in the piperidine ring were isolated as pyridinium derivatives, possibly due to spontaneous aromatization of its 2,4-dihydroxy-4-(p-chlorophenyl)pipersidine ring.
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The present status and given detailed descriptions of biotransformation, metabolic stability assays, identification of drug metabolizing P450 enzymes, prediction of pharmacokinetic parameters from in vitro metabolism data, structure elucidation of metabolites, CYP450 inhibition assays and CYP 450 induction assays from a drug discovery perspective are presented.
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Prevention of metabolite-mediated toxicity is possible once the mechanism of toxicity has been elucidated and an imbalance between bioactivation of a drug to a toxic metabolite and its detoxification is of prime importance in determining individual susceptibility.
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