Cytochrome P-450 complex formation in the metabolism of phenylalkylamines. 8. Stereoselectivity in metabolic intermediary complex formation with a series of chiral 2-substituted 1-phenyl-2-aminoethanes

Paulsen-Sörman, Ulla; Jonsson, K. Hanna M.; Lindeke, Björn

doi:10.1021/jm00369a018

Cited by 19 publications

(8 citation statements)

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“…l -Methamphetamine hydrochloride was prepared from benzaldehyde in our institution according to previously described methods (Paulsen-Sörman et al 1984; Posakony et al 2002). The purity of the product was >99%.…”

Section: Methodsmentioning

confidence: 99%

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

et al. 2017

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l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1–10 mg/kg. However, plasma pharmacokinetic parameters of 10 mg/kg l-methamphetamine were ≥tenfold those of 1 mg/kg d-methamphetamine. These results clearly indicate that differential psychomotor efficacies of methamphetamine enantiomers are independent of their pharmacokinetic profiles.

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Section: Methodsmentioning

confidence: 99%

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

et al. 2017

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“…s, 1 H), 2.49 (dd J = 13.0, 7.5 Hz, 1 H), 2.76 (m, 1 H), 2.88 (dd, J = 13.0, 5.0 Hz, 1 H), 3.93 (q, J = 6.7 Hz, 1 H), 7.07 (d, J = 6.9 Hz, 2 H), 7.15−7.40 (m, 8 H); 13 C NMR (100.6 MHz, DEPT, CDCl 3 ): δ = 21.0 (CH 3 ), 24.4 (CH 3 ), 42.5 (CH 2 ), 51.9 (CH), 55.3 (CH), 125.9 (CH), 126.5 (CH), 126.8 (CH), 128.2 (CH), 128.4 (CH), 129.3 (CH), 139.5 (C), 145.7 (C); IR: $\tilde {\nu}$ = 3061, 3025, 2961, 2923, 2865, 1602, 1493, 1452, 1370, 1272, 1200, 1127, 1086, 1029, 965, 909, 848, 761, 744, 699 cm −1 ; MS (25 °C): m / z (%) = 224 (2) [M + − CH 3 ], 210 (5), 148 (57), 105 (100), 91 (15), 77 (9), 65 (3); purity by GC: 95.8%. Compound 9f has already been described in reference 12…”

Section: Methodsmentioning

confidence: 99%

“…1 H NMR (400 MHz, D 2 O): δ = 0.88 (t, J = 7.2 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H), 1.42−1.92 (m, 10 H), 2.77−3.37 (m, 6 H), 4.42−4.62 (m, 2 H), 7.02−7.62 m (20 H); 13 C NMR (100.6 MHz, DEPT, D 2 O): δ = 10.7 (CH 3 ), 11.2 (CH 3 ), 21.8 (CH 3 ), 22.0 (CH 3 ), 25.2 (CH 2 ), 26.1 (CH 2 ), 37.8 (CH 2 ), 39.0 (CH 2 ), 59.3 (CH), 59.6 (CH), 61.5 (CH), 61.7 (CH), 129.4 (CH), 130.2 (CH), 130.3 (CH), 130.3 (CH), 131.9 (CH), 131.9 (CH), 132.0 (CH), 132.1 (CH), 132.3 (CH), 132.4 (CH), 132.5 (CH), 132.6 (CH), 138.5 (C), 138.6 (C), 138.6 (C), 139.2 (C); IR: $\tilde {\nu}$ = 2973, 2748, 2706, 2667, 2467, 1582, 1497, 1455, 1382, 1313, 1280, 1213, 1157, 1077, 1032, 968, 924, 765, 742, 699 cm −1 ; MS (25 °C): m / z (%) = 224 (2), 162 (93), 120 (9), 105 (100), 92 (14), 79 (6), 77 (7); purity by GC (amine): > 99%. Compound 10f has already been described in ref 12…”

Section: Methodsmentioning

confidence: 99%

Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes

Bytschkov

Doye

2001

Eur. J. Org. Chem.

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Irradiation of reaction mixtures containing an alkyne, an amine, and a catalytic amount of Cp 2 TiMe 2 in toluene with microwaves at a frequency of 2.45 GHz and a power output of 180−300 W results in fast reactions to give the corresponding hydroamination products. The initially formed imines can easily be reduced to secondary amines by use of H 2 /Pd, LiAlH 4 , or NaCNBH 3 /p-TsOH. The microwave-assisted hydroamination reactions go to completion within one tenth (or less) of the time required for reactions run conventionally in [a]

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“…The most common cases where this happens are with primary amines (which may be generated from secondary or tertiary amines) and methylenedioxyphenyl compounds that yield carbenes. These complexes are recognized by their characteristic Soret spectra at 455 nm that form during the reactions (Franklin and Buening, 1974;Mansuy et al, 1979;Paulsen-Sörman et al, 1984).…”

Section: Types Of Inhibitionmentioning

confidence: 99%

Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications

Guengerich

2022

Biomol Ther (Seoul)

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Drug-drug interactions are important and accordingly are a major issue in the advancement of new chemical entities to patients. In one study (Montané et al., 2018), drug-related deaths accounted for 7% of all deaths in hospital settings. Drug-drug interactions are an issue in this regard. Although some pharmacodynamic issues are involved, a large fraction of the drug-drug interactions is pharmacokinetic in nature.A general overview of the interactions of a chemical with an enzyme is shown in Fig. 1A, where an enzyme involved in the metabolism of a drug is considered. The drug is converted to a product, often called a metabolite. With respect to the parent drug molecule, the product may have unaltered pharmacological activity, lose some or all of its pharmacological activity, be even more active, or be toxic. In the interactions of two drugs, one is sometimes termed the "perpetrator" and one the "victim" (Fig. 1B). In some cases, drug interaction due to enhanced metabolism by induction or allosteric activation may be seen and have clinical consequences (Bolt et al., 1977), but the focus here will be on competitive and irreversible inhibitors that attenuate drug metabolism (as "perpetrators").Recently Yu et al. (2018) evaluated drug-drug interactions in 103 recent drug approvals by the United States Food and Drug Administration (FDA). Of these, 45 were involved as victims (substrates) in interactions with marketed drugs (perpetrators). The therapeutic classes are shown in Fig. 2A, with cancer treatments accounting for more than 1/4. The enzymes involved are primarily cytochrome P450 and transporter enzymes (Fig. 2B), with P450 3A4/5 involved in ~2/3 of the interactions. Of the 103 new drugs, 20 were acting as perpetrators to some extent (Yu et al., 2018), with P450 3A4/5 and P-glycoprotein again being the most prominent enzymes (Fig. 1B). Accordingly, this review will focus on issues of inhibition of P450 3A4 (In general P450 3A4 and 3A5 have similar substrate specificity and are sensitive to the same inhibitors, with some important exceptions (Hardy et al., 2014;Zhu et al., 2014;Kramlinger et al., 2015), but many experiments with drugs were done only with P450 3A4-or 3A4 and 3A5 were not discriminated-and will be referred to as 3A4 in that context). BACKGROUND ON P450SP450s enzymes are the main catalysts involved in the oxidation of chemicals in general (Rendic and Guengerich, 2015), including drugs. The same is true for involvement in Please cite this article in press as: Guengerich, Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications, Biomol. Ther.

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Cytochrome P-450 complex formation in the metabolism of phenylalkylamines. 8. Stereoselectivity in metabolic intermediary complex formation with a series of chiral 2-substituted 1-phenyl-2-aminoethanes

Cited by 19 publications

References 1 publication

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles

Microwave-Assisted Catalytic Intermolecular Hydroamination of Alkynes

Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications

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