Determination of enantiomeric purity of the new D-2 dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) by reversed-phase high-performance liquid chromatography after pre-column derivatization with d(+)-glucuronic acid

Gerding, T. K.; Drenth, Ben F. H.; Grampel, V.J.M. van de; Niemeijer, Nr; Zeeuw, Rokus A. de; Tepper, Pieter G.; Horn, Alan S.

doi:10.1016/s0378-4347(00)83014-5

Cited by 17 publications

(2 citation statements)

References 19 publications

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“…Stereospecific differences in in vitro glucuronidation has been described for E-lO-hydroxy- 1987) and for morphine (Coughtric et al 1989). Only slight differences between the in vitro glucuronidation of (+) and (-) N-0437 were found (Gerding et al 1989). Fig.…”

Section: Resultsmentioning

confidence: 98%

Impact of Structural Differences on the in Vitro Glucuronidation Kinetics of Potentially Dopaminergic Hydroxy‐2‐Aminotetralins and Naphthoxazines Using Rat and Human Liver Microsomes

Jansman

Drenth

Zeeuw

et al. 1991

Pharmacology & Toxicology

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The in vitro glucuronidation of seven monohydroxy-2-aminotetralins and two naphthoxazines has been determined using human and rat liver microsomes. All these compounds stimulate the D2 dopamine receptor. The influence of the position of the phenolic hydroxyl group was studied with rat microsomes in monohydroxy-2-(N,N-dipropylamino)-tretralins. The highest activity and intrinsic clearance was found for 7-OH-DPAT, but the latter values for 5-OH-DPAT and 6-OH-DPAT were much lower by a factor of 9 and 30, respectively. The 8-OH-isomer was not glucuronidated at all. Substitution of a propyl side chain by a thienylethyl-, or phenylethyl side chain, in 5-hydroxy-DPAT, or in (+)-4-propyl-9-hydroxyhexahydronaphthoxazine (PHNO, N-0500), showed a large increase of the UDPGT affinity and intrinsic clearance especially for N-0437. It also resulted for N-0437 in a much higher affinity towards the dopaminergic D2 receptor. Although the glucuronidation activity of human microsomes was found to be considerably lower than that of rat microsomes, the latter phenomenon was clearly visible with human microsomes as well. These findings may have serious implications for the ability of these drugs to adequately reach the brain.

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Section: Resultsmentioning

confidence: 98%

Impact of Structural Differences on the in Vitro Glucuronidation Kinetics of Potentially Dopaminergic Hydroxy‐2‐Aminotetralins and Naphthoxazines Using Rat and Human Liver Microsomes

Jansman

Drenth

Zeeuw

et al. 1991

Pharmacology & Toxicology

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“…During the preparation of this study, Gerding et a1. 16 reported an indirect separation method for determination of the enantiomeric purity of (R)-and (S)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxy-0 1990 Wiley-Liss, Inc.…”

mentioning

confidence: 99%

(R)‐ and (S)‐5‐hydroxy‐2‐(dipropylamino)tetralin (5‐OH DPAT): Assessment of optical purities and dopaminergic activities

et al. 1990

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Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The ability of the enantiomers to change the rat brain DOPA levels was evaluated in vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor antagonist.

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Chiral separation by high performance liquid chromatography. I. Review on indirect separation of enantiomers as diastereomeric derivatives using ultraviolet, fluorescence and electrochemical detection

Srinivas

Igwemezie

1992

Biomedical Chromatography

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The increased attention on the therapeutic implications of stereoisomerism has provided an impetus for the development of analytical methods for enantiomeric separation. The indirect method of separation of enantiomers as diastereomers using high performance liquid chromatography (HPLC) has emerged as an efficient and versatile approach. This is due mainly to the availability of numerous chiral derivatization reagents (CDRs). This article reviews CDRs useful for the development of an indirect HPLC method using ultraviolet, fluorescence and electrochemical detection. In addition, factors crucial for the development of the indirect method are discussed.

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Determination of enantiomeric purity of the new D-2 dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) by reversed-phase high-performance liquid chromatography after pre-column derivatization with d(+)-glucuronic acid

Cited by 17 publications

References 19 publications

Impact of Structural Differences on the in Vitro Glucuronidation Kinetics of Potentially Dopaminergic Hydroxy‐2‐Aminotetralins and Naphthoxazines Using Rat and Human Liver Microsomes

Impact of Structural Differences on the in Vitro Glucuronidation Kinetics of Potentially Dopaminergic Hydroxy‐2‐Aminotetralins and Naphthoxazines Using Rat and Human Liver Microsomes

(R)‐ and (S)‐5‐hydroxy‐2‐(dipropylamino)tetralin (5‐OH DPAT): Assessment of optical purities and dopaminergic activities

Chiral separation by high performance liquid chromatography. I. Review on indirect separation of enantiomers as diastereomeric derivatives using ultraviolet, fluorescence and electrochemical detection

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