Enantiospecificity of Glutamate Carboxypeptidase II Inhibition

التفاصيل البيبلوغرافية
العنوان:	Enantiospecificity of Glutamate Carboxypeptidase II Inhibition
المؤلفون:	Tsukamoto, T., Majer, P., Vitharana, D., Ni, C., Hin, B., Lu, X.-C. M., Thomas, A. G., Wozniak, K. M., Calvin, D. C., Wu, Y., Slusher, B. S., Scarpetti, D., Bonneville, G. W.
المصدر:	Journal of Medicinal Chemistry; April 2005, Vol. 48 Issue: 7 p2319-2324, 6p
مستخلص:	Two representative glutamate carboxypeptidase II (GCP II) inhibitors, 2-(hydroxypentafluorophenylmethyl-phosphinoylmethyl)pentanedioic acid 2 and 2-(3-mercaptopropyl)pentanedioic acid 3, were synthesized in high optical purities (>97%ee). The two enantiomers of 2 were prepared from previously reported chiral intermediates, (R)- and (S)-2-(hydroxyphosphinoylmethyl)pentanedioic acid benzyl esters 8. The synthesis of (R)- and (S)-3 involves the hydrolysis of (R)- and (S)-3-(2-oxo-tetrahydro-thiopyran-3-yl)propionic acids, (R)- and (S)-11, the corresponding optically pure thiolactones delivered by chiral chromatographic separation of the racemic 11. GCP II inhibitory assay revealed that (S)-2 is 40-fold more potent than (R)-2. In contrast, both enantiomers of 3 inhibited GCP II with nearly equal potency. The efficacy observed in subsequent animal studies with these enantiomers correlated well with the inhibitory potency in a GCP II assay.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804