No abstract

catalysed exchange with 90 at% tritiated water to a specific activity of 35 Ci/mmol.

3H and 14C‐Sch 27899 have been prepared by fermentation using the Micromonospora carbonacea organism. In the case of 3H‐Sch 27899, the label was incorporated by a single addition of 100 mCi of 70Ci/mmole L‐[3H‐methyl]‐methionine to two flasks. For 14C‐Sch 27899, 48 mCi of 55 mCi/mmole L‐[14C‐methyl]‐methionine was added in five aliquots to five flasks over a five day period. Both batches were isolated by solvent extraction, oxidized and purified by column chromatography and hplc. An overall incorporation of 7.8% was found from L‐[3H‐methyl]‐methionine and 18.7% from L‐[14C‐methyl]‐methionine. The in vivo stability of label of 3H and 14C‐Sch 27899 was determined, with 14C‐Sch 27899 found to be a better choice for use in in vivo metabolism studies. Copyright © 1999 John Wiley & Sons, Ltd.

Summary3 H-Sch 58235 was prepared at a specific activity of 29.1 Ci/mmol by Ir(COD)(Cy 3 P)PyPF 6 catalysed exchange with tritium gas.14 C-Sch 58235 was prepared in three steps from p-hydroxy[ring-U-14 C]benzaldehyde with an overall radiochemical yield of 21%. 13 C 6 -Sch 58235 was similarly prepared in three steps from p-hydroxy[ring-U-13 C 6 ]benzaldehyde in an overall yield of 41%.

Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [(3) H]SCH 417690 was prepared for CCR5 receptor binding work and [(2) H4 ]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690.