Search

Your search keyword '"TIEN, J.-H."' showing total 27 results
Start Over Author "TIEN, J.-H."
27 results on '"TIEN, J.-H."'

15. Synthesis of HIV Protease Inhibitor ABT-378 (Lopinavir)

Author

Stoner, E. J., Cooper, A. J., Dickman, D. A., Kolaczkowski, L., Lallaman, J. E., Liu, J.-H., Oliver-Shaffer, P. A., Patel, K. M., Paterson, J. B., Jr., Plata, D. J., Riley, D. A., Sham, H. L., Stengel, P. J., and Tien, J.-H. J.

Abstract

A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of acid 5, derived from l-valine, is also reported.

Published
2000

16. Reduction of an Enaminone:  Synthesis of the Diamino Alcohol Core of Ritonavir

Author

Haight, A. R., Stuk, T. L., Allen, M. S., Bhagavatula, L., Fitzgerald, M., Hannick, S. M., Kerdesky, F. A. J., Menzia, J. A., Parekh, S. I., Robbins, T. A., Scarpetti, D., and Tien, J.-H. J.

Abstract

The reduction of (5S)-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2S,3S,5S)-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane (2a). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1. This methodology has been used to produce multikilogram quantities of the diamino alcohol core of Ritonavir and should be general to the synthesis of related diamino hydroxyethylene isosteres.

Published
1999

17. DISPLACEMENT AND ELECTRON-TRANSFER REACTIONS OF SUBSTITUTED 2-CHLORO-1,3,2-BENZODIOXASTIBOLES WITH BASES

Author

McEwen, William, Tien, J. -H., Rembetsy, L. M., Kalbacher, B. J., Lubinkowski, Jacek, Mari, F., Devincenzo, S., Salgueiro, R. M., Hou, J., and Alvarez, J. A.

Abstract

2-Chloro-1,3,2-benzodioxastiboles undergo apparent nucleophilic displacement reactions on antimony in reactions with relatively weak bases. For example, 2-chloro-5-methyl-1,3,2-benzodioxastibole (3) gives 2-(n-butylamino)-5-methyl-1,3,2-benzodioxastibole (14) on treatment with n-butylamine. However, reaction of a 2-chloro-1,3,2-benzodioxastibole with a strong base leads, at least in part, to an apparent electron transfer reaction, with formation of a complex mixture of products. For example, treatment of 2-chloro-5-tert-butyl-1,3,2-benzodioxastibole (2) with phenylmagnesium bromide in tetrahydrofuran, with subsequent acid-catalyzed hydrolysis of the reaction mixture, gives rise to tert-butyl alcohol, catechol, 4-tert-butyl-catechol, phenol, triphenylantimony, biphenyl and methyl-phenylcarbinol.

Published
1988
Full Text
View/download PDF

27. Transdermal-controlled administration of oxycodone.

Author

Tien JH

Subjects
Administration, Cutaneous, Animals, Chromatography, High Pressure Liquid, Diffusion, Drug Delivery Systems, Half-Life, Hydrogen-Ion Concentration, In Vitro Techniques, Mice, Mice, Hairless, Oxycodone pharmacokinetics, Silicone Elastomers, Skin Absorption, Oxycodone administration & dosage
Abstract

The permeability of hairless mouse skin membrane to the weak base narcotic analgesic oxycodone (pKa = 8.53) was investigated. The effects of pH on the solubility and skin permeation rate were also studied. The results of the study of skin permeation of drug through hairless mouse skin suggest that the permeability of oxycodone base is approximately 7.4 times higher than that of protonated oxycodone. The nonionic species of oxycodone, at various drug loadings, was then incorporated in a Dow-Corning silicone elastomer for the evaluation of the release rate and skin permeation rate. It was found that Q/t1/2 is directly proportional to the square root of the drug loading dose, as expected by Higuchi's equation (where Q is the cumulative amount released and t is time). However, the skin permeation rate was observed to increase initially with drug loading and level off at the loading dose of 60 mg/cm3.

Published
1991
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results