Pyrimidine nucleosides as therapeutic and diagnostic agents

Details Pyrimidine nucleosides as therapeutic and diagnostic agents Pyrimidine nucleosides as therapeutic and diagnostic agents

1996-03-27

1999-09-28

Wilson, James O.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 2534, 536 266, 536 268, 536 281, 536 282, 536 283, 536 284, 536 285, 536 2851, 536 2852, 536 2853, 536 2854, 536 2855, 435 23, 530300, C07H 1904

Patent

active

059591005

ABSTRACT:
Modified nucleosides and methods of making and using the nucleosides are disclosed. The compounds can be prepared by reacting nucleoside starting materials that contain a suitable leaving group at one or more of the carbon atoms in the purine or pyrimidine ring, with a vinylstannane, carbon monoxide, and a palladium catalyst to provide 1-ene-3-one intermediates. These intermediates are then reacted with suitably functionalized primary or secondary amines via a Michael reaction. When the intermediate is a 5-position modified pyrimidine ring, and the amine contains a second hydrogen, it can do a second Michael reaction with the ene-one or the ene-imine in the pyrimidine ring. Appropriate modification of the amine reactant can yield products with various bioactivities. The nucleosides can be used therapeutically as anti-cancer, anti-bacterial or anti-viral drugs. The nucleosides can also be used for diagnostic applications, for example, by incorporating a radiolabel or fluorescent label into the molecule. The nucleosides can be used to prepare oligonucleotides for use in various applications, either alone or in combination with other modified nucleosides and/or naturally occurring nucleosides.

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