- INHIBITORS OF E1 ACTIVATING ENZYMES
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This invention relates to compounds that inhibit El activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.
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Page/Page column 132
(2008/06/13)
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- An industrial process for synthesizing lodenosine (FddA)
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Two industrial synthetic approaches to Lodenosine (1, FddA, 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl) adenine) via a purine riboside or a purine 3′-deoxyriboside are described. Several novel applications of deoxygenation and fluorination methods are compared considering reaction yields, economy, safety and environmental concerns.
- Izawa, Kunisuke,Takamatsu, Satoshi,Katayama, Satoshi,Hirose, Naoko,Kozai, Shigetaka,Maruyama, Tokumi
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p. 507 - 517
(2007/10/03)
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- PROCESS FOR PRODUCING NUCLEIC ACID DERIVATIVES
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There can be provided an excellent industrial process for producing compounds having sugar-moiety hydroxyl groups or halogen atoms reduced in nucleic acids or in derivatives thereof by allowing O-thiocarbonyl derivatives of sugar-moiety hydroxyl groups or allowing halogenated derivatives in the sugar-moiety, in the nucleic acids or in derivatives thereof to react with any one of hypophosphorous acids (including salts thereof) and phosphites (esters) which are inexpensive, non-toxic and safely usable as radical reducing agents in industrial scale, in the presence of a radical reaction initiator. The process of the present invention is an industrially useful and highly safe process for reducing sugar-moiety hydroxyl groups and halogen atoms in nucleic acids or derivatives thereof (including nucleic acid-related compounds) at low costs.
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- Convenient synthesis of fluorinated nucleosides with perfluoroalkanesulfonyl fluorides
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Perfluoroalkanesulfonyl fluorides are effective dehydroxy-fluorination agents for the hydroxyl group at the sugar moiety of nucleoside derivatives and give the corresponding fluorinated nucleosides in good yield with an inversion of configuration in a sin
- Takamatsu, Satoshi,Katayama, Satoshi,Hirose, Naoko,De Cock, Etienne,Schelkens, Geert,Demillequand, Marc,Brepoels, Jozef,Izawa, Kunisuke
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p. 849 - 861
(2007/10/03)
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- Improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)adenine (FddA) using triethylamine trihydrofluoride
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An improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)adenine (1, FddA) via a fluorination of 3′-O-benzoyl-5′-O-tritylriboside (4a) using noncorrosive triethylamine trihydrofluoride (Et3N·3HF) is described. The method is suitable for large-scale synthesis. In particular, the synthesis of the pivotal intermediate 4a was much improved in avoidance of the use of toxic tin reagent. Radical deoxygenation with several silanes was also studied. The total yield of FddA from 6-chloropurine riboside (2) in this study was greater than that we reported previously.
- Takamatsu, Satoshi,Maruyama, Tokumi,Katayama, Satoshi,Hirose, Naoko,Izawa, Kunisuke
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p. 2321 - 2324
(2007/10/03)
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- PROCESS FOR PRODUCING NUCLEOSIDE DERIVATIVES
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Nucleoside derivatives wherein the hydroxyl group at the 2'-position has been replaced by a fluorine atom, etc. and the hydroxyl group at the 3'-position has been deoxylated, such as 9-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl) adenine (FddA), etc. and the compounds related thereto can be produced conveniently and at an advantage industrially from a purine riboside, by substituting a halogen atom for the 6-position in the purine riboside, modifying the hydroxyl groups at the 3'-and 5'-positions of the sugar moiety thereof with protecting groups which can not be deprotected (deblocked) under the same condition, further introducing a desired substituent group, such as a fluorine atom, etc. thereinto at the 2'-position of the sugar moiety and then deprotecting (deblocking)-deoxylating the protected hydroxyl group at the 3'-position thereof. Further, processes for producing important intermediates usable in the above production and thus produced novel intermediates are also provided.
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- Synthesis of 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine bearing a selectively removable protecting group
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A facile and practical method to introduce fluorine at the up-side of the 2'-carbon of nucleosides is described. 6-Chloropurine riboside 3 was converted to the 3'-O-benzoate 4a via a stannylene complex, then converted to the 3'-O-benzoyl-5'-O-tritylriboside 5a. In the presence of pyridine, migration of the 3'-benzoyl groups of 4a and 5a to 2'-OH was rather slow. Hence, 5a was reacted with diethylaminosulfur trifluoride (DAST) in CH2Cl2 in the presence of pyridine to give the 2'-deoxy-2'-fluoroarabinoside 6 in good yield. The 3'-O-benzoyl-5'-O-trityl protecting system was easy to deprotect selectively. Thus, treatment of 6 with ammonia in MeOH gave the 5'- O-trityl compound 7, which was subjected to esterification with phenyl chlorothionoformate, radical deoxygenation with tris(trimethylsilyl)silane and acid treatment to afford 9-(2,3-dideoxy-2-fluoro-β-D-threo- pentofuranosyl)adenine (FddA) 2. In addition, acid treatment of 7 gave 9-(2- deoxy-2-fluoro-β-D-arabinofuranosyl)adenine (FdaraA) 1.
- Maruyama, Tokumi,Takamatsu, Satoshi,Kozai, Shigetada,Satoh, Yoshiko,Izawa, Kunisuke
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p. 966 - 970
(2007/10/03)
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