93213-80-0Relevant articles and documents
BENZENESULFONAMIDE INHIBITOR OF CCR2 CHEMOKINE RECEPTOR
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Page/Page column 33-34, (2010/11/25)
Disclosed are compounds of formula (I): or a pharmaceutically acceptable salt thereof, or a solvate thereof, or a combination thereof, as well as compositions of methods of use of the compound, wherein R1, R2, R3, and m ar
Convergent synthesis of polyhalogenated quinoline C-nucleosides as potential antiviral agents
Chen, Jiong J.,Drach, John C.,Townsend, Leroy B.
, p. 4170 - 4178 (2007/10/03)
2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. We proposed to synthesize 2-halo-6,7-dichloro-4-(β-D-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of TCRB. The synthesis used Wittig reactions in two key steps. The first Wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)- 1,2-dideoxy-3,4-O-isopropylideneD-allo-1-enitol (5) as the basic skeleton for the target compounds. The following electrophile-mediated intramolecular cyclization of the cis-alkene (5) was found to afford (1S,2S)-2,5-anhydro-1-bromo6-O-(tert-butyldimethylsilyl)- 1-deoxy-1-(4,5-dichloro-2-nitrophenyl)-3,4-O-isopropylidene-D-allitol (8) as the major product. This α-stereoselectivity was contrary to the literature precedence. A doublebond isomerization was established to be the cause of the unexpected stereochemistry. The bromo group of 8 was displaced by a hydroxyl group. Oxidation of the hydroxy group and the reduction of a phenylnitro group provided (2S)-1-(2-amino-4,5-dichlorophenyl)-2,5-anhydro-6-O- (tert-butyldimethylsilyl)-3,4-O-isopropylidene-D-allose (11), which was subjected to the second Wittig reaction with a phosphacumulene to construct 4-[5-O -(tert-butyldimethylsilyl)-2,3-O- isopropylidene-α-Dribofuranosyl]-6,7-dichloroquinolin-2-one (13). Halogenation followed by deprotection of 13 and led to the synthesis of 4-(α -D-ribofuranosyl)-2,6,7-trichloroquinoline (17) as the major product. The 2-aminophenone α-nucleoside (11) was successfully anomerized to the β-anomer (19), which led to the synthesis of the targeted 2-chloro- and 2-bromo-6,7-dichloro-4-(β-D-ribofuranosyl)quinolines (18 and 21, respectively).
