Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of novel 3'-C-branched 2',3'-dideoxynucleosides have been synthesized and evaluated as anti-HIV agents. Hydroboration of 2',3'-dideoxy-3'-C-methylene nucleoside proceeded regio- and stereoselectively to give 1-(2,3-dideoxy-3-C-hydroxy methyl-5-O-trityl-beta-D-threo-pentofuranosyl)thymine (5) after oxidation. 3'-C-Chloromethyl and 3'-C-iodomethyl 5'-O-protected 2',3'-dideoxynucleosides 9 and 12 were obtained from 5 by reaction with carbon tetrachloride/triphenylphosphine and methyltriphenoxyphosphonium iodide, respectively. Arbuzov reaction of 12 with triethyl phosphite afforded 3'-C-(diethyl-phosphono)methyl 5'-O-protected 2',3'-dideoxynucleoside 14. Compounds 5, 9, 12 and 14 were detritylated to give 1-(3-C-chloromethyl-2,3-dideoxy-beta-D-threo-pentofuranosyl)thymine (10), 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)-thymine (11), 1-(2,3-dideoxy-3-C-iodomethyl-beta-D-threo-pentofuranosyl)thymine (13) and 1-(2,3-dideoxy-3-C-(O,O'-diethylphosphono)methyl-beta-D-threo- pentofuranosyl)thymine (15), respectively. These nucleoside analogues were evaluated for antiviral activity against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro. Compound 5 demonstrated selective antiviral activity against HIV-1 but not HSV-1.
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PMID:Stereoselective synthesis, chemistry and antiviral evaluation of 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)thymine derivatives. 856 13

2',3'-Didehydro-2',3'-dideoxy-9-deazaguanosine (1), its monophosphate prodrug (2), and two analogues, 2',3'-dideoxy-9-deazaguanosine (3) and 2',3'-didehydro-2',3'-dideoxy-9-deazainosine (4), have been synthesized from benzoylated 9-deazaguanosine (5). Basic hydrolysis of 5, selective protection of the 2-amino and 5'-hydroxy functions with isobutyryl and silyl groups, respectively, followed by reaction with thiocarbonyldiimidazole gave the cyclic thiocarbonate, which, upon reaction with triethyl phosphite, followed by deprotection, afforded 1. Treatment of 1 with phenyl methoxyalaninylphosphochloridate and N-methylimidazole gave 2. Catalytic hydrogenation of 1 gave 3. Hydrodediazoniation of 1 with tert-butyl nitrite and tris(trimethylsilyl)silane gave 4. Compounds 1-4 were found to be inactive against the human immunodeficiency virus and exhibited minimal to no cytotoxic activity against the L1210 leukemia, CCRF-CEM lymphoblastic leukemia, and B16F10 melanoma in vitro.
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PMID:Synthesis and biological evaluation of 2',3'-didehydro-2',3'-dideoxy-9-deazaguanosine, a monophosphate prodrug and two analogues, 2',3'-dideoxy-9-deazaguanosine and 2',3'-didehydro-2',3'-dideoxy-9-deazainosine. 1582 19