Activity of an intracellular lymphocyte stimulator is independent of G-protein interactions, [Ca2+]i elevation, phosphoinositide hydrolysis, and protein kinase C translocation.

Goodman, Michael; Speizer, L.A.; Bokoch, Gary M.; Kanter, Joan R.; Brunton, Laurence L.

doi:10.1016/s0021-9258(19)38337-1

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…NMR (DMSO-dg) 1.28, 1.47 (2 s, 6 H, isopropylidene methyls), 6.0 (d, 1 H, C^H), 7.0 (br s, 2 H, NHj), 11.29 (s, 1 , NH), and other sugar protons. Anal.…”

Section: Methodsmentioning

confidence: 99%

“…Trimethylsilyl trifluoromethanesulfonate (4.5 mL, 20 mmol) was added and the mixture stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue flash chromatographed over silica gel with an 8:1 mixture of chloroform-methanol as eluent to yield the title compound which crystallized from a mixture of acetone and hexane (1.25 H, acetyl), 4.19 (m, 1 , 04 ), 5.36,5.85 (2 m, 2 H, CyH and CyH), 6.00 (d, 1 H, J = 3.1 Hz, CrH), 6.05 (br s, 2 , NH2), 11.5 (br s, 1 H, NH). Anal.…”

Section: Methodsmentioning

confidence: 99%

“…The column was eluted initially with water followed by a gradient of aqueous ammonium bicarbonate (0.0-0.2 M; 2 L). The appropriate fractions were pooled, concentrated in vacuo, and lyophilized several times to yield 0.2 g (22%) of the title compound: mp >244 °C (dec); UV (pH 1 and 7) 243, 300 nm; (pH 11) 243, 289 nm; NMR (DMSO-de) 5.60 (d, 1H, CyOH), 5.72 (s, 1H, CVH), 7.15 (br s, 6 H, NH2 and NH/), 11.40 (br s, 1 , NH), and other sugar protons. Anal.…”

Section: Methodsmentioning

confidence: 99%

“…The observed toxicity of 3, the reasons for which remain unclear, precluded further antiviral evaluation of this derivative. 5'-Deoxyribosyl derivative 6 was inactive, suggesting that activation via phosphorylation may be a requirement for activity in this system or that the 5'-OH group may play some other essential role. On the other hand, S'-sulfamate 4 was likewise devoid of significant antiviral activity, suggesting that an intracellular phosphorylated form of 1 may not be the active form of the drug.…”

Section: Antiviral Activitymentioning

confidence: 96%

“…0 Half-daily doses were administered 24 and 18 h prior to virus inoculation. 6 Of mice that died. Survivors lived through 21 days.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and antiviral activity of certain guanosine analogs in the thiazolo[4,5-d]pyrimidine ring system

Kini¹,

Anderson²,

Sanghvi³

et al. 1991

J. Med. Chem.

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Several sugar-modified nucleoside derivatives of the purine analogue 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7-dione (1) were synthesized. Phosphorylation of 1 using POCl3 resulted in 5'-monophosphate 2, which was subsequently converted to 3',5'-cyclic phosphate 3, by reported methods. 5'-Sulfamoyl derivative 4 was synthesized by treatment of the 2,3-O-isopropylidene derivative of 1 with chlorosulfonamide followed by acid deprotection. Compounds 5-7, the 5'-deoxy, the tri-O-acetyl, and the 2'-deoxy derivatives of 1, respectively, were synthesized by glycosylation of 5-aminothiazolo[4,5-d]pyrimidine-2,7-dione, the aglycon of 1, with the appropriate sugar moieties, utilizing the Vorbruggen procedure. Oxidative cleavage of the C2'-C3' bond in 1 followed by reduction with sodium borohydride led to "seco" analogue 8. Nucleosides 2-8 were evaluated for antiviral activity in vivo against the Semliki Forest virus. The activity of compounds 2, 5, and 7 were similar to that of 1. Cyclic phosphate 3 was toxic at the high dose and weakly active at the lower dose. Compounds 4, 6, and 8 were inactive in this system.

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“…NMR (DMSO-dg) 1.28, 1.47 (2 s, 6 H, isopropylidene methyls), 6.0 (d, 1 H, C^H), 7.0 (br s, 2 H, NHj), 11.29 (s, 1 , NH), and other sugar protons. Anal.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%