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A new series of quinolinyl- and phenantridinyl-acetamides were synthesizer and evaluated against bradykinin B1 receptor. In vitro metabolic stability data were reported for the key compounds.The analgesic effect of compound 20 from the phenantridine series was proved in-vivo., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

(4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1-(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. To establish the structure-activity relationship (SAR) and to attempt the improvement of the ADME properties of the lead, a series of compounds were prepared and tested. Several derivatives showed low nanomolar activity both in the binding and in the functional assay. In a formalin-induced hyperalgesia model in mice, 6a and (4-benzylpiperidine-1-yl)-[5(6)-hydroxy-1H-benzimidazol-2-yl]-methanone (60a) were as active as besonprodil (2) after oral administration. A CoMSIA model was developed based on binding data of a series of indole- and benzimidazole-2-carboxamides.

A novel series of oxamides derived from indole-2-carboxamides was identified as potent NR2B selective NMDA receptor antagonists. Several members of this group showed good analgesic activity in the mouse formalin test.

A novel series of indole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the number and position of OH groups on the indole skeleton as well as the substitution of the piperidine ring on the biological activity of the compounds was studied.

1,6-Anhydro-3,4-O-isopropylidene-1-thio-D-mannitol was converted into its sulfoxide which after hydrolysis, acetylation and subsequent Pummerer rearrangement gave the penta-O-acetyl-1-thio-D-mannoseptanose anomers in excellent yield. This anomeric mixture was used as donor for the glycosylation of 4-nitro- and 4-cyanobenzenethiol in the presence of boron trifluoride etherate and trimethylsilyl triflate, respectively, to yield the corresponding thioseptanosides in high yield. The same strategy was applied for the synthesis of the corresponding L-idothioseptanosides using 1,6-anhydro-3,4-O-isopropylidene-1-thio-L-iditol as starting material. The penta-O-acetyl-D-glucothioseptanose donors could not be synthesised the same way, as the Pummerer reaction of the corresponding tetra-O-acetyl-1,6-thioanhydro-1-thio-D-glucitol sulfoxides led to an inseparable mixture of the corresponding L-gulo- and D-glucothioseptanose anomers. Therefore, D-glucose diethyl dithioacetal was converted via its 2,3,4,5-tetra-O-acetyl-6-S-acetyl derivative into an anomeric mixture of its 6-thio-septanose and -furanose peracetates which could be separated by column chromatography. Condensation of the 6-thio-glucoseptanose peracetates with 4-cyano- and 4-nitrobenezenethiol in the presence of boron trifluoride etherate afforded anomeric mixtures of the corresponding thioseptanosides. The D-manno-, L-ido- and D-glucothioseptanosides obtained after Zemplén deacetylation of these mixtures were tested for their oral antithrombotic activity.

Acetolysis of methyl 3,4-di-O-acetyl-2,6-anhydro-D-altropyranoside afforded a mixture containing, besides 1,3,4-tri-O-acetyl-2,6-anhydro-D-altropyranose, the (1R) and (1S) diastereomers of methyl 2,6-anhydro-D-altrose-tetraacetate. Treatment of this mixture with 4-cyanobenzenethiol in the presence of trimethylsilyl triflate resulted in a mixture containing the 3,4,5-tri-O-acetyl-2,6-anhydro-D-altrose bis(4-cyanophenyl) dithioacetal, the corresponding O-methyl S-aryl monothiohemiacetal diastereomers and the beta-thiopyranoside, respectively. Acetolysis of methyl 3,4-di-O-acetyl-2,6-anhydro-D-mannopyranoside led to a mixture of the (1R) and (1S) diastereomers of methyl 2,6-anhydro-D-mannosetetraacetate, which was converted into the corresponding O-methyl S-aryl monothiohemiacetals. Treatment of 1,1,3,4,5-penta-O-acetyl-2,6-anhydro-aldehydo-D-altrose and -D-mannose with 4-cyano- and 4-nitrobenzenethiol, respectively, in the presence of trimethylsilyl triflate afforded the corresponding dithioacetal derivatives. All arylthio derivatives obtained after deacetylation were tested for their oral antithrombotic activity.

1,2,5-Tri-O-acetyl-3,6-anhydro-3-thio-D-glucofuranose was synthesised starting from D-glucose and was used as a donor for the glycosidation of 4-cyano- and 4-nitrobenzenethiol. In the latter reaction, besides an anomeric mixture of the 4-nitrophenyl 2,5-di-O-acetyl-3,6-anhydro-1,3-dithio-D-glucofuranosides, the corresponding 2,6-anhydro-1,2-dithio-D-altrofuranosides were also obtained, formed via a rearrangement of the sugar moiety. A similar rearrangement could be observed during the hydrolysis of the glycosidic bond of methyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-alpha-D-glucopyranoside with aqueous trifluoroacetic acid, affording after acetylation besides 1-O-acetyl-3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-alpha-D-glucopyranose (32alpha), 1,1,5-tri-O-acetyl-3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-D-glucose, methyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-3-thio-beta-D-glucopyranoside and 1,5-di-O-acetyl-2,6-anhydro-3-O-(4-nitrobenzoyl)-2-thio-alpha-D-altrofuranose (40). Glycosidation of 4-cyanobenzethiol with 32alpha in the presence of trimethylsilyl triflate as promoter afforded 4-cyanophenyl 3,6-anhydro-2,4-di-O-(4-nitrobenzoyl)-1,3-dithio-beta-D-glucopyranoside as a minor component only, besides 4-cyanophenyl 3,6-anhydro-2-S-(4-cyanophenyl)-4-O-(4-nitrobenzoyl)-1,2,3-trithio-beta-D-glucopyranoside. When boron trifluoride etherate was used as promoter in the reaction of 32alpha with 4-cyano- and 4-nitrobenzenethiol, the corresponding beta-thioglycosides were obtained, while 40 gave under identical conditions the alpha anomers exclusively. All thioglycosides obtained after deacylation were submitted to biological evaluation. Among these glycosides, the 4-cyanophenyl 3,6-thioanhydro-1,3-dithio-D-glucofuranoside possessed the strongest oral antithrombotic effect.

Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-D-glucitol in methanol with sodium hydroxide afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-D-galactitol, 1,6:2,5-dianhydro-4-O-methyl-1 -thio-D-glucitol, 1 ,6:2,5-dianhydro-3-O-methanesulfonyl-1 -thio-D-glucitol and 1 ,6:2,5-dianhydro-4-deoxy-1-thio-D-erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio-D-xylo-hexitol, the absolute configuration of which was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio-D-hexitol derivatives in which the free OH groups were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of 4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-thio-D-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-alpha-L- (23) and 1-O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-alpha-D-xylo-hexoseptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-D-lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23 and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as promoter. The oral antithrombotic activity of the obtained alpha-thioglycosides was determined in rats, using Pescador's model.

Two independent approaches were investigated for the synthesis of 3,4-di-O-acetyl-1,6:2,5-dianhydro-1-thio-D-glucitol (18), a key intermediate in the synthesis of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-alpha-D-glucoseptanose (13), needed as glycosyl donor. In the first approach 1,6-dibromo-1,6-dideoxy-D-mannitol was used as starting material and was converted via 2,5-anhydro-1,6-dibromo-1,6-dideoxy-4-O-methanesulfonyl-3-O-tetrahydropy ranyl-D-glucitol into 18. The second approach started from 1,2:5,6-di-O-isopropylidene-D-mannitol and the allyl, 4-methoxybenzyl as well as the methoxyethoxymethyl groups were used, respectively, for the protection of the 3,4-OH groups. The resulting intermediates were converted via their 1,2:5,6-dianhydro derivatives into the corresponding 3,4-O-protected 2,5-anhydro-6-bromo-6-deoxy-D-glucitol derivatives. The 1,6-thioanhydro bridge was introduced into these compounds by exchanging the bromine with thioacetate, activating OH-1 by mesylation and treating these esters with sodium methoxide. Among these approaches, the 4-methoxybenzyl protection proved to be the most suitable for a large scale preparation of 18. Pummerer rearrangement of the sulfoxide, obtained via oxidation of 18 gave a 1:9 mixture of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-alpha-L-gulo- (12) and -D-glucoseptanose 13. When 12 or 13 were used as donors and trimethylsilyl triflate as promoter for the glycosylation of 4-cyanobenzenethiol, a mixture of 4-cyanophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-alpha-L-gulo- (58) and -alpha-D-glucoseptanoside (61) was formed suggesting an isomerisation of the heteroallylic system of the intermediate. A similar mixture of 58 and 61 resulted when 18 was treated with N-chloro succinimide and the mixture of chlorides was used in the presence of zinc oxide for the condensation with 4-cyanobenzenethiol. When 4-nitrobenzenethiol was applied as aglycon and boron trifluoride etherate as promoter, a mixture of 4-nitrophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-alpha-L-gulo- (60) and -alpha-D-glucoseptanoside (62) was obtained. Deacetylation of 58, 61 and 62 according to Zemplen afforded 4-cyanophenyl 2,5-anhydro-1,6-dithio-alpha-L-glucoseptanoside (59), 4-cyanophenyl 2,5-anhydro-1,6-dithio-alpha-D-glucoseptanoside (63) and 4-nitrophenyl 2,5-anhydro-1,6-dithio-alpha-D-glucoseptanoside (66), respectively. The 4-cyano group of 63 was transformed into the 4-aminothiocarbonyl, and the 4-(methylthio)(imino)methyl derivative and the 4-nitro group of 66 into the acetamido derivative. All of these thioglycosides displayed a stronger oral antithrombotic effect in rats compared with beciparcil, used as reference.

Tri-O-acetyl-5-thio-D-ribopyranosyl bromide was converted into 3,4-di-O-benzoyl-1,5-anhydro-5-thio-D-erythro-pent-1-enitol (3,4-di-O-benzoyl-5-thio-D-ribal), the azidonitration of which afforded an unstable mixture of 2-azido-3,4-di-O-benzoyl-2-deoxy-1-O-nitro-5-thio-D-pentopyranoside++ + isomers. This was converted without separation into the corresponding 1-O-acetyl derivatives from which an alpha,beta anomeric mixture of the 1-O-acetyl-2-azido-3,4-di-O-benzoyl-2-deoxy-5-thio-D-arabinopyranose+ ++ isomers could be isolated in high yield. Glycosidation of this mixture with 4-cyano- or 4-nitrobenzenethiol, using trimethylsilyl triflate or boron trifluoride etherate, respectively, as promoters gave the corresponding D anomers exclusively. Zemplén debenzoylation afforded 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-beta-D-arabinopyranoside, respectively. When 1-O-acetyl-2-azido-3,4-di-O-benzoyl-2-deoxy-5-thio-D-lyxopyranose was used as glycosyl donor only the corresponding 1 anomers, i.e., 4-cyanophenyl as well as 4-nitrophenyl 2-azido-2-deoxy-1,5-dithio-beta-D-lyxopyranosides, could be isolated after Zemplén debenzoylation in high yield. All four 1,5-dithioglycosides possess significant oral antithrombotic activity.

1,2,3,4-Tetra-O-acetyl-5-thio-D-ribopyranose as well as its 1-bromide were used as donors in the reaction with 4-cyano- and 4-nitrobenzenethiol, to give the corresponding thioglycosides in different anomeric ratios depending on the reaction conditions. Zemplén deacetylation afforded 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-alpha- and beta-D-ribopyranosides, respectively. 1,3,4-Tri-O-acetyl-2-deoxy-5-thio-D-erythro-pentopyranose was synthesized from methyl 2-deoxy-D-erythro-pentofuranoside and was coupled with 4-cyano- and 4-nitrobenzenethiol to give anomeric mixtures from which 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-beta-D-erythro-pentopyranosides were isolated after deacetylation. 1,4-Di-O-acetyl-2,3-dideoxy-5-thio-D-glycero-pentopyranose was obtained starting from 1,2,5,6-di-O-isopropylidene-D-mannitol and used as the donor in the glycosylation reaction with 4-cyano- and 4-nitrobenzenethiol. The resulting anomeric mixtures were separated to give, after deacetylation, 4-cyanophenyl as well as 4-nitrophenyl 2,3-dideoxy-1,5-dithio-beta-D-glycero-pentopyranosides. All of these thioglycosides showed significant antithrombotic activity on rats after oral administration.

5-S-Benzoyl-2,3-O-isopropylidene-5-thio-L-arabinose, prepared from L-arabinose diethyl dithioacetal gave, on treatment with sodium methoxide in methanol, 4-O-benzoyl-2,3-O-isopropylidene-5-thio-L-arabinopyranose 12 which was converted into its 1-O-acetate 14. Hydrolysis of 12 in acetic acid-water afforded, after acetylation, 1,2,3-tri-O-acetyl-4-O-benzoyl-5-thio-L-arabinopyranose 17 which was transformed into 2,3-di-O-acetyl-4-O-benzoyl-5-thio-L-arabinopyranosyl bromide 20. Zemplén deacylation of 17 gave 5-thio-L-arabinopyranose which was converted via 1,2,3,4-tetra-O-acetyl-5-thio-beta-L-arabinopyranose 5 into 2,3,4-tri-O-acetyl-5-thio-beta-L-arabinopyranosyl bromide 6 and into O-(2,3,4-tri-O-acetyl-5-thio-L-arabinopyranosyl) trichloro-acetimidate 7. Glycosidation of 4-nitrophenol with 12 under the Mitsunobu conditions afforded 4-nitrophenyl 4-O-benzoyl-2,3-O-isopropylidene-5-thio-alpha- and beta-L-arabinopyranoside in a approximately 1:2 ratio. Condensation of the glycosyl donors 6, 7, 17, and 20 with 4-cyano- and 4-nitrobenzenethiol yielded, after deacylation, 4-cyano- and 4-nitrophenyl 1,5-dithio-alpha- and beta-L-arabinopyranosides 28 alpha, 28 beta, 29 alpha and 29 beta in different ratios and yields, depending on the reaction conditions applied. In a similar manner the corresponding D-isomers 30 alpha, 30 beta, 31 alpha and 31 beta were also prepared. All of these glycosides, except 28 alpha, showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference.

D-Xylose was converted via 1,2-O-isopropylidene-alpha-D-xylofuranose (4) into 3-O-benzoyl-5-S-benzoyl-1,2-O-isopropylidene-alpha-D-xylofuranose which, after methanolysis, acetylation and subsequent acetolysis afforded 1,2,3,4-tetra-O-acetyl-5-thio-alpha-D-xylopyranose (14) in an overall yield of 36%. Reaction of 4 with thionyl chloride gave a mixture of the diastereomeric cyclic sulfites, the structures of which were established by X-ray crystallography. Their oxidation with sodium periodate afforded the corresponding cyclic sulfate 23. Treatment of 23 with potassium thioacetate gave the potassium salt of 5-S-acetyl-1,2-O-isopropylidene-alpha-D-xylofuranose 3-O-sulfonic acid (26) which, after methanolysis, acetylation and subsequent acetolysis afforded 14 in an overall yield of 56%. Treatment of 4 with sulfuryl chloride gave a mixture containing 5-chloro-3-O-chlorosulfonyl-5-deoxy-1,2-O-isopropylidene-alpha-D- xylofuranose, 3,7,9,11-tetraoxa-4-thia-10-dimethyl-tricyclo[6,3,0, 0(2,6)]undecane S-dioxide and 23 in a 2:3:7 ratio. Tetraacetate 14 was converted into the alpha-1-bromide 18 as well as into the alpha-1-O-trichloroacetimidate 17. These three compounds were used as donors for the glycosylation with 4-cyanothiophenol, affording the 4-cyanophenyl 2,3,4-tri-O-acetyl-1,5-dithio-alpha- (29) and beta-D-xylopyranoside (30) in different ratios, depending on the reaction conditions. When donor 18 was used in the presence of potassium carbonate, besides 29 and 30 two aryl C-glycosylated-thioglycosides, i.e. 4-cyano-2-(2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranosyl)phenyl 2,3,4-tri-O-acetyl-1,5-dithio-alpha- and beta-D-xylopyranoside (32 and 33) as well as 4-cyano-2-(2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranosyl)phenyl disulfide 34 could be isolated as byproducts. Deacetylation of 30 with sodium methoxide in methanol afforded, besides 4-cyano-phenyl 1,5-dithio-beta-D-xylopyranoside (1), the corresponding 4-[(methoxy)(imino)methyl]phenyl glycoside 2. The 4-cyano group of 1 was converted into the 4-aminothiocarbonyl, the 4-(methyl-thio)(imino)methyl, the 4-amidino and the 4-(imino)(hydrazino)methyl group. All of these glycosides showed a significant antithrombotic activity on rats.

Condensation of 5-thio-D-glucopyranose pentaacetate with 4-cyanobenzenethiol, in the presence of trimethylsilyl triflate, gave 4-cyanophenyl 2,3,4,6-tetra-O-acetyl-1,5-dithio-alpha-D-glucopyranoside 7 and 3,4,6-tri-O-acetyl-2,5-anhydro-5-thio-D-mannose bis(4-cyanophenyl) dithioacetal 9 in a 2:3 ratio. The latter is probably formed from the 4-cyanophenyl 2,3,4,6-tetra-O-acetyl-1,5-dithio-beta-D-glucopyranoside 6 via a transannular participation of the ring sulfur atom. When 2,3,4,6-tetra-O-acetyl-5-thio-alpha-D-glucopyranosyl bromide was used as donor and the reaction was carried out in the presence of potassium carbonate, 6, 7, 4-cyano-2-(2,3,4,6-tetra-O-acetyl-5-thio-alpha-D-glucopyranosyl)phenyl and 4-cyano-2-(2,3,4,6-tetra-O-acetyl-5-thio-beta-D-glucopyranosyl)phenyl 1,5-dithio-beta-D-glucopyranoside (14 and 16) were formed in a 23:4:2:1 ratio. The mechanism of formation of 14 and 16 is discussed. Condensation of 2,3,4,-tri-O-acetyl-6-deoxy-5-thio-alpha-D-glucopyranosyl bromide with 4-cyanobenzenethiol in the presence of potassium carbonate gave 4-cyanophenyl 2,3,4-tri-acetyl-6-deoxy-1,5-dithio-alpha- and beta-D-glucopyranoside (29 and 30) as well as 4-cyano-2-(2,3,4-tri-O-acetyl-6-deoxy-5-thio-alpha-D-glucopyranosyl)phen yl 2,3,4-tri-O-acetyl-6-deoxy-1,5-dithio-beta-D-glucopyranoside in a ratio of approximately 1:8:1. Compound 30 could be obtained in a higher overall yield using 2 as starting material and converting it via its 4-cyanophenyl 2,3,4-tri-O-acetyl-6-O-methanesulfonyl-1,5-dithio-beta-D-glucopyranoside derivative into the 4-cyanophenyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-1,5-dithio-beta-D-glucopyranoside 33 which gave 30 on reduction with sodium borohydride-nickel(II) chloride. Treatment of 33 with silver acetate gave 4-cyanophenyl 2,3,4-tri-O-acetyl-6-deoxy-1,5-dithio-beta-D-xylo-hex-5-enopyranoside 35. The compounds obtained on deacetylation of 6, 9, 14, 30 and 35 showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference.

L-Arabinose diethyl dithioacetal was converted, via its 4-azido-5-S-benzoyl-4-deoxy-2,3-O-isopropylidene-5-thio-D-xylose diethyl dithioacetal, into 4-azido-4-deoxy-5-thio-alpha-D-xylo-pyranose triacetate 29. Glycosidation of 29 with 4-cyanothiophenol in the presence of trimethylsilyl triflate gave the 4-cyanophenyl 2,3-di-O-acetyl-4-azido-4-deoxy-1,2-dithio-alpha- and -beta-D-xylopyranosides 31 and 33 as well as 3-O-acetyl-2,5-anhydro-4-azido-4-deoxy-5-thio-D-lyxose bis (4-cyanophenyl) dithioacetal 34 in a 8:2:1 respective ratio. Treatment of 29 with hydrogen bromide in acetic acid yielded a 1:4 mixture of 2,3-di-O-acetyl-4-azido-4-de-oxy-5-thio-D-xylopyranosyl bromide 38 and 2,3-di-O-acetyl-5-bromo-5-deoxy-4-thio-L-arabinofuranosyl bromide 40. Reaction of the mixture of bromides 38 and 40 with 4-cyanothiophenol in the presence of potassium carbonate afforded the expected 31 and 33 only in traces, while 2-(1R,2S,-1,2-di-O-acetyl-1,2-dihydroxy-but-3-en-1-yl)-5-cyano-1, 3-benzo-dithiole and 4-cyanophenyl 2,3-di-O-acetyl-5-S-(4-cyanophenyl)-1,4,5-trithio-alpha-L-ar abinofuranoside (42) were isolated in 18% and 20% yield, respectively. The formation of these two derivatives is tentatively explained by involvement of a radical reaction mechanism. When O-(2,3-di-O-acetyl-4-azido-4-deoxy-5-thio-alpha-D-xylopyranosyl) trichloroacetimidate was used as donor and boron trifluoride ethyl etherate as promoter, 31 and 33 were formed in excellent yield (96%) in a 2:1 ratio. The glycosides, obtained on deacetylation of 33, 34 and 42 showed a significant antithrombotic activity on rats.

Three routes were investigated for the conversion of D-glucose into the title compound. In the first approach, reduction of the 5,6-thiirane ring of 5,6-dideoxy-5, 6-epithio-1,2-O-isopropylidene-alpha-D-glucofuranose (17) as well as that of its 3-O-allyl derivative (13) with lithium aluminium hydride was investigated; 17 afforded the corresponding 6-deoxy derivative besides di-, tri-, and poly-mers, whereas only polymers were formed from 13. In the second approach, the oxirane ring of 3-O-allyl-5,6-anhydro-1,2-O-isopropylidene-beta-L-idofuranose was reduced by sodium borohydride and the resulting 6-deoxy derivative was converted into the 5-thiobenzoate; the corresponding hex-4-enofuranose was formed as a byproduct. In the third approach partial mesylation of methyl 5-thio-alpha-D-glucopyranoside was attempted, but the 6-mesylate 27 could be isolated only in modest yield (28%) together with rearranged 2,5-thioanhydromannofuranoside derivatives. The mechanism of this rearrangement is discussed in detail. The 6-mesylate 27 was converted via the 6-iodo derivative into the title compound.

A series of 1,5-diaryl-3-(substituted amino)-1 H-1,2,4-triazoles was synthesized and assayed in the rat adjuvant induced arthritis model. Several compounds showed significant anti-inflammatory activity.