A facile synthesis of certain 4‐ and 4,5‐disubstituted 1‐β‐d‐ribofuranosylpyrazoles

Abstract

A number of pyrazole ribonucleosides, structurally related to AICA riboside and ribavirin have been prepared and evaluated for their biological activity in vitro. Deisopropylidenation of 5‐amino‐1‐(2,3‐O‐isopropylidene‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (6) with aqueous trifluoroacetic acid gave 5‐amino‐1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (7). Conventional transformation of the carbonitrile function of 7 gave the AICA riboside congener (2) and related 5‐amino‐1‐(β‐D‐ribofuranosyl)‐pyrazoles (8–10). Acetylation of 7 at low temperature gave the versatile intermediate 5‐amino‐1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (15). Non‐aqueous diazotization of 15 with isoamylnitrite in dibromomethane or diiodomethane gave the corresponding C5‐bromo 13 and C5‐iodo 16 derivatives. Compounds 13 and 16 were subsequently transformed into 5‐bromo‐1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carboxamide (11) and the 5‐iodo analog 25. However, a similar nonaqueous diazotization of 15 in dichloromethane afforded the deaminated product 1‐(2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrazole‐4‐carbonitrile (22). Treatment of 22 with ammonium hydroxide/hydrogen peroxide gave the ribavirin congener 1‐(β‐D‐ribofuranosyl)pyrazole‐4‐carboxamide (18). Similar treatment of 22 with hydrogen sulfide in pyridine or hydroxylamine in ethanol gave the 4‐thiocarboxamide 19 and 4‐carboxamidoxime 20 derivatives, respectively. Catalytic hydrogenation of 20 afforded 1[β‐D‐ribofuranosyl)pyrazole‐4‐carboxamidine (21). These pyrazole nucleosides are devoid of any significant antiviral or antitumor activity in vitro.

Synthesis of Novel 4-(4-Methoxybenzene Sulphonyl)-3, 5-Dimethyl/3-Methyl-5-Phenyl/3, 5- Diphenyl/3, 5-Dimethyl-1-Phenyl/3- Methyl -1, 5- Diphenyl /1, 3, 5-Triphenyl Pyrazole

“…The pyrazole ring has pulled in much consideration as it has turned out to be genuinely available and indicates diverse biological activity. 1,2 The significance of pyrazole lies in the way that they can be viably utilized as antiinflammatory 3 , anticonvulsant 4 , antibacterial agents 5,6 , antitumor 7 , antiviral 8 and CNS depressant 9 . The compound contains sulphonyl group which has been a focus of attention for their diversified biological activities 10 .Sulfones involve one of a kind position in the medication business with their bactericidal 11,12 and antimalarial 13 activity.…”

Synthesis of Novel Pyrazole Derivatives From Diaryl 1,3-Diketones (Part-I)

“…The selection of pyrazole derivative in the field of clinical medicine, is undoubtedly the principal practical application that one can come across because of their considerable antitumor 8 , antiviral 9 , pesticidal 10 action. It is interest to note that pyrazoles are reported as well known pharmaceuticals 5 " 7 .…”