Synthesis and antimitotic properties of ortho-substituted polymethoxydiarylazolopyrimidines

Abstract

Ortho-substituted polymethoxydiarylazolopyrimidines were synthesized using polymethoxysubstituted benzaldehydes and acetophenones as starting material. X-ray crystallography data clearly confirmed that the subsequent cyclization of 3-amino-1,2,4-triazole with ketoaldehydes yielded polymethoxyphenylsubstituted 6,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines as single isomers. All compounds were evaluated in vivo using phenotypic sea urchin embryo assay. 6-(4-Methoxyphenyl)-7-(3,4,5-trimethoxyphenyl)pyrazolo [1,5-a]pyrimidine showed antimitotic microtubule destabilizing activity. The importance of aryl rings substituents in diaryltriazolopyrimidines for their antiproliferative antitubulin effect has been suggested.

Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents

“… a Reagents and conditions: (a) ref ; (b) NaOH–EtOH, rt, 24 h; (c) AcCl–Pyridine, CH 2 Cl 2 , rt, 3 h; (d) PhI­(OAc) 2 , MeOH–H + , rt, 8 h; (e) EtOH–H + , N 2 H 4 ·2HCl, reflux, 1 h; (f) EtOH–H + , NH 2 OH·HCl, reflux, 2 h. …”

“…Solvents, benzaldehydes, and ethyl bromoacetate were purchased from Acros Organics (Belgium) at the highest commercial quality and used as received. Synthesis of aldehydes, acids, benzylic alcohols, benzyl chlorides, benzoyl chlorides, and acetophenones was described earlier. ,, 3-Amino-4,5-diarylpyrazoles 2 , 3-amino-4,5-diarylisoxazoles 4 , 5-amino-3,4-diarylisoxazoles 6 , 3,4-diarylisoxazoles 5 , and diaryl-1,2,3-triazoles 7 – 9 were synthesized according to published procedures. For safe handling of compounds, the recommendations described in CA4MSDS were used, including description of first aid measures, extinguishing media, accidental release measures, handling, storage, exposure controls, and personal protection…”

“…For safe handling of compounds, the recommendations described in CA4MSDS were used, including description of first aid measures, extinguishing media, accidental release measures, handling, storage, exposure controls, and personal protection. 76 General Procedure for the Preparation of Chalcones 13.. 64,77 NaOH (60 mmol) was added to a vigorously stirred solution of benzaldehyde 11 (20 mmol) and arylacetophenone 12 (20 mmol) in EtOH (150 mL) at +5 °C (ice bath). The reaction mixture was stirred at room temperature for 24 h, concentrated in vacuo, the residue was treated with distilled water (130 mL), neutralized with 15% HCl, and extracted with CH 2 Cl 2 (3 × 80 mL).…”