15285-16-2Relevant academic research and scientific papers
Nucleophilic ring-opening of the azole and azine moieties in 6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-ones
Ulomsky,Voronin,Rusinov,Chupakhin
, p. 682 - 688 (2007/10/03)
The effects of the nature of the nucleophile and the structure of 6-nitrotriazolo[1,5-a]pyrimidinones on the direction of the ring opening were investigated. The triazole ring is opened under the action of strong bases, such as alkoxides or alkalis, to form 2-cyanoaminopyrimidinones and then 2-aminopyrimidinones. The results of the reactions with N-nucleophiles depend on the accessibility of position 5 of the heterocycle. Thus, sterically hindered secondary amines react with 5-methyltriazolopyrimidinones to give 2-guanidinopyrimidinones and then 2-aminopyrimidinones. In the absence of a substituent at position 5, the azine ring is opened to form 4-alkyl-3-amino-1,2,4-triazoles and 3-amino-2-nitroacrylamides. Under the action of primary amines, only the pyrimidine fragment is cleaved.
Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia
Naito, Youichiro,Akahoshi, Fumihiko,Takeda, Shinji,Okada, Takehiro,Kajii, Masahiko,Nishimura, Hiroko,Sugiura, Masanori,Fukaya, Chikara,Kagitani, Yoshio
, p. 3019 - 3029 (2007/10/03)
In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1- [(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the airway through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1- [(methylamino)(thiocarbonyl)]-1H-triazole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally (ip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD50 value of >2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D4 (LTD4) or platelet-activating factor (PAF)- induced responses. Taken together, these results suggest 23c as a novel candidate for the treatment of chronic asthma. Further studies are now underway.
NITROAZINES. 15. CONTRACTION OF THE PYRIMIDINE RING IN 6-NITROAZOLOPYRIMIDINES
Rusinov, V. L.,Myasnikov, A. V.,Chupakhin, O. N.,Aleksandrov, G. G.
, p. 530 - 533 (2007/10/02)
It is shown that contraction of the pyrimidine ring occurs when 6-nitro-7-oxo-4,7-dihydroazolopyrimidines are heated with hydrazine hydrate.Complexes of 4-nitropyrazole with 5-aminoazoles, the structures of which were proved by x-ray diffraction analysis, are formed in a similar reaction of nitrosubstituted azolopyrimidines that do not contain an oxo function.
