61862-66-6Relevant academic research and scientific papers
A long-range tautomeric effect on a new Schiff isoniazid analogue, evidenced by NMR study and X-ray crystallography
Tǎnase, Constantin I.,Drǎghici, Constantin,Shova, Sergiu,Hanganu, Anamaria,Gal, Emese,Munteanu, Cristian V. A.
, p. 14459 - 14468 (2018/08/29)
Long-range tautomerism to a N,O-aminal thereby closing a tetrahydrofuran ring was evidenced for an isoniazid analogue, whose accidental synthesis is presented in the paper. The isoniazid analogue was synthesized by the reaction of isoniazid with 2-hydroxy-tetrahydrofuran which was demonstrated to exist in old THF together with other peroxides, especially 2-HOO-THF. The same compound was efficiently obtained from a THF containing 2-HOO-THF, by reducing this peroxide in the presence of isoniazid. The 2,4-dinitrophenylhydrazone was also synthesized. The oxidation of 1,4-butanediol and the reaction of the resulting mono-aldehyde with isoniazid gave the same compound. The existence of the linear tautomer was evidenced in the NMR spectra in DMSO-d6 and was confirmed by X-ray analysis to be the single tautomer in the crystal. The cyclic N,O-aminal tautomer was found in the NMR spectra in CDCl3, resulting from an intramolecular HCl-catalyzed addition of the hydroxyl group to the double bond CHN of the linear tautomer, thereby closing a tetrahydrofuran ring. This is a favoured cyclization according to Baldwin's rules (5-exo-trig). The same tautomerism was also present for two isoniazid analogues obtained from two lactols, used in prostaglandin synthesis. The compounds 1, 4, 6 and INH had no antibacterial or antifungal activity.
Formation pathways of γ-butyrolactone from the furan ring of tegafur during its conversion to 5-fluorouracil
Yamamiya, Ikuo,Yoshisue, Kunihiro,Matsushima, Eiji,Nagayama, Sekio
scheme or table, p. 1267 - 1276 (2011/05/05)
Tegafur (FT) is a 5-fluorouracil (5-FU) prodrug that has been clinically used for various cancer chemotherapies. The following metabolites of FT were identified in patients: 5-FU, fluoro-β-alanine, and γ-butyrolactone (GBL) and its acidic form, γ-hydroxybutyrate (GHB). GBL/GHB, which is probably generated from the furan ring of FT, inhibits tumor cell angiogenesis, contributing to the antitumor effect of FT-based therapies. In the present study, we identified the metabolites formed from the furan ring of FT by CYP2A6 and thymidine phosphorylase (TPase) using 2,4-dinitrophenylhydrazine derivatization procedures and clarified the metabolic pathway of FT to GBL/GHB. Succinaldehyde (SA) and 4-hydroxybutanal (4-OH-BTL) were produced as the metabolites because of the cleavage of the furan ring of FT during its conversion to 5-FU in cDNA-expressed CYP2A6 and purified TPase, respectively; however, GBL/GHB was hardly detected in cDNA-expressed CYP2A6 and purified TPase. GBL/GHB was formed after human hepatic microsomes or cDNA-expressed CYP2A6 mixed with cytosol were incubated with FT. Furthermore, 4-OH-BTL was converted to GBL/GHB in the microsomes and cytosol. These results suggest that GBL/GHB is generated from FT through the formation of SA and 4-OH-BTL but not directly from FT. Furthermore, the amount of 5-FU and GBL/GHB formed in the hepatic S9 was markedly decreased in the presence of a CYP2A6 inhibitor, suggesting that GBL/GHB may be mainly generated through the CYP2A6-mediated formation of SA. Copyright
Cyclic α-acetoxynitrosamines: Mechanisms of decomposition and stability of α-hydroxynitrosamine and nitrosiminium ion reactive intermediates
Chahoua, Latifa,Cai, Hongliang,Fishbein, James C.
, p. 5161 - 5169 (2007/10/03)
A study of the kinetics and mechanism of the decay of α-acetoxy-N- nitrosopyrrolidine and α-acetoxy-N-nitrosopiperidine are reported. The compounds differ in reactivity by more than 2 orders of magnitude at physiological pH. On the basis of thermodynamic
