- Method for synthesizing carboxamide triazole
-
The invention relates to a method for synthesizing carboxamide triazole. The method for synthesizing carboxamide triazole comprises the following steps: (1) sequentially carrying out halogenation reaction and azide substitution reaction by adopting a one-
- -
-
Paragraph 0046-0053
(2021/02/13)
-
- Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex i
-
Disruption of mitochondrial function selectively targets tumour cells that are dependent on oxidative phosphorylation. However, due to their high energy demands, cardiac cells are disproportionately targeted by mitochondrial toxins resulting in a loss of cardiac function. An analysis of the effects of mubritinib on cardiac cells showed that this drug did not inhibit HER2 as reported, but directly inhibits mitochondrial respiratory complex I, reducing cardiac-cell beat rate, with prolonged exposure resulting in cell death. We used a library of chemical variants of mubritinib and showed that modifying the 1H-1,2,3-triazole altered complex I inhibition, identifying the heterocyclic 1,3-nitrogen motif as the toxicophore. The same toxicophore is present in a second anti-cancer therapeutic carboxyamidotriazole (CAI) and we demonstrate that CAI also functions through complex I inhibition, mediated by the toxicophore. Complex I inhibition is directly linked to anti-cancer cell activity, with toxicophore modification ablating the desired effects of these compounds on cancer cell proliferation and apoptosis.
- Allen, Timothy E. H.,Chung, Injae,Fischer, Peter,Hardy, Rachel,Harvey, Robert F.,Hirst, Judy,Kellam, Barrie,Macfarlane, Marion,Mistry, Sarah,Pryde, Kenneth R.,Serreli, Riccardo,Stephenson, Zo? A.,Stoneley, Mark,Willis, Anne E.
-
-
- Preparation of Solid Polyfunctional Alkynylzinc Pivalates with Enhanced Air and Moisture Stability for Organic Synthesis
-
We report the preparation of solid and air-stable polyfunctionalized alkynylzinc pivalates from the corresponding alkynes using TMPZnOPiv (TMP=2,2,6,6-tetramethylpiperidyl) as base. These organozinc pivalates are obtained as powders under mild conditions
- Chen, Yi-Hung,Tüllmann, Carl Phillip,Ellwart, Mario,Knochel, Paul
-
supporting information
p. 9236 - 9239
(2017/07/24)
-
- Novel compositions and processes for preparing 5-amino or substituted amino 1,2,3-triazoles and triazoles orotate formulations
-
New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of
- -
-
-
- NOVEL COMPOSITIONS AND PROCESSES FOR PREPARING 5-AMINO OR SUBSTITUTED AMINO 1,2,3-TRIAZOLES AND TRIAZOLE OROTATE FORMULATIONS
-
New polymorphs of 5-amino or substituted amino 1, 2, 3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes o
- -
-
-
- Benzylated 1,2,3-triazoles as anticoccidiostats
-
Substituted 5-amino-4-carbamoyl-1,2,3-triazoles 3a-w were prepared by two synthetic schemes and evaluated in vivo for anticoccidial activity. Both schemes proceeded by brominating appropriately substituted toluenes 4a-s,v to 5a-s,v. In Scheme I, the brominated benzyl analogues 5 were converted to the corresponding benzyl azides 6, which were treated with cyanoacetamide to yield 1-substituted-5-amino-4-carbamoyl-1,2,3-triazoles 3. In Scheme II, the benzyl halides 5 were employed to alkylate the sodium salt of 5-amino-4-carbamoyl-1,2,3-triazole (7). Preliminary screening data against Eimeria acervulina and E. tenella in chickens suggested structural requirements for maximizing activity. Further evaluation against a relatively resistant series of eight Eimeria field isolates revealed L-651,582 (3a) to be a highly effective coccidiostat. However, unacceptable tissue residues precluded further development. Mechanistic studies on this series of 5-amino-4-carbamoyl-1,2,3-triazoles and, in particular, on L-651,582 (3a) revealed that its mode of action does not involve inhibition of IMP dehydrogenase, but probably interferes with host cell calcium entry. In addition, L-651,582 has been found to have antiproliferative activity in several disease models and was recently reported to possess antimetastatic activity in a model of ovarian cancer progression.
- Bochis,Chabala,Harris,Peterson,Barash,Beattie,Brown,Graham,Waksmunski,Tischler,Joshua,Smith,Colwell,Wyvratt Jr.,Fisher,Tamas,Nicolich,Schleim,Wilks
-
p. 2843 - 2852
(2007/10/02)
-
- An Improved Procedure for the Preparation of 1-Benzyl-1H-1,2,3-triazoles from Benzyl Azides.
-
A procedure for the preparation of substituted 1-benzyl-1H-1,2,3-triazoles from benzyl azides under very mild conditions is described.The method provides improved yields and extends the scope of the Dimroth Reaction to other types of active methylene compound to those previously used.Benzyl azides react with active methylene compounds in dimethyl sulphoxide catalysed by potassium carbonate at 35-40 deg C to give 1H-1,2,3-triazoles usually in good yield.Acetonitrile derivatives gave 5-amino-1H-1,2,3-triazoles whereas diethyl malonate gave 5-hydroxy-1H-1,2,3-triazoles. 1H-1,2,3-Triazole-4-carboxylate esters and 1H-1,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and β-diketones respectively.Benzyl methyl ketone reacted to give 5-methyl-4-phenyl-1H-1,2,3-triazole, but acetone and acetophenone failed to react.Other active methylene compounds which did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate and ethyl nitroacetate.
- Cottrell, Ian F.,Hands, David,Houghton, Peter G.,Humphrey, Guy R.,Wright, Stanley H. B.
-
p. 301 - 304
(2007/10/02)
-
- 5-amino or substituted amino 1,2,3-triazoles
-
Novel 5-amino or substituted amino 1,2,3-triazoles are disclosed as having anticoccidial activity. The compounds are useful for controlling coccidiosis when administered in minor quantities to animals, in particular to poultry, usually in admixture with a
- -
-
-