4813-03-0Relevant academic research and scientific papers
Designing new antitubercular isoniazid derivatives with improved reactivity and membrane trafficking abilities
de Faria, Catarina Fraz?o,Moreira, Tania,Lopes, Pedro,Costa, Henrique,Krewall, Jessica R.,Barton, Callie M.,Santos, Susana,Goodwin, Douglas,Machado, Diana,Viveiros, Miguel,Machuqueiro, Miguel,Martins, Filomena
, (2021/10/29)
Isoniazid (INH) is one of the two most effective first-line antitubercular drugs and is still used at the present time as a scaffold for developing new compounds to fight TB. In a previous study, we have observed that an INH derivative, an hydrazide N′-substituted with a C10acyl chain, was able to counterbalance its smaller reactivity with a higher membrane permeability. This resulted in an improved performance against the most prevalent Mycobacterium tuberculosis (Mtb) resistant strain (S315T), compared to INH. In this work, we have designed two new series of INH derivatives (alkyl hydrazides and hydrazones) with promising in silico properties, namely membrane permeabilities and spontaneous IN* radical formation. The kinetics, cytotoxicity, and biological activity evaluations confirmed the in silico predictions regarding the very high reactivity of the alkyl hydrazides. The hydrazones, on the other hand, showed very similar behavior compared to INH, particularly in biological tests that take longer to complete, indicating that these compounds are being hydrolyzed back to INH. Despite their improved membrane permeabilities, the reactivities of these two series are too high, impairing their overall performance. Nevertheless, the systematic data gathered about these compounds have showed us the need to find a balance between lipophilicity and reactivity, which is paramount to devise better INH-based derivatives aimed at circumventing Mtb resistance.
Synthesis and analgesic activity of new pyridine-based heterocyclic derivatives
Nigade, Ganesh,Chavan, Pradeep,Deodhar, Meenakshi
experimental part, p. 27 - 37 (2012/06/01)
A series of new heterocyclic derivatives having a pyridine nucleus were synthesized. 4-(5-(2-Chlorophenyl)- 4H-1,2,4-triazol-3-yl)pyridine (7c) and 4-(5-(2- Nitrophenyl)-4H-1,2,4-triazol-3-yl)pyridine (7d) presented the best analgesic profie of this series in hot-plate, tail-flick, and formalin-induced licking tests, which was partially prevented by pretreatment with mecamylamine, a nicotinic receptor antagonist. Springer Science+Business Media, LLC 2010.
Cyclothiomethylation of carboxylic acid hydrazides with aldehydes and H2S
Akhmetova,Khairullina,Tyumkina,Nelyubina,Smol'yakov,Bushmarinov,Starikova,Abdullin,Kunakova
experimental part, p. 425 - 433 (2011/02/16)
The cyclothiomethylation of carboxylic acid hydrazides RCONHNH2 (R = C5H4N, Ph, 2-MeOC6H4, or 4-HOC6H4CH2) with formaldehyde and H 2S at 70 °C affords predo
Triorganotin(IV) Complexes of Isonicotinoyl Hydrazones
Chauhan, A. K. S.,Mishra, Brajesh
, p. 234 - 235 (2007/10/02)
Five-coordinated triorganotin(IV) complexes of isonicotinoyl hydrazones (LH) of various aldehydes or ketones with the formula R3SnL (where R=Bu, Ph, or Bz and L=anion of the hydrazone) have been synthesised.The complexes are monomeric in benzene and non-electrolytes in methanol; they have been assigned trigonal-bipyramidal geometry.
