75144-12-6Relevant academic research and scientific papers
ARALKYL DIAMINE DERIVATIVES AND USES THEREOF AS ANTIDEPRESSANTS
-
Paragraph 0165, (2013/03/28)
Aralkyl diamine derivative of the following formula, pharmaceutically acceptable salts or uses thereof as antidepressants. The derivatives have triplex inhibiting activities of the reuptake of 5-HT, dopamine and noradrenalin, which can be administered to the patients in need of such treatment in the form of compositions orally or injectedly et al.
Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain
Du, Xiaohui,Guo, Chun,Hansell, Elizabeth,Doyle, Patricia S.,Caffrey, Conor R.,Holler, Tod P.,McKerrow, James H.,Cohen, Fred E.
, p. 2695 - 2707 (2007/10/03)
American trypanosomiasis, or Chagas' disease, is the leading cause of heart disease in Latin America. Currently there is an urgent need to develop antitrypanosomal therapy due to the toxicity of existing agents and emerging drug resistance. A novel series of potent thio semicarbazone small-molecule inhibitors of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of these inhibitors have been shown to be trypanocidal. We initially discovered that 3′-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure mammalian cell cultures infected with T. cruzi. 3′-Bromopropiophenone thio semicarbazone showed no toxicity for mammalian cells at concentrations that were trypanocidal. Following this lead, more than 100 compounds were designed and synthesized. A specific structure-activity relationship (SAR) was established, and many potent analogues with IC50 values in the low nanomolar range were identified. Eight additional analogues were trypanocidal in a cell culture assay, and this indicates that aryl thio semicarbazone is a productive scaffold for killing the parasites. Kinetic studies show that these are time-dependent inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led to a proposed mechanism of interaction as well as insight into the SAR of the thio semicarbazone series. The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy.
Evaluation of some Mannich bases derived from substituted acetophenones against P-388 lymphocytic leukemia and on respiration in isolated rat liver mitochondria
Dimmock,Shyam,Hamon,Logan,Raghavan,Harwood,Smith
, p. 887 - 894 (2007/10/02)
Series of 3-dimethylamino-1-aryl-1-propanone hydrobromides (IV) and 3-dimethylamino-2-dimethylaminomethyl-1-aryl-1-propanone dihydrobromides (V) were synthesized. Evaluation of these derivatives against P-388 lymphocytic leukemia growth revealed that two compounds show promise as antineoplastic agents. Compounds of the V series were unstable in phosphate buffer (in contrast to series IV), and when the same nuclear substituent was present in both series of compounds, V was ~ 100 times more active than IV in both the stimulation and inhibition of respiration of mitochondria isolated from rat liver cells. Representatives from both series showed that respiration in mitochondria was affected by changing the pH of the aqueous buffer from 7.4 to 6.9 or 6.4 and by reducing the temperature from 37° to 20°. The compounds showed reactivity toward a biomimetic thiol.
