13886-01-6Relevant academic research and scientific papers
Discovery of a potent non-oxime reactivator of nerve agent inhibited human acetylcholinesterase
de Koning, Martijn Constantijn,Horn, Gabriele,Worek, Franz,van Grol, Marco
, p. 151 - 160 (2018/08/10)
Organophosphorous (OP) compounds (such as nerve agents) inhibit the enzyme acetylcholinesterase (AChE) by covalent phosphylation of a key serine residue in the active site of the enzyme resulting in severe symptoms and ultimately death. OP intoxications are currently treated by administration of certain oxime compounds. The presently fielded oximes reactivate OP-inhibited AChE by liberating the phosphylated serine. Recent research towards new reactivators was predominantly devoted to design, synthesis and evaluation of new oxime-based compounds dedicated to overcoming some of the major limitations such as their intrinsic toxicity, their permanent charge which thwarts penetration of brain tissues and their inability to effectively reactivate all types of nerve agent inhibited AChEs. However, in over six decades of research only limited success has been achieved, indicating that there is a need for alternative classes of compounds that could reactivate OP-inhibited AChE. Recently, a number of non-oxime compounds was discovered in which the 4-amino-2-((diethylamino)methyl)phenol (ADOC) motif proved to be able to reactivate OP-inhibited AChE to some extent. In this paper several structural derivatives of ADOC were synthesized and screened for their ability to reactivate human AChE (hAChE) inhibited by the nerve agents VX, sarin, tabun, cyclosarin and paraoxon. We here disclose that one of those compounds showed a remarkable ability to reactivate OP-inhibited hAChE in vitro and that it is the most potent non-oxime reported to date.
Aromatic amino analogues of artemisinin: Synthesis and in vivo antimalarial activity
Sriram, Dharmarajan,Devakaram, Ruth Vandana,Dinakaran, Murugesan,Yogeeswari, Perumal
supporting information; experimental part, p. 524 - 532 (2011/10/31)
Nine orally active novel artemisinin derivatives were prepared from artemisinin by four-step synthesis, and the compounds were evaluated in the rodent model using multidrug resistant Plasmodium yoelii nigeriensis. All of the compounds exhibited antimalarial activities with the ED50 ranging from 5.41 mg/kg-12.4 mg/kg. Among them, artemisinin derivative bearing N-(4-hydroxy-3- ((4-phenylpiperazin-1-yl)methyl)phenyl) moiety (5f) was found to be the most active compound and was found to be three times more potent than artemisinin (ED50 16.4 mg/kg). Birkhaeuser Boston 2009.
Pyrido[3,2-b]indol-4-yl-amines - Synthesis and investigation of activity against malaria
Goerlitzer,Kramer,Meyer,Walter,Jomaa,Wiesner
, p. 243 - 250 (2007/10/03)
Starting with 3-aminoindole-2-carboxylic acid ester 1 the annulated pyrido[3,2-b]indoles 6 and 8 were synthesized as key substances. The 4-chloropyridine derivative 8 reacted with the phenol Mannich bases 11 and the novaldiamine base 13, respectively, to yield the amodiaquine and cycloquine analogues 12 as well as the chloroquine analogue 14. The stability of the compounds 12 and 14 were proven by the half wave potentials measured by differential pulse voltammetry. Compounds 12 and 14 were tested for in vitro antimalarial activity using a chloroquine sensitive and a chloroquine resistant Plasmodium falciparum strain. The highest activity was shown by 12g with IC 50 values of 50 nM and 38 nM, respectively. The in vivo activity of 12g was tested in Plasmodium vinckei infected mice resulting in ED50 values of 22 mg/kg and 26 mg/kg after intraperitoneal and oral administration, respectively.
Microwave-induced Mannich reaction - Synthesis of some Mannich derivatives of p-aminophenol
Mahesh,Perumal, R. Venkatesha
, p. 1012 - 1014 (2007/10/03)
Mono and bis substituted dialkylamino alkyl-p-aminophenol 3 are prepared by treating paracetamol 1 with formaldehyde and appropriate secondary amines followed by deacetylation using 6 M HCI in unmodified domestic microwave oven in unsealed borosil vessels
Synthesis of new arylaminoquinoxalines and their antimalarial activity in mice
Rangisetty,Gupta,Prasad,Srinivas,Sridhar,Parimoo,Veeranjaneyulu
, p. 1409 - 1413 (2007/10/03)
2-Arylaminoquinoxalines were prepared by the condensation of 2-chloroquinoxaline with the appropriate Mannich bases in the presence of HCI. To synthesize the Mannich bases, 4-acetamidophenol was reacted with formaldehyde and dialkylamine to yield 3-[(dial
Isoquinolylquinoline Derivatives: Part IV - Synthesis of Some 4-Substituted 3-(3',4'-Dihydro-3'-methyl-1'-isoquinolyl)-7-chloroquinoline Derivatives as Possible Trypanocidal Agents
Das, Michael,Chaudhuri, Subhankar,Ray, Manotosh R.,Chakravorti, S. S.
, p. 1072 - 1078 (2007/10/02)
Cyclisation of the amide Ib using PPA and POCl3 affords the corresponding 3-methyl-3,4-dihydroisoquinolylquinoline derivative (IIIa) which on treatment with POCl3 is converted into IIIb.This compound (IIIb) reacts with ammonia (gas), hydrazine hydrate, mo
