Acetylcholinesterase inhibitors design

Mary, A., Renko, D. Z., Guillou, C., Thai, C. Potent acetylcholinesterase inhibitors design, synthesis, and structure-activity relationships of te-interacting ligands in the galanthamine series. Bioorg. Med. Chem. 1998, 6, 1835-1850. 

SippL, W., Contreras, J.M., Parrot, I., Rival, Y.M., and Wermuth, C.G. Stmcture-based 3D QSAR and design of novel acetylcholinesterase inhibitors. 

Rival RM, Wermuth CG. Design, synthesis and structure-activity relationships of a series of 3-[2-(l-benzylpiperi-din-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. 

FIFRA microcosm experimental unit. An example of a microcosm experimental unit designed to test the effects of a herbicide on an aquatic environment. This particular setup does not include fish since the predatory effects would tend to hide lower trophic level effects upon the invertebrate populations. Typically, a FIFRA microcosm experiment includes fish species, especially when acetylcholinesterase inhibitors or other toxicants particularly effective against animal species are tested. 

Based on a molecular design strategy derived from rationalizations concerning the topography of the catalytic area of acetylcholinesterase, inhibitors based on compounds (266) and (267) were identified (335, 336). Study of an extended series (structure 268 and congeners of 266 and 267) revealed that one compound (268 R = H Y = H / = 3 and... 

Design, synthesis, and assessment of anticholinesterase activity of 2-(2-(4-Renzylpiperazin-l-yl)ethyl)isoindoline-l,3-dione derivatives showed that some of these compounds can function as potential acetylcholinesterase inhibitors with a potency comparable to that of donepezil [170]. 

Valasani KR, Chaney MO, Day VW, Shidu Yan S (2013) Acetylcholinesterase inhibitors Structure based design, synthesis, pharmacophore modeling, and virtual screening. J Chem Inf Model 53 2033-2046... 

Shen Y, Li B, Xu H, Zhang G (2013) Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors. Pharmazie 68 307-310... 

The design of bifunctional acetylcholinesterase inhibitors was achieved in order to obtain potent and selective derivatives. Bis-tetrahydroaminacrine showed a simultaneous interaction with the active site and the peripheral site (allosteric site) of the enzyme resulting in an improvement of potency and selectivity. ... 

Acetylcholinesterase inhibitors has been a productive approach in the design of insecticides starting with the phosphate esters such as malathion and continuing on to carbamate esters such as carbaryl. For the latter, leads came from two carbamate reversible cholinesterase inhibitors used in medicine, the natural product physostigmine and the synthetic derivative, neostigmine. 

Contreras, J. M., Parrot, 1., Sippl, W., Rival, Y. M., Wermuth, C. G. Design, synthesis, and structure-activity relationships of a series of 3-[2-(l-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors. J. Med. Chem. 2001, 44(17), 2707-2718. 

For example, acetylcholinesterase inhibitor galanthamine and anticancerous agent narciclasine and crinine, could be produced commercially by such newly designed plant breeding programs. 

Pastorin G, Marchesan S, Hoebeke J, Da Ros T, Ehret-Sabatier L, Briand J-P, Prato M, Bianco A (2006) Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase. Org. Biomol. Chem. 4 2556-2562. 

In this self-inhibition study, three stealth inhibitors, compounds 14, 15, and 16, were designed and used in the dynamic systems (Scheme 8). A11 structures were designed to contain an aromatic moiety and appended sulfonate groups in order to be easily soluble in aqueous solution. Dithiolesters 14 and 15 were functionalized in the para- and meta-positions, respectively, while compound 16 was monofunc-tionalized. These compounds were challenged with acetylcholinesterase in the dynamic system in neutral buffer solution, and the reactions were followed by... 

In a discovery project that is reminiscent of the discovery of captopril, scientists at Takeda created a hypothetical structure for the active site of acetylcholinesterase, based on SAR from previous biochemical and medicinal chemical work (141). The model consisted of (in addition to the serine protease-like catalytic machinery) an anionic binding site separating two discrete hydrophobic binding sites. This model was then used to design inhibitors of the enzyme (reviewed i n ref. 142). One set of analogs examined were based on the N-((o-phthalimidylalkyl)-iV-(a)-phenylalkyl)-amine (scaffold 66). An iterative process of testing. 

Of an extensive series of 1-benzyl-4-[2-(/V -benzoylamino)ethyl]piperidme derivatives, designed and evaluated as inhibitors of acetylcholinesterase, the sulfone derivative (273) was the most potent (342). 

A new series of acetophenone derivatives which possess alkyl-amine side chains were designed, synthesized, and assayed as acetylcholinesterase and butyrylcholinesterase inhibitors [183],... 

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