137892-92-3Relevant articles and documents
Synthesis and α4β2 nicotinic affinity of 2- pyrrolidinylmethoxyimines and prolinal oxime ethers
Pallavicini, Marco,Moroni, Barbara,Bolchi, Cristiano,Clementi, Francesco,Fumagalli, Laura,Gotti, Cecilia,Vailati, Silvia,Valoti, Ermanno,Villa, Luigi
, p. 5827 - 5830 (2004)
Homochiral E and Z isomers of N-methylprolinal O-isopropyloxime and (1-methyl-2-pyrrolidinyl)methoxyimines were synthesized as candidate bioisosteres of nicotine and its isoxazolic analogue ABT 418. Two of them, namely (S)-2-isopropylideneaminooxymethyl- and (Z)-(S)-2- ethylideneaminooxymethyl-1-methylpyrrolidine, proved to bind at α4β2 nicotinic acetylcholine receptor with submicromolar affinity and remarkable selectivity over α7 and muscarinic receptors thus supporting the hypothesized bioisosteric relationship between their methyloxyimino group and the aromatic heterocycles of the reference ligands.
A novel series of IKKβ inhibitors part II: Description of a potent and pharmacologically active series of analogs
Cushing, Timothy D.,Baichwal, Vijay,Berry, Karen,Billedeau, Roland,Bordunov, Viola,Broka, Chris,Browner, Michelle F.,Cardozo, Mario,Cheng, Peng,Clark, David,Dalrymple, Stacie,Degraffenreid, Michael,Gill, Adrian,Hao, Xiaolin,Hawley, Ronald C.,He, Xiao,Labadie, Sharada S.,Labelle, Marc,Lehel, Csaba,Lu, Pu-Ping,McIntosh, Joel,Miao, Shichang,Parast, Camran,Shin, Youngsook,Sjogren, Eric B.,Smith, Marie-Louise,Talamas, Francisco X.,Tonn, George,Walker, Keith M.,Walker, Nigel P.C.,Wesche, Holger,Whitehead, Chris,Wright, Matt,Jaen, Juan C.
, p. 423 - 426 (2011)
A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model.
Rigidified acetylcholine mimics: Conformational requirements for binding to neuronal nicotinic receptors
Villeneuve, Gerald,Cecyre, Danielle,Lejeune, Helene,Drouin, Marc,Lan, Ruoxi,Quirion, Remi
, p. 3847 - 3851 (2007/10/03)
Rigidified derivatives have been designed and synthesized assuming the g+t conformer of acetylcholine (N-C-C-O=+60°, C-C-O-C=180°) as active conformation for binding to cytisine sensitive neuronal nicotinic receptors. The SAR of the compounds evaluated, along with those of more flexible analogues, support the g+t conformer hypothesis and highlight the stringent steric limitation of this nicotinic receptor sub-type. Compound 3e has low μM affinity for cytisine sensitive nicotinic receptor binding sites while being selective with regard to the α-bungarotoxin sensitive subclass. We also report few compounds with μM affinity for the α-bungarotoxin sensitive subclass.
