31954-92-4Relevant academic research and scientific papers
Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands
Imming, Peter,Klaperski, Paul,Stubbs, Milton T,Seitz, Gunther,Guendisch, Daniela
, p. 375 - 388 (2001)
We have developed one-step syntheses of halogenated derivatives of (-)-cytisine featuring a halogen substituent at positions 3, 5 or 3 and 5 of the 2-pyridone fragment, and prepared the novel bioisosteric thiocytisine by oxygen-sulphur exchange. The affinities of these pyridone-modified analogs of (-)-cytisine for (α4)2(β2)3 and α7* nAChRs in rat forebrain membranes were determined by competition with (±)-[3H]epibatidine and [3H]MLA, respectively. The 3-halocytisines 7 possess subnanomolar affinities for (α4)2(β2)3 nAChRs, higher than those found for (-)-cytisine as well as for the 5-halocytisines 8 and 3,5-dihalocytisines 6. In contrast to the parent alkaloid the 3-halogenated species display much a higher affinity for the α7* nAChR subtype. The most potent molecule was 3-bromocytisine (7b) with preferential selectivity (200-fold) for the (α4)2(β2)3 subtype [Ki = 10 pM (α4β2) and 2.0 nM (α7*)]. Replacement of the lactam with a thiolactam pharmacophore to thiocytisine (12) resulted in a subnanomolar affinity for the (α4)2(β2)3 nAChR subtype (Ki = 0.832 nM), but in a drastic decrease of affinity for the α7* subtype; thiocytisine (12) has a Ki value of 4000 nM (α7*), giving a selectivity of 4800-fold for the neuronal (α4)2(β2)3-nAChR and thus displaying the best affinity-selectivity profile in the series under consideration.
New 12-N-β-hydroxyethylcytisine derivatives with potential antiarrhythmic activity
Tsypysheva,Koval'Skaya,Khalilova,Bakhtina, Yu.,Khisamutdinova,Gabdrakhmanova,Lobov,Zarudii,Yunusov
, p. 333 - 336 (2014/07/08)
12-N-β-Hydroxyethylcytisine derivatives containing Cl, Br, and nitro groups on the 2-pyridone core were synthesized. Their antiarrhythmic activity was studied in vivo.
In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: Implications for Parkinson's Disease
Abin-Carriquiry, J. Andres,Costa, Gustavo,Urbanavicius, Jessika,Cassels, Bruce K.,Rebolledo-Fuentes, Marco,Wonnacott, Susan,Dajas, Federico
, p. 80 - 84 (2008/12/22)
Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's Disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-l-phenylalanine-induced dyskinesias an
