geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

New analogues of epiboxidine incorporating the 4,5-dihydroisoxazole nucleus: synthesis, binding affinity at neuronal nicotinic acetylcholine receptors, and molecular modeling investigations


, : New analogues of epiboxidine incorporating the 4,5-dihydroisoxazole nucleus: synthesis, binding affinity at neuronal nicotinic acetylcholine receptors, and molecular modeling investigations. Chemistry & Biodiversity 6(2): 244-259

A group of novel 4,5-dihydro-3-methylisoxazolyl derivatives, structurally related to epiboxidine (=(1R,4S,6S)-6-(3-methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane), was prepared via 1,3-dipolar cycloaddition of acetonitrile oxide to different olefins. Target compounds 1a and 1b, 2a and 2b, 3, 4, and 5 were tested for affinity at neuronal nicotinic heteromeric (alpha4beta2) and homomeric (alpha7) acetylcholine receptors. Notably, diastereoisomers 1a and 1b were characterized by a massive drop of the affinity at the alpha4beta2 subtypes (K(i) values spanning the range 4.3-126 microM), when compared with that of epiboxidine (K(i)=0.6 nM). Therefore, the replacement of the 3-methylisoxazole ring of epiboxidine with the 4,5-dihydro-3-methylisoxazole nucleus is detrimental for the affinity at alpha4beta2 receptors. A comparable lack of affinity/selectivity for the two nAChR subtypes under study was evidenced for the remaining epiboxidine-related dihydroisoxazole derivatives 2a and 2b, and 3-5. Diastereoisomers 1a and 1b, and spirocyclic derivative 3 were docked into molecular models of the receptor subtypes under study, and their binding mode was compared with that of reference ligands endowed with high binding affinity.

US$19.90

PMID: 19235154

DOI: 10.1002/cbdv.200800077


Other references

D.Lisle, Melchior O., 1967: Note on some new or little-known Coleoptera Lucanidae. Descriptions are given of Sphenognathus metallescens (Colombia), Cyclommatus speciosus var. misimaensis (Misima Island, archipelago of the Louisiades), C. subtilis (Sumatra), Prosopocoelus congoanus, P. neopomeraniesis (New Pomerania), Psalidoremu...

Anonymous, 1947: PROVIDING eye care in industry. American Journal of Nursing 47(4): 241-241

Guan, Z.; Zhang, G-min.; Ma, P.; Liu, L-hong.; Zhou, T-yan.; Lu, W., 2012: Application of Fourier amplitude sensitivity test in Chinese healthy volunteer population pharmacokinetic model of tacrolimus. In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Beside...

Wei, Z.M.; Xu, Z.H., 1990: Protoplast culture and plant regeneration of soyabean Glycine max L. and G. soja. In a study on plant regeneration of soyabeans, protoplasts isolated from immature cotyledons of 6 cultivars of Glycine max and G. soja line SH-1 were cultured on K8P liquid medium with 0.2 mg 2,4-D, 1 mg NAA and 0.5 mg ZT [zeatin]/litre. The proto...

Eanes, E.D., 1976: The interaction of supersaturated calcium phosphate solutions with apatitic substrates. The in vitro formation of calcium phosphates from supersaturated solutions seeded with apatite was examined. Reaction kinetics were followed by monitoring solution Ca, Mg, and PO4. Seeds and reaction products were examined chemically and by X-ray...

Sakai, Masaki., 1995: Mating behavior in the male cricket. Nature and Insects, 3011: 10-16

Craig, JL.; Douglas, ME., 1978: Aspects of the ecology of bellbirds on Tiritiri Island. New Zealand Journal of Ecology, 1: 178-179

Sugimoto, K-Ji.; Asahina, M.; Shimada, A.; Ichikawa, K.; Wakabayashi, M.; Sekiguchi, Y.; Izumi, H.; Ota, Y.; Komatsu, N.; Noguchi, M., 2015: IgG3 subclass-positive primary thymic MALT lymphoma without trisomy 3 and trisomy 18: report of a case and review of literature. The patient, a 42-year-old man, was diagnosed as having an anterior mediastinal tumor. Examination of the resected tumor showed findings consistent with a primary thymic mucosa-associated lymphoid tissue lymphoma, stage IA. Postoperative (18)F-flu...

Chan, W.Ling.; Pejnovic, N.; Hamilton, H.; Liew, T.Vun.; Popadic, D.; Poggi, A.; Khan, S.M., 2005: Atherosclerotic abdominal aortic aneurysm and the interaction between autologous human plaque-derived vascular smooth muscle cells, type 1 NKT, and helper T cells. Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic, and inflammatory nature of this disease of the cardiovascular system complicates targ...

Nakahara, S., 1997: Scirtothrips perseae (Thysanoptera: Thripidae), a new species infesting avocado in southern California. Scirtothrips perseae sp. nov. is described. It is a pest of avocado in southern California.