- Bioactivity-guided synthesis of tropine derivatives as new agonists for melatonin receptors
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Twenty-three tropine derivatives as new melatonin receptor (MT1 and MT2) agonists were synthesized and evaluated on HEK293 cells in vitro. Derivatives 1f, 1i, 1j, 1m-1s and 1t exhibited increased agonisting activities on MT1 and MT2 receptors compared to the substrate tropine. Particularly, compound 1r showed significant agonistic activities on MT1 and MT2 receptors with EC50 values of 0.20 and 0.24 mM, respectively. The preliminary structure-activity relationships (SARs) of tropine derivatives were summarized for further investigation on melatonin receptor agonists.
- Yin, Xiu-Juan,Geng, Chang-An,Huang, Xiao-Yan,Chen, Hao,Ma, Yun-Bao,Chen, Xing-Long,Sun, Chang-Li,Yang, Tong-Hua,Zhou, Jun,Zhang, Xue-Mei,Chen, Ji-Jun
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p. 45059 - 45063
(2016/06/06)
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- Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein
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Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the α7 and α4β2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes.
- Edink, Ewald,Akdemir, Atilla,Jansen, Chimed,Elk, René Van,Zuiderveld, Obbe,De Kanter, Frans J.J.,Van Muijlwijk-Koezen, Jacqueline E.,Smit, August B.,Leurs, Rob,De Esch, Iwan J.P.
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supporting information; experimental part
p. 1448 - 1454
(2012/04/04)
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- NOVEL BENZOOXAZOL- AND BENZOOXATHIOL-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel benzooxazol- and benzooxathiol-2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 10-11
(2009/04/25)
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- NOVEL PHENOXAZIN-3-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel phenoxazin-3-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 10
(2009/04/25)
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- 8-AZA-BICYCLO[3.2.1]OCTANE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel 8-aza-bicyclo[3.2.1]octane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 13
(2008/06/13)
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- Synthesis of tropeines and allosteric modulation of ionotropic glycine receptors
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Twenty esters of 3α- and 3β-hydroxy(nor)tropanes and two amides of 3α-aminotropane were prepared with substituted benzoic acids. These (nor)tropeines inhibited [3H]strychnine binding to glycine receptors in synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied to determine the dissociation constants (KA) of the tropeines having strong negative cooperativities with [3H]strychnine binding (α > 10). KA values about 10 nM are well below those of known allosteric agents. Low concentrations (0.1KA) of the (nor)tropeines potentiated the displacing effects of glycine. Positive cooperativity with glycine (β1) decreased with the increase in concentration and binding affinity of tropeines. Displacing potencies were also measured for [3H]granisetron binding to 5-HT3 type serotonin receptors of rat cerebral cortex. Selectivities to glycine receptors versus 5-HT3 receptors varied within 4 orders of magnitude. Nortropeines might serve as a lead to high-affinity selective allosteric modulators of glycine receptors.
- Maksay, Gabor,Nemes, Péter,Biró, Tímea
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p. 6384 - 6391
(2007/10/03)
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- Parallel modification of tropane alkaloids
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Various tropane alkaloids have been prepared by structural modification of the readily available natural product, scopolamine 1. Reaction of isocyanates with 6,7-dehydrotropine 5 provided a number of urethanes 6a-e. Reductive amination of tropinone 7 and subsequent reaction with isocyanates provided ureas 9a-f. Mitsunobu inversion of the C-3 alcohol of tropine 10 afforded the epimeric ester 11.
- Aberle, Nicholas S.,Ganesan,Lambert, John N.,Saubern, Simon,Smith, Reg
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p. 1975 - 1977
(2007/10/03)
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- A NEW SYNTHETIC ROUTE TO TROPANE ALKALOIDS. PSEUDOTROPINE AND TROPACOCAINE
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Pseudotropine and tropacocaine have been synthesized by a facile route involving the nitroso cycloaddition followed by internal SN2 displacement.
- Iida, Hideo,Watanabe, Yohya,Kibayashi, Chihiro
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p. 5091 - 5094
(2007/10/02)
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