共查询到20条相似文献,搜索用时 0 毫秒
1.
Monique Math-Allainmat Marie Le Gall Carole Jellimann Jean Andrieux Michel Langlois 《Bioorganic & medicinal chemistry》1999,7(12):954-2952
Naphthalene melatoninergic ligands with alkyl groups (Me, Et, Pr, Bz) in the β position of the ethylamido chain were synthesised. The affinity of the compounds for chicken brain melatonin receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. An increase in the affinity was observed with the β-methyl derivatives and the greatest increase was seen with the (−) enantiomers. The introduction of a 2- or 7-MeO group on the naphthalene ring and the lengthening (Et, Pr) of the alkylamido chain gave potent compounds such as (−)1h (Ki=24 pM). The functional activity of these compounds was evaluated by the aggregation of melanophores in Xenopus laevis tadpoles. The potency to produce lightening of the skin of Xenopus laevis was related to the affinities values of the molecules at melatonin chicken brain receptors. The most potent ligands were found to be full agonists and compound 1h was 25 fold more potent than melatonin in this bioassay. 相似文献
2.
Poissonnier-Durieux S Ettaoussi M Pérès B Boutin JA Audinot V Bennejean C Delagrange P Caignard DH Renard P Berthelot P Lesieur D Yous S 《Bioorganic & medicinal chemistry》2008,16(18):8339-8348
A series of naphthalenic analogues of melatonin were prepared and evaluated as melatonin receptor MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable variations of the C-3 phenyl and the acyl group on the C-1 side chain. Surprisingly, in contrast with what had been previously described in other series (2-benzylindoles, 2-benzylbenzofurans and 3-phenyltetralins), the presence of a C-3 phenyl with a functional group on the meta position seems to be primordial for MT(2) affinity and selectivity. Indeed, N-[2-(3-(3-hydroxymethylphenyl)-7-methoxynaphth-1-yl)ethyl]acetamide (21) is one of the best MT(2) selective ligands described until now and behaves as an antagonist. 相似文献
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《Bioorganic & medicinal chemistry letters》2014,24(4):1026-1030
Novel small molecule HDM2 inhibitor, substituted piperidine, was identified. Initial SAR study indicated potential for several position optimizations. Additional potency enhancement was achieved by introducing a sidechain off the aromatic ring. DMPK study of one of the active compounds has shown a moderate oral PK and reasonable bioavailability. 相似文献
5.
Martin Dunkel Vivian Reither Susanne Ebel-Will János Ludwig 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):799-801
Abstract 2′-Difluoromethyl modified nucleoside analogs 4 and 9 have been prepared and converted into phosphoramidites for the incorporation into hammerhead ribozymes. 相似文献
6.
Amaresh Mishra Christian Uhrich Egon Reinold Martin Pfeiffer Peter Bäuerle 《Liver Transplantation》2011,1(2):265-273
We report the synthesis of novel acceptor‐substituted oligothiophenes and their application in m‐i‐p type planar heterojunction solar cells. Optical absorption spectra and electrochemical properties of the dyes are investigated. The determined energy levels of these dyes suggest that they should be ideal for use in heterojunction solar cells. We further investigate the influence of acceptor groups on the device performance by introducing 1,1‐dicyano‐2‐methyl‐vinyl and 1,1‐dicyano‐2‐phenyl‐vinyl groups, respectively, as acceptor units. Photovoltaic devices incorporating these dyes show an open circuit voltage of up to 0.96 V and power conversion efficiencies in the range of 1.5–3.0% under full sun illumination (simulated AM 1.5G sunlight, 100 mW cm?2). 相似文献
7.
Mattson RJ Catt JD Keavy D Sloan CP Epperson J Gao Q Hodges DB Iben L Mahle CD Ryan E Yocca FD 《Bioorganic & medicinal chemistry letters》2003,13(6):1199-1202
Optimization of a benzyl piperazine pharmacophore produced N-acyl-4-indanyl-piperazines that bind with high affinity to melatonergic MT(2) receptors. (R)-4-(2,3-dihydro-6-methoxy-1H-inden-1-yl)-N-ethyl-1-piperazine-carboxamide fumarate (13) is a water soluble, selective MT(2) agonist, which produces advances in circadian phase in rats at doses of 1-56 mg/kg that are no different from those of melatonin at 1 mg/kg. Unlike melatonin, 13 produced only weak contractile effects in rat tail artery. 相似文献
8.
Karageorge GN Bertenshaw S Iben L Xu C Sarbin N Gentile A Dubowchik GM 《Bioorganic & medicinal chemistry letters》2004,14(23):5881-5884
A series of tetrahydroisoquinolines has yielded potent MT(2) receptor antagonists, which are selective versus the MT(1) receptor. 相似文献
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Pégurier C Curtet S Nicolas JP Boutin JA Delagrange P Renard P Langlois M 《Bioorganic & medicinal chemistry》2000,8(1):163-171
Focused small libraries of melatonin receptor ligands from arylalkylamine derivatives were synthesised by combinatorial chemistry using the mix and split method in the solid phase. A library of 108 compounds was then synthesised from 12 arylalkyl amines and nine carboxylic acids. The compound mixtures were evaluated on chicken brain melatonin and recombinant human mt1 and MT2 receptors. Deconvolution of the most potent mixture demonstrated the superiority of 3-methoxy and 2,5-dimethoxy substitution on the phenyl ring with isopropyl, propyl and ethyl amido chains. Several compounds with nanomolar affinity for human melatonin receptors were obtained. 相似文献
11.
Synthesis,Characterization, Antimicrobial Activity,and Docking Studies of New Triazolic Tripodal Ligands 下载免费PDF全文
Tarik Harit Reda Bellaouchi Yahya Rokni Abdelkhalek Riahi Fouad Malek Abdeslam Asehraou 《化学与生物多样性》2017,14(12)
The synthesis and characterization of new N‐donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme. 相似文献
12.
One hundred and four acid amido compounds have been prepared by condensing 2-mercapto benzoic acid and its 5-bromo, 3, 5-dibromo and 3, 5-dichloro derivatives with 2-amino-4-substituted thiazoles and their 5-halogenated derivatives via the acid chloride. All these compounds have been tested against Helminthosporium. Four of the compounds were tested for their antibacterial, antihelminthic activities and also for their hypoglycemic activity. 相似文献
13.
Xia M Hou C Demong D Pollack S Pan M Brackley J Singer M Matheis M Cavender D Wachter M 《Bioorganic & medicinal chemistry letters》2008,18(12):3562-3564
The synthesis and biological evaluation of a series of substituted dipiperidine alcohols are described. Structure-activity relationship studies led to the discovery of potent CCR2 antagonists displaying IC(50) values in the nanomolar or subnanomolar range. The cinnamoyl compounds had higher binding affinities than the corresponding urea analogs. 相似文献
14.
Marc Belmans Eddy Esmans Roger Dommisse Jozef Lepoivre Frank Alderweireldt Jan Balzarini 《Nucleosides, nucleotides & nucleic acids》2013,32(4):523-538
Abstract Condensation of 2-lithio-pyridine and the four isomers of 2-lithio-picoline with 2,4:3,5-di-O-benzylidene-aldehydo-D-ribose, gives the D-allo- and D-altro-isomers of 2-(2,4:3,5-di-O-benzylidenepentitol-l-yl)-pyridine and the corresponding isomers of the four picoline-addition products in a good yields. On treatment with dilute hydrochloric acid or formic acid the corresponding pentitols were obtained. None of these pentitols showed an inhibitory effect on virus replication or tumor cell growth. 相似文献
15.
Hagmann WK Caldwell CG Chen P Durette PL Esser CK Lanza TJ Kopka IE Guthikonda R Shah SK MacCoss M Chabin RM Fletcher D Grant SK Green BG Humes JL Kelly TM Luell S Meurer R Moore V Pacholok SG Pavia T Williams HR Wong KK 《Bioorganic & medicinal chemistry letters》2000,10(17):1975-1978
A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM. 相似文献
16.
Elitza S. Sevova Michael A. Goren Kevin J. Schwartz Fong-Fu Hsu John Turk Brian G. Fox James D. Bangs 《The Journal of biological chemistry》2010,285(27):20580-20587
The Trypanosoma brucei genome has four highly similar genes encoding sphingolipid synthases (TbSLS1–4). TbSLSs are polytopic membrane proteins that are essential for viability of the pathogenic bloodstream stage of this human protozoan parasite and, consequently, can be considered as potential drug targets. TbSLS4 was shown previously to be a bifunctional sphingomyelin/ethanolamine phosphorylceramide synthase, whereas functions of the others were not characterized. Using a recently described liposome-supplemented cell-free synthesis system, which eliminates complications from background cellular activities, we now unambiguously define the enzymatic specificity of the entire gene family. TbSLS1 produces inositol phosphorylceramide, TbSLS2 produces ethanolamine phosphorylceramide, and TbSLS3 is bifunctional, like TbSLS4. These findings indicate that TbSLS1 is uniquely responsible for synthesis of inositol phosphorylceramide in insect stage parasites, in agreement with published expression array data (17). This approach also revealed that the Trypanosoma cruzi ortholog (TcSLS1) is a dedicated inositol phosphorylceramide synthase. The cell-free synthesis system allowed rapid optimization of the reaction conditions for these enzymes and site-specific mutagenesis to alter end product specificity. A single residue at position 252 (TbSLS1, Ser252; TbSLS3, Phe252) strongly influences enzymatic specificity. We also have used this system to demonstrate that aureobasidin A, a potent inhibitor of fungal inositol phosphorylceramide synthases, does not significantly affect any of the TbSLS activities, consistent with the phylogenetic distance of these two clades of sphingolipid synthases. These results represent the first application of cell-free synthesis for the rapid preparation and functional annotation of integral membrane proteins and thus illustrate its utility in studying otherwise intractable enzyme systems. 相似文献
17.
Alessia Carocci Alessia Catalano Claudio Bruno Angelo Lovece Maria Grazia Roselli Maria Maddalena Cavalluzzi Francesco De Santis Annalisa De Palma Maria Rosaria Rusciano Maddalena Illario Carlo Franchini Giovanni Lentini 《Bioorganic & medicinal chemistry》2013,21(4):847-851
Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT1 and MT2 melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2′,7′-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H2O2-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor, too. 相似文献
18.
《Bioscience, biotechnology, and biochemistry》2013,77(7):1062-1065
2-(Substituted benzylamino)-2-thiazolines (SBAT) were synthesized by a hydrochloric acid-catalyzed cyclization of the corresponding thioureas, using a reaction of 2-methylthio-2-thiazoline with substituted benzylamines or by alkylating 2-amino-2-thiazoline. 2-(Alkylthio)-2-thiazolines were obtained by alkylating 2-mercaptothiazoline. Most of the SBAT compounds activated adenylate cyclase in homogenates of cockroach ventral nerve cords; the effect of introducing substituents at the phenyl of the SBAT compounds on octopaminergic agonist activity was not significant. 2-[β-(Substituted phenyl)ethylamino]-2-thiazolines and 2-(alkylthio)-2-thiazolines were not significant octopaminergic agonists. Washing removed nearly all of the activity of one of the SBAT compounds, suggesting that the SBAT compounds bound reversibly to the octopaminergic receptor. 相似文献
19.
Epperson JR Deskus JA Gentile AJ Iben LG Ryan E Sarbin NS 《Bioorganic & medicinal chemistry letters》2004,14(4):1023-1026
A series of 4-substituted anilides with human melatonergic affinity is reported. Butyramides 26, 39, 42, 52, 57, and 58 all demonstrated subnanomolar MT(2) binding affinity and MT(2) selectivity of at least 70-fold over the MT(1) receptor. Compound 26 demonstrated full agonism at the MT(2) receptor. 相似文献
20.
Stefan Tasler Oliver Müller Tanja Wieber Thomas Herz Stefano Pegoraro Wael Saeb Martin Lang Rolf Krauss Frank Totzke Ute Zirrgiebel Jan E. Ehlert Michael H.G. Kubbutat Christoph Schchtele 《Bioorganic & medicinal chemistry》2009,17(18):6728-6737
Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range. 相似文献