- Toward the definition of stereochemical requirements for MT 2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives
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New derivatives of 4-phenyl-2-propionamidotetralin (4-P-PDOT) were prepared and tested on cloned MT1 and MT2 receptors, with the purpose of merging previously reported pharmacophores for nonselective agonists and for MT2-selective antagonists. A 8-methoxy group increases binding affinity of both (±)-cis- and (±)-trans-4-P-PDOT, and it can be bioisosterically replaced by a bromine. Conformational analysis of 8-methoxy-4-P-PDOT by molecular dynamics, supported by NMR data, revealed an energetically favored conformation for the (2S,4S)-cis isomer and a less favorable conformation for the (2R,4S)-trans one, fulfilling the requirements of a pharmacophore model for nonselective melatonin receptor agonists. A new superposition model, including features characteristic of MT2- selective antagonists, suggests that MT1/MT2 agonists and MT2 antagonists can share the same arrangement for their pharmacophoric elements. The model correctly predicted the eutomers of (±)-cis- and (±)-trans-4-P-PDOT. The model was validated by preparing three dihydronaphthalene derivatives, either able or not able to reproduce the putative active conformation of 4-P-PDOT. (Figure presented)
- Bedini, Annalida,Lucarini, Simone,Spadoni, Gilberto,Tarzia, Giorgio,Scaglione, Francesco,Dugnani, Silvana,Pannacci, Marilou,Lucini, Valeria,Carmi, Caterina,Pala, Daniele,Rivara, Silvia,Mor, Marco
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experimental part
p. 8362 - 8372
(2012/02/14)
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- Diastereo- and enantioselective hydrogenation of a challenging enamide derived from 4-phenyl-2-tetralone: An appealing shortcut towards enantiopure cis-2-aminotetraline derivatives
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A clean, efficient, and diasteroselective (dr >95%) catalytic hydrogenation of the enamide N-(4- phenyl-3, 4-dihydronaphthalen-2-yl) propionamide (2a) using palladium on carbon is performed. This procedure provides the melatonin receptor ligand (±)-cis-4-
- Lucarini, Simone,Alessi, Matteo,Bedini, Annalida,Giorgini, Giorgia,Piersanti, Giovanni,Spadoni, Gilberto
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scheme or table
p. 550 - 554
(2010/08/13)
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- A concise method for the synthesis of 2-tetralone by titanium tetrachloride-promoted cyclization of 4-aryl-2-hydroxybutanal diethyl acetal
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4-Aryl-2-hydroxybutanal diethyl acetal, prepared from the reaction of benzyl Grignard reagent and glycidaldehyde diethyl acetal, was treated with titanium tetrachloride to give 2-tetralone in good yield. This highly efficient transformation involves tande
- Hon, Yung-Son,Devulapally, Rammohan
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scheme or table
p. 5713 - 5715
(2009/12/09)
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- TiCl4-promoted intramolecular cyclization of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones: an expedient method to prepare 2-tetralones
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DABCO is a very effective catalyst in the formation of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones 12 from the corresponding α-carbonatoaldehyde. Intramolecular cyclization of cyclic carbonates 12 promoted by TiCl4 affords 2-tetralones 13 contain
- Hon, Yung-Son,Devulapally, Rammohan
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experimental part
p. 2831 - 2834
(2009/09/30)
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- THERAPEUTIC COMPOUNDS
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The invention relates to protein binding interacting/binding compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating 5-HT2C disorders, including diseases and disorders medi
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Page/Page column 41
(2009/01/23)
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- An improved synthesis of cis-4-phenyl-2-propionamidotetralin (4-P-PDOT): A selective MT2 melatonin receptor antagonist
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A novel, efficient and diastereoselective procedure was developed for the gram-scale synthesis of cis-4-phenyl-2-propionamidotetralin (4-P-PDOT), a selective MT2 melatonin receptor antagonist. The synthetic strategy involved the conversion of 4
- Lucarini, Simone,Bedini, Annalida,Spadoni, Gilberto,Piersanti, Giovanni
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p. 147 - 150
(2008/09/20)
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- Conformation by NMR of two tetralin-based receptor ligands
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The conformation in solution of 1-phenyl-3-propionamido-1,2,3,4-tetrahydronaphthalene and 1-phenyl-3-(N,N-dimethylamino)-1,2,3,4-tetrahydronaphthalene has been determined by a combination of nuclear magnetic resonance measurements and molecular mechanics
- Gatti, Giuseppe,Piersanti, Giovanni,Spadoni, Gilberto
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p. 469 - 476
(2007/10/03)
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- Synthesis of tritium labelled 4P-PDOT, a selective melatonin receptor antagonist
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A selective MT2 melatonin receptor antagonist, 4-phenyl-2-propionamidotetralin (4P-PDOT), was prepared as a tritium-labelled compound with high specific activity and radiochemical purity. Catalytic hydrogenation of a unique vinyl bromo precursor 10 was us
- Rhee, Sung W.,Tanga, Mary J.
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p. 925 - 932
(2007/10/03)
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- Electrophilic additions to styrylsilanes: the effect of changing the ligands on silicon
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Styrylsilanes readily undergo addition of carbon electrophiles and protons.The products of the reaction depend upon the non-participating substituents on silicon.Thus, while (E)-β-(trimethylsilyl)styrene 4 readily reacts with electrophiles, the reaction products did not contain silicon or new C-C bonds; even in the presence of aryl-substituted carbon electrophiles, the favored reaction was protiodesilylation.In contrast, (E)-β-(trichlorosilyl)styrene 2 did not participate in the reaction with carbon electrophiles or reasonably strong protic acids.However, with triflic acid, 2 cleanly and diastereoselectively dimerized producing after methylation 25, as shown by an X-ray crystal sructure analysis.The simple change of a methyl for a chloro group 3 under the same conditions produced a different diastereomer 19 along with a trimer 21.The reasons for the changes in reaction mechanism are discussed. β-effect / electrophilic addition / styrylsilane / leaving group ability / ligand effect / diastereoselective indane synthesis
- Brook, Michael A.,Henry, Courtney,Jefferson, Elizabeth,Jueschke, Ralf,Sebastian, Thomas,et al.
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p. 559 - 568
(2007/10/02)
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- REACTION OF PHENOLS AND THEIR DERIVATIVES WITH AROMATIC COMPOUNDS IN THE PRESENCE OF ACIDIC AGENTS. XIII. REACTION OF DERIVATIVES OF 2-NAPHTHOL WITH BENZENE. REGIOSELECTIVITY AND REACTION MECHANISM
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1-Methyl and 1-phenyl-2-naphthols react with benzene in the presence of aluminum chloride with the formation of 1-methyl-4-phenyl- and 1,4-diphenyl-2-tetralones respectively. 1,3-Naphthalenediol and its dimethyl ether enter into an analogous reaction in the presence of aluminum chloride or in the HF-SbF5 system with the formation of 3-phenyl-1-naphthol and its methyl ether respectively.It was concluded that the regioselectivity and other features of the condensations are due to the reactivity of the key intermediates of the reaction, i.e., the diprotonated forms of the 2-naphthols (dications) or, for the analogs in the presence of aluminum halides, the mono-C-protonated complexes of the tautomeric keto forms of naphthols with the aluminum halides.The latter agrees with the results from MNDO quantum-chemical calculations for the dications.
- Koltunov, K. Yu.,Repinskaya, I. B.,Shakirov, M. M.,Shchegoleva, L. N.
-
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- Synthesis and Pharmacological Evaluation of 1-Phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes as Ligands for a Novel Receptor with ?-like Neuromodulatory Activity
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Certain novel 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3-aminotetralins, PATs) produced stimulation (ca. 30percent above basal levels) of tyrosine hydroxylase (TH) activity at 0.1 μM concentrations in rodent brain tissue. This effect on T
- Wyrick, Steven D.,Booth, Raymond G.,Myers, Andrew M.,Owens, Constance E.,Kula, Nora S.,et al.
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p. 2542 - 2551
(2007/10/02)
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- SYNTHESE DU METHOXYCARBONYL-3 INDENE ET DE METHOXYCARBONYL-4 DIHYDRO-1,2 NAPHTALENES. OBTENTION DES β-TETRALONES A PARTIR DES α-TETRALONES CORRESPONDANTES
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The synthesis of variously substituted 3-methoxycarbonylindene and 4-methoxycarbonyl-1,2-dihydronaphthalenes is described.A simple and efficient method for the transformation of 1-tetralone into 2-tetralone is reported.
- Vebrel, Joel,Carrie, Robert
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p. 161 - 166
(2007/10/02)
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- Friedel-Crafts Reactions of Some Vinyisilanes
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Substituted cyclohexenylsilanes (2), (5), (9), and (13) undergo Friedel-Crafts reactions to give substitution products, site-selectively at the carbon atom carrying the trimethylsilyl group. β-Trimethylsilylstyrene (17) similary gives more substitution in Friedel-Crafts reactions with benzoyl chloride and with phenylacetyl chloride than styrene itself.The syntheses of the silanes are reported, and some limitations of the idea identified.
- Fleming, Ian,Pearce, Andrew
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p. 2485 - 2489
(2007/10/02)
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- CONDENSATION OF PHENOLS AND THEIR DERIVATIVES WITH AROMATIC COMPOUNDS IN THE PRESENCE OF ACIDIC AGENTS. V. REACTIONS OF CHLORINE-SUBSTITUTED NAPHTHOLS WITH BENZENE
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Substitution of the chlorine at position 1 by a phenyl residue occurs readily in the reaction of 1-chloro- and 1,4-dichloro-2-naphthols with benzene in the presence of aluminum chloride and hydrogen chloride. 4-Chloro-2-naphthol reacts with considerably great difficulty, giving a small yield of 4-phenyl-2-naphthol.The possibility of using a mixture of 4- and 2-chloro-1-naphthols for the production of 3-phenyl-1-naphthol was demonstrated.The possible reaction paths are discussed.
- Repinskaya, I. B.,Savel'ev, V. A.,Makarova, Z. S.,Koptyug, V. A.
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p. 1463 - 1466
(2007/10/02)
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