The Experts below are selected from a list of 1470 Experts worldwide ranked by ideXlab platform
Danial D. M. Wayner - One of the best experts on this subject based on the ideXlab platform.
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Tris(trimethylsilyl)silane (TTMSS) : Formation of carbon-centered radicals from Oxathiolane and thiazolidine derivatives
Tetrahedron Letters, 1991Co-Authors: Prabhat Arya, M. Lesage, Danial D. M. WaynerAbstract:Abstract Tris(trimethylsilyl)silane (TTMSS) is an efficient reagent for the formation of carbon-centered radicals from 1,3-Oxathiolane, 5-oxo-1,3-Oxathiolane, N(methylcarbonyl)-1,3-thiazolidine and N(ethoxycarbonyl)-1,3- thiazolidine derivatives by the selective cleavage of the carbon-sulphur bond.
Dei S. - One of the best experts on this subject based on the ideXlab platform.
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Muscarinic antagonists with multiple stereocenters: Synthesis, affinity profile and functional activity of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl) pyrrolidine sulfoxide derivatives
2008Co-Authors: Dei S., Bellucci C., Buccioni M., Ferraroni M., Guandalini L., Manetti D., Marucci G., Matucci R., Nesi M., Romanelli M.n.Abstract:Completing a long-lasting research on 1,3-Oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl- 2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity
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Muscarinic subtype affinity and functional activity profile of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine and 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine derivatives
2005Co-Authors: Dei S., Bellucci C., Buccioni M., Manetti D., Marucci G., Angeli P., Gualtieri F, Matucci R.Abstract:Starting from two previously studied muscarinic full agonists, characterized by a 1,3-dioxotane ((+)-1) and a 1,3-Oxathiolane ((+)-2) cycle. two new series of muscarinic ligands were designed, obtained by the steric complication of the parent compounds produced by freezing the aminoalkyl chain into a pyrrolidine ring. Both tertiary amines and the corresponding iodomethyl derivatives were synthesised and studied, and several compounds of the series which behaved as muscarinic agonists have been selected, on the basis of preliminary binding experiments on rat cortex homogenates, for the present work.Results are presented obtained from testing the affinity of the selected compounds against cloned human muscarinic receptors expressed in CHO cells. in order to evaluate subtype selectivity. Their functional activity on classical models Of M-1-M-4 receptors, in guinea pig and rabbit tissues is also reported.With respect to parent compounds, the new molecules present some selectivity toward hm2 receptors; fair M-2 selectivity is also evident in functional studies, where these compounds behave as partial agonists. Among the other compounds of the series (2S, 4'R, 2'S)-1,1-dimethyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidinium iodide (-)-3 and (2R, 5'S, 2'S)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine (+)-5 present a promising pharmacological profile. Compound (-)-3 shows modest hm2 selectivity in binding experiments but a clearcut M-2 selectivity in functional tests, where it behaves as a weak antagonist on M-1 and M-4 subtypes, as a weak full agonist on the M-3 subtype and as a potent partial agonist on M-2 Subtype. Tertiary amine (+)-5 presents a quite similar profile but appears more interesting since, lacking a permanent charge on the nitrogen atom, it may represent an interesting tool to study CNS muscarinic receptors.Our results confirm that sterical complication of parent compounds (+)-1 and (+)-2 produces more selective muscarinic agonists. (c) 2005 Elsevier Inc. All rights reserved
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Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and of their iodomethylates.
Elsevier Science Limited:Oxford Fulfillment Center PO Box 800 Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000 011 44 1865 843699 EMAIL: as, 2003Co-Authors: Dei S., Bellucci C., Guandalini L., Manetti D., Matucci R., Romanelli M.n., M. Buccioni, Ferrarono M, Gualtieri F, Scapecchi SAbstract:Four out of the eight possible stereoisomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and the corresponding iodomethylates have been synthesised. They were formally derived from hybridisation of potent though unselective agonists studied before, such as 1,3-dioxolane 1 and 1,3-Oxathiolane 2, with the structure of nicotine. It was expected that, by exalting the molecular complexity of the parent compounds, in particular through stereochemical complication in the proximity of the critical cationic head of the molecule, the chance to find agonists able to discriminate among cholinergic receptors subtypes would increase. The relative and absolute configuration of the compounds obtained has been established by means of NMR spectroscopy and X-ray crystallography. In preliminary studies, their binding affinity has been evaluated on rat brain nicotinic and muscarinic receptors. While none of the compounds showed any nicotinic affinity up to the dose of 10 μM, most of the iodomethylates were endowed with promising affinity for the muscarinic receptors
Marucci G. - One of the best experts on this subject based on the ideXlab platform.
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Muscarinic antagonists with multiple stereocenters: Synthesis, affinity profile and functional activity of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl) pyrrolidine sulfoxide derivatives
2008Co-Authors: Dei S., Bellucci C., Buccioni M., Ferraroni M., Guandalini L., Manetti D., Marucci G., Matucci R., Nesi M., Romanelli M.n.Abstract:Completing a long-lasting research on 1,3-Oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl- 2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity
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Muscarinic subtype affinity and functional activity profile of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine and 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine derivatives
2005Co-Authors: Dei S., Bellucci C., Buccioni M., Manetti D., Marucci G., Angeli P., Gualtieri F, Matucci R.Abstract:Starting from two previously studied muscarinic full agonists, characterized by a 1,3-dioxotane ((+)-1) and a 1,3-Oxathiolane ((+)-2) cycle. two new series of muscarinic ligands were designed, obtained by the steric complication of the parent compounds produced by freezing the aminoalkyl chain into a pyrrolidine ring. Both tertiary amines and the corresponding iodomethyl derivatives were synthesised and studied, and several compounds of the series which behaved as muscarinic agonists have been selected, on the basis of preliminary binding experiments on rat cortex homogenates, for the present work.Results are presented obtained from testing the affinity of the selected compounds against cloned human muscarinic receptors expressed in CHO cells. in order to evaluate subtype selectivity. Their functional activity on classical models Of M-1-M-4 receptors, in guinea pig and rabbit tissues is also reported.With respect to parent compounds, the new molecules present some selectivity toward hm2 receptors; fair M-2 selectivity is also evident in functional studies, where these compounds behave as partial agonists. Among the other compounds of the series (2S, 4'R, 2'S)-1,1-dimethyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidinium iodide (-)-3 and (2R, 5'S, 2'S)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine (+)-5 present a promising pharmacological profile. Compound (-)-3 shows modest hm2 selectivity in binding experiments but a clearcut M-2 selectivity in functional tests, where it behaves as a weak antagonist on M-1 and M-4 subtypes, as a weak full agonist on the M-3 subtype and as a potent partial agonist on M-2 Subtype. Tertiary amine (+)-5 presents a quite similar profile but appears more interesting since, lacking a permanent charge on the nitrogen atom, it may represent an interesting tool to study CNS muscarinic receptors.Our results confirm that sterical complication of parent compounds (+)-1 and (+)-2 produces more selective muscarinic agonists. (c) 2005 Elsevier Inc. All rights reserved
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Pharmacological Characterization of Chiral Muscarinic Antagonists cis-2-Phenyl-2-cyclohexyl-r-5-[(dimethylamino)-methyl]1,3-Oxathiolane-3-oxide Methiodide
Medpharm Scientific Publishers GmBH:Postfach 101061 D-70009 Stuttgart Germany:011 49 711 25820 EMAIL: service@medpharm.de INTERNET: http: www.medpharm, 1992Co-Authors: Angeli P., Balduini W., Brasili Livio, Cantalamessa F., Cattabeni F., Marucci G.Abstract:. Cis-2-phenyl-2-cyclohexyl-r-5 [(dimethylamino)-methyl]-1,3-Oxathiolane cis [(\ub1)1] and trans [(\ub1)2] 3-oxide methiodides together with the enantiomers (+)2 and (-)2 where evaluated for their antimuscarinic activity in functional (in vivo and in vitro) and in binding studies. The results indicate that in all the receptor subtypes the trans isomer (\ub1)2 is more active than the cis one (\ub1)1. Of the two enantiomers, (+)2 displays the highest affinity while the values of eudismic ratios, although large, are similar for all the subtypes. Furthermore, the tested Oxathiolanes show a small degree of selectivity in binding studies while in functional studies selectivity is absent
Olof Ramström - One of the best experts on this subject based on the ideXlab platform.
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Multienzymatic cascade synthesis of an enantiopure (2R,5R)-1,3-Oxathiolane anti-HIV agent precursor
Molecular Catalysis, 2019Co-Authors: Yansong Ren, Olof RamströmAbstract:Abstract An enantiopure (2R,5R)-1,3-Oxathiolane was obtained using a multienzymatic cascade protocol. By employing a combination of surfactant-treated subtilisin Carlsberg and Candida antarctica lipase B, the absolute configuration of the resulting 1,3-Oxathiolane ring was efficiently controlled, resulting in an excellent enantiomeric excess (>99%). This enantiopure 1,3-Oxathiolane derivative is a key precursor to anti-HIV agents, such as lamivudine, through subsequent N-glycosylation.
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Multienzymatic, one-pot cascade synthesis of enantiopure lamivudine precursor (2R, 5R)-1,3-Oxathiolane
2016Co-Authors: Yansong Ren, Olof RamströmAbstract:Multienzymatic, one-pot cascade synthesis of enantiopure lamivudine precursor (2R, 5R)-1,3-Oxathiolane
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Chirality Control in Enzyme-Catalyzed Dynamic Kinetic Resolution of 1,3-Oxathiolanes.
The Journal of organic chemistry, 2015Co-Authors: Yansong Ren, Olof RamströmAbstract:The origin of enantioenrichment in enzyme-catalyzed dynamic kinetic resolution of 1,3-Oxathiolane derivatives, key intermediates for asymmetric lamivudine synthesis, was elucidated. The chirality control could be determined by chiral HPLC and NOE NMR spectroscopy using a modified 1,3-Oxathiolane compound obtained through enzyme-catalyzed selective hydrolysis. Solvent-dependent stereoselectivity was observed under biphasic conditions using different organic solvents with phosphate buffer.
Matucci R. - One of the best experts on this subject based on the ideXlab platform.
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Muscarinic antagonists with multiple stereocenters: Synthesis, affinity profile and functional activity of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl) pyrrolidine sulfoxide derivatives
2008Co-Authors: Dei S., Bellucci C., Buccioni M., Ferraroni M., Guandalini L., Manetti D., Marucci G., Matucci R., Nesi M., Romanelli M.n.Abstract:Completing a long-lasting research on 1,3-Oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl- 2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity
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Muscarinic subtype affinity and functional activity profile of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine and 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine derivatives
2005Co-Authors: Dei S., Bellucci C., Buccioni M., Manetti D., Marucci G., Angeli P., Gualtieri F, Matucci R.Abstract:Starting from two previously studied muscarinic full agonists, characterized by a 1,3-dioxotane ((+)-1) and a 1,3-Oxathiolane ((+)-2) cycle. two new series of muscarinic ligands were designed, obtained by the steric complication of the parent compounds produced by freezing the aminoalkyl chain into a pyrrolidine ring. Both tertiary amines and the corresponding iodomethyl derivatives were synthesised and studied, and several compounds of the series which behaved as muscarinic agonists have been selected, on the basis of preliminary binding experiments on rat cortex homogenates, for the present work.Results are presented obtained from testing the affinity of the selected compounds against cloned human muscarinic receptors expressed in CHO cells. in order to evaluate subtype selectivity. Their functional activity on classical models Of M-1-M-4 receptors, in guinea pig and rabbit tissues is also reported.With respect to parent compounds, the new molecules present some selectivity toward hm2 receptors; fair M-2 selectivity is also evident in functional studies, where these compounds behave as partial agonists. Among the other compounds of the series (2S, 4'R, 2'S)-1,1-dimethyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidinium iodide (-)-3 and (2R, 5'S, 2'S)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine (+)-5 present a promising pharmacological profile. Compound (-)-3 shows modest hm2 selectivity in binding experiments but a clearcut M-2 selectivity in functional tests, where it behaves as a weak antagonist on M-1 and M-4 subtypes, as a weak full agonist on the M-3 subtype and as a potent partial agonist on M-2 Subtype. Tertiary amine (+)-5 presents a quite similar profile but appears more interesting since, lacking a permanent charge on the nitrogen atom, it may represent an interesting tool to study CNS muscarinic receptors.Our results confirm that sterical complication of parent compounds (+)-1 and (+)-2 produces more selective muscarinic agonists. (c) 2005 Elsevier Inc. All rights reserved
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Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and of their iodomethylates.
Elsevier Science Limited:Oxford Fulfillment Center PO Box 800 Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000 011 44 1865 843699 EMAIL: as, 2003Co-Authors: Dei S., Bellucci C., Guandalini L., Manetti D., Matucci R., Romanelli M.n., M. Buccioni, Ferrarono M, Gualtieri F, Scapecchi SAbstract:Four out of the eight possible stereoisomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and the corresponding iodomethylates have been synthesised. They were formally derived from hybridisation of potent though unselective agonists studied before, such as 1,3-dioxolane 1 and 1,3-Oxathiolane 2, with the structure of nicotine. It was expected that, by exalting the molecular complexity of the parent compounds, in particular through stereochemical complication in the proximity of the critical cationic head of the molecule, the chance to find agonists able to discriminate among cholinergic receptors subtypes would increase. The relative and absolute configuration of the compounds obtained has been established by means of NMR spectroscopy and X-ray crystallography. In preliminary studies, their binding affinity has been evaluated on rat brain nicotinic and muscarinic receptors. While none of the compounds showed any nicotinic affinity up to the dose of 10 μM, most of the iodomethylates were endowed with promising affinity for the muscarinic receptors
