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Takehisa Kunieda - One of the best experts on this subject based on the ideXlab platform.
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Catalytic dissymmetrization of meso -2-Imidazolidinones: alternative route to chiral synthons for 1,2-diamines
Tetrahedron Letters, 2004Co-Authors: Tadao Ishizuka, Hirofumi Matsunaga, Tomokazu Katahira, Ryushi Seo, Takehisa KuniedaAbstract:The chiral functionalization of a simple heterocycle, 1,3-dihydro-2-imidazolone, was achieved by the highly enantioselective monodeacylation of meso-1,3-diacetyl-2-Imidazolidinones via an oxazaborolidine-catalyzed borane reduction. This kinetically controlled dissymmetrization is sufficiently effective to provide a synthetic route to either enantiomer of (4S, 5S)- or (4R, 5R)-4,5-dimethoxy-2-Imidazolidinone derivatives, which serve as chiral synthons for threo-1,2-diamines.
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Unusual N-acylation of sterically congested trans-4,5-disubstituted 2-Imidazolidinones: remarkably facile CC bond formation
Tetrahedron Letters, 2001Co-Authors: Alaa A.-m. Abdel-aziz, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Abstract Sterically congested trans -4,5-di- tert -butyl-2-Imidazolidinone (DTBIm) and trans -4,5-di-(1-adamantyl)-2-Imidazolidinone (DAIm), which are prepared from the parent 1,3-dihydro-2-imidazolone, undergo an unusual N -acylation reaction with acyl chlorides in the presence of organic amines to give the 3-oxoacyl derivatives.
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An unusual enhancement of chiral induction by chiral 2-Imidazolidinone auxiliaries
Tetrahedron Letters, 2000Co-Authors: Alaa A.-m. Abdel-aziz, Junko Okuno, Shinsuke Tanaka, Tadao Ishizuka, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Diastereoselectivity which is induced by the use of 2-Imidazolidinone auxiliaries is greatly dependent on the N-substituents of the heterocycles, among which the bulky arenesulfonyl group is the moiety of choice. Reactions of this type afford an excellent level of diastereoselection in the methylation of N%-butyryl-2-Imidazolidinones via the metal enolates. © 2000 Published by Elsevier Science Ltd.
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Facile enantiodivergence of meso-1,3-diacyl-2-Imidazolidinones to chiral 2-Imidazolidinone auxiliaries
Tetrahedron Letters, 1998Co-Authors: Kazuhiro Yokoyama, Tadao Ishizuka, Naoko Ohmachi, Takehisa KuniedaAbstract:Abstract The enantioselective monodeacylation of meso -1,3-diacetyl-2-Imidazolidinones, by treatmenmt with the lithium salts of sterically constrained N , N -dimethylaminoalcohol gives 1-acetyl-2-Imidazolidinones in 89% ee. The latter compounds serve as good precursors for efficient chiral auxiliaries.
Jiangchun Zhong - One of the best experts on this subject based on the ideXlab platform.
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sequential 3 2 cycloaddition rearrangement reaction of imidazolone nitrones and allenoates for the efficient synthesis of functionalized Imidazolidinone
Tetrahedron Letters, 2012Co-Authors: Xi Wu, Risong Na, Min Wang, Jiangchun ZhongAbstract:Abstract Sequential [3+2] cycloaddition/rearrangement reaction of imidazolone nitrones and allenoates is described. The reaction was carried out in refluxing toluene to provide the methylene Imidazolidinone derivatives in high yield. It provides a simple and convenient strategy for the synthesis of functionalized Imidazolidinones.
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Sequential [3+2] cycloaddition/rearrangement reaction of imidazolone nitrones and allenoates for the efficient synthesis of functionalized Imidazolidinone
Tetrahedron Letters, 2012Co-Authors: Honglei Liu, Jiangchun Zhong, Min Wang, Jun Liu, Hongchao GuoAbstract:Abstract Sequential [3+2] cycloaddition/rearrangement reaction of imidazolone nitrones and allenoates is described. The reaction was carried out in refluxing toluene to provide the methylene Imidazolidinone derivatives in high yield. It provides a simple and convenient strategy for the synthesis of functionalized Imidazolidinones.
Alaa A.-m. Abdel-aziz - One of the best experts on this subject based on the ideXlab platform.
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An Alternative Route for Synthesis of Chiral 4-Substituted 1-Arenesulfonyl-2-Imidazolidinones: Unusual Utility of (4S,5S)- and (4R,5R)-4,5-Dimethoxy-2-Imidazolidinones and X-Ray Crystallography
Journal of Chemistry, 2013Co-Authors: Ibrahim A. Alswaidan, Amer M. Alanazi, Adel S. El-azab, Alaa A.-m. Abdel-azizAbstract:An unusual synthesis of (S)-1-arenesulfonyl-4-(1-adamantyl)-2-Imidazolidinones 15a–d and (R)-1-arenesulfonyl-4-tert-butyl-2-Imidazolidinones 19a–d has been developed from trans-1-apocamphanecarbonyl-4,5-dimethoxy-2-Imidazolidinones 6 and 7 as chiral synthons. Diastereomerically pure trans-1-apocamphanecarbonyl-4,5-dimethoxy-2-Imidazolidinones 6 and 7 were successfully subjected to regioselective reduction using bulky organocuprates that afforded 1-apocamphanecarbonyl-5-methoxy-2-Imidazolidinones 10 and 11. This new finding was used for synthesis of chiral 4-substituted 2-Imidazolidinones 15a–d and 19a–d through the corresponding intermediates 13 and 17 by treatment with steric bulky tert-butylcuprate or 1-adamantylcuprate.
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Unusual N-acylation of sterically congested trans-4,5-disubstituted 2-Imidazolidinones: remarkably facile CC bond formation
Tetrahedron Letters, 2001Co-Authors: Alaa A.-m. Abdel-aziz, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Abstract Sterically congested trans -4,5-di- tert -butyl-2-Imidazolidinone (DTBIm) and trans -4,5-di-(1-adamantyl)-2-Imidazolidinone (DAIm), which are prepared from the parent 1,3-dihydro-2-imidazolone, undergo an unusual N -acylation reaction with acyl chlorides in the presence of organic amines to give the 3-oxoacyl derivatives.
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An unusual enhancement of chiral induction by chiral 2-Imidazolidinone auxiliaries
Tetrahedron Letters, 2000Co-Authors: Alaa A.-m. Abdel-aziz, Junko Okuno, Shinsuke Tanaka, Tadao Ishizuka, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Diastereoselectivity which is induced by the use of 2-Imidazolidinone auxiliaries is greatly dependent on the N-substituents of the heterocycles, among which the bulky arenesulfonyl group is the moiety of choice. Reactions of this type afford an excellent level of diastereoselection in the methylation of N%-butyryl-2-Imidazolidinones via the metal enolates. © 2000 Published by Elsevier Science Ltd.
Jens Kristian Perregaard - One of the best experts on this subject based on the ideXlab platform.
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serotonin 5 ht2 receptor dopamine d2 receptor and α1 adrenoceptor antagonists conformationally flexible analogues of the atypical antipsychotic sertindole
Journal of Medicinal Chemistry, 1996Co-Authors: Kim Andersen, John Hyttel, Tommy Liljefors, Jens Kristian PerregaardAbstract:Conformationally flexible analogues of the atypical antipsychotic sertindole (1-[2-[4-[5-chloro -1-(4-fluorophenyl)-1H-indol-3-yl]-4-piperidinyl]ethyl]-2-imidazolidi non e) were synthesized. Replacement of the 4-piperidinyl ring in sertindole by a 2-(methylamino)ethoxy group or a 2-(methylamino)ethyl group (e.g. 1-[2-[2-[5-chloro-1-(4-fluorophenyl)-1H -indol-3-yloxy]ethyl-methylamino]ethyl]-2-Imidazolidinone and 1-[3-[[2-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl] -ethyl]methylamino]propyl]-2-Imidazolidinone results in binding affinities for serotonin 5-HT2A and dopamine D2 receptors, as well as alpha 1 adrenoceptors, which are very similar to those of sertindole. (Methylamino)alkyl groups of other chain lengths, 3-(methylamino)propyloxy groups, and 2-(methylamino)ethylsulfanyl groups do not have such properties. The capability of the 2-(methylamino)ethoxy group and the 2-(methylamino)ethyl group to replace the 4-piperidinyl ring in sertindole is reflected in molecular modeling studies using recently published receptor-interaction models for 5-HT2 and D2 receptors. Structure-affinity investigations concerning the substituents in the indole nucleus and the 2-Imidazolidinone ring system in the 2-(methylamino)ethoxy and the 2-(methylamino)ethyl analogues of sertindole have led to high affinity serotonin 5-HT2A receptor antagonists with selectivity versus dopamine D2 receptors and alpha 1 adrenoceptors (e.g. 1-[2-[[2-[6-chloro-1-(4-fluorophenyl) -1H-indol-3-yloxy]ethyl]methylamino]-ethyl]-2-Imidazolidinone and 1-[3-[[2-[6-chloro-1-(4-fluorophenyl) -1H-indol-3-yl]ethyl]methylamino]propyl]-2-Imidazolidinone). The latter derivative has also high selectivity for 5-HT2A receptors versus serotonin 5-HT2C receptors. Replacement of the basic amino group by nitrogen-containing six-membered rings has led to 5-chloro-1-(4-fluorophenyl)-3-[(4-methylpiperazinyl)-ethoxy]-1H-in dole, which has high affinity for dopamine D2, versus low affinity for serotonin 5-HT2A receptors and alpha 1 adrenoceptors.
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Selective, centrally acting serotonin 5-HT2 antagonists. 1. 2- and 6-substituted 1-phenyl-3-(4-piperidinyl)-1H-indoles.
Journal of medicinal chemistry, 1992Co-Authors: Jens Kristian Perregaard, Kim Andersen, John Hyttel, Connie SánchezAbstract:A series of 1-[2-[4-(1H-indol-3-yl)-1-piperidinyl]ethyl]-2-Imidazolidinones has been synthesized. The 1-position of the indole is substituted with phenyl groups and in the 2- or 6-positions are additional substituents. An analogous series with the Imidazolidinone ring opened to corresponding urea derivatives was also prepared. High potency and selectivity for 5-HT2 receptors (as compared with D2 and alpha 1 receptor affinities) were obtained with medium-large substituents such as 6-chloro, 6-methyl, and 6-trifluoromethyl or a 2-methyl substituent. Larger 6-substituents such as isopropyl considerably reduced activity, while the smaller 6-fluoro substituent afforded unselective compounds. Selective 5-HT2 antagonists were found by combining 6-substitution with both unsubstituted 1-phenyl and substituted 1-phenyl groups (2-F, 4-F, 4-Cl). However, 3-substitution of the phenyl group markedly reduced 5-HT2 receptor affinity, especially with a 3-trifluoromethyl substituent. Introduction of a 3-(2-propyl) substituent in the Imidazolidinone ring reduced binding to alpha 1 adrenoceptors with a factor of 3-8. Practically no influence on 5-HT2 and D2 receptor affinities were found by the presence of this substituent compared to the 3-unsubstituted derivatives. Compounds with potent receptor binding also potently inhibited the quipazine-induced head twitch syndrome in rats. The compounds were equally active after oral and subcutaneous administration and they had a long duration of action (> 24 h). Especially urea derivatives were found to be considerably more potent at 24 h than at 2 h after subcutaneous administration. Some of the compounds potently inhibited isolation-induced aggression in mice, an effect which, however, did not correlate to 5-HT2 receptor-mediated activities. On the basis of these structure-activity studies 1-[2-[4-[6-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1- piperidinyl]ethyl]-3-(2-propyl)-2-Imidazolidinone (Lu 26-042, compound 4c) was selected for further pharmacological and toxicological investigations.
Hirofumi Matsunaga - One of the best experts on this subject based on the ideXlab platform.
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Catalytic dissymmetrization of meso -2-Imidazolidinones: alternative route to chiral synthons for 1,2-diamines
Tetrahedron Letters, 2004Co-Authors: Tadao Ishizuka, Hirofumi Matsunaga, Tomokazu Katahira, Ryushi Seo, Takehisa KuniedaAbstract:The chiral functionalization of a simple heterocycle, 1,3-dihydro-2-imidazolone, was achieved by the highly enantioselective monodeacylation of meso-1,3-diacetyl-2-Imidazolidinones via an oxazaborolidine-catalyzed borane reduction. This kinetically controlled dissymmetrization is sufficiently effective to provide a synthetic route to either enantiomer of (4S, 5S)- or (4R, 5R)-4,5-dimethoxy-2-Imidazolidinone derivatives, which serve as chiral synthons for threo-1,2-diamines.
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Unusual N-acylation of sterically congested trans-4,5-disubstituted 2-Imidazolidinones: remarkably facile CC bond formation
Tetrahedron Letters, 2001Co-Authors: Alaa A.-m. Abdel-aziz, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Abstract Sterically congested trans -4,5-di- tert -butyl-2-Imidazolidinone (DTBIm) and trans -4,5-di-(1-adamantyl)-2-Imidazolidinone (DAIm), which are prepared from the parent 1,3-dihydro-2-imidazolone, undergo an unusual N -acylation reaction with acyl chlorides in the presence of organic amines to give the 3-oxoacyl derivatives.
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An unusual enhancement of chiral induction by chiral 2-Imidazolidinone auxiliaries
Tetrahedron Letters, 2000Co-Authors: Alaa A.-m. Abdel-aziz, Junko Okuno, Shinsuke Tanaka, Tadao Ishizuka, Hirofumi Matsunaga, Takehisa KuniedaAbstract:Diastereoselectivity which is induced by the use of 2-Imidazolidinone auxiliaries is greatly dependent on the N-substituents of the heterocycles, among which the bulky arenesulfonyl group is the moiety of choice. Reactions of this type afford an excellent level of diastereoselection in the methylation of N%-butyryl-2-Imidazolidinones via the metal enolates. © 2000 Published by Elsevier Science Ltd.
