51908-64-6Relevant academic research and scientific papers
Facile Synthesis of 2-Aminocyclobutenylphosphonates
Al Quntar, A. A. A.,Dembitsky, V.,Dweik, H.
, p. 137 - 142 (2020)
The addition of various amines to diethyl 4-chlorobut-1-yn-1-ylphosphonate produced novel biologically potent substituted diethyl 2-aminocyclobut-1-en-1-ylphosphonates in 70–83% isolated yield. This regioselective reaction was carried out at room temperat
Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor
Fyfe, Tim J.,Kellam, Barrie,Sykes, David A.,Capuano, Ben,Scammells, Peter J.,Lane, J. Robert,Charlton, Steven J.,Mistry, Shailesh N.
, p. 9488 - 9520 (2019/11/11)
Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side effects (EPSs) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with contrasting kinetic profiles. Haloperidol displays fast association/slow dissociation at the D2R, whereas clozapine exhibits relatively slow association/fast dissociation. Recently, we have provided evidence that slow dissociation from the D2R predicts hyperprolactinemia, whereas fast association predicts EPS. Unfortunately, clozapine can cause severe side effects independent of its D2R action. Our results suggest an optimal kinetic profile for D2R antagonist APDs that avoids EPS. To begin exploring this hypothesis, we conducted a structure-kinetic relationship study of haloperidol and revealed that subtle structural modifications dramatically change binding kinetic rate constants, affording compounds with a clozapine-like kinetic profile. Thus, optimization of these kinetic parameters may allow development of novel APDs based on the haloperidol scaffold with improved side-effect profiles.
Synthesis of the ortho / meta / para isomers of relevant pharmaceutical compounds by coupling a Sonogashira reaction with a regioselective hydration
Leyva-Perez, Antonio,Cabrero-Antonino, Jose R.,Rubio-Marques, Paula,Al-Resayes, Saud I.,Corma, Avelino
, p. 722 - 731 (2014/04/03)
Aryl ketones substituted in ortho, meta, and para position are prepared by a palladium-catalyzed Sonogashira reaction followed by a regioselective hydration of the so-formed alkyne with triflimidic acid or a gold catalyst, under catalytic conditions. This methodology opens a way to obtain substituted aryl alkyl ketones from readily available starting materials, haloarenes, and terminal alkynes. The syntheses of the different regioisomers of haloperidol, melperone, pipamperone, and ibuprofen are presented. Structure-activity relationships for these compounds are studied with dopaminergic and cyclooxigenase binding assays.
Regioselective hydration of alkynes by iron(III) Lewis/Bronsted catalysis
Cabrero-Antonino, Jose R.,Leyva-Perez, Antonio,Corma, Avelino
experimental part, p. 11107 - 11114 (2012/09/22)
The triflimide iron(III) salt [Fe(NTf2)3] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the FeIII cation mediated by the weakly-coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh3/[Fe(NTf2)3] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf2)3] hydrolyzes under the reaction conditions and that catalytically less active BrAonsted species are formed, which points to a Lewis/Bronsted co-catalysis. This triflimide-based catalytic system is regioselective for the hydration of internal aryl-alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone-like structure, is shown. Just add water! The triflimide iron(III) salt [Fe(NTf2)3] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields (see scheme). Copyright
Copper-catalyzed asymmetric 1,4-addition of alkenyl alanes to N-substituted-2-3-dehydro-4-piperidones
Mueller, Daniel,Alexakis, Alexandre
supporting information; experimental part, p. 1842 - 1845 (2012/06/18)
Readily available vinyl alanes are used in the Cu-catalyzed asymmetric conjugate addition reaction to N-substituted-2-3-dehydro-4-piperidones. The enhanced reactivity of recently developed and easily prepared phosphine amine ligands in combination with inexpensive Cu(II)naphtenate (CuNp) allows the introduction of a great variety of alkenyl, alkyl, and aryl aluminums in high enantioselectivity.
Palladium(0)-catalyzed addition of Me3SnSnMe3 to alkyl 2-alkynoates and N,N-dimethyl-2-alkynamides. Facile preparation of alkyl (Z)- and (E)-2,3-bis(trimethylstannyl)-2-alkenoates and (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides
Piers, Edward,Skerlj, Renato T.
, p. 2468 - 2482 (2007/10/02)
Treatment (tetrahydrofuran (THF), room temperature or reflux) of the alkyl 2-alkynoates 9-26 with (Me3Sn)2 in the presence of a Pd(0) catalyst ((Ph3P)4Pd) provides good to excellent yields of the corresponding alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates 47-64.The latter substances are thermally labile and, as demonstrated by a number of examples, are transformed upon heating (75-95 deg C) into the thermodynamically more stable E isomers.The Pd(0)-catalyzed addition of (Me3Sn)2 to N,N-dimethyl-2-alkynamides 44-46 is quite slow and the initially formed products (Z)-N,N -dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides) rearrange to the corresponding E isomers at room temperature.
