65451-89-0Relevant academic research and scientific papers
Optimization of 2-alkoxyacetates as acylating agent for enzymatic kinetic resolution of chiral amines
Oláh, Márk,Kovács, Dániel,Katona, Gabriel,Hornyánszky, Gábor,Poppe, László
, p. 3663 - 3670 (2018/06/04)
In this study, the activity of acetic acid esters modified with electron withdrawing 2-alkoxy-groups was investigated as acylating agent in kinetic resolution (KR) of racemic amines. A homologous series of the isopropyl esters of four 2-alkoxyacetic acids (2-methoxy-, 2-ethoxy-, 2-propoxy- and 2-butoxyacetic acids) were prepared and investigated for enantiomer selective N-acylation, catalyzed by lipase B from Candida antarctica, under batch and continuous-flow conditions. In the first set of experiments, isopropyl 2-propoxyacetate showed the highest effectivity with all of the four racemic amines [(±)-1-phenylethylamine, (±)-4-phenylbutan-2-amine, (±)-heptan-2-amine and (±)-1-methoxypropane-2-amine] in the set enabling excellent conversions (≥46%) and enantiomeric excess values (ee ≥ 99%) with each amines in continuous-flow mode KRs under the optimized reaction conditions. In a second set of experiments, KRs of five additional amines – being substituted derivatives of (±)-1-phenylethylamine – further demonstrated the usefulness of isopropyl 2-propoxyacetate – being the best acylating agent in the first set of KRs – in KRs leading to (R)-N-propoxyacetamides with high ee values (≥99.8%).
Nonpeptide urotensin-II receptor antagonists: A new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits
Lawson, Edward C.,Luci, Diane K.,Ghosh, Shyamali,Kinney, William A.,Reynolds, Charles H.,Qi, Jenson,Smith, Charles E.,Wang, Yuanping,Minor, Lisa K.,Haertlein, Barbara J.,Parry, Tom J.,Damiano, Bruce P.,Maryanoff, Bruce E.
experimental part, p. 7432 - 7445 (2010/06/19)
We have discovered two related chemical series of nonpeptide urotensin-II (U-II) receptor antagonists based on piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. Antagonist 7a exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. In advanced pharmacological testing, 7a blocked the effects of U-II in vitro in a rat aortic ring assay and in vivo in a rat ear-flushmodel. Adiscussion of U-II receptor antagonist pharmacophores is presented, and a specifically defined model is suggested from tricycle 13, which has a high degree of conformational constraint.
Alternative and complementary approaches to the asymmetric synthesis of C3 substituted NH free or N-substituted isoindolin-1-ones
Lamblin, Marc,Couture, Axel,Deniau, Eric,Grandclaudon, Pierre
, p. 111 - 123 (2008/09/17)
Complementary synthetic approaches to enantiomerically pure C3 alkylated or arylated NH free or N-substituted isoindolinones have been developed. The key step is elaboration of diversely substituted 2-alkyl- and arylbenzylamines, which can be submitted to a bis-metallation process followed by interception with a carbonylating agent. They can be also converted into N-alkylbromobenzylcarbamates or into bromobenzyldicarbamates and the assembly of the titled compounds can be readily ensured by reliance upon the Parham cyclization process.
UROTENSIN II RECEPTOR ANTAGONISTS
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Page/Page column 203, (2010/11/28)
The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.
