338945-89-4Relevant academic research and scientific papers
Highly diastereoselective alkylation of vicinal dianions of chiral succinic acid derivatives: A new general strategy to (R)-β-arylmethyl-γ- butyrolactones
Pohmakotr, Manat,Soorukram, Darunee,Tuchinda, Patoomratana,Prabpai, Samran,Kongsaeree, Palangpon,Reutrakul, Vichai
, p. 4315 - 4318 (2007/10/03)
The vicinal dianions derived from chiral succinic acid derivatives, 1,4-bis[(4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidin-1-yl]butane-1,4-dione and 1,4-bis[(4S,5R)-3,4-dimethyl-2-oxo-5-phenylimidazolidin-1-yl]butane-1,4- dione react with arylmethyl bromides with high diastereo- and regio-selectivity to provide the corresponding chiral α-arylmethylated succinic acid derivatives; the (R)-products are converted into (R)-β-arylmethyl-γ- butyrolactones and (R)-α-arylmethyl-γ-butyrolactones.
Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1
Ahmad,Doweyko,Dugar,Grazier,Ngu,Wu,Yost,Chen,Gougoutas,DiMarco,Lan,Gavin,Chen,Dorso,Serafino,Kirby,Atwal
, p. 3302 - 3310 (2007/10/03)
A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC50 = 3.5 μM) shows inhibitory activity comparable to cariporide (IC50 = 3.4 μM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC50 = 0.003 μM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.
The practical synthesis of (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine via optical resolution of 2-(3-methoxybenzyl)succinic acid
Yanagi,Kikuchi,Takeuchi,Ishikawa,Nishimura,Kamijo,Yamamoto
, p. 340 - 344 (2007/10/03)
We describe the practical synthetic route for (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine [(2S)-2-amino-7-methoxytetraline; (S)-AMT]. (2R)-2-(3-Methoxybenzyl)succinic acid [(R)-1] was obtained by the optical resolution of 2-(3-methoxybenzyl)succinic
