95020-73-8Relevant academic research and scientific papers
Access to Cyclic β-Amino Acids by Amine-Catalyzed Enantioselective Addition of the γ-Carbon Atoms of α,β-Unsaturated Imines to Enals
Luo, Guoyong,Huang, Zhijian,Zhuo, Shitian,Mou, Chengli,Wu, Jian,Jin, Zhichao,Chi, Yonggui Robin
supporting information, p. 17189 - 17193 (2019/11/13)
Disclosed herein is a new catalytic approach for an efficient access to cyclic β-amino acids widely found in bioactive small molecules and peptidic foldamers. Our method involves addition of the remote γ-carbon atoms of α,β-unsaturated imines to enals by iminium organic catalysis. This highly chemo- and stereo-selective reaction affords cyclic β-amino aldehydes that can be converted to amino acids bearing quaternary stereocenters with exceptional optical purities. Our study demonstrates the unique power of organic catalytic remote carbon reactions in rapid synthesis of functional molecules.
Structure-Activity Studies on Benzhydrol-Containing Nipecotic Acid and Guvacine Derivatives as Potent, Orally-Active Inhibitors of GABA Uptake
Pavia, Michael R.,Lobbestael, Sandra J.,Nugiel, David,Mayhugh, Daniel R.,Gregor, Vlad E.,et al.
, p. 4238 - 4248 (2007/10/02)
The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs.A series of compounds is reported which explores the structure-activity relationships (SAR) in this series.Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring.The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of 1 μM (including 5, Table I; 37, 43, Table IV; and 44, Table V).Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.
