168960-17-6Relevant articles and documents
Regioselective hydroarylations and parallel kinetic resolution of Vince lactam
Kamlet, Adam S.,Preville, Cathy,Farley, Kathleen A.,Piotrowski, David W.
, p. 10607 - 10610 (2013)
Two regioselective and complementary hydroarylation reactions of an unsymmetrical cyclic olefin have been developed. The products can be transformed in one step into constrained γ-amino acids. Regioselective arylation of Vince lactam is controlled by the choice of phosphine ligand enantiomer and the substituent on the amide nitrogen atom. The method was extended to a general regiodivergent parallel kinetic resolution of the racemic lactam. Copyright
Mechanism-Based Design of 3-Amino-4-Halocyclopentenecarboxylic Acids as Inactivators of GABA Aminotransferase
Shen, Sida,Doubleday, Peter F.,Weerawarna, Pathum M.,Zhu, Wei,Kelleher, Neil L.,Silverman, Richard B.
supporting information, p. 1949 - 1955 (2020/03/04)
Aminotransferases are pyridoxal 5′-phosphate-dependent enzymes that catalyze reversible transamination reactions between an amino acid and an α-keto acid, playing a critical role in cellular nitrogen metabolism. It is evident that γ-aminobutyric acid aminotransferase (GABA-AT), which balances the levels of inhibitory and excitatory neurotransmitters, has emerged as a promising therapeutic target for epilepsy and cocaine addiction based on mechanism-based inactivators (MBIs). In this work, we established an integrated approach using computational simulation, organic synthesis, biochemical evaluation, and mass spectrometry to facilitate our design and mechanistic studies of MBIs, which led to the identification of a new cyclopentene-based analogue (6a), 25-times more efficient as an inactivator of GABA-AT compared to the parent compound (1R,3S,4S)-3-amino-4-fluorocyclopentane carboxylic acid (FCP, 4).
Fluorinated conformationally restricted γ-aminobutyric acid aminotransferase inhibitors
Lu, Hejun,Silverman, Richard B.
, p. 7404 - 7412 (2008/02/01)
On the basis of the structures of several potent inhibitor molecules for γ-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger kinact/K1 values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.
