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Synthesis of 3,3‐Dimethylglutamic Acid Derivatives as DPP‐IV Inhibitors and Evaluation of Their Chemical Stability
Author(s) -
Hsu Tsu,
Tsai TingYueh,
Tseng YaJu,
Chiou MeiChun,
Lu ChengTai,
Chao YuSheng,
Jiaang WeirTorn
Publication year - 2011
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201190049
Subject(s) - chemistry , dipeptide , substituent , nitrile , amide , amine gas treating , intramolecular force , stereochemistry , peptide bond , combinatorial chemistry , organic chemistry , amino acid , biochemistry , enzyme
A novel five‐step synthesis of Boc‐3,3‐dimethylglutamic acid α‐ethyl ester 11 is reported. All the steps are high yielding and simple to carry out. By use of the 3,3‐dimethylglutamic acid building block, we successfully discovered a novel class of DPP‐IV inhibitors, Glu‐Pro‐Nitrile dipeptide mimics 2 , with high potency (IC 50 < 40 nM). The consequence of 3,3‐dimethyl substituent on the rate of intramolecular cyclization between N ‐terminal amine and 5‐position amide bond in different buffer solutions was also evaluated.