Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists.

@article{Chiba2006SynthesisBE,
  title={Synthesis, biological evaluation, and pharmacokinetic study of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives as VLA-4 antagonists.},
  author={Jun Chiba and Gensuke Takayama and Tohru Takashi and Mika Yokoyama and Atsushi Nakayama and John J. Baldwin and Edward McDonald and Kevin Joseph Moriarty and Christopher Sarko and Kurt W. Saionz and Robert Swanson and Zahid Hussain and Angela S. Wong and Nobuo Machinaga},
  journal={Bioorganic \& medicinal chemistry},
  year={2006},
  volume={14 8},
  pages={
          2725-46
        }
}
4-(Pyrrolidinyl)methoxybenzoic acid derivatives as a potent, orally active VLA-4 antagonist.
TLDR
A novel series of benzoic acid derivatives as VLA-4 antagonists with good activity and moderate lipophilicity demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg.
Discovery of trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid: an orally active, selective very late antigen-4 antagonist.
We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4
Synthesis and Conformational Properties of 3,4-Difluoro-l-prolines.
TLDR
The reported analogues thus expand the scope of available fluorinated proline analogues as tools to tailor proline's distinct conformational and dynamical properties, allowing for the interrogation of its role in, for instance, protein stability or folding.
4-Fluoro and 4-Hydroxy Pyrrolidine-thioxotetrahydropyrimidinones: Organocatalysts for Green Asymmetric Transformations in Brine.
TLDR
The synthesis of both trans- and cis-diastereomers of pyrrolidinine-thioxotetrahydropyrimidinone bearing either a fluorine or a hydroxyl group was accomplished and the new catalysts could efficiently catalyze the reactions in brine, without the use of organic solvent, and by employing an almost stoichiometric amount of reagents.
Practical syntheses of 4-fluoroprolines.
Fluorine-Containing Prolines: Synthetic Strategies, Applications, and Opportunities.
Fluorinated prolines play an important role in peptide studies, protein engineering, medicinal chemistry, drug discovery, and agrochemistry. Since the first synthesis of 4-fluoroprolines by Gottlieb
4-chloroprolines: synthesis, conformational analysis, and effect on the collagen triple helix.
TLDR
These data, which are consistent with previous work on 4-fluoroprolines and 4-methylprolines, support the importance of stereoelectronic and steric effects in the stability of the collagen triple helix and provide another means to modulate that stability.
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A shift in strategy to identifying VLA-4 antagonists that would be suitable as candidates for inhalation therapy resulted in the preparation of compounds with exception tight binding properties, which were superior to BIO-1211 in the ovalbumin-sensitized mouse model of eosinophil trafficking to the lung.
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