77225-89-9

Upstream product

• 7536-55-2 N-tert-butyloxycarbonylasparagine 
• 65710-57-8 3-{[(benzyloxy)carbonyl]amino}-N-(tert-butoxycarbonyl)-L-alanine 
• 75-65-0 tert-butyl alcohol 
• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 77255-62-0 tert-butyl 3-N-carbobenzoxy-(S)-2,3-diaminopropionate 
• 76387-70-7 (S)-3-amino-2-tert-butoxycarbonylaminopropionic acid 

Downstream Products

• 77215-54-4 tert-butyl 2-<(tert-butoxycarbonyl)amino>-3-aminopropanoate 
• 918906-33-9 C₂₉H₄₄BrN₅O₁₀S 

Relevant academic research and scientific papers

THERAPEUTIC COMPOUNDS AND METHODS

Disclosed herein are compounds of formula I: (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, and R3 may any of the values defined herein, as well as compositions comprising such compounds. Also disclosed are methods for treating diseases including neurodegenerative disorders such as Parkinson's Disease and Alzheimer's Disease.

Inhibition of glyoxalase I: The first low-nanomolar tight-binding inhibitors

A series of rational modifications to the structure of known S-(N-aryl-N-hydroxycarbamoyl)glutathione-based glyoxalase I inhibitors culminated in the discovery of the first single-digit nanomolar inhibitor. This study makes available key information about possible means to address the issues of metabolic instability, low potency, and synthetic complexicity that have plagued the area of glyoxalase I inhibition. Knowledge garnered from this study has implications in the design of inhibitors with higher conformational definition and lower peptidic character.

Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs

Plethoras of CNS-active drugs fail to effect their pharmacologic response due to their in vivo inability to cross the blood-brain barrier (BBB). The classical prodrug approach to overcome this frailty involves lipophilic derivatives of the polar drug, but we herein report a novel approach by which endogenous transporters at BBB are exploited for brain drug delivery. The crucial role played by glutathione in pathogenesis of Parkinson's and the presence of its influx transporters at the basolateral membrane of BBB served as the basis for our anti-Parkinson prodrug design strategy. A metabolically stable analogue of glutathione is used as a carrier for delivery of dopamine and adamantamine. An account of successful syntheses of these prodrugs along with their transport characteristics and stability determination is discussed.

A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I

The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistance toward γ-glutamyltranspeptidase mediated breakdown. This compound is viewed as a potential lead for the development of second-generation glyoxalase-I inhibitors wherein, the problems pertaining to metabolism and selectivity are overcome.