14296-92-5Relevant articles and documents
Bioinspired design for the assembly of Glypromate neuropeptide conjugates with active pharmaceutical ingredients
Silva-Reis, Sara C.,Dos Santos, A. Catarina V.D.,García-Mera, Xerardo,Rodríguez-Borges, José E.,Sampaio-Dias, Ivo E.
, p. 21049 - 21063 (2020)
Neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, are a class of heterogeneous pathologies of the central nervous system (CNS) affecting millions of people worldwide. CNS-related pathologies represent a global health burden in developed and developing countries with no curative treatments currently available. Thus, the development of novel multitarget neuroprotective drugs is a health priority. In this work, a bioinspired methodology in solution-phase for the assembly and regioselective conjugation of Glypromate neuropeptide with active pharmaceutical ingredients (APIs) is described. The main purpose is to design new hybrid molecules which may offer increased systemic resistance of Glypromate towards proteases and/or allow the controlled release of both APIs and the neuroprotective peptide within CNS. For the synthesis of such peptide-hybrid compounds (R)-1-aminoindane, amantadine, and memantine were selected as APIs for conjugation with Glypromate. Furthermore, capping strategies are explored to prepare Glypromate conjugates with more favorable pharmacodynamic profiles by masking polar exposed groups. Overall, this synthetic approach led to the development of a small library of 12 conjugates with improved drug-like properties in comparison with Glypromate, paving the way for the discovery of novel CNS multitarget drugs. Additionally, by exploring the bis-functionalization of glutamate, the formation of chiral glutarimides is disclosed for the first time employing TBTU as the coupling reagent. This unusual reactivity of TBTU with glutamate offers a new synthetic approach for the preparation of chiral glutarimide alkaloids.
Ferrocene tripeptide Gly-Pro-Arg conjugates: Synthesis and inhibitory effects on Alzheimer's Aβ1-42 fibrillogenesis and Aβ-induced cytotoxicity in vitro
Zhou, Binbin,Li, Chun-Lan,Hao, Yuan-Qiang,Johnny, Muya Chabu,Liu, You-Nian,Li, Juan
, p. 395 - 402 (2013)
Alzheimer's disease (AD) is the most common cause of dementia, and currently there is no clinical treatment to cure it or to halt its progression. Aggregation and fibril formation of β-amyloid peptides (Aβ) are central events in the pathogenesis of AD. Ma
STAT DEGRADERS AND USES THEREOF
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, (2021/09/26)
The present invention provides compounds, compositions thereof, and methods of using the same.
Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation
Fuentes de Arriba, ángel L.,Lenci, Elena,Sonawane, Mahendra,Formery, Odilon,Dixon, Darren J.
, p. 3655 - 3659 (2017/03/21)
A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C6H5)3]2 (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides.
