153460-97-0Relevant academic research and scientific papers
Parallel synthesis and structure-activity relationships of a series of highly potent, selective, and neutral factor Xa inhibitors
Bauer, Shawn M.,Goldman, Erick A.,Huang, Wenrong,Su, Ting,Wang, Lingyan,Woolfrey, John,Wu, Yanhong,Zuckett, Jingmei F.,Arfsten, Ann,Huang, Brian,Kothule, Jaya,Lin, Joyce,May, Bridget,Sinha, Uma,Wong, Paul W.,Hutchaleelaha, Athiwat,Scarborough, Robert M.,Zhu, Bing-Yan
, p. 4045 - 4050 (2004)
Parallel synthesis and iterative optimization led to the discovery of a series of potent and specific factor Xa inhibitors demonstrating excellent in vitro activity with promising pharmacokinetics.
N-Pyrrolidine-based α/β-peptides incorporating ABOC, a constrained bicyclic β-amino acid, for asymmetric aldol reaction catalysis
Milbeo, Pierre,Maurent, Kelly,Moulat, Laure,Lebrun, Aurélien,Didierjean, Claude,Aubert, Emmanuel,Martinez, Jean,Calmès, Monique
, p. 1706 - 1715 (2016/03/08)
A series of N-pyrrolidine-based α,β-peptide catalysts incorporating a constrained 2-aminobicyclo[2.2.2]octane carboxylic acid (ABOC) residue were synthesized and evaluated in the asymmetric aldol reaction from acetone and some p-substituted benzaldehydes. Their catalytic properties were shown to be highly dependent on the amino acid sequences and on the absolute configuration of the ABOC residue that played a determinant role. Among the peptides tested, the heterochiral tripeptide H-Pro-(R)-ABOC-Asp-OCH3 13, that adopts a turn conformation in the solid state, proved to be the most efficient catalyst affording β-hydroxy ketones in high yields and good enantioselectivities (up to 87%).
Multistimuli-responsive supramolecular organogels formed by low-molecular-weight peptides bearing side-chain azobenzene moieties
Fatás, Paola,Bachl, Jürgen,Oehm, Stefan,Jiménez, Ana I.,Cativiela, Carlos,Díaz Díaz, David
, p. 8861 - 8874 (2013/07/26)
This work demonstrates that the incorporation of azobenzene residues into the side chain of low-molecular-weight peptides can modulate their self-assembly process in organic solvents leading to the formation of stimuli responsive physical organogels. The major driving forces for the gelation process are hydrogen bonding and π-π interactions, which can be triggered either by thermal or ultrasound external stimuli, affording materials having virtually the same properties. In addition, a predictive model for gelation of polar protic solvent was developed by using Kamlet-Taft solvent parameters and experimental data. The obtained viscoelastic materials exhibited interconnected multistimuli responsive behaviors including thermal-, photo-, chemo- and mechanical responses. All of them displayed thermoreversability with gel-to-sol transition temperatures established between 33-80 °C and gelation times from minutes to several hours. Structure-property relationship studies of a designed peptide library have demonstrated that the presence and position of the azobenzene residue can be operated as a versatile regulator to reduce the critical gelation concentration and enhance both the thermal stability and mechanical strength of the gels, as demonstrated by comparative dynamic rheology. The presence of N-Boc protecting group in the peptides showed also a remarkable effect on the formation and properties of the gels. Despite numerous examples of peptide-based gelators known in the literature, this is the first time in which low-molecular-weight peptides bearing side chain azobenzene units are used for the synthesis of "intelligent" supramolecular organogels. Compared with other approaches, this strategy is advantageous in terms of structural flexibility since it is compatible with a free, unprotected amino terminus and allows placement of the chromophore at any position of the peptide sequence. Intelligent response: The incorporation of the azobenzene moiety into the side chain of low-molecular-weight peptides allows for the preparation of multistimuli-responsive supramolecular organogels. The presence and position of the azobenzene residue act as a versatile regulator to reduce the minimum gelation concentration and enhance both the thermal stability and mechanical strength of the materials (see figure). Copyright
Combined Lewis acid and Br?nsted acid-mediated reactivity of glycosyl trichloroacetimidate donors
Gould, Nathan D.,Liana Allen,Nam, Brandon C.,Schepartz, Alanna,Miller, Scott J.
, p. 36 - 42 (2013/11/19)
Biomimetic conditions for a synthetic glycosylation reaction, inspired by the highly conserved functionality of carbohydrate active enzymes, were explored. At the outset, we sought to generate proof of principle for this approach to developing catalytic systems for glycosylation. However, control reactions and subsequent kinetic studies showed that a stoichiometric, irreversible reaction of the catalyst and glycosyl donor was occurring, with a remarkable rate variance depending upon the structure of the carboxylic acid. It was subsequently found that a combination of Br?nsted acid (carboxylic acid) and Lewis acid (MgBr2) was unique in catalyzing the desired glycosylation reaction. Thus, it was concluded that the two acids act synergistically to catalyze the desired transformation. The role of the catalytic components was tested with a number of control reactions and based on these studies a mechanism is proposed herein.
Phosphate prodrugs for amines utilizing a fast intramolecular hydroxy amide lactonization
Nicolaou, Michails G.,Yuan, Chong-Sheng,Borchardt, Ronald T.
, p. 8636 - 8641 (2007/10/03)
A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2'-hydroxy-4',6'-dimethylphenyl)-3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-α-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2'-(dibenzylphosphono)oxy-4',6'-dimethylphenyl]-3,3-dimethylpropion ic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by the small variations observed in the Michaelis-Menten parameters (K(m) and V(max)) of the phosphate prodrugs. Results obtained from this study suggest that such a phosphate prodrug system may be applied to a variety of structurally diverse amine-containing drugs.
