182618-33-3Relevant academic research and scientific papers
Design and synthesis of Fmoc-SPPS-ready iodoarene amino acid pre-catalysts and their reactivity in the catalytic oxytosylation of ketones
Brummel, Beau R.,Giambalvo, Lauren N.,Gross, Kristopher G.,Kobra, Khadijatul,Lex, Timothy R.,McMillen, Colin D.,Panda, Soham,Pennington, William T.,Swasy, Maria I.,Whitehead, Daniel C.
supporting information, (2020/02/22)
A small suite of iodo-aryl amide containing amino acids were synthesized and assessed as catalysts for the hypervalent iodine(III) mediated α-oxytosylation of ketones. The efficiency of each catalyst was determined by comparing the relative rates of catalysis in the direct α-oxytosylation of propiophenone. In addition, these catalysts can be easily converted to congeners that are suitable for Fmoc-solid phase peptide synthesis for facile incorporation into a chiral peptide framework. This work facilitates the broader goal of our program to develop peptide-based enantioselective catalysts for hypervalent iodine chemistry.
Total synthesis of padanamides A and B
Long, Bohua,Tang, Shoubin,Chen, Ligong,Qu, Shiwei,Chen, Bo,Liu, Junyang,Maguire, Anita R.,Wang, Zhuo,Liu, Yuqing,Zhang, Hui,Xu, Zhengshuang,Ye, Tao
supporting information, p. 2977 - 2979 (2013/05/22)
The first total syntheses of padanamides A and B have been achieved, unambiguously confirming their structures. The Royal Society of Chemistry.
Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
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Page/Page column 41, (2008/06/13)
The present application describes sulfonylaminovalerolactams and derivatives thereof of Formula I: or pharmaceutically acceptable salt forms thereof, wherein ring G is a mono- or bicyclic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.
An assessment of the mechanistic differences between two integrin α4β1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis
Leone,Giza,Gill,Dolinski,Yang,Perper,Scott,Lee,Cornebise,Wortham,Nickerson-Nutter,Chen,Lepage,Spell,Whalley,Petter,Adams,Lobb,Pepinsky
, p. 1150 - 1162 (2007/10/03)
Integrin α4β1 plays an important role in inflammatory processes by regulating the migration of lymphocytes into inflamed tissues. Here we evaluated the biochemical, pharmacological, and pharmacodynamic properties and efficacy in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, of two types of α4β1 inhibitors, the anti-rat α4 monoclonal antibody TA-2 and the small molecule inhibitor BIO5192 [2(S)-{[1(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino} 4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}amino)- pentanoylamino]-butyric acid]. TA-2 has been extensively studied in rats and provides a benchmark for assessing function. BIO5192 is a highly selective and potent (KD of 4β1. Dosing regimens were identified for both inhibitors, which provided full receptor occupancy during the duration of the study. Both inhibitors induced leukocytosis, an effect that was used as a pharmacodynamic marker of activity, and both were efficacious in the EAE model. Treatment with TA-2 caused a decrease in α4 integrin expression on the cell surface, which resulted from internalization of α4 integrin/TA-2 complexes. In contrast, BIO5192 did not modulate cell surface α4β1. Our results with BIO5192 indicate that α4β7 does not play a role in this model and that blockade of α4β1/ligand interactions without down-modulation is sufficient for efficacy in rat EAE. BIO5192 is highly selective and binds with high affinity to α4β1 from four of four species tested. These studies demonstrate that BIO5192, a novel, potent, and selective inhibitor of α4β1 integrin, will be a valuable reagent for assessing α4β1 biology and may provide a new therapeutic for treatment of human inflammatory diseases.
Modification of receptor selectivity and functional activity of cyclic cholecystokinin analogues
Amblard, Muriel,Rodriguez, Marc,Lignon, Marie-Francoise,Galas, Marie-Christine,Bernad, Nicole,Aumelas, Andre,Martinez, Jean
, p. 171 - 180 (2007/10/03)
We reported earlier on the synthesis and biological activity at the CCK-B receptor of cyclized derivatives of CCK. These peptides, in which the positions 28 and 31 were replaced by lysine residues, were bridged by a succinyl moiety. To determine the importance of the nature and size of the cyclic structure, cyclic analogues were synthesized in which: (i) the lysine residues were replaced by ornithine and diaminobutyric acid and (ii) the succinic moiety was replaced by a malonic, adipic and glutaric moiety. They were tested For their ability to inhibit the specific binding of 125I-BH-CCK-8 to CCK receptors in rat pancreatic acini and guinea pig brain membranes. They were also evaluated for their ability to stimulate amylase secretion from rat pancreatic acini. The potency and selectivity of these analogues were compared with those obtained with CCK-4 and compound JIMV320, a potent and selective CCK-B receptor ligand synthesized earlier in our laboratory.
127. C-glycoside analogues of N4-(2-Acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine: synthesis and conformational analysis of a cyclic C-glycopeptide
Hoffmann, Matthias,Burkhart, Fred,Hessler, Gerhard,Kessler, Horst
, p. 1519 - 1532 (2007/10/03)
The synthesis of C-glycosidic analogues 15-22 of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine (ASn(N4GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-glycosidic linkage is presented. The peptide cyclo(-D-Pro-Phe-Ala-CGaa-Phe-Phe-) (CGaa = C-glycosylated amino acid; 24) was prepared to demonstrate that 3-[(3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D- guloheptonoyl)amino]-2-[(9H-fluoren-9-yloxycarbonyl)amino]propanoic acid (22) can be used in solid-phase peptide synthesis. The conformation of 24 was determined by NMR and molecular-dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C-glycosylated amino acids 15-21 were prepared by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-β-D-glycero-D-gulo- heptonic acid (4) with diamino-acid derivatives 8-14 in 83-96% yield. The synthesis of 4 was performed from 2-(acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucopyranosyl)tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the glycoheptonamide 7 in 52% from 2. Compound 2 was obtained from 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (1) by chlorination and addition of tributyltinlithium in 74% yield. A procedure for a multigram-scale synthesis of 1 is given.
