30845-22-8Relevant academic research and scientific papers
Oxadiazole and thiadiazole compounds and preparation methods and applications thereof
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Paragraph 0099-0102, (2019/07/04)
The invention discloses oxadiazole and thiadiazole compoundsand preparation methods and applications thereof.The compounds is shown as a formula I or a formula II.The oxadiazole or thiadiazole compound or a pharmaceutically acceptable salt, racemate, opti
NOVEL HIGH AFFINITY QUINOLINE-BASED KINASE LIGANDS
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Paragraph 0307, (2014/01/09)
Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.
Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity
Proteau-Gagne, Arnaud,Rochon, Kristina,Roy, Melissa,Albert, Pierre-Julien,Guerin, Brigitte,Gendron, Louis,Dory, Yves L.
supporting information, p. 5267 - 5269 (2013/09/23)
Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.
An eco-sustainable erbium(III) triflate catalyzed formation and cleavage of tert -butyl ethers
Procopio, Antonio,Costanzo, Paola,Curini, Massimo,Nardi, Monica,Oliverio, Manuela,Paonessa, Rosina
experimental part, p. 73 - 78 (2011/03/19)
An eco-compatible method, which permits the formation or cleavage of tert-butyl ethers of alcohols and phenols, is proposed. The protection step is performed in solvent-free conditions at room temperature using catalytic amount of Er(OTf)3. The catalyst is easily- recovered from the aqueous phase and reused several times without significant loss of activity. The deprotection step developed is also highly eco-friendly since the tert-butyl group is removed very quickly from alcohols and phenols in methanol using MW irradiation-. Georg Thieme Verlag Stuttgart · New York.
Universal peptidomimetics
Ko, Eunhwa,Liu, Jing,Perez, Lisa M.,Lu, Genliang,Schaefer, Amber,Burgess, Kevin
supporting information; scheme or table, p. 462 - 477 (2011/04/16)
This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.
Novel high affinity quinoline-based kinase ligands
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Page/Page column 108; 109, (2008/06/13)
Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.
Flexible and convergent total synthesis of cyclotheonamide B
Bastiaans, Harold M.M.,Van der Baan, Juul L.,Ottenheijm, Harry C.J.
, p. 3880 - 3889 (2007/10/03)
A convergent approach using two key intermediates, segment A [a L-proline-L-α-hydroxy-β-homoarginine-D-phenylalamine (Pro-hArg-D-Phe) tripeptide] and segment B [a vinylogous L-tyrosine-L-2,3-diaminopropanoic acid (vTyr-Dpr) dipeptide], was developed for the synthesis of cyclotheonamide B. The starting compound for the preparation of the hArg moiety 7, the predominant part of segment A, was N(α)-(benzyloxycarbonyl)-N(ω),N(ω)'-bis(tert-butyloxycarbonyl)-l-ar ginine methyl ester (15), which was converted into the aldehyde 16 and subsequently homologated using [tris(methylthio)methyl]lithium as a carboxylic acid anion equivalent. Coupling with properly protected Pro and D-Phe derivatives gave smoothly the desired Pro-hArg-D-Phe tripeptide derivative 24. The key feature of segment B, i.e., the L-tyrosine-derived α,β-unsaturated γ-amino acid 4, was prepared by a Wadsworth-Emmons olefination of the aldehyde 29 derived from N-(tert-butyloxycarbonyl), O-tert-butyl-L-tyrosine methyl ester (28). Selective N-(tert-butyloxycarbonyl) removal in the presence of the aryl tert-butyl ether present in the fully protected segment B, i.e., 32, was achieved by treatment with trimethylsilyl triflate/2,6-lutidine to give vTyr-Dpr dipeptide derivative 34 in quantitative yield. Coupling of the key intermediates 24 and 34 using 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) afforded the protected linear pentapeptide 35 in high yield. Treatment of 35 with Pd(PPh3)4/morpholine resulted in simultaneous removal of the C-terminal allyl group and the N-terminal allyloxycarbonyl group to yield 36. Ring closure was effected under dilution conditions by treatment with TBTU/1-hydroxybenzotriazole/4-(dimethylamino)pyridine and gave the protected cyclopentapeptide 37 in 61% yield. Oxidation of the hydroxyl group with Dess-Martin periodinane (24 h, 40°C) in the presence of tert-butyl alcohol gave 38, which was then subjected to O,N-deprotection with trifluoroacetic acid/thioanisole. Subsequent HPLC purification afforded cyclotheonamide B in an overall yield of 1.8% in 17 steps.
Total synthesis of cyclotheonamide B, a facile route towards analogues
Bastiaans, Harold M. M.,Van Der Baan, Juul L.,Ottenheijm, Harry C. J.
, p. 5963 - 5966 (2007/10/02)
A flexible, convergent synthesis of cyclotheonamide B (1b) was developed, starting from the constituent amino acids, using conventional benzyl-, t-butyl- and allyl-based protecting groups. By modification of the key intermediates, this approach allows the preparation of cyclotheonamide analogues.
On the Double Bond Isostere of the Peptide Bond: Preparation of an Enkephalin Analogue
Hann, Michael M.,Sammes, Peter G.,Kennewell, Peter D.,Taylor, John B.
, p. 307 - 314 (2007/10/02)
Methodology for preparing dipeptide analogues in which a carbon -carbon double bond replaces the normal amide bond is described.Thus, the protected tyrosylglycine analogue, (S)-trans-5-t-butyloxycarbonylamino-6-(4-t-butoxyphenyl)hex-3-enoic acid has been synthesised and incorporated into the Leu-enkephalin analogue (3) by condensation with glycylphenylalanyl-leucine.The enkephalin analogue retained biological activity.The significance of this isosteric replacement of the amide group is discussed.
