78392-35-5Relevant academic research and scientific papers
Synthesis and Biological Evaluation of Endocannabinoid Uptake Inhibitors Derived from WOBE437
M?der, Patrick,Bartholom?us, Ruben,Nicolussi, Simon,Baumann, Alice,Weis, Melanie,Chicca, Andrea,Rau, Mark,Sim?o, Ana Catarina,Gertsch, Jürg,Altmann, Karl-Heinz
supporting information, p. 145 - 154 (2020/06/02)
WOBE437 ((2E,4E)-N-(3,4-dimethoxyphenethyl)dodeca-2,4-dienamide, 1) is a natural product-derived, highly potent inhibitor of endocannabinoid reuptake. In this study, we synthesized almost 80 analogues of 1 with different types of modifications in the dodecadienoyl domain as well as the dimethoxyphenylethyl head group, and we investigated their effects on anandamide uptake into U937 cells. Intriguingly, none of these analogues was a more potent inhibitor of anandamide uptake than WOBE437 (1). At the same time, a number of WOBE437 variants exhibited potencies in the sub-100 nM range, with high selectivity over inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase; two compounds were virtually equipotent with 1. Interestingly, profound activity differences were observed between analogues in which either of the two methoxy substituents in the head group had been replaced by the same bulkier alkoxy group. Some of the compounds described here could be interesting departure points for the development of potent endocannabinoid uptake inhibitors with more drug-like properties.
The preparation method of the levodopa intermediate derivatives
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Paragraph 0063; 0064; 0065, (2017/10/13)
The invention relates to a preparation method for a levodopa intermediate derivative. The preparation method comprises: in a solvent, reacting 3, 4-dimethoxybenzene phenylalanine shown as formula I with (+)-tartaric acid derivative to obtain the salt of a [(-)-3, 4-dimethoxybenzene phenylalanine]2.(+)- tartaric acid derivative. The solvent includes an alcohol solvent and an ester solvent. The racemization method includes: in the solvent, under the action of an aldehyde or ketone catalyst, reacting the 3, 4-dimethoxybenzene phenylalanine shown as formula I at 0-90DEG C for 0.5-24 h. The preparation method for the levodopa intermediate derivative provided by the invention has simple steps, and the prepared enantiomer has high purity and is low in cost, thus being applicable to industrial production. (reaction formula).
Fixation and recycling of nitrogen monoxide through carbonitrosation reactions
De Salas, Cristina,Heinrich, Markus R.
supporting information, p. 2982 - 2987 (2014/06/10)
The removal of nitrogen monoxide from gas streams through complexation to iron(ii) ions in aqueous dimethylsulfoxide can be combined with a new variant of the Meerwein arylation, which incorporates the previously complexed NO into organic compounds to give oximes as final products. The first step of this two-step process has been evaluated regarding the effectiveness of the NO absorption and the sensitivity of the aqueous iron(ii)-DMSO solution towards oxygen from air, in both cases in comparison with the known BioDeNOx process. The subsequent Meerwein arylation, which was designed with the intention to make use of nitrogen monoxide as the simplest nitrogen-centered radical scavenger, is shown to tolerate an exceptionally broad spectrum of substituents on the aromatic core of the diazonium salts including electron-donating as well as electron-withdrawing substituents. Under simple conditions the resulting oximes can be converted to racemic amino acid esters. This journal is the Partner Organisations 2014.
Synthesis of aromatic α-aminoesters: Palladium-catalyzed long-range arylation of primary Csp3-H bonds
Aspin, Sam,Goutierre, Anne-Sophie,Larini, Paolo,Jazzar, Rodolphe,Baudoin, Olivier
, p. 10808 - 10811 (2013/01/15)
Remote control: The title reaction for β-Iζ arylation of α-amino esters with aryl bromides is described. This reaction, which occurs selectively at the terminal position of linear alkyl chains, gives rise to synthetically useful (hetero)arylalanines and homologues after debenzylation (see scheme). Copyright
Electronically rich N-substituted tetrahydroisoquinoline 3-carboxylic acid esters: Concise synthesis and conformational studies
Al-Horani, Rami A.,Desai, Umesh R.
experimental part, p. 2027 - 2040 (2012/04/04)
Recent work in our laboratory has shown that the highly substituted, electronically rich 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants.10 The synthesis
Designing nonsaccharide, allosteric activators of antithrombin for accelerated inhibition of factor Xa
Al-Horani, Rami A.,Liang, Aiye,Desai, Umesh R.
experimental part, p. 6125 - 6138 (2011/10/30)
Antithrombin is a key regulator of coagulation and prime target of heparins, clinically used anticoagulants. Heparins induce a two-step conformational activation of antithrombin, a process that has remained challenging to target with molecules devoid of t
The structure-activity relationship of the series of non-peptide small antagonists for p56lck SH2 domain
Park, See-Hyoung,Oh, Hyun-Sik,Kang, Mi-Ae,Cho, Hyeongjin,Prasad, Joshi Bishnu,Won, Jonghwa,Lee, Keun-Hyeung
, p. 3938 - 3950 (2008/02/13)
The antagonists for the SH2 domain are regarded as novel therapeutic candidates for cancer, autoimmune disease, and chronic inflammatory disease. Previously, we identified rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyl-lactic acid; RosA) from Prunella vulgaris as an antagonist for the p56lck SH2 domain by screening natural products. RosA not containing phosphotyrosine surrogate had a considerable inhibitory activity for T-cell antigen receptor (TCR)-induced interleukin (IL)-2 expression, and subsequent T-cell proliferation in vitro cell assay. To investigate the structure-activity relationship of RosA and to identify a novel p56lck SH2 antagonist with more potent in vitro T-cell inhibitory activity, we synthesized several analogs of RosA by using rational design. All synthesized compounds were tested in vitro binding activity for the SH2 domain and in vitro T-cell inhibitory activity. All four hydroxyl groups of RosA were essential for binding with the p56lck SH2 domain and T-cell inhibitory activity. Unexpectedly, conformationally less constrained analogs 4 and 9 showed a more potent binding affinity for the SH2 domain than that of RosA, and chirality of the analog did not play an important role in protein binding. We successfully identified several RosA analogs with a more potent T-cell inhibitory activity than that of RosA. Overall results revealed important structural requirements of the p56lck SH2 antagonists for in vitro T-cell inhibitory activity and in vitro protein binding activity.
New synthetic amino acids for the design and synthesis of peptide-based metal ion sensors
Torrado, Alicia,Imperiali, Barbara
, p. 8940 - 8948 (2007/10/03)
The syntheses of two new nonstandard amino acids, Flu (6) and XBp (20), and a new synthesis of Dmd (12) are reported. These residues exhibit fluorescence, metal-coordination, and fluorescence-quenching properties, respectively. These building blocks have been incorporated into peptides via solid phase peptide synthesis to afford the prototype for a photoinduced electron transfer-based metal ion chemosensor. The fluorescence of the peptides is modulated upon metal binding. This results from a metal ion-induced conformational change that brings the side chains of the Flu and Dmd amino acids into proximity, thereby favoring photoinduced electron transfer (PET) fluorescence quenching.
ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
Schoellkopf, Ulrich
, p. 2085 - 2092 (2007/10/02)
Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
