- Expanding the repertoire of nitrilases with broad substrate specificity and high substrate tolerance for biocatalytic applications
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Enzymatic conversion of nitriles to carboxylic acids by nitrilases has gained significance in the green synthesis of several pharmaceutical precursors and fine chemicals. Although nitrilases from several sources have been characterized, there exists a scope for identifying broad spectrum nitrilases exhibiting higher substrate tolerance and better thermostability to develop industrially relevant biocatalytic processes. Through genome mining, we have identified nine novel nitrilase sequences from bacteria and evaluated their activity on a broad spectrum of 23 industrially relevant nitrile substrates. Nitrilases from Zobellia galactanivorans, Achromobacter insolitus and Cupriavidus necator were highly active on varying classes of nitriles and applied as whole cell biocatalysts in lab scale processes. Z. galactanivorans nitrilase could convert 4-cyanopyridine to achieve yields of 1.79 M isonicotinic acid within 3 h via fed-batch substrate addition. The nitrilase from A. insolitus could hydrolyze 630 mM iminodiacetonitrile at a fast rate, effecting 86 % conversion to iminodiacetic acid within 1 h. The arylaliphatic nitrilase from C. necator catalysed enantioselective hydrolysis of 740 mM mandelonitrile to (R)-mandelic acid in 4 h. Significantly high product yields suggest that these enzymes would be promising additions to the suite of nitrilases for upscale biocatalytic application.
- Rayavarapu, Pratima,Shah, Shikha,Sunder, Avinash Vellore,Wangikar, Pramod P.
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Read Online
- Copper-catalyzed: N -(hetero)arylation of amino acids in water
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An environmentally benign, mild, cost-effective and gram-scalable copper-catalyzed method for the N-(hetero)arylation of zwitterionic natural and unnatural amino acids using 2-isobutyrylcyclohexanone as a β-diketone ligand and aryl bromides as coupling partners in water for 50 min at 90 °C under microwave irradiation is reported. Electronically and sterically diverse aryl coupling partners were inserted efficiently, including challenging heteroaryl electrophilic partners in high yields without affecting the enantiopurity of the product.
- Sharma, Krishna K.,Mandloi, Meenakshi,Rai, Neha,Jain, Rahul
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Read Online
- Mechanosynthesis of sydnone-containing coordination complexes
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N-Phenyl-4-(2-pyridinyl) sydnone was shown to act as a four-electron donor N,O-ligand in unprecedented coordination complexes featuring three different metallic centers (Co, Cu, and Zn). Starting with various anilines, the use of a ball-mill efficiently enabled the synthesis of N-arylglycines, subsequent nitrosylation and cyclization into sydnones, and further metalation.
- Pétry, Nicolas,Vanderbeeken, Thibaut,Malher, Astrid,Bringer, Yoan,Retailleau, Pascal,Bantreil, Xavier,Lamaty, Frédéric
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Read Online
- Reagent-free continuous thermal tert-butyl ester deprotection
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Continuous processing enables the use of non-standard reaction conditions such as high temperatures and pressures while in the liquid phase. This expands the chemist's toolbox and can enable previously unthinkable chemistry to proceed with ease. For a series of amphoteric amino acid derivatives, we have demonstrated the ability to hydrolyze the tert-butyl ester functionality in protic solvent systems. Using a continuous plug flow reactor at 120–240 °C and 15–40 min reaction times, no pH modification or additional reagents are needed to achieve the desired transformation. The method was then expanded to encompass a variety of more challenging substrates to test selectivity and racemization potential. The acid products were generally isolated as crystalline solids by simple solvent exchange after the deprotection reaction in good to high yield and purity.
- Cole, Kevin P.,Ryan, Sarah J.,Groh, Jennifer McClary,Miller, Richard D.
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Read Online
- Soluble Polymer-Supported Synthesis of α-Amino Acid Derivatives
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A practical and efficient synthesis of N-substituted α-amino acid derivatives on soluble polymer support is described.
- Hu, Chunling,Chen, Zuxing,Yang, Guichun
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Read Online
- Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage
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So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1β, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.
- Wang, Kun,Wu, Jia-Jing,Xin–Zhang,Zeng, Qing-Xuan,Zhang, Na,Huang, Wei-Jin,Tang, Sheng,Wang, Yan-Xiang,Kong, Wei-Jia,Wang, You-Chun,Li, Ying-Hong,Song, Dan-Qing
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- Water-Involved Ring-Opening of 4-Phenyl-1,2,4-triazoline-3,5-dione for “Photo-Clicked” Access to Carbamoyl Formazan Photoswitches In Situ
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Cyclic azodicarbonyl derivatives, particularly 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), commonly serve as arenophile, dienophile, enophile and electrophile. Perplexed by its instability in aqueous environment, there are few studies focused on the transient intermediate produced by hydrolysis of PTAD to achieve synthetic significance. Herein, we describe a “photo-click” method that involves nitrile imine (NI) from diarylsydnone to capture the diazenecarbonyl-phenyl-carbamic acid (DACPA) generated by water-promoted ring-opening of PTAD. DFT calculation reveal that H-bonding interactions between PTAD and water are vital to form DACPA which exhibited an umpolung effect during ligation by nature bond orbit (NBO) analysis. The ultra-fast ligation resulted in carbamoyl formazans, as a unique Z?E photo-switchable linker on target molecules, including peptide and drugs, with excellent anti-fatigue performance. This strategy is showcased to construct highly functionalized carbamoyl formazans in situ for photo-pharmacology and material studies, which also expands the chemistry of PTAD in aqueous media.
- Deng, Pengchi,Du, Guangxi,Jiang, Shichao,Shen, Xin,Su, Zhishan,Xie, Xinyu,Yu, Zhipeng,Zhang, Yan,Zhao, Xiaohu,Zheng, Yuanqin,Zhou, Yuqiao
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supporting information
(2021/12/22)
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- Perovskite as Recyclable Photocatalyst for Annulation Reaction of N-Sulfonyl Ketimines
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A sustainable and cost-effective manner for the photocatalytic annulation reaction of N-sulfonyl ketimines with N-arylglycines to synthesize imidazolidine-fused sulfamidates (31 examples) by employing CsPbBr3 as a heterogeneous photocatalyst has been developed. The catalyst CsPbBr3 can be simply recovered from the reaction mixture and reused at least five times without an obvious reduction in its photocatalytic reactivity, exhibiting a high catalyst economic feature.
- Chen, Xiaolan,Qu, Lingbo,Shi, Anzai,Sun, Kai,Yu, Bing,Zhao, Yufen
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supporting information
(2022/01/04)
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- Structure-activity relationships and mechanistic studies of novel mitochondria-targeted, leishmanicidal derivatives of the 4-aminostyrylquinoline scaffold
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A new class of quinoline derivatives, bearing amino chains at C-4 and a styryl group at C-2, were tested on Leishmania donovani promastigotes and axenic and intracellular Leishmania pifanoi amastigotes. The introduction of the C-4 substituent improves the activity, which is due to interference with the mitochondrial activity of the parasite and its concomitant bioenergetic collapse by ATP exhaustion. Some compounds show a promising antileishmanial profile, with low micromolar or submicromolar activity on promastigote and amastigote forms and a good selectivity index.
- Staderini, Matteo,Piquero, Marta,Abengózar, María ángeles,Nachér-Vázquez, Montserrat,Romanelli, Giulia,López-Alvarado, Pilar,Rivas, Luis,Bolognesi, Maria Laura,Menéndez, J. Carlos
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- AMINOAMIDE COMPOUNDS
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Compounds with amino amide linkers and pharmaceutical compositions and medicaments comprising such compounds are disclosed. The compounds modulate protein function of 1L-1β, IL-2, IL-6, TNF-α, CK1α, GSPT1, aiolos, ikaros or helios, or combinations thereof. In addition, methods of making such compounds and their uses for treating or ameliorating diseases, disorders, or conditions associated with protein malfunction, such as cancer, are provided.
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Paragraph 0167
(2020/01/08)
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- Novel sydnone derivatives carrying azidomethyl-1,2, 4-oxadiazole unit and their 1,3-dipolar cycloadditions
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A series of 1,2,4-oxadiazolymethyl sydnones carrying azido group were synthesized and subjected to react with a variety of alkenic and acetylenic dipolarophilic reagents; N-phenyl maleimide, phenyl vinyl sulfone, and phenyl propiolic acid. All the new products are identified by spectral/physical data including high-resolution mass measurements and X-ray diffraction data.
- Dürüst, Ya?ar,Y?ld?z, Elif,Karaku?, Hamza,Kariuki, Benson M.
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p. 660 - 670
(2017/03/24)
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- Microwave-promoted N-arylation of imidazole and amino acids in the presence of Cu2O and CuO in poly(ethylene glycol)
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Copper(I)-catalyzed N-arylation of imidazole with iodobenzene, its derivatives, and bromobenzene in poly(ethylene glycol) under microwave irradiation was studied. The influence of the following factors on the yield of arylation product was investigated: the nature of the source of copper and ligand, type of poly(ethylene glycol) (PEG) used, and substituents in iodoarene. An optimal catalytic system was selected: CuO/l-Hys/Cs2CO3/PEG-400, a possibility of recycling of copper-containing catalyst was demonstrated. N-Arylation of eight natural amino acids using catalysis with Cu2O/Cs2CO3/PEG-400 and microwave irradiation was studied, the dependence of the reaction results on temperature, duration of the process, and the ratio of the starting reagents was found. The highest yields of the target products were reached in the case of leucine, valine, and phenylalanine.
- Yakushev,Averin,Colacino,Lamaty,Beletskaya
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p. 1243 - 1248
(2017/02/05)
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- FUNCTIONALIZED FLUORINE CONTAINING PHTHALOCYANINE MOLECULES
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Functionalized fluorine containing phthalocyanine molecules, methods of making, and methods of use in diagnostic applications and disease treatment are disclosed herein. In some embodiments, the fluorine containing phthalocyanine molecules are functionalized with a reactive functional group or at least one cancer-targeting ligand (CTL). The CTL can facilitate more efficient binding and/or internalization to a cancer cell than to a healthy cell. The CTL can inhibit expression of oncoprotein in some embodiments. The pthalocyanine moiety can be used in diagnostic applications, such as fluorescence labeling of a cancer cell, and/or treatment applications, such as catalyzing formation of a reactive oxygen species (ROS) which can contribute to cell death of a cancer cell.
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- Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF
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Catechol-based inhibitors of ERCC1-XPF endonuclease activity were identified from a high-throughput screen. Exploration of the structure-activity relationships within this series yielded compound 13, which displayed an ERCC1-XPF IC50 of 0.6 μM, high selectivity against FEN-1 and DNase I and activity in nucleotide excision repair, cisplatin enhancement and γH2AX assays in A375 melanoma cells. Screening of fragments as potential alternatives to the catechol group revealed that 3-hydroxypyridones are able to inhibit ERCC1-XPF with high ligand efficiency, and elaboration of the hit gave compounds 36 and 37 which showed promising ERCC1-XPF IC50 values of 10 μM.
- Chapman, Timothy M.,Gillen, Kevin J.,Wallace, Claire,Lee, Maximillian T.,Bakrania, Preeti,Khurana, Puneet,Coombs, Peter J.,Stennett, Laura,Fox, Simon,Bureau, Emilie A.,Brownlees, Janet,Melton, David W.,Saxty, Barbara
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supporting information
p. 4097 - 4103
(2015/11/03)
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- N-Functionalized Amino Acids Promoted Aerobic Copper-Catalyzed Oxidation of Benzylic Alcohols in Water
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Instead of traditional N,N-bidentate ligands, N-functionlized amino acids were used as powerful N,O-bidentate ligands in aerobic copper/TEMPO-catalyzed system for promoting oxidation of benzylic alcohols. Under the optimized reaction conditions, a wide range of primary and secondary benzylic alcohols have been efficiently converted into aldehydes and ketones with good to excellent yields in water.
- Zhang, Guofu,Lei, Jie,Han, Xingwang,Luan, Yuxin,Ding, Chengrong,Shan, Shang
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supporting information
p. 779 - 784
(2015/03/30)
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- Room temperature N-arylation of amino acids and peptides using copper(i) and β-diketone
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A mild and efficient method for the N-arylation of zwitterionic amino acids, amino acid esters and peptides is described. The procedure provides the first room temperature synthesis of N-arylated amino acids and peptides using CuI as a catalyst, diketone as a ligand, and aryl iodides as coupling partners. The method is equally applicable for using relatively inexpensive aryl bromides as coupling partners at 80 °C. Using this procedure, electronically and sterically diverse aryl halides, containing reactive functional groups were efficiently coupled in good to excellent yields.
- Sharma, Krishna K.,Sharma, Swagat,Kudwal, Anurag,Jain, Rahul
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supporting information
p. 4637 - 4641
(2015/04/27)
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- Catalyst-free photoredox addition-cyclisations: Exploitation of natural synergy between aryl acetic acids and maleimide
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Suitably functionalised carboxylic acids undergo a previously unknown photoredox reaction when irradiated with UVA in the presence of maleimide. Maleimide was found to synergistically act as a radical generating photoxidant and as a radical acceptor, negating the need for an extrinsic photoredox catalyst. Modest to excellent yields of the product chromenopyrroledione, thiochromenopyrroledione and pyrroloquinolinedione derivatives were obtained in thirteen preparative photolyses. In situ NMR spectroscopy was used to study each reaction. Reactant decay and product build-up were monitored, enabling reaction profiles to be plotted. A plausible mechanism, whereby photo-excited maleimide acts as an oxidant to generate a radical ion pair, has been postulated and is supported by UV/Vis. spectroscopy and DFT computations. The radical-cation reactive intermediates were also characterised in solution by EPR spectroscopy. UVA photolyses of aryloxy-, arylthio- and arylamino-acetic acids with maleimide yield oxa-, thia- and aza-tricyclo pyrroledione derivatives in the absence of a photoredox catalyst (see scheme). An intriguing mechanism has been proposed and has been supported and supplemented by NMR monitoring experiments, DFT computations and UV/Vis and EPR spectroscopy.
- Manley, David W.,Mills, Andrew,O'Rourke, Christopher,Slawin, Alexandra M. Z.,Walton, John C.
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supporting information
p. 5492 - 5500
(2014/05/20)
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- Immunomodulatory peptides
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The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.
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- Aerobic synthesis of biocompatible copper nanoparticles: Promising antibacterial agent and catalyst for nitroaromatic reduction and C-N cross coupling reaction
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Herein, we report the synthesis of copper nanoparticles at ambient conditions using biopolymer, pectin, as a protecting agent and hydrazine as a reducing agent. The obtained nanoparticles catalyze the reduction of nitroaromatic compounds in aqueous solution and also catalyze the C-N cross coupling of amines with bromobenzene in good yields. This journal is the Partner Organisations 2014.
- Venkatakrishnan, Showmya,Veerappan, Ganapathy,Elamparuthi, Elangovan,Veerappan, Anbazhagan
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p. 15003 - 15006
(2014/04/17)
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- GADD45BETA TARGETING AGENTS
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Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.
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- Regioselective reaction: Synthesis, characterization and pharmacological activity of some new Mannich and Schiff bases containing sydnone
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A novel series of 1-substituted aminomethyl-3-[1-(4-isobutylphenyl)ethyl]- 4-(3-aryl-4-sydnonylidene) amino-1,2,4-triazol-5-thiones (9), was prepared from the 3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino 5-mercapto-1,2,4-triazoles (8) by aminomethylation with formaldehyde and secondary amine. The structures of Schiff bases (8) and Mannich bases (9) were characterized on the basis of IR, NMR, mass spectra1 data and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Mannich bases (9) carrying piperidine and morpholine residues showed promising anti-inflammatory and analgesic activity.
- Nithinchandra,Kalluraya,Aamir,Shabaraya
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experimental part
p. 597 - 604
(2012/09/11)
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- Use of diphenyliodonium bromide in the synthesis of some N-phenyl-amino acids
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The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO3, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, 1H, and 13C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.
- McKerrow, Jason D.,Al-Rawi, Jasim M. A.,Brooks, Peter
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experimental part
p. 1161 - 1179
(2010/04/28)
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- Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines
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A strategy for the stereoselective preparation of enantiomerically enriched cis-2,6-disubstituted piperazines from amino acid precursors is described. The target compounds are generated in 95-99% ee with good to excellent levels of diastereoselectivity (usually 14:1 to >20:1) using Pd-catalyzed carboamination reactions between aryl or alkenyl halides and substituted ethylenediamine derivatives to form the heterocyclic rings. The synthesis requires only 4-5 steps from commercially available amino acids, and allows for the modular construction of piperazines bearing different substituents at N1, N4, C2, and C6. The use of this strategy for the construction of 2,3-disubstituted piperazines, fused bicyclic piperazines, and tetrahydroquinoxalines is also reported. In addition, the mechanism of the key carboamination reactions is discussed, and new models that predict and explain the stereochemical outcome of these transformations are presented.
- Nakhla, Josephine S.,Schultz, Danielle M.,Wolfe, John P.
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scheme or table
p. 6549 - 6570
(2011/02/25)
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- Convenient access to 1,3,4-trisubstituted pyrazoles carrying 5-nitrothiophene moiety via 1,3-dipolar cycloaddition of sydnones with acetylenic ketones and their antimicrobial evaluation
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Novel 1-aryl-3-(5-nitro-2-thienyl)-4-aroyl-pyrazoles 7 have been synthesized by the 1,3-dipolar cycloaddition of 3-arylsydnones 3 with 1-aryl-3-(5-nitro-2-thienyl)-2-propyn-1-ones 6. The newly synthesized compounds were well characterized by elemental analysis, IR, 1H NMR and mass spectral studies. They were also screened for their antibacterial and antifungal activities against a variety of microorganisms and the results of such studies have been discussed in this article.
- Satheesha Rai,Kalluraya, Balakrishna,Lingappa,Shenoy, Shaliny,Puranic, Vedavati G.
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p. 1715 - 1720
(2008/12/20)
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- Fully enzymatic resolution of chiral amines: Acylation and deacylation in the presence of Candida antarctica lipase B
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A fully enzymatic methodology for the resolution of chiral amines has been demonstrated. Candida antarctica lipase B (CaLB)-catalyzed acylation with N-methyl-and N-phenylglycine, as well as analogues having the general formula R1-X-CH2CO2R2 (R1 = Me, Ph; X = O, S) afforded the corresponding enantioenriched amides, which were subsequently enzymatically hydrolyzed. Surprisingly, CaLB also proved to be the catalyst of choice for this latter step. The heteroatom in the acyl donor profoundly influences both the enzymatic acylation and deacylation; the O-substituted reagents performed best with regard to enantioselectivity as well as reaction rate in synthesis and hydrolysis.
- Ismail, Hilda,Lau, Rute Madeira,Van Rantwijk, Fred,Sheldon, Roger A.
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experimental part
p. 1511 - 1516
(2009/08/07)
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- Synthesis and evaluation of phenyl substituted sydnones as potential DPPH-radical scavengers
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A series of phenyl substituted sydnones has been synthesized and their radical-scavenging activity has been studied on DPPH free radical. Out of eighteen compounds screened, nine compounds show interesting activity. A mechanism is presented whereby sydnones scavenge DPPH radical through donating H-atom at 4th-position. Its strong radical-scavenging activity mainly arises from 1, 2, 3-oxadiazolium-5-olate ring. Different substituents and their positions on the phenyl ring differently influence DPPH scavenging activity and therefore, may provide clues to design and develop better free-radical scavenging sydnones with multiple activities.
- Mallur, Shanta G.,Tiwari,Raju, B. China,Babu, K. Suresh,Ali, A. Zehra,Sastry,Rao, J. Madhusudana
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p. 1686 - 1689
(2008/09/19)
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- Microwave-assisted synthesis of N-arylglycines: Improvement of sydnone synthesis
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Reactions of anilines with ethyl bromoacetate under microwave irradiation have afforded N-arylglycines that are subsequently converted to their N-nitroso derivatives with a combination of silica chloride or periodic acid, wet SiO2 and sodium nitrite in CH2Cl2 with satisfactory yields. In the final step, the use of 1,3-dibromo-5,5-dimethylhydantoin (DBH) as a new and effective reagent for dehydration of N-nitroso-N-arylglycines to sydnones was successfully examined.
- Azarifar, Davood,Bosra, Hassan Ghasemnejad,Zolfigol, Mohammad-Ali,Tajbaksh, Mahmood
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p. 175 - 181
(2007/10/03)
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- Copper-catalyzed aryl amination in aqueous media with 2- dimethylaminoethanol ligand
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Copper-catalyzed amination of aryl bromides and iodides under mild conditions has been developed with 2-dimethylaminoethanol as ligand and water as solvent. A variety of hydrophilic and hydrophobic aryl halide substrates have been aminated in good yield with a variety of amino acids, amino alcohols and peptides. This method has successfully N-arylated some hydrophilic amino compounds not available by other methods.
- Lu, Zhikuan,Twieg, Robert J.
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p. 2997 - 3001
(2007/10/03)
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- Process for producing optically active alpha-amino acid and optically active alpha-amino acid amine
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The present invention provides a process for efficiently producing an optically active α-amino acid and an optically active α-amino acid amide. After contacting with cells or processed cells thereof having an ability to asymmetrically hydrolyse, a water solvent is substituted with at least one solvent selected from the group consisting of linear, branched, or cyclic alcohol having 3 or more carbon atoms and the optically active α-amino acid is preferentially precipitated from the alcohol solution. The addition of basic compounds, particularly potassium compounds to the alcohol solution containing the optically active α-amino acid amide, which is obtained after the separation of the optically active α-amino acid, enables the purification of the amide without the inclusion of amino acid into amino acid amide. Thus, the amide is subjected to the step of racemization and then recycled.
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- Compounds for inhibiting β-amyloid peptide release and/or its synthesis
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Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis.
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- Methods and compounds for inhibiting β-amyloid peptide release and/or its synthesis
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Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.
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- Compounds for inhibiting β-amyloid peptide release and/or its synthesis
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Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis.
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- Synthesis of SB-214857 using copper catalysed amination of arylbromides with L-aspartic acid
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An efficient synthesis of a 1,4-benzodiazepine was accomplished using copper catalysed amination of an arylbromide with the soluble bis-tetrabutylammonium salt of L-aspartic acid as a key step.
- Clement,Hayes,Sheldrake,Sheldrake,Wells
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p. 1423 - 1427
(2007/10/03)
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- Hydride reduction of 4-Nitro-1-phenylazoles
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Hydride reduction of 4-nitro-1-phenylimidazole and 2-methyl-4-nitro-1-phenylimidazole to the respective 1-phenyl-4-oximinoimidazolidines by metal hydrides was studied under different conditions. 1-Aryl-4-oximinoimidazolidines were hydrolyzed to the respective imidazolidinones. For a comparison hydride reduction of 4-nitro-1-phenylpyrazole to the corresponding azoxy compound was carried out too.
- Suwinski,Wagner
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p. 1575 - 1580
(2007/10/03)
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- Substituted quinoxaline-2-ones as glutamate receptor antagonists
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A novel series of substituted quinoxaline 2-ones useful as neuroprotective agents are taught. Novel intermediates, processes of preparation, and pharmaceutical compositions containing the compounds are also taught. The compounds are glutamate receptor antagonists and are useful in the treatment of stroke, cerebral ischemia, or cerebral infarction resulting from thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia, seizure disorders, pain, Alzheimer's, Parkinson's, and Huntington's Diseases.
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- Fatty acid analogs and prodrugs
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Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitrites thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which x is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5.
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- N-heteroarenesulfonyl-protected amino acid reagents for peptide synthesis
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This invention relates to the use of heteroarenesulfonyl groups as protecting groups for amino groups, particularly the amino groups of amino acids, and specifically to nitrogen-protected (N-protected) amino acid reagents, which are particularly well-suited for use in peptide syntheses. In particular, the N-protected amino acid reagent is an N-heteroarenesulfonyl-protected amino acid halide. The heteroarenesulfonyl protecting groups are readily removed under relatively mild conditions.
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- Synthesis of a novel bismesoionic phenylsydnonyl-muenchnone system as an in-situ intermediate intended for the preparation of phenylsydnonyl-heterocycles
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The title bismesoionic system was generated in-situ by the treatment of N-(3-phenylsydnonyl-4-carbonyl)-N-substituted amino acid with acid anhydride. The sydnonyl muenchnone reacted with DMAD and gave phenylsydnonyl-pyrrole.
- Lo, Chok Wah,Chan, Wing Lai,Szeto, Yau Shan,Yip, Chiu Wing
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p. 513 - 514
(2007/10/03)
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- Fatty acid analogs and prodrugs
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Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L--Ala, L--Ile, L--Phe, L--Trp, L--Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5,
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- Synthesis and reactions of 9,10-diazatetracyclo-[6.3.0.0.4,110.5.9]undecanes
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The tandem 1,3-dipolar cycloaddition between sydnones and 1,5-cyclooctadiene provides 9,10-diazatetracyclo[6.3.0.0.4,110.5,9]undecanes (the Weintraub reaction) in modest to good yields.
- Gribble, Gordon W.,Hirth, Bradford H.
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p. 719 - 726
(2007/10/03)
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- Heterocyclic amines useful in the therapy of asthma and imflammation of the respiratory tract
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Compounds of the formula STR1 wherein A, Y, X, B and D are described in the specification are disclosed. The compounds possess activity in treating asthma and other pathologies of the respiratory tract.
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- Synthesis and antiinflammatory, analgesic, and antipyretic testing of 4- [1-oxo-(3-substituted aryl)-2-propenyl]-3-phenylsydnones and of 3-[4-[3- (substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones
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Two series of styrylcarbonyl 3-phenylsydnone derivatives, 4-[1-oxo-(3- substituted aryl)-2-propenyl]-3-phenylsydnones (series I, 1-21) and 3-[4-[3- (substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones (series II, 22-40), were synthesized and evaluated pharmacologically at a dose of 100 mg/kg po. Eleven compounds in series I plus one in series II and six in series I plus seven in series II were active in the carrageenan-induced edema and acetic acid- induced writhing assays, respectively. Compound 35 in the latter assay showed activity somewhat similar to that of the positive control drug, aspirin, administered at the same dosage. Compounds 11, 17, and 23 showed activity in both assays, and 23 also was active in the adjuvant-induced arthritis assay.
- Satyanarayana,Rao
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p. 263 - 266
(2007/10/02)
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- 4-METHOXY-5-METHYL-PYRAN-3-OL NATURAL PRODUCTS AND DERIVATIVES THEREOF
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Novel antibiotic substances, including novel natural products, having the general formula wherein R1 and R2 are as defined herein, are disclosed. These compounds have been found to be cytochrome P450 inhibitors.
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- Optically active ester derivatives, preparation process thereof, liquid crystal materials and a light switching element
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Disclosed are herein optically active ester derivatives represented by the formula (I): STR1 (wherein R1 represents an alkyl group having 3 to 20 carbon atoms; R2 represents an optically active alkyl or alkoxyalkyl group having 3 to 15 carbon atoms optionally substituted by halogen atoms; Y represents --O--, --COO-- or --OCO--; X represents --COO-- or --OCO--; l represents a number of 1 or 2; k and m each represents a number of 0 or 1; n represents a number of 1 to 6), preparation processes therefor, liquid crystal materials containing such ester derivatives as active ingredient, and a light switching element using said liquid crystal materials as liquid crystal element.
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- Novel spergualin-related compounds and compositions
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The present invention relates to novel spergualin-related compounds represented by the general formula [I]: STR1 wherein X is --(CH2)1?5 or STR2 Y is a hydrogen atom or a residue obtained by removing a hydroxyl group from the carboxyl group of an amino acid or a peptide; m is 0, 1 or 2 and n is 1 or 2, with the proviso that Y is not a hydrogen atom when n is 2 and m is 0. This compounds are stable and exhibit a high immunosuppressive activity.
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- 1-Phenyl-2-aminocarbonylindole compounds, preparation thereof and pharmaceutical compositions containing them
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New 1-phenyl-2-aminocarbonylindole compounds are described which have the general formula I STR1 where R1 is a hydrogen atom, or a lower alkyl, alkenyl, cycloalkylalkyl radical, R2 is a hydrogen atom or a lower alkyl radical, R3 is a hydrogen or halogen atom, or a lower alkyl, hydroxyl or lower alkoxy radical, R4 is a hydrogen or halogen atom, or a lower alkyl, hydroxyl or lower alkoxy radical, or, if R3 is a hydrogen atom, R4 may be a nitro or trifluoromethyl radical, or R3 and R4 together denote a methylenedioxy or ethylenedioxy radical, R5 has the meanings given for R3, R6 has the meanings given for R4, R7 is a hydrogen atom or, if R5 and R6 are lower alkoxy radicals, R7 may also be a lower alkoxy radical, R8 and R9 are each a hydrogen atom or a lower alkyl radical or, together with the nitrogen atom, form a heterocyclic group, and Z is an alkylene chain which is optionally substituted by hydroxyl. The compounds have pharmaceutical properties, in particular antiarrhythmic properties. The compounds may be in the form of the free bases or acid addition salts. Pharmaceutical compositions containing these compounds are described as is a method of preparing them. Valuable intermediates for the production of these compounds and methods of preparing the intermediates are also described.
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- 1-phenyl-2-aminocarbonylindole compounds, preparation thereof and pharmaceutical compositions containing them
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Novel 1-phenyl-2-aminocarbonylindole compounds are disclosed having the general formula I STR1 wherein R1 is an aliphatic or aromatic acyl group or an optionally substituted benzyl group; R2 is hydrogen or a lower alkyl radical; R3 is a hydrogen, a halogen, a lower alkyl radical, or a lower alkoxy radical; R4 is hydrogen, a halogen, a lower alkyl radical, or a lower alkoxy radical; R5 has the significance given R3 ; R6 has the significance given for R4, or R6 is nitro or trifluoromethyl; R7 and R8 each represent hydrogen or a lower alkyl radical, or together with a nitrogen atom form a heterocyclic group; and Z signifies an alkylene chain optionally substituted by hydroxy or acyloxy. The compounds have pharmacological, in particular antiarrhythmic, properties.
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- Stereoselective resolution of phenylglycine derivatives with enzyme resins
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The invention relates to a process for the stereo-selective resolution of DL-phenylglycine derivatives by hydrolyzing the ester or amide groups of N-acyl-L-phenylglycine esters or amides in N-acyl-DL-phenylglycine esters or amides by the action of enzymes, separating the N-acyl-D-phenylglycine esters or amides from the N-acyl-L-phenylglycines and then, if appropriate, subjecting the ester or amide groups of the D-enantiomers and the acyl groups to acid hydrolysis, characterized in that enzyme which are bonded to carriers are allowed to act on the N-acyl-DL-phenylglycine esters or amides in an inert two-phase mixture consisting of water-immiscible organic solvent and water.
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- SUBSTITUTED PEPTIDE COMPOUNDS
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Substituted peptide compounds of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.
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- Terpene hydroxysulfonic acids and corresponding hydroxysulfonate salts
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Optically active terpene hydroxysulfonate salts are made by sulfonating an optically active terpene epoxide of the p-menthane family, with a sulfonating agent selected from a sulfite, a bisulfite, or a thiosulfate.
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