- (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative as well as preparation method and application thereof
-
The invention discloses a (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative shown as a formula (I) or an optical isomer, a diastereomer and racemate mixture and pharmaceutically acceptable salt thereof as well as a preparation method and application of the (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative. It is shown by comparison of results of a positive control group and a model group on lymphedema prevention experiments that the compound disclosed in the invention shows obvious anti-edema activity.
- -
-
Paragraph 0047; 0106-0110
(2021/02/10)
-
- Nickel-catalyzed deallylation of aryl allyl ethers with hydrosilanes
-
An efficient and mild catalytic deallylation method of aryl allyl ethers is developed, with commercially available Ni(COD)2 as catalyst precursor, simple substituted bipyridine as ligand and air-stable hydrosilanes. The process is compatible with a variety of functional groups and the desired phenol products can be obtained with excellent yields and selectivity. Besides, by detection or isolation of key intermediates, mechanism studies confirm that the deallylation undergoes η3-allylnickel intermediate pathway.
- Ding, Guangni,Fan, Sijie,Wang, Jingyang,Wang, Yu,Wu, Xiaoyu,Xie, Xiaomin,Yang, Liqun,Zhang, Zhaoguo
-
supporting information
(2021/09/28)
-
- NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds
-
A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).
- Lu, Guan-Han,Huang, Tzu-Chia,Hsueh, Hsiao-Chin,Yang, Shin-Cherng,Cho, Ting-Wei,Chou, Ho-Hsuan
-
supporting information
p. 4839 - 4842
(2021/05/25)
-
- N-transfer reagent and method for preparing the same and its application
-
Provided are a novel N-transfer reagent and a method for preparing the same and its application. The N-transfer reagent is represented by the following Formula (I): The various novel N-transfer reagents of the present invention can be quickly prepared by employing different nitrobenzene precursors. The N-transfer reagents can directly convert a variety of amino compounds into diazo compounds under mild conditions. Particularly, the N-transfer reagents can facilitate the synthesis of the diazo compounds. The application of synthesizing diazo compounds of the present invention can greatly decrease the difficulty in operation, increase the safety during experiments, reduce the cost of production and the environmental pollution, and enhance the industrial value of diazo compounds.
- -
-
Page/Page column 24; 49-50; 55-56
(2021/06/25)
-
- Discovery of a series of ester-substituted NLRP3 inflammasome inhibitors
-
The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Aberrant activation by a wide range of exogenous and endogenous signals can lead to chronic, low-grade inflammation. It has attracted a great deal of interest as a drug target due to the association with diseases of large unmet medical need such as Alzheimer's disease, Parkinson's disease, arthritis, and cancer. To date, no drugs specifically targeting inhibition of the NLRP3 inflammasome have been approved. In this work, we used the known NLRP3 inflammasome inhibitor CP-456,773 (aka CRID3 or MCC 950) as our starting point and undertook a Structure-Activity Relationship (SAR) analysis and subsequent scaffold-hopping exercise. This resulted in the rational design of a series of novel ester-substituted urea compounds that are highly potent and selective NLRP3 inflammasome inhibitors, as exemplified by compounds 44 and 45. It is hypothesized that the ester moiety acts as a highly permeable delivery vehicle and is subsequently hydrolyzed to the carboxylic acid active species by carboxylesterase enzymes. These molecules are greatly differentiated from the state-of-the-art and offer potential in the treatment of NLRP3-driven diseases, particularly where tissue penetration is required.
- Harrison, David,Boutard, Nicolas,Brzozka, Krzysztof,Bugaj, Marta,Chmielewski, Stefan,Cierpich, Anna,Doedens, John R.,Fabritius, Charles-Henry R.Y.,Gabel, Christopher A.,Galezowski, Michal,Kowalczyk, Piotr,Levenets, Oleksandr,Mroczkowska, Magdalena,Palica, Katarzyna,Porter, Roderick A.,Schultz, David,Sowinska, Marta,Topolnicki, Grzegorz,Urbanski, Piotr,Woyciechowski, Jakub,Watt, Alan P.
-
supporting information
(2020/10/02)
-
- NOVEL TRF1 MODULATORS AND ANALOGUES THEREOF
-
Novel TRF1 modulators and analogues thereof. There is provided compounds of Formula I, wherein R, R1, R2 and X have meanings written in the description. Such compounds are useful as TRF1 inhibitors and, for that reason, as medicaments, in the treatment of cancer, particularly high cancer stem cell cancer like glioblastoma and lung cancer, and can be also useful for the development of additional TRF1 inhibitors and increasing knowledge about TRF1 activity.
- -
-
Paragraph 0053; 0164-0165; 0174-0175
(2020/03/26)
-
- Total Synthesis of Herquline B and C
-
The total syntheses of (-)-herquline B (2) and a heretofore-unrecognized congener, (+)-herquline C (3), are described. The syntheses require 14 and 13 steps, respectively, and feature a key oxazoline reduction that sets the stage for piperazine construction.
- Cox, Joshua B.,Kimishima, Aoi,Wood, John L.
-
supporting information
p. 25 - 28
(2019/01/16)
-
- ((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies
-
The emergence and global spread of metallo-β-lactamase (MBL) mediated resistance to almost all β-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis.
- Liu, Sha,Jing, Li,Yu, Zhu-Jun,Wu, Chengyong,Zheng, Yongxiang,Zhang, En,Chen, Qiang,Yu, Yamei,Guo, Li,Wu, Yong,Li, Guo-Bo
-
p. 649 - 660
(2018/02/10)
-
- Synthesis, in vitro antimicrobial, antioxidant, and antidiabetic activities of thiazolidine–quinoxaline derivatives with amino acid side chains
-
Abstract: A novel protocol for the rapid assembly of a hybrid framework based on amino acid, thiazolidine and quinoxaline scaffolds has been demonstrated by microwave irradiation. The quinoxalines with amino acid side chains 5a–5c were prepared in three steps from 2,4-dinitrofluorobenzene and the amino acids, valine, methionine, and tyrosine and subsequently reacted with four different aldehydes and thioglycolic acid to produce thiazolidine–quinoxaline hybrids with amino acid side chains 6a–6l. All synthesized compounds were evaluated for their in vitro antimicrobial, antioxidant, and antidiabetic activities. Compounds 6f, 6j, and 6k showed broad spectrum antimicrobial activity against Gram +ve and Gram –ve bacteria, whilst 6h, 6k, and 6l showed the best antioxidant activity in the same order of magnitude to that of ascorbic acid. Four of the compounds, 5c, 6d, 6g, and 6k showed activity against α-glucosidase and α-amylase similar to acarbose. Those compounds showing antibacterial activity possessed 4-fluorophenyl and 4-methoxyphenyl groups along with methionine and tyrosine side chains while the compounds showing antioxidant, α-glucosidase, and α-amylase activity contained 4-nitrophenyl and 4-methoxyphenyl groups on the thiazolidine moiety with mainly methionine and tyrosine side chains. The α-glucosidase and α-amylase inhibitory compound 5c did not have a thiazolidine moiety and 6d was the only active compound with a valine amino acid side chain. Compound 6k with a tyrosine side chain and a 4-methoxyphenylthiazolidine moiety on the quinoxaline scaffold showed good bioactivity in all three assays.
- Shintre, Suhas A.,Ramjugernath, Deresh,Islam, Md Shahidul,Mopuri, Ramgopal,Mocktar, Chunderika,Koorbanally, Neil A.
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p. 2141 - 2151
(2017/08/03)
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- Ferrocene-modified amino acids: synthesis and in vivo bioeffects on hippocampus
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A method for the ferrocene modification of amino acids of natural and synthetic origin has been developed. In the in vivo studies, the hippocampal electrical activity under the action of ferrocenyl(phenylpyrazolyl)glycine (1) was assessed. A meaningful rise (up to 25% compared to the control) in the response amplitudes of the focal potentials of the hippocampal region СА1 after intraperitoneal administration of compound 1 at the dose of 2.0 mg kg–1 was established.
- Rodionov,Snegur,Simenel,Dobryakova, Yu. V.,Markevich
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p. 136 - 142
(2017/07/05)
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- Method for synthesizing tyrosine framework type periodic mesoporous organosilicas materials
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The invention relates to a method for preparing tyrosine framework type periodic mesoporous organosilicas materials. The method for synthesizing the tyrosine framework type periodic mesoporous organosilicas materials includes esterifying tyrosine in methanol by the aid of thionyl chloride; carrying out acrylation on the tyrosine by the aid of hydrazine hydrate and carrying out reaction on the tyrosine and isocyanic acid propyltriethoxysilane to obtain tyrosine organosilicas precursors; hydrolyzing the tyrosine organosilicas precursors and surfactants under acidic conditions to form PMO (periodic mesoporous organosilicas) materials; removing the surfactants from the PMO materials by means of extraction to ultimately form PMO materials with specific morphological structures. The tyrosine is used as a substrate. The methanol is used as a solvent. The method has the advantages synthesis reaction raw materials are simple and are easily available, synthesis operation is simple and convenient and is easy to implement, and the method is high in yield and low in energy consumption and is safe and inexpensive; the tyrosine framework type periodic mesoporous organosilicas materials prepared by the aid of the method have important application prospects in the fields of biosensors, catalyst carriers, adsorbents, sustained-release medicine capsules, chromatographic separation and the like.
- -
-
Paragraph 0024
(2017/08/29)
-
- A PRODUCING METHOD OF D-FORM OR L-FORM AMINO ACID DERIVATIVES HAVING A THIOL GROUP
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This invention provides a producing method of an optical active D-form and/or L-form amino acid having a thiol group on its side chain by a simple method with good yield. This invention provides a producing method of an amino acid derivative having a thiol group on its side chain, and an intermediate thereof, wherein the producing method is characterized by producing an intermediate composition comprising a D-form and L-form of amino acid derivate having a thiol group at β -position, reacting D- or L-amino acid selective hydrolytic enzyme, and isolating the hydrolyzed D- or L-amino acid derivative.
- -
-
Paragraph 0164; 0165
(2016/10/31)
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- Method for preparing alanine derivative
-
The invention discloses a method for preparing an alanine derivative represented by a formula (I) shown in the description. The alanine derivative can serve as synthesis intermediates of opium receptor regulators, such as a synthesis intermediate of eluxadoline. According to the method, chiral tyrosine which is cheap and readily available serves as an initial raw material, a bran-new synthesis route for preparing the alanine derivative is provided, the total yield of the entire reaction route is high, the cost is low, the reaction conditions are mild, and the operation is simple and safe, so that the method is applicable to large-scale industrial production.
- -
-
Paragraph 0111; 0112; 0113
(2016/10/10)
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- NOVEL PRODRUGS AND COMBINATIONS FOR TREATMENT OF HYPERTENSION AND CARDIOVASCULAR DISEASES
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The invention relates a pharmaceutical composition comprising (i) prodrugs of NEP inhibitors, (ii) mutual prodrugs of angiotensin receptor antagonist and a NEP inhibitor, (iii) a combination of an angiotensin receptor antagonist prodrug and a NEP inhibitor and (iv) a combination of angiotensin receptor antagonist including prodrug, a NEP inhibitor prodrug and a diuretic drug (v) a combination of angiotensin receptor antagonist, a NEP inhibitor prodrug and a calcium channel blocker. The angiotensin receptor antagonist is selected from the group selected from the group consisting of allisartan, elisartan, candesartan, eprosartan, irbesartan, losartan, saprisartan, tasosartan, telmisartan and valsartan. The invention also includes a method for treating hypertension, heart failure such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), glaucoma and stroke.
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Page/Page column 14
(2015/11/17)
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- Solvent-induced helical assembly and reversible chiroptical switching of chiral cyclic-dipeptide-functionalized naphthalenediimides
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Understanding the roles of various parameters in orchestrating the preferential chiral molecular organization in supramolecular self-assembly processes is of great significance in designing novel molecular functional systems. Cyclic dipeptide (CDP) chiral auxiliary-functionalized naphthalenediimides (NCDPs 1-6) have been prepared and their chiral self-assembly properties have been investigated. Detailed photophysical and circular dichroism (CD) studies have unveiled the crucial role of the solvent in the chiral aggregation of these NCDPs. NCDPs 1-3 form supramolecular helical assemblies and exhibit remarkable chiroptical switching behaviour (M- to P-type) depending on the solvent composition of HFIP and DMSO. The strong influence of solvent composition on the supramolecular chirality of NCDPs has been further corroborated by concentration and solid-state thin-film CD studies. The chiroptical switching between supramolecular aggregates of opposite helicity (M and P) has been found to be reversible, and can be achieved through cycles of solvent removal and redissolution in solvent mixtures of specific composition. The control molecular systems (NCDPs 4-6), with an achiral or D-isomer second amino acid in the CDP auxiliary, did not show chiral aggregation properties. The substantial roles of hydrogen bonding and π-π interactions in the assembly of the NCDPs have been validated through nuclear magnetic resonance (NMR), photophysical, and computational studies. Quantum chemical calculations at the ab initio, semiempirical, and density functional theory levels have been performed on model systems to understand the stabilities of the right (P-) and left (M-) handed helical supramolecular assemblies and the nature of the intermolecular interactions. This study emphasizes the role of CDP chiral auxiliaries on the solvent-induced helical assembly and reversible chiroptical switching of naphthalenediimides.
- Manchineella, Shivaprasad,Prathyusha,Priyakumar, U. Deva,Govindaraju
-
supporting information
p. 16615 - 16624
(2014/01/06)
-
- Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor
-
The Eph receptor-ephrin system is an emerging target for the development of novel antiangiogenetic agents. We recently identified lithocholic acid (LCA) as a small molecule able to block EphA2-dependent signals in cancer cells, suggesting that its (5β)-cholan-24-oic acid scaffold can be used as a template to design a new generation of improved EphA2 antagonists. Here, we report the design and synthesis of an extended set of LCA derivatives obtained by conjugation of its carboxyl group with different α-amino acids. Structure-activity relationships indicate that the presence of a lipophilic amino acid side chain is fundamental to achieve good potencies. The l-Trp derivative (20, PCM126) was the most potent antagonist of the series disrupting EphA2-ephrinA1 interaction and blocking EphA2 phosphorylation in prostate cancer cells at low μM concentrations, thus being significantly more potent than LCA. Compound 20 is among the most potent small-molecule antagonists of the EphA2 receptor.
- Incerti, Matteo,Tognolini, Massimiliano,Russo, Simonetta,Pala, Daniele,Giorgio, Carmine,Hassan-Mohamed, Iftiin,Noberini, Roberta,Pasquale, Elena B.,Vicini, Paola,Piersanti, Silvia,Rivara, Silvia,Barocelli, Elisabetta,Mor, Marco,Lodola, Alessio
-
supporting information
p. 2936 - 2947
(2013/05/22)
-
- Iron-catalyzed oxidative C - H/C - H cross-coupling: An efficient route to α-quaternary α-amino acid derivatives
-
Fully loaded: A coordinating activation strategy has been developed to furnish α-quaternary α-amino acids through the iron(III)-catalyzed oxidative functionalization of α-C(sp3) - H bonds of α-tertiary α-amino acid esters. The reaction exhibits a broad substrate scope for both α-amino acids and nucleophiles (Nu) as well as good functional-group tolerance (see scheme, DTBP=di-tert-butyl peroxide, DCE=1,2-dichloroethane). Copyright
- Li, Kaizhi,Tan, Guangying,Huang, Jingsheng,Song, Feijie,You, Jingsong
-
supporting information
p. 12942 - 12945
(2014/01/06)
-
- Enzymatic synthesis of chiral phenylalanine derivatives by a dynamic kinetic resolution of corresponding amide and nitrile substrates with a multi-enzyme system
-
Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of (R)-phenylalanine and non-natural (R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of (R)-phenylalanine with 84% yield and 99% ee from (RS)-phenylalaninamide (400 mM) in 22 h. (R)-Tyrosine and 4-fluoro-(R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various (S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to (R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. Copyright
- Yasukawa, Kazuyuki,Asano, Yasuhisa
-
supporting information
p. 3327 - 3332
(2013/01/15)
-
- Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: Synthesis, stability, antiviral activity, and in vivo transport studies
-
Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC 50 values for the prodrugs (50 0.3-35 μM); there was no cytoxicity with KB or HFF cells at ≤100 μM. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (30-1732 min) with differences of 3-10× between phostonate diastereomers. The tyrosine alkylamide derivatives of 3 and 4 were the most stable. (l)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs 5%).
- Zakharova, Valeria M.,Serpi, Michaela,Krylov, Ivan S.,Peterson, Larryn W.,Breitenbach, Julie M.,Borysko, Katherine Z.,Drach, John C.,Collins, Mindy,Hilfinger, John M.,Kashemirov, Boris A.,McKenna, Charles E.
-
experimental part
p. 5680 - 5693
(2011/10/18)
-
- ANTICANCER AGENTS BASED ON AMINO ACID DERIVATIVES
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The present invention provides compounds of formula (I): in which T is L or -A-NH-C(O)-L-; L is -(CH2)n- or -(CH2)p-Z-; A is -(CH2)m- or an alkyl component of a naturally occurring amino acid; R is -CO2R1, -CH2OH, -C(O)NH(hydroxyphenyl) or C(S)NH(hydroxyphenyl); R1 is H or is C1-C12 alkyl; X is -OH, OSO2R2, -Cl, -Br, or -I; R2 is C1-C12 alkyl or -CF3; Z is phenyl or naphthyl; m is an integer having a value of 1 to 20; n is an integer having a value of 1 to 20; and p is an integer having a value of 1 to 20 or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. These compounds can be useful as anticancer agents.
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Page/Page column 23
(2011/02/24)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 64
(2010/12/31)
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- Synthesis of D- and L-tyrosine-chlorambucil analogs active against breast cancer cell lines
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A series of d- and l-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of d- and l-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the d- and l-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line.
- Desc?teaux, Caroline,Leblanc, Valérie,Brasseur, Kevin,Gupta, Atul,Asselin, éric,Bérubé, Gervais
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scheme or table
p. 7388 - 7392
(2011/02/25)
-
- Synthesis and structure revision of tyroscherin, and bioactivities of its stereoisomers against IGF-1-dependent tumor cells
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Synthesis of the proposed structure of tyroscherin, a growth inhibitor of IGF-1-dependent cancer cells, was succeeded by one-pot Julia coupling. However, spectral data of the synthetic compound were not identical with those of natural tyroscherin. The stereochemistry of tyroscherin is revised to be 2S,3R,8R,10R by syntheses of stereoisomers. Synthetic tyroscherin showed more potent activity than its stereoisomers against IGF-1-dependent cancer cells.
- Ishigami, Ken,Katsuta, Ryo,Shibata, Chié,Hayakawa, Yoichi,Watanabe, Hidenori,Kitahara, Takeshi
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experimental part
p. 3629 - 3638
(2009/09/25)
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- New cyclic peptides via ring-closing metathesis reactions and their anti-bacterial activities
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As part of a program investigating cyclic peptides with an internal aromatic hydrophobic scaffold as potential novel anti-bacterial agents, we explored the synthesis of simple tyrosine-based systems. These were prepared via key intermediates containing internal allylglycine and allyltyrosine residues for subsequent ring-closing metathesis reactions. Although the resulting anti-bacterial activity against Staphylococcus aureus was modest, this represents a novel and simple route to this class of compounds. One intermediate acyclic dipeptide precursor showed good activity against S. aureus with an MIC of 7.8 μg/mL. Crown Copyright
- Boyle, Timothy P.,Bremner, John B.,Coates, Jonathan,Deadman, John,Keller, Paul A.,Pyne, Stephen G.,Rhodes, David I.
-
experimental part
p. 11270 - 11290
(2009/04/06)
-
- Tandem multi-step synthesis of C-carboxyazlactones promoted by N-heterocyclic carbenes
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Cascade reaction sequences incorporating N-heterocyclic carbene-based organocatalysis have been developed that allow the direct preparation of a range of (±)-4-phenoxycarbonylazlactones in good isolated yields (66-84%) from the corresponding N-p-anisoyl amino acids. The Royal Society of Chemistry.
- Campbell, Craig D.,Duguet, Nicolas,Gallagher, Katherine A.,Thomson, Jennifer E.,Lindsay, Anita G.,O'Donoghue, AnnMarie C.,Smith, Andrew D.
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supporting information; body text
p. 3528 - 3530
(2009/02/05)
-
- Marked small molecule libraries: A truncated approach to molecular probe design
-
A truncated approach to the design of molecular probes from small molecule libraries is outlined, based upon the incorporation of a bioorthogonal marker. The applicability of this strategy to small molecule chemical genetics screens has been demonstrated using analogues of the known stress activated protein kinase (SAPK) pathway activator, anisomycin. Compounds marked with a propargyl group have shown activation of the SAPK pathways comparable to that induced by their parent structures, as demonstrated by immunoblot assays against the downstream target JNK1/2. The considerable advantages of this new approach to molecular probe design have been illustrated through the rapid development of a functionally active fluorescent molecular probe, through coupling of the marked analogues to fluorescent azides using the copper(i)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. Active molecular probes generated in this study were used to investigate cellular uptake through FACS analysis and confocal microscopy. This journal is The Royal Society of Chemistry.
- Inverarity, Iain A.,Hulme, Alison N.
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p. 636 - 643
(2008/03/27)
-
- PEPTIDIC COMPOUNDS
-
The present invention provides a compound of formula (I), (II), (III) and (IV) as defined herein and pharmaceutically acceptable derivatives thereof. The present invention further provides use of the compounds of the present invention in the treatment of bacterial infection and in the treatment of HIV infection. Also provided are pharmaceutical compositions comprising the compounds of the present invention.
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Page/Page column 152
(2008/06/13)
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- An improved solid-phase methodology for the synthesis of putative hexa- and heptapeptide intermediates in vancomycin biosynthesis
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The biosynthesis of the vancomycin aglycone involves three oxidative phenol coupling reactions, each catalyzed by a discrete cytochrome P450-like enzyme. Studies on the mechanism and specificity of the enzyme (called OxyB) catalyzing the first coupling, require access to suitable linear peptide precursors, each conjugated as a thioester to a peptide carrier domain of the vancomycin non-ribosomal peptide synthetase. An efficient route to representative free linear peptides is described here. The method makes use of Alloc-chemistry during solid-phase assembly of the peptide backbone, but importantly and in contrast to earlier efforts, largely avoids the use of amino acid side chain protecting groups. In this way, the target linear peptides can be released directly from the solid support under very mild conditions. The Royal Society of Chemistry 2005.
- Li, Dong Bo,Robinson, John A.
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p. 1233 - 1239
(2007/10/03)
-
- NOVEL LYSOPHOSPHATIDIC ACID RECEPTOR SELECTIVE ANTAGONISTS
-
The present invention is directed to compositions comprising lysophosphatidic acid analogs and methods of using such analogs as agonist or antagonists of LPA receptor activity. In addition the invention is directed to LPA receptor agonists that vary in the degree of selectivity at individual LPA receptors (i.e. LPA1, LPA2 and LPA3). More particularly the present invention is directed to LPA analogs wherein the glycerol is replaced with ethanolamine and a variety of substitutions have been linked at the second carbon atom.
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Page/Page column 78
(2008/06/13)
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- Derivatives of hydroxyphenyl, a method for preparing thereof and their pharmaceutical composition
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The present invention relates to derivatives of hydroxyphenyl, a method for preparing thereof and their pharmaceutical composition, more particularly the compounds of the present invention specifically inhibit the activation of T lymphocyte by src homology region 2(SH2) domain of T lymphocyte (lck), so that they can be used for the treatment, prevention and/or diagnosis of graft rejection, autoimmune diseases, inflammatory diseases, etc.
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Page/Page column 33
(2008/06/13)
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- Derivatives of hydroxyphenyl, a method for preparing thereof and their pharmaceutical composition
-
The present invention relates to derivatives of hydroxyphenyl, a method for preparing thereof and their pharmaceutical composition, more particularly the compounds of the present invention specifically inhibit the activation of T lymphocyte by src homology region 2(SH2) domain of T lymphocyte (lck), so that they can be used for the treatment, prevention and/or diagnosis of graft rejection, autoimmune diseases, inflammatory diseases, etc.
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-
-
- An aldol-based approach to the synthesis of the antibiotic anisomycin
-
Chemical equation presented A new approach to the synthesis of the antibiotic anisomycin is reported that relies upon a key aldol disconnection. The glycolate aldol coupling proceeds in 75% yield and with >95% diastereoselectivity, which allows the 13-step synthesis to proceed in 35% overall yield.
- Hulme, Alison N.,Rosser, Edward M.
-
p. 265 - 267
(2007/10/03)
-
- beta -thiopropionyl-aminoacid derivatives and their use as beta -lactamase inhibitors
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PCT No. PCT/EP97/00516 Sec. 371 Date Jan. 13, 1999 Sec. 102(e) Date Jan. 13, 1999 PCT Filed Feb. 3, 1997 PCT Pub. No. WO97/30027 PCT Pub. Date Aug. 21, 1997A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a beta -lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an in vivo hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.
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- A synthetic route to the tripeptide unit of geodiamolicle-B
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A better route to the tripeptide unit of geodiamolide-B is investigated using the corresponding amino acids L-alanine and N-methyl-D-tyrosine.
- Beiagali,Kocienski
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p. 562 - 565
(2007/10/03)
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- Polypeptide compound and a process for preparation thereof
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A polypeptide compound having antimicrobial activity of the following general formula: STR1 wherein R1 is hydrogen or acyl group, R2 is hydroxy or acyloxy, R3 is hydroxysulfonyloxy, and R4 is hydrogen or carbamoyl, with proviso that R1 is not palmitoyl, when R2 is hydroxy, R3 is hydroxysulfonyloxy and R4 is carbamoyl, and a pharmaceutically acceptable salt thereof.
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