- Syntheses and physical properties of ferrocene derivatives (XIII)
-
Two monosubstituted ferrocene derivatives, 8-[4-(4-methoxyphenoxycarbonyl)phenoxycarbonyl]octyl 4-ferrocenylbenzoate (MPAF-8) and 9-[4-(4-methoxyphenoxycarbonyl)phenoxycarbonyl] nonyl 4-ferrocenylbenzoate (MPAF-9), were synthesized and their phase transition behavior was studied using a differential scanning calorimeter, a polarizing microscope and an X-ray diffractometer. MPAF-8 exhibited two liquid crystalline phases in both heating and cooling processes at approximately room temperature. In the heating process, a crystal-crystal phase transition behavior was ascertained. The phase transition behavior of MPAF-9 was very similar to that of MPAF-8 except for the behavior of the crystal-crystal phase transition in the heating process. In MPAF-8, one crystalline phase was transformed into another crystalline phase completely. On the other hand, this transformation was observed in part in MPAF-9, and as a result, the melting behavior was observed two times in the heating process.
- Nakamura,Setodoi,Hanasaki
-
-
Read Online
- Chemoproteomic profiling reveals cellular targets of nitro-fatty acids
-
Nitro-fatty acids are a class of endogenous electrophilic lipid mediators with anti-inflammatory and cytoprotective effects in a wide range of inflammatory and fibrotic disease models. While these beneficial biological effects of nitro-fatty acids are mainly attributed to their ability to form covalent adducts with proteins, only a small number of proteins are known to be nitro-alkylated and the scope of protein nitro-alkylation remains undetermined. Here we describe the synthesis and application of a clickable nitro-fatty acid probe for the detection and first global identification of mammalian proteins that are susceptible to nitro-alkylation. 184 high confidence nitro-alkylated proteins were identified in THP1 macrophages, majority of which are novel targets of nitro-fatty acids, including extended synaptotagmin 2 (ESYT2), signal transducer and activator of transcription 3 (STAT3), toll-like receptor 2 (TLR2), retinoid X receptor alpha (RXRα) and glucocorticoid receptor (NR3C1). In particular, we showed that 9-nitro-oleate covalently modified and inhibited dexamethasone binding to NR3C1. Bioinformatic analyses revealed that nitro-alkylated proteins are highly enriched in endoplasmic reticulum and transmembrane proteins, and are overrepresented in lipid metabolism and transport pathways. This study significantly expands the scope of protein substrates targeted by nitro-fatty acids in living cells and provides a useful resource towards understanding the pleiotropic biological roles of nitro-fatty acids as signaling molecules or as multi-target therapeutic agents.
- Chen, Yi-Ting,Fang, Ming-Yu,Hsiao, Wan-Chi,Huang, Kuan-Hsun,Ke, Yi-Yu,Pan, Pei-Yun,Tsou, Lun K.,Tu, Wei-Ju,Zhang, Mingzi M.
-
-
- A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
-
Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.
- González-Gil, Inés,Zian, Debora,Vázquez-Villa, Henar,Hernández-Torres, Gloria,Martínez, R. Fernando,Khiar-Fernández, Nora,Rivera, Richard,Kihara, Yasuyuki,Devesa, Isabel,Mathivanan, Sakthikumar,Del Valle, Cristina Rosell,Zambrana-Infantes, Emma,Puigdomenech, María,Cincilla, Giovanni,Sanchez-Martinez, Melchor,Rodríguez De Fonseca, Fernando,Ferrer-Montiel, Antonio V.,Chun, Jerold,López-Vales, Rubén,López-Rodríguez, María L.,Ortega-Gutiérrez, Silvia
-
supporting information
p. 2372 - 2390
(2020/01/02)
-
- Tandem IBX-Promoted Primary Alcohol Oxidation/Opening of Intermediate β,γ-Diolcarbonate Aldehydes to (E)-γ-Hydroxy-α,β-enals
-
A tandem IBX-promoted oxidation of primary alcohol to aldehyde and opening of intermediate β,γ-diolcarbonate aldehyde to (E)-γ-hydroxy-α,β-enal has been developed. Remarkably, the carbonate opening delivered exclusively (E)-olefin and no over-oxidation of γ-hydroxy was observed. The method developed has been extended to complete the stereoselective total synthesis of both (S)- and (R)-coriolides and d-xylo- and d-arabino-C-20 guggultetrols.
- Kumari, Anupama,Gholap, Sachin P.,Fernandes, Rodney A.
-
p. 2278 - 2290
(2019/06/17)
-
- Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors
-
We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure–activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological profiles. The connection of two weak ligands—N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC50] = 8.6 μM) and 2-(methylthio)benzo[d]oxazole (IC50 = 31 μM)—via a linker comprising a 6 methylene group chains yielded a highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50 = 0.004 μM) toward aortic ACAT. This head-to-tail design made it possible to markedly enhance the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity based on the double-induced fit mechanism. At doses of 1 and 3 mg/kg, 3h significantly decreased the lipid-accumulation areas in the aortic arch to 74 and 69%, respectively without reducing the plasma total cholesterol level in high fat- and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic effect of 3h in vivo via its direct action on aortic ACAT and its powerful modulator of cholesterol level. This molecule is a potential therapeutic agent for the treatment of diseases involving ACAT-1 overexpression.
- Shibuya, Kimiyuki,Kawamine, Katsumi,Miura, Toru,Ozaki, Chiyoka,Edano, Toshiyuki,Mizuno, Ken,Yoshinaka, Yasunobu,Tsunenari, Yoshihiko
-
p. 4001 - 4013
(2018/06/26)
-
- Iron Catalysis for Room-Temperature Aerobic Oxidation of Alcohols to Carboxylic Acids
-
Oxidation from alcohols to carboxylic acids, a class of essential chemicals in daily life, academic laboratories, and industry, is a fundamental reaction, usually using at least a stoichiometric amount of an expensive and toxic oxidant. Here, an efficient and practical sustainable oxidation technology of alcohols to carboxylic acids using pure O2 or even O2 in air as the oxidant has been developed: utilizing a catalytic amount each of Fe(NO3)3·9H2O/TEMPO/MCl, a series of carboxylic acids were obtained from alcohols (also aldehydes) in high yields at room temperature. A 55 g-scale reaction was demonstrated using air. As a synthetic application, the first total synthesis of a naturally occurring allene, i.e., phlomic acid, was accomplished.
- Jiang, Xingguo,Zhang, Jiasheng,Ma, Shengming
-
supporting information
p. 8344 - 8347
(2016/07/26)
-
- DEOXYNOJIRIMYCIN DERIVATIVES AND METHODS OF THEIR USING
-
The present application provide novel iminosugars and their use in treatment of viral infections, such as Dengue infection and Influenza A infection. The present inventors discovered certain deoxynojirimycin derivatives may be effective against one or more viruses, which may be, for example, a Dengue virus and/or a virus belonging to the Orthomyxoviridae family, such as an Influenza A virus. In particular, such deoxynojirimycin derivatives may be useful for treating a disease or condition caused by or associated with one or more viruses. In certain embodiments, the deoxynojirimycin derivatives may increase a survival rate or probability for a subject infected with one or more viruses, which may be, for example, a Dengue virus and/or a virus belonging to the Orthomyxoviridae family, such as an Influenza A virus.
- -
-
Paragraph 0021
(2016/08/29)
-
- QUINONE BASED NITRIC OXIDE DONATING COMPOUNDS FOR OPHTHALMIC USE
-
The present invention relates to novel nitric oxide donor compounds for the use in the treatment and/or prophylaxis of hypertensive glaucoma, normotensive glaucoma and ocular hypertension.
- -
-
Page/Page column 81
(2014/05/24)
-
- Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites
-
N-Myristoyltransferase (NMT) has been shown to be essential in Leishmania and subsequently validated as a drug target in Plasmodium. Herein, we discuss the use of antifungal NMT inhibitors as a basis for inhibitor development resulting in the first sub-micromolar peptidomimetic inhibitors of Plasmodium and Leishmania NMTs. High-resolution structures of these inhibitors with Plasmodium and Leishmania NMTs permit a comparative analysis of binding modes, and provide the first crystal structure evidence for a ternary NMT-Coenzyme A/myristoylated peptide product complex. This journal is
- Olaleye, Tayo O.,Brannigan, James A.,Roberts, Shirley M.,Leatherbarrow, Robin J.,Wilkinson, Anthony J.,Tate, Edward W.
-
supporting information
p. 8132 - 8137
(2015/01/08)
-
- QUINONE BASED NITRIC OXIDE DONATING COMPOUNDS
-
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.
- -
-
Page/Page column 86
(2013/05/21)
-
- COVALENT INHIBITION OF BACTERIAL QUORUM SENSING
-
Inhibitors of bacterial communication, such as quorum sensing, and method of use and manufacture thereof.
- -
-
Page/Page column 17
(2011/02/24)
-
- HETEROATOM CONTAINING SUBSTITUTED FATTY ACIDS
-
Activated fatty acids, pharmaceutical compositions including activated fatty acids, methods for using activated fatty acids to treat a variety of diseases, and methods for preparing activated fatty acids are provided herein.
- -
-
Page/Page column 18
(2011/04/24)
-
- Covalent inhibition of bacterial quorum sensing
-
Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (QS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C12-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence.
- Amara, Neri,Mashiach, Roi,Amar, Dotan,Krief, Pnina,Spieser, Stephane A. H.,Bottomley, Matthew J.,Aharoni, Amir,Meijler, Michael M.
-
supporting information; experimental part
p. 10610 - 10619
(2009/12/04)
-
- Construction of supramolecular multi-component assemblies by using allosteric interactions
-
Supramolecular complexes between two cavity-appended porphyrin hosts and three bifunctional guests are described. The host with a single cavity exclusively forms dimers with the bifunctional guests, while the double cavity host yields tetramers and higher order assemblies. The role of allosteric interactions in the binding and assembly process is highlighted.
- Veling, Nico,Thomassen, Paul J.,Thordarson, Pall,Elemans, Johannes A.A.W.,Nolte, Roeland J.M.,Rowan, Alan E.
-
p. 8535 - 8542
(2008/12/21)
-
- Synthesis of trans-vaccenic acid and cis-9-trans-11-conjugated linoleic acid
-
The preparation of the monounsaturated fatty acid, trans-vaccenic acid 4 (TVA), using both Wittig and one-pot Julia-Kocieński olefination protocol, was achieved in good yield. Similarly a Wittig approach was employed for the stereoselective synthesis of cis-9-trans-11-conjugated linoleic acid 2 from trans-2-nonenal and (8-carboxyoctyl)triphenylphosphonium bromide 12.
- Duffy, Patricia E.,Quinn, Sonia M.,Roche, Helen M.,Evans, Paul
-
p. 4838 - 4843
(2007/10/03)
-
- Synthesis of nitrolipids. All four possible diastereomers of nitrooleic acids: (E)- and (Z)-, 9- and 10-nitro-octadec-9-enoic acids
-
Unsaturated fatty acids are nitrated endogenously to produce nitrated lipids. Recent studies have shown that these nitrated lipids have high chemical reactivity and profound biological implications. We report an efficient, scalable synthesis which is regiospecific and stereoselective for all possible isomers of nitrated oleic acid: (E)- and (Z)-, 9- and 10-octadec-9-enoic acids.
- Woodcock, Steven R.,Marwitz, Adam J. V.,Bruno, Paulo,Branchaud, Bruce P.
-
p. 3931 - 3934
(2007/10/03)
-
- Synthesis and 19F NMR study of RF-oleic acid-F13
-
A seven-step synthesis of Z-13,13,14,14,15,15,16,16,17,17,18,18, 18-tridecafluoro-octadec-9-enoic acid (oleic acid-F13) is reported. The key step is a Wittig reaction to form the C9-C10 double bond with a Z:E isomeric ratio greater than 20:1. The 19F nuclear magnetic resonance (NMR) spectrum is included and unambiguous assignments have been made with the aid of 19F-19F correlation NMR spectroscopy (COSY spectra).
- Buchanan, Gerald W.,Smits, Rufus,Munteanu, Elena
-
p. 255 - 259
(2007/10/03)
-
- Anilide compounds, including use thereof in ACAT inhibitition
-
The invention provides novel anilide compounds and pharmaceutical compositions comprising them. The invention relates to compounds of a formula: where Ar is an optionally-substituted aryl group; R4and R5are the same or different, and each is a hydrogen atom, a lower alkyl group, or a lower alkoxy group; and R4and R5may together form a lower alkylene group of which one or more methylene moieties may optionally be substituted by oxygen and/or sulfur atoms; X is —NH—, or oxygen or sulfur atom; Y is —NH—, an oxygen or sulfur atom, or a sulfoxide or sulfone group; Z is a single bond, or —NH6—; R6represents a hydrogen atom or a lower alkylene group; and n is an integer of from 0 to 15; and their salts and solvates. The compounds of the invention are useful as pharmaceutical compositions, especially as acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitors.
- -
-
-
- Endothelin antagonist
-
An endothelin antagonist comprising as the active ingredient a prostanoic acid derivative wherein the α-chain has eight or more skeletal carbon atoms.
- -
-
-
- Studies related to in vivo C-H activation: Synthesis and influence of 8,8- and 11,11-dimethyl oleic and 11,11-dimethyl linoleic acids on Δ12- desaturation of C. sorokiniana
-
The synthesis of three acids was achieved using the Wittig reaction in order to study their in vivo influence on the Δ12-desaturase of Chlorella sorokiniana. It was shown that the introduction of two methyls near the double bond prevent the desaturation of these exogenous acids while they seem to be accurately incorporated. This functionality could be of interest for the design of new thiaoleic acids as probes of the different oxidation processes.
- Poulain, Sophie,Noiret, Nicolas,Fauconnot, Laetitia,Nugier-Chauvin, Caroline,Patin, Henri
-
p. 3595 - 3604
(2007/10/03)
-
