- Convergent and Practical Synthesis of Fluorescent Triphenylamine Derivatives and Their Localization in Living Cells
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In the search for new fluorescent triphenylamine (TP) derivatives, we studied the influence of the position and substitution of diverse heterocyclic substituents. A library of 10 fluorescent triphenylamines bearing either oxazoles or thiazoles and pyridiniums, substituted at different positions has been developed. The approach is based on a convergent C?H activation reaction between pyridine-oxazoles or pyridine-thiazoles and di-iodo triphenylamine. We showed that the nature and substitution pattern of the 5-membered- (oxazole, thiazole) or 6-membered heterocycle (pyridine) has a strong influence on their fluorescence properties and on their localization in living cells as they stain either the nucleus or mitochondria.
- Auvray, Marie,Franck, Xavier,Gallavardin, Thibault,Leleu, Stéphane,Mahuteau-Betzer, Florence,Mougeot, Romain,Oger, Samuel
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supporting information
(2022/02/09)
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- Investigation of ‘head-to-tail’-connected oligoaryl n,o-ligands as recognition motifs for cancer-relevant G-quadruplexes
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Oligomeric compounds, constituted of consecutive N,O-heteroaromatic rings, introduce useful and tunable properties as alternative ligands for biomolecular recognition. In this study, we have explored a synthetic scheme relying on Van Leusen oxazole formation, in conjunction with C–H activation of the formed oxazoles and their subsequent C–C cross-coupling to 2-bromopyridines in order to assemble a library of variable-length, ‘head-to-tail’-connected, pyridyl-oxazole ligands. Through investigation of the interaction of the three longer ligands (5-mer, 6-mer, 7-mer) with cancer-relevant G-quadruplex structures (human telomeric/22AG and c-Myc oncogene promoter/Myc2345-Pu22), the asymmetric pyridyl-oxazole motif has been demonstrated to be a prominent recognition element for G-quadruplexes. Fluorescence titrations reveal excellent binding affinities of the 7-mer and 6-mer for a Na+-induced antiparallel 22AG G-quadruplex (KD = 0.6 × 10?7 M?1 and 0.8 × 10?7 M?1, respectively), and satisfactory (albeit lower) affinities for the 22AG/K+ and Myc2345-Pu22/K+ G-quadruplexes. All ligands tested exhibit substantial selectivity for G-quadruplex versus duplex (ds26) DNA, as evidenced by competitive F rster resonance energy transfer (FRET) melting assays. Additionally, the 7-mer and 6-mer are capable of promoting a sharp morphology transition of 22AG/K+ G-quadruplex.
- Rizeq, Natalia,Georgiades, Savvas N
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- Improvement of the Van Leusen reaction in the presence of β-cyclodextrin: A green and efficient synthesis of oxazoles in water
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An efficient approach for the synthesis of oxazoles through the Van Leusen reaction in the presence of β-cyclodextrin is described. In aqueous medium using β-cyclodextrin as a supramolecular catalyst, tosylmethyl isocyanide was deprotonated by triethylami
- Rahimzadeh, Golnaz,Kianmehr, Ebrahim,Mahdavi, Mohammad
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p. 923 - 926
(2017/12/18)
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- A One-Pot Tandem Approach for the Synthesis of 5-(Het)aryloxazoles from Substituted (Het)aryl Methyl Alcohols and Benzyl Bromides
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A new modified van Leusen strategy has been developed for the synthesis of biologically significant 5-substituted oxazoles by the reaction of (het)aryl methyl alcohols or benzyl bromides as precursors with tosylmethylisocyanide (TosMIC) under basic conditions. This method is efficient, takes place under mild reaction conditions, and is tolerant of various functional groups with high yield.
- Vinay Kumar, Koravangala S.,Swaroop, Toreshettahally R.,Rajeev, Narasimhamurthy,Vinayaka, Ajjampura C.,Lingaraju, Gejjalagere S.,Rangappa, Kanchugarakoppal S.,Sadashiva, Maralinganadoddi P.
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supporting information
p. 1363 - 1366
(2016/06/01)
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- Linear and Branched Pyridyl-Oxazole Oligomers: Synthesis and Circular Dichroism Detectable Effect on c-Myc G-Quadruplex Helicity
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Five unprecedented pyridyl-oxazole oligomers exhibiting either linear or branched connectivity of their subunits were developed as a family of potential G-quadruplex-interacting ligands. Our synthesis employed variations of a key Pd/Cu-mediated C-C cross-coupling/C-H activation reaction to gain access to the oligomer products from a small set of substituted pyridine building blocks. The effect of the compounds on the conformation of a c-myc oncogene promoter G-quadruplex was investigated by circular dichroism under various conditions. Some or all of the compounds induced detectable helicity enhancement in low-cation and Na+-rich Tris-HCl (pH 7.4) buffers, respectively, in which the helix was only partially prefolded.
- Rizeq, Natalia,Georgiades, Savvas N.
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p. 122 - 131
(2016/01/26)
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- Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([11C]MPPO) Based on α-Ketoheterocyclic Scaffold
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Fatty acid amide hydrolase (FAAH) is one of the principle enzymes for metabolizing endogenous cannabinoid neurotransmitters such as anandamide, and thus regulates endocannabinoid (eCB) signaling. Selective pharmacological blockade of FAAH has emerged as a potential therapy to discern the endogenous functions of anandamide-mediated eCB pathways in anxiety, pain, and addiction. Quantification of FAAH in the living brain by positron emission tomography (PET) would help our understanding of the endocannabinoid system in these conditions. While most FAAH radiotracers operate by an irreversible ("suicide") binding mechanism, a FAAH tracer with reversibility would facilitate quantitative analysis. We have identified and radiolabeled a reversible FAAH inhibitor, 7-(2-[11C]methoxyphenyl)-1-(5-(pyridin-2-yl)oxazol-2-yl)heptan-1-one ([11C]MPPO) in 13% radiochemical yield (nondecay corrected) with >99% radiochemical purity and 2 Ci/μmol (74 GBq/μmol) specific activity. The tracer showed moderate brain uptake (0.8 SUV) with heterogeneous brain distribution. However, blocking studies with a potent FAAH inhibitor URB597 demonstrated a low to modest specificity to the target. Measurement of lipophilicity, metabolite, and efflux pathway analysis were also performed to study the pharmacokinetic profile of [11C]MPPO. In all, we reported an efficient radiolabeling and preliminary evaluation of the first-in-class FAAH inhibitor [11C]MPPO with α-ketoheterocyclic scaffold. (Chemical Equation Presented).
- Wang, Lu,Yui, Joji,Wang, Qifan,Zhang, Yiding,Mori, Wakana,Shimoda, Yoko,Fujinaga, Masayuki,Kumata, Katsushi,Yamasaki, Tomoteru,Hatori, Akiko,Rotstein, Benjamin H.,Collier, Thomas Lee,Ran, Chongzhao,Vasdev, Neil,Zhang, Ming-Rong,Liang, Steven H.
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p. 109 - 118
(2016/02/05)
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- Synthesis of a 'propeller-like' oligoheteroaryl with alternating pyridine and oxazole motifs
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The molecular architecture of oligomeric pyridyl-oxazole compounds is key to determining their mode of interaction with G-quadruplex DNA structures, which is a family of prominent anticancer biomolecular targets. We report herein an efficient synthetic route that begins with chelidamic acid and affords, in just seven steps, an unusual 'propeller-like' pyridyl-oxazole architecture with alternating pyridine and oxazole rings, that has not been yet validated as a G-quadruplex binder. The synthesis employs Van Leusen chemistry for the construction of oxazole rings from aldehydes, and two Pd(II)/Cu(I)-mediated cross-coupling reactions involving C-H activation of oxazoles for the formation of C-C bonds between bromopyridine intermediates and oxazole fragments. This modular synthesis was designed to be amenable to the construction of analogues.
- Georgiades, Savvas N.,Rizeq, Natalia
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supporting information
p. 489 - 493
(2015/04/14)
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- Highly regioselective palladium-catalyzed direct arylation of oxazole at C-2 or C-5 with aryl bromides, chlorides, and triflates
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Complementary palladium-catalyzed methods for direct arylation of oxazole with high regioselectivity (>100:1) at both C-5 and C-2 have been developed for a wide range of aryl and heteroaryl bromides, chlorides, iodides, and triflates. C-5 arylation is pre
- Strotman, Neil A.,Chobanian, Harry R.,Guo, Yan,He, Jiafang,Wilson, Jonathan E.
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supporting information; experimental part
p. 3578 - 3581
(2010/11/04)
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- Synthesis of 2-TIPS-oxazol-5-ylboronic acid pinacol ester: efficient route to 5-(het)aryloxazoles via Suzuki cross-coupling reaction
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A facile synthetic route to the new 2-TIPS-oxazol-5-ylboronic acid pinacol ester was described herein. Its reactivity toward Suzuki cross-coupling reaction was studied to provide various 5-(het)aryloxazoles. A wide range of functions on the aryl moiety ar
- Primas, Nicolas,Bouillon, Alexandre,Lancelot, Jean-Charles,Rault, Sylvain
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experimental part
p. 6348 - 6353
(2009/12/04)
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- TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and are useful for treatment of malconditions involving that enzyme.
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Page/Page column 41
(2009/01/24)
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- Structure-activity relationships of α-ketooxazole inhibitors of fatty acid amide hydrolase
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A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, K, - 2.6 nM), with 5hh (aryl -3-ClPh, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM, or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.
- Hardouin, Christophe,Kelso, Michael J.,Romero, F. Anthony,Rayl, Thomas J.,Leung, Donmienne,Hwang, Inkyu,Cravatt, Benjamin F.,Boger, Dale L.
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p. 3359 - 3368
(2008/02/13)
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- Reactions between weinreb amides and 2-magnesiated oxazoles: A simple and efficient preparation of 2-acyl oxazoles
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(Chemical Equation Presented) Treatment of oxazole or 5-aryl oxazoles with i-PrMgCl smoothly generates the corresponding 2-Grignard reagents, which react with Weinreb amides to provide exclusively 2-acyl oxazole products.
- Pippel, Daniel J.,Mapes, Christopher M.,Mani, Neelakandha S.
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p. 5828 - 5831
(2008/02/09)
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- NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
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Acetylcholine receptor ligands of formula I wherein A, Ar1 and Ar2 are as described in the specification, diastereoisomers, enantiomers, pharmaceutically-acceptable salts, methods of making, pharmaceutical compositions containing and methods for using the same.
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Page/Page column 31
(2010/11/08)
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- 1,3-BENZOTHIAZINONE DERIVATIVES AND USE THEREOF
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This invention provides a compound represented by the formula (I) :wherein R1 is a hydrogen atom, a halogen atom, hydroxy, nitro, optionally halogenated alkyl, alkoxy optionally having substituents, acyl or amino optionally having substituents;R2 is pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each of which may have substituents;n is 1 or 2; or a salt. And this invention provides a safe pharmaceutical comprising the compound of the formula (I) , which has an excellent apoptosis inhibitory effect and MIF binding effect, for preventing and/or treating heart disease, nervous degenerative disease, cerebrovascular disease, central nervous infectious disease, traumatorathy, demyelinating disease, bone and articular disease, kidney disease, liver disease, osteomyelodysplasia, AIDS, cancer, and the like.
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