- A bis-urea naphthalene macrocycle displaying two crystal structures with parallel ureas
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Herein we synthesized a bis-urea macrocycle from 2,7-dimethylnaphthalene that displays an unusual parallel urea conformation. The naphthalenes also adopt a bowl shape over the anticipated parallel planar orientation. Crystallization of the macrocycle from different solvent systems affords two solvated forms. 1·DMSO·(H2O)2 has an extended columnar structure where parallel macrocycles are linked by intervening hydrogen bonded water molecules. In 1·(MeOH)2 direct hydrogen-bonds link the macrocycles into chains, which hydrogen-bond with methanol molecules to form a layered structure.
- Geer, Michael F.,Smith, Mark D.,Shimizu, Linda S.
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Read Online
- COMPOUNDS USEFUL IN HIV THERAPY
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The invention relates to compounds of Formula (I), (Ia), (Ib), (II) or (III), salts thereof, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.
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Page/Page column 242
(2020/06/19)
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- Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands
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The chemokine receptor CXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis. With the aim of enhancing the binding affinity and anti-HIV activity of a potent CXCR4 ligand as a lead, 23 low molecular weight compounds containing dipicolylamine (Dpa) and cyclam cationic moieties with varying spacers and spatial positioning were designed, synthesized and biologically evaluated. All of the synthesized compounds screened at 1.0 μM in the NanoBRET assay system exhibited >70% inhibition of the binding of a competitive probe TAMRA-Ac-TZ14011 (10 nM) to CXCR4 in the presence of zinc (II) ion. Furthermore, selected compounds 3, 8, 9, 19 and 21 with spatial distances between the next carbon to Dpa and the next carbon to cyclam within the range of 6.5–7.5 ? showed potent binding affinity selective for CXCR4 with IC50 values of 1.6, 7.9, 5.7, 3.5 and 4.5 nM, respectively, with corresponding high anti-HIV activity with EC50s of 28, 13, 21, 28 and 61 nM, respectively, in the presence of zinc (II) ion. Some compounds with remarkably more potent CXCR4-binding affinity than that of an initial lead were obtained. These compounds interact with different but overlapping amino acid residues of CXCR4. The present studies have developed new low molecular weight CXCR4 ligands with high CXCR4-binding and anti-HIV activities, which open avenue into the development of more potent CXCR4 ligands.
- Sakyiamah, Maxwell M.,Kobayakawa, Takuya,Fujino, Masayuki,Konno, Makoto,Narumi, Tetsuo,Tanaka, Tomohiro,Nomura, Wataru,Yamamoto, Naoki,Murakami, Tsutomu,Tamamura, Hirokazu
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supporting information
p. 1130 - 1138
(2019/02/16)
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- Distance between Metal Centres Affects Catalytic Efficiency of Dinuclear CoIII Complexes in the Hydrolysis of a Phosphate Diester
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Dinuclear CoIII complex catalysed hydrolysis of bis-p-nitrophenylphosphate, a DNA model substrate, is reported. The catalysts were designed in such a way that the two CoIII ions cannot be contemporaneously involved in the complexation of the substrate or transition state. Experimental evidence of the involvement of such a remote metal centre in the catalysis of the hydrolysis of a phosphate diester is provided. This contribution amounts to a ca. 64-fold rate acceleration for the second-order rate constants of the best dinuclear complex over the mononuclear one, which is apparently due to general acid or H-bonding catalysis. Furthermore, there is significant distance dependence for this catalytic contribution and, in this case, it appears that the best distance (as estimated by DFT calculations) is ca. 7.7 ?. This may indicate that the presence of metal centres in close proximity, as required for mechanism proposals in which all metals are directly involved in transition-state coordination, is not the only option for rate acceleration in natural phosphate hydrolysis.
- Bencze, Eva Szusanna,Zonta, Cristiano,Mancin, Fabrizio,Prins, Leonard J.,Scrimin, Paolo
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p. 5375 - 5381
(2018/10/26)
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- Helical Threads: Enantiomerically Pure Carbo[6]Helicene Oligomers
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We report the synthesis of enantiomerically pure carbo[6]helicene oligomers with buta-1,3-diyne-1,4-diyl bridges between the helicene nuclei. The synthesis of monomeric (±)-2,15-bis[(triisopropylsilyl)ethynyl]carbo[6]helicene was achieved in 25 % yield over six steps. Pure (+)-(P)- and (?)-(M)-enantiomers were obtained by HPLC on a chiral stationary phase. The dimeric (+)-(P)2- and (?)-(M)2-configured and the tetrameric (+)-(P)4- and (?)-(M)4-configured oligomers were obtained by sequential oxidative acetylenic coupling. The ECD spectra of the tetrameric oligomers displayed large Cotton effect intensities of Δ?=?851 m?1 cm?1 at λ=370 nm ((M)4-enantiomer). We transformed the buta-1,3-diyne-1,4-diyl bridge in the dimeric (P)2 and (M)2 oligomer by heteroaromatization into a thiene-2,5-diyl linker. Although the resulting chromophore showed reduced ECD intensities, it exhibited a remarkably strong fluorescence emission at 450–500 nm, with an absolute quantum yield of 25 %.
- Schaack, Cédric,Sidler, Eric,Trapp, Nils,Diederich, Fran?ois
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supporting information
p. 14153 - 14157
(2017/10/17)
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- Synthesis and structures of dinuclear Silver(I) and Copper(II) complexes of a semirigid naphthalene-bridged bipyrazolyl ligand
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Reactions of a semirigid bipyrazole, 2,7-bis(4′-methylene-1H- 3′,5′-diphenylpyrazole) naphthalene (H2L) with Ag(I) or Cu(II) salts yielded four dinuclear complexes, namely, [Ag2(H 2L)2(NO3)2] (1), [Ag 2(H2L)2](ClO4)2 (2), [Ag2(H2L)2](BF4)2 (3), and [Cu2(H2L)2Cl4] (4). X-ray analysis illustrates that the three Ag(I) complexes are structurally similar and exhibit a rectangular shape, while the Cu(II) complex features an intramolecular π-stacking between two naphthalene-moieties and is much more compressed compared with those Ag(I) complexes. Two different conformations, namely cis, cis- and trans, trans-, have been observed for this bipyrazolyl ligand in its Ag(I) and Cu(II) complexes, respectively. Graphical Abstract: A semirigid naphthalene-bridged bipyrazole and its four dinuclear silver(I) or copper(II) complexes have been prepared and the crystal structures of the metal complexes have been studied by X-ray diffraction.[Figure not available: see fulltext.]
- Duan, Peng-Cheng,Jin, Rui-Wen,Wang, Zi-Xuan,Yang, Guang
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p. 448 - 454
(2013/09/02)
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- Trigonal prismatic Cu(i) and Ag(i) pyrazolato nanocage hosts: Encapsulation of S8 and hydrocarbon guests
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Two neutral hexanuclear trigonal prismatic cage molecules have been synthesized by coupling two planar triangular M3pz 3-panels, M = Cu(i) and Ag(i), in eclipsed geometry. The ~230 A3 cage volume can be either vacant or occupied by neutral guests. The crystal structures of the M6-cyclohexane and Ag 6-S8 host-guest species have been determined.
- Duan, Peng-Cheng,Wang, Zhao-Yang,Chen, Jing-Huo,Yang, Guang,Raptis, Raphael G.
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supporting information
p. 14951 - 14954
(2013/10/22)
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- Secondary interactions in crystals of all ten isomers of Di(bromomethyl)naphthalene
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The packing of all ten isomers of di(bromomethyl)naphthalene is analysed; nine of the structures were determined here, one (the 1,8-isomer) was already known. The 1,5- and 2,6-isomers display crystallographic inversion symmetry and the 2,7-isomer mirror symmetry through the central bond. For the 1,2-, 1,7- and 2,7-isomers, the bromomethyl groups point to the same side of the ring system, and for all other isomers to opposite sides. As expected, the molecules are linked into aggregates by various types of interactions: weak hydrogen bonds CH...Br, Br...Br interactions, CH...π contacts, π ...π stacking and Br...π contacts. The weak hydrogen bonds tend to be numerous but relativelyi; long, and do not combine to form readily recognisable patterns; a more readily assimilated view of the packing is based on the Br...Br interactions, which are observed for all isomers except 1,7 and 2,3, and in some cases lead to aggregation to form quadrilaterals or chains. With decreasing frequency, the interactions π ...π, C-H...π and Br...π are observed, but the latter are rare (just two examples) and very asymmetric, with contacts to only one or two carbons.
- Jones, Peter G.,Kus, Piotr
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experimental part
p. 433 - 444
(2010/10/01)
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- Synthesis of kurasoin B using phase-transfer-catalyzed acylimidazole alkylation
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The hydroxy ketone natural product kurasoin B is synthesized using a phase-transfer-catalyzed alkylation reaction with benzyloxyacetyl imidazole. A biscinchonidinium dimethylnaphthalene catalyst allowed for high yield and near complete selectivity (99% ee
- Christiansen, Michael A.,Butler, Aaron W.,Hill, Amanda R.,Andrus, Merritt B.
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body text
p. 653 - 657
(2009/08/07)
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- Phase-transfer catalyzed asymmetric arylacetate alkylation
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Phenethyl arylacetates are alkylated under phase-transfer conditions with cinchona catalysts with alkyl halides in high yield with excellent enantioselectivity (84-99% ee) following recrystallization. Cinchonidine (CD) derived catalyst gave the (R)-product and cinchonine (CN) catalyst produced the (S)-product. The phenethyl (PE) ester group is removed, using ammonium formate and catalytic Pd/C, to give alkylated carboxylic acid products in high selectivity. The utility of the approach is demonstrated by a direct synthesis of (S)-naproxen.
- Andrus, Merritt B.,Harper, Kaid C.,Christiansen, Michael A.,Binkley, Meisha A.
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supporting information; experimental part
p. 4541 - 4544
(2009/12/03)
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- Unique behavior of 2,6-bis(bromomethyl)naphthalene as a highly active organic DNA crosslinking molecule
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Among 14 bis-halomethylated naphthalenes and quinolines, 2,6-bis(bromomethyl)naphthalene was found to have highly active crosslinking activity on DNA. The unique behavior of high microbial mutagenicity, even though it had a low propensity to form double-strands in linearized plasmid DNA, suggested that it would offer a new seed, capable of forming intrastrand crosslinks similar to cisplatin. The electron withdrawal extent of the halogen atoms, the substitution patterns of two halomethyl groups, and the introduction of a nitrogen atom into the aromatic nucleus had remarkable effects on the activity of the molecule.
- Higashi, Toshinori,Uemura, Koichi,Inami, Keiko,Mochizuki, Masataka
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supporting information; experimental part
p. 3568 - 3571
(2009/09/27)
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- Phase-transfer-catalyzed asymmetric acylimidazole alkylation
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(Chemical Equation Presented) 2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at -40°C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6-20 h) under mild conditions, consistent with an ion-pair mechanism. The products are readily converted to useful ester products using methyltriflate and sodium methoxide, via a dimethylacylimidazolium intermediate without racemization. The process is efficient, direct, and amenable to other electrophiles and transformations that proceed through an enolate intermediate.
- Andrus, Merritt B.,Christiansen, Michael A.,Hicken, Erik J.,Gainer, Morgan J.,Bedke, D. Karl,Harper, Kaid C.,Mikkelson, Shawn R.,Dodson, Daniel S.,Harris, David T.
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p. 4865 - 4868
(2008/03/14)
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- Polymeric chiral phase-transfer catalysts derived from cinchona alkaloids for enantioselective synthesis of α-amino acids
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A series of dimeric/trimeric chiral quaternary ammonium salts derived from cinchona alkaloids were designed as efficient and practical chiral phase-transfer catalysts (PTCs). Presented are the details on the development of the dimeric PTCs for the synthesis of optically active α-amino acid derivatives and the optimization of the reaction variables suitable for the dimeric PTCs. The 1,3-phenyl- and the 2,7-naphthyl-linked dimeric PTCs showed excellent catalytic capability on the reactivity and enantioselectivity in the catalytic phase-transfer alkylation of N-(diphenylmethylene)glycine tert-butyl ester (1). A variety of α-amino acid derivatives were obtained with high enantiopurities using the dimeric PTCs, especially the 2,7-naphthyl-dimer 41, in a very practical manner.
- Lee, Jeong-Hee,Yoo, Mi-Sook,Jung, Ji-Hee,Jew, Sang-sup,Park, Hyeung-geun,Jeong, Byeong-Seon
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p. 7906 - 7915
(2008/02/09)
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- Enzymatic approach to unnatural glycosides with diverse aglycon scaffolds using glycosyltransferase VinC
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Glycosyltransferase VinC was explored for a construction of glycoside libraries using dTDP-vicenisamine and structurally unrelated unnatural aglycons, and new unnatural vicenisaminides were successfully constructed. Structural elements of aglycon recognit
- Minami, Atsushi,Uchida, Rei,Eguchi, Tadashi,Kakinuma, Katsumi
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p. 6148 - 6149
(2007/10/03)
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- Dinuclear zinc(II) dithiocarbamate macrocycles: Ditopic receptors for a variety of guest molecules
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The synthesis of a series of dinuclear zinc(II) dithiocarbamate (dtc) macrocyclic receptors containing aryl spacer groups of different sizes is reported. As evidenced from 1H NMR titration investigations, these receptors have the ability to bin
- Wong, Wallace W. H.,Curiel, David,Cowley, Andrew R.,Beer, Paul D.
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p. 359 - 364
(2007/10/03)
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- The synthesis of some new derivatives of 2,7-dimethylnaphthalene in an attempted synthesis of coronene
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The 10, 21- dibromo- 2,13- dithia- [3,3] (2,7) naphthalenophane (2) has been synthesised in four steps from 2,7-dimethylnaphthalene, and a preparation of 2,7- bis (hydroxymethyl) naphthalene (10) and the study of its halogenation in order to synthesise the new coronene (1) has been described.
- Larkem,Larkem,Messadi
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p. 413 - 426
(2007/10/03)
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- Design, Synthesis, and in Vitro Biological Evaluation of Small Molecule Inhibitors of Estrogen Receptor α Coactivator Binding
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Nuclear receptors (NRs) complexed with agonist ligands activate transcription by recruiting coactivator protein complexes. In principle, one should be able to inhibit the transcriptional activity of the NRs by blocking this transcriptionally critical receptor-coactivator interaction directly, using an appropriately designed coactivator binding inhibitor (CBI). To guide our design of various classes of CBIs, we have used the crystal structure of an agonist-bound estrogen receptor (ER) ligand binding domain (LBD) complexed with a coactivator peptide containing the LXXLL signature motif bound to a hydrophobic groove on the surface of the LBD. One set of CBIs, based on an outside-in design approach, has various heterocyclic cores (triazenes, pyrimidines, trithianes, cyclohexanes) that mimic the tether sites of the three leucines on the peptide helix, onto which are appended leucine residue-like substituents. The other set, based on an inside-out approach, has a naphthalene core that mimics the two most deeply buried leucines, with substituents extending outward to mimic other features of the coactivator helical peptide. A fluorescence anisotropy-based coactivator competition assay was developed to measure the specific binding of these CBIs to the groove site on the ER-agonist complex with which coactivators interact; control ligand-binding assays assured that their interaction was not with the ligand binding pocket. The most effective CBIs were those from the pyrimidine family, the best binding with Ki values of ca. 30 μM. The trithiane- and cyclohexane-based CBIs appear to be poor structural mimics, because of equatorial vs axial conformational constraints, and the triazene-based CBIs are also conformationally constrained by amine-substituent-to-ring resonance overlap, which is not the case with the higher affinity alkyl-substituted pyrimidines. The pyrimidine-based CBIs appear to be the first small molecule inhibitors of NR coactivator binding.
- Rodriguez, Alice L.,Tamrazi, Anobel,Collins, Margaret L.,Katzenellenbogen, John A.
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p. 600 - 611
(2007/10/03)
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- Highly enantioselective and practical cinchona-derived phase-transfer catalysts for the synthesis of α-amino acids
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A new class of naphthalene-based dimeric cinchona alkaloids 1 are very efficient and practical phase-transfer catalysts in the alkylation of a glycine derivative. The mild reaction conditions and the high catalytic efficiency (high yields and ee values) could make these alkaloids practical catalysts in the industrial synthetic process for natural and nonnatural chiral α-amino acids.
- Park, Hyeung-Geun,Jeong, Byeong-Seon,Yoo, Mi-Sook,Lee, Jeong-Hee,Park, Mi-Kyoung,Lee, Yeon-Ju,Kim, Mi-Jeong,Jew, Sang-Sup
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p. 3036 - 3038
(2007/10/03)
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- The first helical-chiral phosphane ligands: rac-[5]- and rac-[6]-heliphos
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The syntheses of two helical, chiral phosphanes in their racemic forms are described. Their helicene backbone was built up using an improved photocyclization approach. The phosphorus functionalities were introduced in the last step. Up to now, separation of the enantiomers of the helicene phosphanes could be achieved analytically but not on a preparative scale.
- Terfort, Andreas,Goerls, Helmar,Brunner, Henri
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