- Naphthyl ketones: A new class of Janus kinase 3 inhibitors
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Potent inhibition of Janus kinase 3 was found for a series of naphthyl(β-aminoethyl)ketones (e.g. 7, pIC50 = 7.1 ± 0.3). Further studies indicated that these compounds fragment in less than 1 h by retro-Michael reaction in the Jak3 in vitro ELISA assay procedure. The breakdown product of 7,2-naphthylvinyl ketone (22, pIC50 = 6.8 ± 0.3) showed very similar inhibitory activity to 7. Compounds 7 (in neutral buffer) and 22 will be useful pharmacological tools for the investigation of the Janus tyrosine kinase Jak3. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Brown, George R.,Bamford, Andrea M.,Bowyer, Jonathan,James, Daniel S.,Rankine, Neil,Tang, Eric,Torr, Vanessa,Culbert, Eric J.
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- Platinum(II) complexes with π-conjugated, naphthyl-substituted, cyclometalated ligands (RC∧N∧N): Structures and photo- and electroluminescence
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The crystal structures and photophysical properties of mononuclear [(RC∧N∧N)PtX](ClO4)n ((RC∧N∧N) = 3-(6′-(2″-naphthyl)-2′-pyridyl)isoquinolinyl and derivatives; X = Cl, n = 0; X = PPh3 or PCy3, n = 1), dinuclear [(RC∧N∧N)2Pt2(μ-dppm)]-(ClO4) 2 (dppm = bis(diphenyphosphi-no)methyl) and trinuclear [(RC∧N∧N)3Pt3(μ-dpmp)](ClO4) 3 (dpmp = bis(diphenylphosphinomethyl)phenylphosphine) complexes are presented. The crystal structures show extensive intra- and/or intermolecular π...π interactions; the two (RC∧N∧N) planes of [(RC∧N∧N)2Pt2(μ-dppm)]-(ClO4) 2 (R = Ph, 3,5-tBu2Ph or 3,5-(CF3) 2Ph) are in a nearly eclipsed configuration with torsion angles close to 0°. [(RC∧N∧N)PtCl], [(RC∧N∧N)2Pt 2-(μ-dppm)](ClO4)2, and [(RC∧N∧N) 3Pt(μ-dpmp)](ClO4)3 are strongly emissive with quantum yields of up to 0.68 in CH2Cl2 or MeCN solution at room temperature. The [(RC∧N∧N)PtCl] complexes have a high thermal stability (Td = 470-549°C). High-performance light-emitting devices containing [(RC∧N∧N)PtCl] (R = H or 3,5-tBu 2Ph) as a light-emitting material have been fabricated; they have a maximum luminance of 63 000 cd m-2 and CIE 1931 coordinates at x = 0.36, y = 0.54.
- Kui, Steven C. F.,Sham, Iona H. T.,Cheung, Cecil C. C.,Ma, Chun-Wah,Yan, Beiping,Zhu, Nianyong,Che, Chi-Ming,Fu, Wen-Fu
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Read Online
- Stereoselective Construction of γ-Lactams via Copper-Catalyzed Borylacylation
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A versatile and highly stereoselective borylative cyclization to generate polyfunctionalized γ-lactams has been developed. The stereoselective synthesis of these key ring systems is crucial due to their ubiquity in natural products. We report the diastero- and enantioselective construction of di- and trisubstituted γ-lactam cores, with examples containing an enantioenriched quaternary carbon.
- Bajohr, Jonathan,Lautens, Mark,Polishchuk, Iuliia,Torelli, Alexa,Whyte, Andrew
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supporting information
p. 7915 - 7919
(2020/11/02)
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- Luminescent PtII Complexes of Tridentate Cyclometalating 2,5-Bis(aryl)-pyridine Ligands
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Bis-cyclometalated PtII complexes of dianionic 2,5-bis(aryl)-pyridine ligands (L1–6)2–, carrying various cyclometalating or pending aryl groups, are synthesised in two steps. The reactions of H2L protoligands with K2[PtCl4] in acetic acid give the mono-cyclometalated complexes [Pt(HL)Cl]2. Heating these complexes in hot DMSO (dimethyl sulfoxide) yields the double-cyclometalated DMSO complexes [Pt(L1–6)(DMSO)]. The reaction of [Pt(L4)(DMSO)] with N,N-dimethylimidazolium iodide in the presence of KOtBu as the base gives the carbene complex [Pt(L4)(Me2Imd)]. Detailed photophysical studies reveal the intense orange luminescence of these complexes in CH2Cl2 solution, with quantum yields up to 0.22, and increased quantum yields of up to 1.00 in glassy frozen CH2Cl2/MeOH (1:1) and up to 0.44 in PMMA matrices. Detailed electrochemistry (including spectroelectrochemistry) reveals reversible ligand-based first reductions at –2.1 to –2.3 V, irreversible Pt-centred oxidations at around 0.8 V and electrochemical band gaps of 2.8–3.0 eV. Further reduction waves at very negative potentials interfere with the solvent (THF with traces of water) discharge and can be traced, with UV/Vis spectroelectrochemistry, to Pt-centred reductions for the DMSO complexes and to a second ligand-centred reduction for the Me2Imd complex from. The photo/electrochemical properties can be roughly correlated with the ligand pattern and suggest their use in optoelectronic applications.
- Krause, Maren,Kourkoulos, Dimitrios,González-Abradelo, Darío,Meerholz, Klaus,Strassert, Cristian A.,Klein, Axel
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supporting information
p. 5215 - 5223
(2017/10/18)
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- Pt coordination compound containing quinazoline ligands as well as preparation method and application of Pt coordination compound
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The invention relates to a Pt coordination compound containing quinazoline ligands. The Pt coordination compound is expressed in a general formula [Pt(XYZ)C]B,wherein XYZ is tridentate provided in a formula (1a) or (1b); and C is a monodentate prov
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Paragraph 0095; 0097
(2017/06/02)
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- Evaluation of alkylating and intercalating properties of mannich bases for cytotoxic activity
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A series of new "hybrid compounds", Mannich base derivatives of planar polycyclic/heterocyclic starting materials, was designed and synthesized. The structures of the compounds were confirmed by spectroscopic methods and elemental analysis. Cytotoxicity of compounds was investigated in three cancer cell lines (PC3, HeLa, and MCF7) and one non-tumoral cell line (293 HEK). We tested the DNA-intercalating capability of the molecules by ethidium bromide (EtBr) fluorescence displacement experiment. Compounds' alkylation potency was investigated via in vitro incubation test using 2-mercaptoethanol, a biomimetic nucleophile. The five of the compounds (7s, 9d, 10b, 11b, 12c) are reported for first time in the literature. Our results suggest that compound 9d has a biological activity close to the reference compound doxorubicin, an intercalating agent in clinical use.
- Istanbullu, Huseyin,Erzurumlu, Yalcin,Kirmizibayrak, Petek Ballar,Erciyas, Ercin
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p. 1096 - 1106
(2015/04/14)
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- Synthesis and anti-tubercular activity of conformationally-constrained and bisquinoline analogs of TMC207
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One of the most significant breakthroughs in the battle against tuberculosis is the recent approval of the quinoline compound, TMC207, for the treatment of drug-resistant tuberculosis. To gain insight into the molecular determinants of the activity of TMC207 and to evaluate the scope of quinoline compounds as anti-tubercular agents, we synthesized a series of TMC207 derivatives and evaluated their anti-tubercular activity. Making the lateral chain of the drug rigid by linking it to an adjacent phenyl substituent resulted in a decrease in activity. In contrast, replacing a phenyl substituent of TMC207 with a quinoline moiety gave bisquinolines that demonstrated potent anti-tubercular activity in in vitro experiments, in ex vivo mouse bone marrow macrophage assays, and also in the in vivo mouse model of the disease. These results provide new guiding principles for modifying the TMC207 scaffold to develop efficacious anti-tubercular drugs and set the stage for the development of bisquinolines as a promising new class of anti-tubercular agents.
- Kalia, Dimpy,Anil Kumar,Meena, Gajanand,Sethi, Kashmir Prasad,Sharma, Rohit,Trivedi, Priyanka,Khan, Shaheb Raj,Verma, Ajay Singh,Singh, Shyam,Sharma, Sandeep,Roy, Kuldeep K.,Kant, Ruchir,Krishnan, Manju Yasodha,Singh, Bhupendra N.,Sinha, Sudhir,Chaturvedi, Vinita,Saxena, Anil K.,Dikshit, Dinesh K.
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p. 1554 - 1563
(2015/08/24)
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- A novel antifungal agent with broad spectrum: 1-(4-Biphenylyl)-3-(1H- imidazol-1-yl)-1-propanone
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A series of (1-substituted aryl)-3-(1H-imidazol-1-yl)-1-propanones was synthesized through the N-alkylation of imidazole with 3-dimethylamino-1- (substituted aryl)-1-propanone hydrochlorides (ketonic Mannich bases). A second series of N1-substituted imidazoles was obtained by the reduction of the carbonyl function of the imidazole-ketones in the previous series by means of NaBH4. All of the compounds were evaluated for antifungal activity against 16 strains of Candida, and 3-(1H-imidazol-1-yl)-1-(4-biphenylyl)-1- propanone emerged as a broad-spectrum antifungal agent. Several 3-(1H-imidazol-1-yl)-1-(2′-(substituted benzyl)oxyphenyl)-1-propanones were also active towards Candida kefyr. Copyright
- Roman, Gheorghe,Mare?, Mihai,Nǎstasǎ, Valentin
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p. 110 - 118
(2013/04/10)
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- 1-(Naphthyl-n-propyl)imidazole derivatives
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Compounds of the formula STR1 wherein Z is C1 and C4 alkoxymethylene, hydroxymethylene, esterified hydroxymethylene, carbonyl, or ketal-protected carbonyl, and the pharmaceutically acceptable acid addition salts thereof, are useful a
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- 1-(Naphthylalkyl)-1H-imidazole derivatives, a new class of anticonvulsant agents
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Potent anticonvulsant activity has been demonstrated for a large number of 1-(naphthylalkyl)-1H-imidazoles containing a variety of functional groups in the alkylene bridge. The presence of a small oxygen function in the bridge, in general, confers a high
- Walker,Wallach,Hirschfeld
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