- Modified benzoxazolone derivative as 18-kDa TSPO ligand
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We have synthesized six new congeners of acetamidobenzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8?±?1.2?nm) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phen
- Kumari, Neelam,Chadha, Nidhi,Srivastava, Pooja,Mishra, Lokesh Chandra,Bhagat, Sunita,Mishra, Anil K.,Tiwari, Anjani K.
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Read Online
- Acridine Orange Hemi(Zinc Chloride) Salt as a Lewis Acid-Photoredox Hybrid Catalyst for the Generation of α-Carbonyl Radicals
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A readily accessible organic-inorganic hybrid catalyst is reported for the reductive fragmentation of α-halocarbonyl compounds. The robust hybrid catalyst is a self-stabilizing combination of ZnCl2 Lewis acid and acridine orange as the photoactive organic dye. Mechanistic specifics of this hybrid catalyst have been studied in detail using both photophysical and electrochemical experiments. A systematic study enabled the discovery of the appropriate Lewis acid for the effective LUMO stabilization of α-halocarbonyl compounds and thereby lowering of reduction potential within the range of a standard organic dye. This strategy resolves the issues like dehalogenative hydrogenation or homo-coupling of alkyl radicals by guiding the photoredox cycle through an oxidative quenching pathway. The cooperativity between the photoactive organic dye and the Lewis acid counterparts empowers functionalization with a wide range of coupling partners through efficient and controlled generation of alkyl radicals and serves as an appropriate alternative to the expensive late transition metal-based photocatalysts. To demonstrate the application potential of this cooperative catalytic system, four different synthetic transformations of α-carbonyl bromides were explored with broad substrate scopes.
- Das, Sanju,Mandal, Tanumoy,De Sarkar, Suman
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supporting information
p. 755 - 765
(2021/12/10)
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- Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with PotentIn VitroAntiproliferative Activity
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Heme oxygenase-1 (HO-1) promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates with poor prognosis and chemoresistance, suggesting the inhibition of HO-1 as a possible antitumor strategy. Accordingly, compounds7iand7l-pemerged for their potency against HO-1 and were investigated for their anticancer activity against prostate (DU145), lung (A549), and glioblastoma (U87MG, A172) cancer cells. The selected compounds showed the best activity toward U87MG cells. Compound7lwas further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that7lcan reduce cell invasivity acting through modulation of HO-1 expression.
- Fallica, Antonino N.,Sorrenti, Valeria,D’Amico, Agata G.,Salerno, Loredana,Romeo, Giuseppe,Intagliata, Sebastiano,Consoli, Valeria,Floresta, Giuseppe,Rescifina, Antonio,D’Agata, Velia,Vanella, Luca,Pittalà, Valeria
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p. 13373 - 13393
(2021/09/20)
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- Synthesis of Oxindole Derivatives via Intramolecular C–H Insertion of Diazoamides Using Ru(II)-Pheox Catalyst
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This work presented the efficient intramolecular aromatic C–H insertion of diazoacetamide. The 1a–1o diazo compounds (except for 1k) were converted into their corresponding oxindoles via an intramolecular C–H insertion reaction in the presence of a Ru catalyst. The Ru-Pheox catalyst was shown to be highly efficient in this transformation in terms of the regioselectivity, producing the desired products in excellent yield (99%). The efficiency of the Ru catalyst reached 580 (TON) and 156 min?1 (TOF).
- Phan Thi Thanh, Nga,Dang Thi Thu, Huong,Tone, Masaya,Inoue, Hayato,Iwasa, Seiji
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- A copper(II)-mediated radical cross-dehydrogenative coupling/sulfinic acid elimination approach to 2-quinolones
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A new cyclisation procedure to prepare 4-carboxy-quinolin-2-ones via a one-pot Cu(II)-mediated radical cross-dehydrogenative coupling/sulfinic acid elimination of linear anilides is described. Extensions to more complex substrates are also reported as are
- Gorman, Ryan M.,Hurst, Timothy E.,Petersen, Wade F.,Taylor, Richard J.K.
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- Electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds
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The intramolecular C(sp3)-H/C(sp2)-H cross-coupling of 1,3-dicarbonyl compounds has been achieved through Cp2Fe-catalyzed electrochemical oxidation. The key to the success of these dehydrogenative cyclization reactions is
- Wu, Zheng-Jian,Li, Shi-Rui,Long, Hao,Xu, Hai-Chao
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supporting information
p. 4601 - 4604
(2018/05/14)
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- Site-Selective Conversion of Azido Groups at Carbonyl α-Positions to Diazo Groups in Diazido and Triazido Compounds
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This paper reports on the selective conversion of alkyl azido groups at the carbonyl α-position to diazo compounds. Through β-elimination of dinitrogen, followed by hydrazone formation/decomposition, α-azidocarbonyl moieties were transformed into α-diazo carbonyl groups in one step. As these reaction conditions do not involve aryl or general alkyl azides, site-selective conversions of di- and triazides were achieved. Through this method, the successive site-selective conjugation of the triazido molecule with three different components is demonstrated.
- Yokoi, Taiki,Tanimoto, Hiroki,Ueda, Tomomi,Morimoto, Tsumoru,Kakiuchi, Kiyomi
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p. 12103 - 12121
(2018/10/09)
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- Transfer Hydro-dehalogenation of Organic Halides Catalyzed by Ruthenium(II) Complex
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A simple and efficient Ru(II)-catalyzed transfer hydro-dehalogenation of organic halides using 2-propanol solvent as the hydride source was reported. This methodology is applicable for hydro-dehalogenation of a variety of aromatic halides and α-haloesters and amides without additional ligand, and quantitative yields were achieved in many cases. The potential synthetic application of this method was demonstrated by efficient gram-scale transformation with catalyst loading as low as 0.5 mol %.
- You, Tingjie,Wang, Zhenrong,Chen, Jiajia,Xia, Yuanzhi
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p. 1340 - 1346
(2017/02/10)
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- Transition-Metal-Free Fluoroarylation of Diazoacetamides: A Complementary Approach to 3-Fluorooxindoles
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An efficient transition-metal-free fluoroarylation reaction of N-aryl diazoacetamides with NFSI (N-fluorobenzenesulfonimide) is described. This reaction directly provides 3-fluorooxindole derivatives in yields of 67-93% with high selectivity via a carbene
- Dong, Kuiyong,Yan, Bin,Chang, Sailan,Chi, Yongjian,Qiu, Lihua,Xu, Xinfang
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p. 6887 - 6892
(2016/08/16)
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- AUTOTAXIN INHIBITOR COMPOUNDS
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Described herein are compounds that are autotaxin inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with autotaxin activity.
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Paragraph 00426
(2015/04/15)
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- Synthesis of α-Functionalized Trichloromethylcarbinols
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A new series of α-functionalized trichloromethylcarbinols have been synthesized from corresponding α-halomethyl ketones, esters, and amides in 48-78% overall yields. Reactivity of nitrates obtained in the first step was dependent on the electron-withdrawi
- Ram, Ram N.,Soni, Vineet Kumar
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p. 8922 - 8928
(2015/09/15)
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- A Direct C-H/Ar-H Coupling Approach to Oxindoles, Thio-oxindoles, 3,4-Dihydro-1 H-quinolin-2-ones, and 1,2,3,4-Tetrahydroquinolines
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A copper(II)-catalysed approach to oxindoles, thio-oxindoles, 3,4-dihydro-1H-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines via formal C-H, Ar-H coupling is described. In a new variant, copper(II) 2-ethylhexanoate has been identified as an inexpensive and efficient catalyst for this transformation, which utilises atmospheric oxygen as the re-oxidant. Copper(II) 2-ethylhexanoate: The synthesis of oxindoles, thio-oxindoles, 3,4-dihydro-1H-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines from linear precursors by direct C-H, Ar-H coupling by using a single copper catalyst is reported (see scheme; DIPEA=diisopropylethylamine, EWG=electron-withdrawing group). The cyclisations are simple to perform, run open to the air, are moisture insensitive, and use an inexpensive catalyst.
- Hurst, Timothy E.,Gorman, Ryan M.,Drouhin, Pauline,Perry, Alexis,Taylor, Richard J. K.
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supporting information
p. 14063 - 14073
(2016/02/18)
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- Nucleophilic substitution reactions of N-methyl α-bromoacetanilides with benzylamines in dimethyl sulfoxide
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Kinetic studies of the reactions of N-methyl-Y-a-bromoacetanilides with substituted X-benzylamines have been carried out in dimethyl sulfoxide at 25.0 °C. The Hammett plots for substituent X variations in the nucleophiles (log kN vs σX) are slightly bipha
- Adhikary, Keshab Kumar,Lee, Hai Whang
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experimental part
p. 857 - 862
(2012/01/13)
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- Synthesis and structure-activity relationship studies in translocator protein ligands based on a pyrazolo[3,4-b]quinoline scaffold
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As a further development of our large program focused on the medicinal chemistry of translocator protein [TSPO (18 kDa)] ligands, a new class of compounds related to alpidem has been designed using SSR180575, emapunil, and previously published pyrrolo[3,4-b]quinoline derivatives 9 as templates. The designed compounds were synthesized by alkylation of the easily accessible 4-methyl-2-phenyl-1H-pyrazolo[3,4-b]quinolin-3(2H)-one derivatives 13-15 with the required bromoacetamides. Along with the expected 2-(4-methyl-3-oxo-2- phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide derivatives 10, 2-(4-methyl-3-oxo-2-phenyl-2H-pyrazolo[3,4-b]quinolin-9(3H)-yl)acetamide isomers 11 were isolated and characterized. The high TSPO affinity shown by new pyrazolo[3,4-b]quinoline derivatives 10 and especially 11 leads the way to further expand the chemical diversity in TSPO ligands and provides new templates and structure-affinity relationship data potentially useful in the design of new anxiolytic and neuroprotective agents.
- Cappelli, Andrea,Bini, Giulia,Valenti, Salvatore,Giuliani, Germano,Paolino, Marco,Anzini, Maurizio,Vomero, Salvatore,Giorgi, Gianluca,Giordani, Antonio,Stasi, Luigi Piero,Makovec, Francesco,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Concas, Alessandra,Porcu, Patrizia,Biggio, Giovanni
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supporting information; experimental part
p. 7165 - 7175
(2011/12/04)
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- QUINUCLIDINE DERIVATIVES AS MUSCARINIC M3 RECEPTOR ANTAGONISTS
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The invention provides named compounds of formula (I), wherein R4 is a N-substituted quinuclidine (I) pharmaceutical compositions containing them and a process for preparing the pharmaceutical compositions. Their use in therapy for’ the treatment of conditions mediated by M3 muscarinic receptors, such as chronic obstructive pulmonary disease is also disclosed.
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Page/Page column 34
(2011/08/02)
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- QUINUCLIDINE DERIVATIVES AS MUSCARINIC M3 RECEPTOR ANTAGONISTS
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The invention provides named compounds of formula (I ), wherein R4 is a N- sustituted quinuclidine ( I ) pharmaceutical compositions containing them and a process for preparing the pharmaceutical compositions. Their use in therapy for' the treatment of conditions mediated by M3 muscarinic receptors, such as chronic obstructive pulmonary disease is also disclosed.
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Page/Page column 88-89
(2009/12/23)
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- NOVEL HETEROCYCLIC COMPOUND
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A drug having a high affinity for benzodiazepine ω3 receptors and showing curative and preventive effects for anxiety and depression, which comprises as the active ingredient, for example, a compound of the formula (1): wherein R1 an
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Page/Page column 33
(2010/11/24)
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- Solid phase approaches to N-heterocycles using a sulfur linker cleaved by SmI2
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A sulfur HASC (α-hetero-atom substituted carbonyl) linker has been utilized in solid-phase approaches to oxindoles and tetrahydroquinolones. The route to oxindoles employs the first Pummerer cyclizations on solid phase, whereas the route to tetrahydroquinolones involves a microwave-assisted Heck reaction followed by a Michael cyclization. In both cases, the linker is cleaved in a traceless fashion by electron transfer from samarium(II) iodide. The routes illustrate the compatibility of the linker system with a number of reaction types and its utility for library synthesis.
- McAllister, Laura A.,Turner, Kristy L.,Brand, Stephen,Stefaniak, Mark,Procter, David J.
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p. 6497 - 6507
(2007/10/03)
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- THERAPEUTICS
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The present invention relates to the use of a compound of formula (I); wherein: R1 comprises a carbonyl group and R2 is a hydrocarbyl group; optionally wherein said ring is further substituted; or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use in one or more of: modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; modulating calcium spikes in mammalian cells; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes; treating diseases in one or more of brain, heart, pancreatic cells (e.g. pancreatic acinar and pancreatic beta cells), immune cells, T-cells, haemopoietic cells including phagocytes by modulating the release of intracellular calcium from a store controlled by nicotinic acid adenine dinucleotide phosphate; treating diseases in one or more of brain, heart, and T-cells by modulating calcium spikes in mammalian cells.
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Page/Page column 57
(2008/06/13)
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- Substitution-reduction: An alternative process for the [ 18F]N-(2-fluoroethylation) of anilines
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Substitution of a halo atom (chloro or bromo) in easily prepared N-haloacetyl-anilines with no-carrier added (NCA) cyclotron-produced [ 18F]fluoride ion (18F, t1/2 = 109.8 min; β+ = 96.9%), followed by reduction with borane-tetrahydrofuran (BH3-THF), provides an alternative route to NCA [ 18F]N-(2-fluoroethyl)-anilines. This two-step and one-pot process is rapid (～50 min) and moderately high yielding (～40% decay-corrected radiochemical yield (RCY) overall). In the nucleophilic substitution reaction, 18-crown-6 is preferred to Kryptofix 222 as complexing agent for the solubilization of the counter-ion (K+), derived from an added metal salt, in acetonitrile. Weakly basic potassium bicarbonate is preferred as the added metal salt. Inclusion of a small amount of water, equating to 4-5 molar equivalents relative to 18-crown-6, base or precursor (held in equimolar ratio), is beneficial in preventing the adsorption of radioactivity onto the wall of the glass reaction vessel and for achieving high RCY in the nucleophilic substitution reaction. BH3-THF is effective for the rapid reduction of the generated [18F]N-fluoroacetyl-aniline to the [ 18F]N-(2-fluoroethyl)-aniline. Copyright
- Briard, Emmanuelle,Pike, Victor W.
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p. 217 - 232
(2007/10/03)
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- (+)-cis-N-ethyleneamino-N-normetazocine derivatives. Novel and selective sigma ligands with antagonist properties.
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A series of (+)-cis-N-normetazocine derivatives has been described, and their affinities for sigma1, sigma2, and phencyclidine (PCP) sites and opioid, muscarinic (M2), dopamine (D2), and serotonin (5-HT2) receptors were evaluated. The effect of the N-subs
- Ronsisvalle,Marrazzo,Prezzavento,Pasquinucci,Vittorio,Pittala,Pappalardo,Cacciaguerra,Spampinato
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p. 1574 - 1580
(2007/10/03)
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- Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor agonist activity. 1. Optimization of the agonist "trigger"
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Directed screening of compounds selected from the Glaxo registry file for contractile activity on the isolated guinea pig gallbladder (GPGB) identified a series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor agonist activity. Agonis
- Aquino, Christopher J.,Armour, Duncan R.,Berman, Judd M.,Birkemo, Larry S.,Carr, Robin A. E.,Croom, Dallas K.,Dezube, Milana,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Head, Julie E.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Miller, Laurence J.,Queen, Kennedy L.,Rimele, Thomas J.,Smith, David N.,Sugg, Elizabeth E.
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p. 562 - 569
(2007/10/03)
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- N-phenylglycinamide CCK antagonists and pharmaceutical compositions containing them
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Compounds of formula: STR1 in which R1 represents a hydrogen atom, an alkyl or alkoxycarbonyl radical or a phenyl radical, optionally substituted, R2 represents an alkoxy, optionally substituted cycloalkyloxy, cycloalkylalkyloxy, phenylalkyloxy, polyfluoroalkyloxy or cinnamyloxy radical or a radical --NR5 R6, R3 represents a phenylamino radical in which the phenyl ring is optionally substituted, an optionally substituted phenyl radical or a naphthyl, indolyl or quinolyl radical, R4 represents a substituted phenyl radical, R5 and R6, which may be identical or different, represent a hydrogen atom or an alkyl, optionally substituted phenyl, indanyl, cycloalkylalkyl, cycloalkyl or phenylalkyl radical, or alternatively R5 and R6, together with the nitrogen atom to which they are attached, form a heterocycle, their preparation and medicinal products containing them.
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- Cycloadditions, 7. Intramolecular Diels-Alder Reactions of Allenecarboxanilides; Variation of the Substituents in the p-Position of the Aniline Nucleus
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The N-methyl-1,2-propadiene-1-carboxanilides 6a-h, differently substituted in the p-position, are synthesized by Wittig reaction of the carbamoylmethylenephosphoranes 5 with ketene.They isomerize by thermolysis in boiling xylene to give the tricycles 7a-h, the products of the intramolecular Diels-Alder reaction, and in some cases also to the quinolones 9, the products of a cyclization reaction.The order of the reaction and the influence of the substituents upon the rate of the intramolecular Diels -Alder reaction are determined by 1H-NMR spectroscopy.
- Diehl, Klaus,Himbert, Gerhard,Henn, Lothar
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p. 2430 - 2443
(2007/10/02)
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