- Versatile Cp*Co(III)(LX) Catalyst System for Selective Intramolecular C-H Amidation Reactions
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Herein, we report the development of a tailored cobalt catalyst system of Cp*Co(III)(LX) toward intramolecular C-H nitrene insertion of azidoformates to afford cyclic carbamates. The cobalt complexes were easy to prepare and bench-stable, thus offering a convenient reaction protocol. The catalytic reactivity was significantly improved by the electronic tuning of the bidentate LX ligands, and the observed regioselectivity was rationalized by the conformational analysis and DFT calculations of the transition states. The superior performance of the newly developed cobalt catalyst system could be broadly applied to both C(sp2)-H and C(sp3)-H carbamation reactions under mild conditions.
- Chang, Sukbok,Jung, Hoimin,Kim, Dongwook,Lee, Jeonghyo,Lee, Jia,Park, Juhyeon
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supporting information
p. 12324 - 12332
(2020/08/06)
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- POLYAMINO BIARYL COMPOUNDS AND THEIR USE
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The present invention is directed to novel compounds of Formula I and pharmaceutically acceptable salts or solvates thereof, and their use.
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Page/Page column 59-60
(2020/02/06)
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- AGENT FOR OXIDATIVE DYEING OF HAIR CONTAINING ANISOLE DERIVATIVES
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The present disclosure relates to agents for the oxidative coloring of keratinic fibers, which are characterized in hat they contain derivatives of anisole as novel developer molecules.
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Paragraph 0268-0270
(2019/06/14)
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- A phenotypic approach to the discovery of compounds that promote non-amyloidogenic processing of the amyloid precursor protein: Toward a new profile of indirect β-secretase inhibitors
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Dysregulation of the Amyloid Precursor Protein (APP) processing leading to toxic species of amyloid β peptides (Aβ) is central to Alzheimer's disease (AD) etiology. Aβ peptides are produced by sequential cleavage of APP by β-secretase (BACE-1) and γ-secretase. Lysosomotropic agent, chloroquine (CQ), has been reported to inhibit Aβ peptide production. However, this effect is accompanied by an inhibition of lysosome-mediated degradation pathways. Following on from the promising activity of two series of APP metabolism modulators derived from CQ, we sought to develop new series of compounds that would retain the inhibitory effects on Aβ production without altering lysosome functions. Herein, we applied a ligand-based pharmacophore modeling approach coupled with de novo design that led to the discovery of a series of biaryl compounds. Structure-activity relationship studies revealed that minor modifications like replacing a piperidine moiety of compound 30 by a cyclohexyl (compound 31) allowed for the identification of compounds with the desired profile. Further studies have demonstrated that compounds 30 and 31 act through an indirect mechanism to inhibit β-secretase activity. This work shows that it is possible to dissociate the inhibitory effect on Aβ peptide secretion of CQ-derived compounds from the lysosome-mediated degradation effect, providing a new profile of indirect β-secretase inhibitors.
- Gay, Marion,Evrard, Caroline,Descamps, Florian,Carato, Pascal,Renault, Nicolas,Coevoet, Mathilde,Eddarkaoui, Sabiha,Baud, Catherine,Larchanché, Paul-Emmanuel,Buée, Luc,El Bakali, Jamal,Vingtdeux, Valérie,Sergeant, Nicolas,Melnyk, Patricia
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p. 104 - 125
(2018/10/04)
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- Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands
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The 4-benzylpiperidine moiety is a central structural element of potent N-methyl-d-aspartate (NMDA) receptor antagonists containing the GluN2B subunit. To obtain novel GluN2B ligands suitable for positron emission tomography, the benzylpiperidine moiety was replaced with fluorinated ω-phenylalkylamino groups. For this purpose three primary propyl- and butylamines 7 a–c and one butyraldehyde 7 d bearing a fluorine atom and an ω-phenyl moiety were prepared in 3- to 7-step syntheses. Compounds 7 a–d were attached to various scaffolds of potent GluN2B antagonists (scaffold hopping) instead of the original 4-benzylpiperidine moiety. Although benzoxazol-2-ones and indoles with a benzylpiperidine moiety show high GluN2B affinity, the corresponding fluorophenylalkylamine derivatives did not result in high Glu2B affinity. Moderate GluN2B affinity was observed for a 3-(fluoroalkyl)-substituted tetrahydro-1H-3-benzazepine (Ki=239 nm). However, high GluN2B affinity was obtained for the tetrahydro-5H-benzo[7]annulen-7-amines 12 a–c (Ki=17–30 nm). Docking studies resulted in the same binding pose for 12 a as for the lead compound Ro 25-6981. It can be concluded that some GluN2B ligands (benzoxazolones, indoles) do not tolerate replacement of the 4-benzylpiperidine moiety with flexible fluorinated phenylalkyl side chains, but other scaffolds such as tetrahydro-3-benzazepines and -benzo[7]annulenes retain interaction with NMDA receptors containing the GluN2B subunit.
- Thum, Simone,Schepmann, Dirk,Kalinin, Dmitrii V.,Ametamey, Simon M.,Wünsch, Bernhard
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supporting information
p. 2522 - 2529
(2018/11/23)
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- Novel Compounds as Autotaxin Inhibitors and Pharmaceutical Compositions Comprising the Same
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The present invention relates to a novel autotaxin inhibitor compound for preventing and treating disease or symptoms due to an increase in concentration of lysophosphatidic acid or activation of autotaxin. The present invention further relates to a pharmaceutical composition containing the same. The novel compound of the present invention is an autotaxin inhibitor which inhibits production of lysophosphatidic acid, and thus is useful for treating or preventing cardiovascular disease, cancer, metabolic disease, kidney disease, liver disease, inflammatory diseases, nervous disease, respiratory disease, desmoid disease, eye disease, cholestatic symptoms, other types of chronic pruritus or acute, or chronic rejection of transplanted organs.COPYRIGHT KIPO 2017
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Paragraph 0541-0544
(2018/05/17)
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- Method for producing 5-nitro-2aminophenol
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The invention relates to a method for producing 5-nitro-2aminophenol.Ortho-aminophenol, urea and sulfuric acid have a cyclization reaction in a three-mouth round-bottom flask to obtain a benzoxazolone compound, then the obtained benzoxazolone compound, acidic imidazolium ionic liquid and nitric acid are placed in the round-bottom flask for a nitration reaction to obtain 6-nitryl benzoxazolone, and finally 5-nitro-2aminophenol is obtained through hydrolysis of sodium hydroxide.According to the method, in the step that the obtained benzoxazolone compound, acidic imidazolium liquid and nitric acid are placed in the round-bottom flask for the nitration reaction to obtain 6-nitryl benzoxazolone, the acidic imidazolium ionic liquid takes the place of 1,2-dichloroethane solvent in the prior art, the safety coefficient is remarkably improved, cost is low, and environmental friendliness is achieved.
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- Comparative study of conventional and microwave-assisted synthesis of novel 6-(arylideneamino)benzo[d]oxazol-2(3H)-ones with potential antibacterial activity
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(Formula presented) The synthesis and characterization of novel class of Schiff bases derivatives 6-(Benzylideneamino)benzo[d]oxazol-2(3H)-ones (5a-d and 6a-d), derived from the condensation reactions of different aromatic aldehydes with 6-amino-2(3H)-benzoxazolone and 3-methyl-6-amino-2(3H)-benzoxazolone, using conventional and microwave irradiation methods was described. The structure of all newly synthesized compounds has been proven by using various spectral methods such as IR, 1H-NMR and 13C-NMR. The results confirmed that benzoxazolinonic amino group reacted with aromatic aldehydes to form the desired Schiff bases.
- Adjeroud, Yasmina,Chabane, Hanane,Liacha, Messaoud
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p. 111 - 117
(2016/07/15)
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- Sulfenylation of β-Diketones Using C- H Functionalization Strategy
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Sulfenylation of β-diketones is challenging as β-diketones undergo deacylation after sulfenylation in the reaction medium. The sulfenylation of β-diketones without deacylation under metal-free conditions at ambient temperature via a cross dehydrogenative coupling (CDC) strategy is reported. The resultant products can be further manipulated to form α,α-disubstituted β-diketones and pyrazoles.
- Varun, Begur Vasanthkumar,Gadde, Karthik,Prabhu, Kandikere Ramaiah
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supporting information
p. 2944 - 2947
(2015/06/30)
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- BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS
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The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.
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Page/Page column 40; 43
(2015/12/11)
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- Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies
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Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.
- Bach, Anders,Pizzirani, Daniela,Realini, Natalia,Vozella, Valentina,Russo, Debora,Penna, Ilaria,Melzig, Laurin,Scarpelli, Rita,Piomelli, Daniele
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supporting information
p. 9258 - 9272
(2015/12/23)
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- Experimental and theoretical investigation of the intramolecular cyclisation of N-(benzoxazolinon-6-Yl) Maleimide derivatives
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A new N-H and N-CH3 2(3H)-benzoxazolones substituted at the C6 position in the aromatic ring by imide group (maleimides) has been synthesized in good yields. The regioselectivity of the cyclisation step has been investigated through DFT calculations at the B3LYP/6-31G (d,p) level of theory. The obtained results indicate that the maleimide is favored both kinetically and thermodynamically as observed experimentally.
- Yahia, Wassila,Nacereddine, Abdelmalek Khorief,Seddiki, Khemissi,Liacha, Messaoud,Nippert
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p. 853 - 859
(2015/11/24)
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- Development of benzo[d]oxazol-2(3H)-ones derivatives as novel inhibitors of Mycobacterium tuberculosis InhA
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A series of twenty seven substituted 2-(2-oxobenzo[d]oxazol-3(2H)-yl)acetamide derivatives were designed based on our earlier reported Mycobacterium tuberculosis (MTB) enoyl-acyl carrier protein reductase (InhA) lead. Compounds were evaluated for MTB InhA inhibition study, in vitro activity against drug-sensitive and -resistant MTB strains, and cytotoxicity against RAW 264.7 cell line. Among the compounds tested, 2-(6-nitro-2-oxobenzo[d]oxazol-3(2H)-yl)-N-(5-nitrothiazol-2-yl)acetamide (30) was found to be the most promising compound with IC50 of 5.12 ± 0.44 μM against MTB InhA, inhibited drug sensitive MTB with MIC 17.11 μM and was non-cytotoxic at 100 μM. The interaction with protein and enhancement of protein stability in complex with compound 30 was further confirmed biophysically by differential scanning fluorimetry.
- Pedgaonkar, Ganesh S.,Sridevi, Jonnalagadda Padma,Jeankumar, Variam Ullas,Saxena, Shalini,Devi, Parthiban Brindha,Renuka, Janupally,Yogeeswari, Perumal,Sriram, Dharmarajan
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p. 6134 - 6145
(2015/02/19)
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- Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)- benzothiazolone derivatives
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A simpler and efficient "green" method using solid sodium hydroxide in a solvent mixture of acetone/water was found to catalyze N-acylation of 2(3H)-benzoxazolones and 2(3H)-benzothiazolones for facile and rapid synthesis of N-acyl derivatives in excellent yields. This method was applied to the synthesis of a series of 132 compounds employing a variety of acyl chlorides. Graphical abstract: [Figure not available: see fulltext.]
- Guenadil, Faouzi,Aichaoui, Hocine,Kapanda, Coco N.,Lambert, Didier M.,McCurdy, Christopher R.,Poupaert, Jacques H.
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experimental part
p. 67 - 80
(2011/09/20)
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- NIROGENOUS HETEROCYCLIC DERIVATIVES SUBSTITUTED WITH CYCLIC GROUPS
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It was found out that the nitrogen-containing heterocyclic derivative represented by the formula (I) specifically binds to a receptor of NR1/NR2B, and is used as a NR2B receptor antagonist. A compound represented by: wherein Z is N or CR1, A1 is a nitrogen-containing aromatic monocyclic group which is optionally substituted, a nitrogen-containing aromatic fused cyclic group which is optionally substituted etc., A2 is an aromatic hydrocarbon cyclic group or an aromatic heterocyclic group, each optionally having a substituent, R1, R2, Ra, Rb, Rc and Rd are each independently hydrogen, hydroxy, etc., w is 2 or 3, t is 1 or 2, X is -(CR3R4)m-, -CO(CR3R4)n-, -CONR5(CR3R4)n- etc., m is an integer of 1 to 4, n is an integer of 0 to 4, R3 and R4 are each independently hydrogen, halogen, hydroxy etc., and R5 is hydrogen or lower alkyl, or a pharmaceutically acceptable salt, or a solvate thereof.
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Page/Page column 68
(2008/12/08)
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- Pentacyclic kinase inhibitors
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The invention provides novel kinase inhibitors that are useful as therapeutic agents for example in the treatment malignancies where the compounds have the general formula I wherein A, X, Y, Z, Ra, Rb, Rc, R1, R2, R3 and m are defined herein.
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Page/Page column 51
(2010/11/25)
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- PYRIMIDINE KINASE INHIBITORS
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The invention provides novel kinase inhibitors that are useful as therapeutic agents for example in the treatment malignancies where the compounds have the general formula (I) wherein ring A, X, Y, Z, R1, R2, R3, R4, m and n are as defined herein.
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Page/Page column 37
(2008/06/13)
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- The optimization for cyclization reaction of 2-(2-carbomethoxyethynyl) aniline derivatives and formal synthesis of pyrroloquinoline quinone and its analogue utilizing a sequential coupling-cyclization reaction
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The reaction conditions for the Pd-catalyzed cyclization reaction of 2-(2-carbomethoxyethynyl)aniline derivatives were investigated. The amounts of Pd(PPh3)4, methyl propiolate, and ZnBr2 could be significantly reduced compared with those reported in our preliminary publication by careful tuning of the solvent and the reaction temperature. In addition to the above results, formal syntheses of pyrroloquinoline quinone (PQQ) and its analogue from 2-amino-5-nitrophenol using a Pd-complex-catalyzed sequential coupling-cyclization reaction between methyl propiolate and 2-iodoaniline derivatives are described.
- Hiroya, Kou,Matsumoto, Shigemitsu,Ashikawa, Masayasu,Kida, Hitomi,Sakamoto, Takao
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p. 12330 - 12338
(2007/10/03)
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- Analogues of the Cyclic Hydroxamic Acid 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one: Decomposition to Benzoxazolinones and Reaction with β-Mercaptoethanol
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Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl α-(o-nitrophenoxy)-α-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group.A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring .The pKa values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series.They correlated well with ? in a linear free energy relationship (LFER) yielding values of ρ = 0.71 (with ?p) for pKa1 (the hydroxamic acid) and ρ = 1.6 (with ρm) for pKa2 (the phenol).A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and ?+ (ρ = -1.1).The rates of hydroxamic acid reduction to lactams by β-mercaptoethanol were also investigated.It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3 - 5) had measurable rates of reduction. 1H NMR spectra recorded during this reaction in D2O buffers (pD 9), however, showed that compounds 1, 2, 6 - 9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol.The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.
- Atkinson, Jeffrey,Morand, Peter,Arnason, John T.,Niemeyer, Hermann M.,Bravo, Hector R.
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p. 1788 - 1800
(2007/10/02)
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- o-Hydroxyphenylureas. Intermediates in the urea fusion synthesis of 2-benzoxazolinones
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o-Hydroxyphenylureas have been identified as intermediates in the urea fusion synthesis of 2-benzoxazolinones. The pyrolysis of these intermediates represents a new alternate synthesis of the benzoxazolinone ring system.
- Nachman
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p. 1423 - 1425
(2007/10/02)
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