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On the basis of our recently resolved first cocrystal structure of Mdm4 in complex with a small molecule inhibitor (PDB ID 3LBJ), we devised an approach for the generation of potential Mdm4 selective ligands. We performed the Ugi four-component reaction (Ugi-4CR) in 96-well plates with an indole fragment, which is specially designed to mimic Trp23, a key amino acid for the interaction between p53 and Mdm4. Generally the reaction yielded mostly precipitates collected by 96-well filter plates. The best hit compound was found to be active and selective for Mdm4 (Ki = 5 muM, 10-fold stronger than Mdm2). This initial hit may serve as the starting point for designing selective p53-Mdm4 inhibitor with higher affinity.

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Benzofuran – Wikipedia,
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The invention relates to a compounds as anti application. The invention also provides a novel compound. The compounds of this invention can be used in the anti-Tb and its drug-resistant strain, and has a low toxicity of liver, has good application prospect. (by machine translation)

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The present invention provides substituted pyridine derivatives of formula (I), which may be therapeutically useful as as anti-bacterial agents, more particulalrly FabI inhibitors. Formula (I) in which R1 to R5 and L have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage anti-bacterial agents, more particularly FabI inhibitors. The present invention also provides methods for synthesizing and administering the FabI inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitor compounds to gether with a pharmaceutically acceptable carrier, diluent or excipient therefor

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The present invention concerns compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; =Q is =O or =NR3; X is a covalent bond or a bivalent radical of formula ?O?, ?S?, ?NR3?; R1 is Ar1; Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula ?O?CH2?CH2?O? or ?O?CH2?CH2?CH2?O?; R2 is Ar2; Ar2C1-6alkyl; Het or HetC1-6alkyl; R3 is hydrogen or C1-6alkyl; R4 is hydrogen; C1-4alkyl; C1-4alkyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4alkyloxycarbonyl or Ar3; R5 is hydrogen; hydroxy; Ar3; Ar3C1-6alkyloxy; di(Ar3)C1-6alkyloxy; Ar3C1-6alkylthio; di(Ar3)C1-6alkylthio; Ar3C1-6alkylsulfoxy; di(Ar3)C1-6alkylsulfoxy; Ar3C1-6alkylsulfonyl; di(Ar3)C1-6alkylsulfonyl; ?NR7R8; C1-6alkyl substituted with ?NR7R8; or a radical of formula (a-1) or (a-2); R4 and R5 may also be taken together; R6 is hydroxy; C1-6alkyloxy; C1-6alkyl or Ar3C1-6alkyl; Ar1, Ar2 and Ar3 are phenyl or substituted phenyl; Ar2 is also naphtalenyl; and Het is an optionally substituted monocyclic or bicyclic heterocycle; as substance P antagonists; their preparation, compositions containing them and their use as a medicine.

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Benzofuran – Wikipedia,
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We describe the PdII-catalyzed decarboxylative Heck reaction of aromatic carboxylic acids with an array of electronically unbiased olefins, which allows regioselective formation of less common branched products in good yield. This protocol enables the use of inexpensive, stable, and readily available aromatic carboxylic acids as aryl reagents, thus providing an attractive method for the synthesis of useful alpha-alkyl vinylarenes.

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The invention relates to a heterocyclic carboxylic acid compound decarboxylate the method, the heterocyclic carboxylic acid compound is soluble in the non-proton hydroxylated solvent N, N – dimethyl formamide, in the 85 C -150 C, organic acid as catalyst under the condition of decarboxylation. The invention compared with the prior art in the decarboxylation method, reaction to obtain the decarboxylation product yield is higher, and does not require the use of expensive metal catalyst; at the same time, compared with the DMSO, in the invention of the solvent (DMF) is more stable, difficult to decompose under the high temperature, also can be recycled, and the cost is reduced. The operation of the invention process is simple, zero pollution, environmental protection, it has very good application prospect. (by machine translation)

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By using Pd(TFA)2/PCy3 as a catalyst, a broad range of aromatic carboxylic acids, including heteroaromatic carboxylic acids, efficiently underwent decarboxylative coupling with an array of polyfluoroarenes in the presence of stoichiometric amount of silver salts to generate biaryls. Silver salts were adjusted to the reactivity of aromatic carboxylic acids to efficiently suppress the protodecarboxylation and therefore improve decarboxylative cross-couplings. It was established that the palladium complex containing the PCy3 ligand was capable of catalyzing the decarboxylation of electron-rich aromatic carboxylic acids, and silver salts promoted the decarboxylation of both electron-rich and -deficient ones. To explain the two different decarboxylation processes, two possible reaction pathways are proposed, which were further supported by the facts that the stoichiometric arylpalladium complex can directly arylate pentafluorobenzene in the presence of PCy3 and the arylpalladium complex can catalyze the decarboxylative coupling of 2,4-dimethoxybenzoic acid with pentafluorobenzene. The kinetic isotope effect of 4.0 clearly showed that theC-H bond cleavage of polyfluoroarenes is involved in the rate-determining step.

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A copper-catalyzed procedure enabling dynamic carbon isotope exchange is described. Utilizing the universal precursor [14C]CO2, this protocol allows to insert, in one single step, the desired carbon tag into carboxylic acids with no need of structural modifications. Reducing synthetic costs and limiting the generation of radioactive waste, this procedure will facilitate the access to carboxylic acids containing drugs and accelerate early 14C-based ADME studies supporting drug development.

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A variety of beta-aryl ketones and aldehydes were facilely synthesized via a Pd(II)/Ag2CO3-mediated decarboxylative Heck type reaction between readily available benzoic acid derivatives and allylic alcohols under mild conditions. The control experiments indicated that this transformation may proceed via a hydrogen migration process.

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The development of a palladium-catalyzed decarboxylative coupling reaction of arene carboxylates with olefinic substrates is described. The optimized procedure for decarboxylative palladation employs Pd(O2CCF3)2 as catalyst (0.2 equiv) in the presence of Ag2CO3 (3 equiv) in the solvent 5% DMSO-DMF and proceeds at temperatures of 80-120 C with a wide range of arene carboxylates and alkenes as substrates. The process is proposed to proceed by an initial Ar-SE reaction involving ipso attack of an electrophilic Pd(II) intermediate on an arene carboxylate to form an arylpalladium(II) species with loss of carbon dioxide. This intermediate is then proposed to react with an olefinic substrate by steps common to the Heck coupling process. Reoxidation of the liberated Pd(0) in situ is proposed to establish the catalytic cycle. Copyright

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Reference:
Benzofuran – Wikipedia,
Benzofuran | C8H2763O – PubChem