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INDOLE AND PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (I): wherein Ra, Rb, Rc, Rd, R3, R4, R5, A1, A2, T and W are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.

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Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[b]thiophenes

A novel series of benzo[b]thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1.

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Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides under Mild Conditions

The combination of Cu(acac)2 and N,N?-bis(4-hydroxyl-2,6-dimethylphenyl)oxalamide (BHMPO) provides a powerful catalytic system for hydroxylation of (hetero)aryl halides. A wide range of (hetero)aryl chlorides bearing either electron-donating or -withdrawing groups proceeded well at 130 C, delivering the corresponding phenols and hydroxylated heteroarenes in good to excellent yields. When more reactive (hetero)aryl bromides and iodides were employed, the hydroxylation reactions completed at relatively low temperatures (80 and 60 C, respectively) at low catalytic loadings (0.5 mol % Cu).

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Benzothiophene – Wikipedia,
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AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS

The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of alpha7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.

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Copper(I) Oxide/N,N?-Bis[(2-furyl)methyl]oxalamide-Catalyzed Coupling of (Hetero)aryl Halides and Nitrogen Heterocycles at Low Catalytic Loading

An easily prepared oxalic diamide is a powerful ligand for the copper-catalyzed coupling of aryl halides with nitrogen heterocycles. Only 1?2 mol% each of copper(I) oxide and N,N?-bis[(2-furyl)methyl]oxalamide (BFMO) are needed to form N-arylation products under mild conditions. More than 10 different types of nitrogen heterocycles are compatible with these conditions, thereby giving the corresponding N-arylation products. (Figure presented.).

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Migratory Arylboration of Unactivated Alkenes Enabled by Nickel Catalysis

An unprecedented arylboration of unactivated terminal alkenes, featuring 1,n-regioselectivity, has been achieved by nickel catalysis. The nitrogen-based ligand plays an essential role in the success of this three-component reaction. This transformation displays good regioselectivity and excellent functional-group tolerance. In addition, the incorporation of a boron group into the products provides substantial opportunities for further transformations. Also demonstrated is that the products can be readily transformed into pharmaceutically relevant molecules. Unexpectedly, preliminary mechanistic studies indicate that although the metal migration favors the alpha-position of boron, selective and decisive bond formation is favored at the benzylic position.

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Benzothiophene – Wikipedia,
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Electric Literature of 4923-87-9, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 4923-87-9, molcular formula is C8H5BrS, introducing its new discovery.

Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (Ki) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC50) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the ?mepacrine binding site? with the new, solubility-providing vectors oriented toward the surface of the large active site.

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Benzothiophene – Wikipedia,
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Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents

A series of novel 1-substituted-2-aryl imidazoles (SAI) were designed and synthesized based on our previously reported ABI (2-Aryl-4-Benzoyl Imidazole) analogs and on the structure of combretastatin A-4 (CA-4). These compounds showed potent antiproliferative activities against six human cancer cell lines with IC50 values in nano molar range. Among them, compound 3X exhibited the best anticancer activity with an average IC50 value of ?100 nM. The compound maintains the mechanism of action by inhibiting tubulin polymerization, thus causing cell arrest at G2/M phase and apoptosis. In vivo efficacy studies indicated that 3X was highly effective in suppressing tumor growth in a MDA-MB-468 xenograft model of nude mouse with a TGI (Tumor Growth Suppression) of 77% at 60 mg/kg without causing significant toxicity. In addition, 3X displayed significantly better water solubility (36.70 mug/mL) than CA-4 (2.83 mug/mL). Molecular modeling study indicated that 3X binds well to the colchicine binding site in tubulin. Our results suggest that the novel SAI analogs deserve further investigation as potential anticancer agents.

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Novel benzo-fused heteroaryl sulfamide derivatives useful as anticonvulsant agents

The present invention is directed to novel benzo-fused heteroaryl sulfamide derivatives, pharmaceutical compositions containing them and their use in the treatment of epilepsy and related disorders.

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NEW SUBSTITUTED BENZONAPHTHATHIOPHENE COMPOUNDS FOR ORGANIC ELECTRONICS

The present invention provides compounds of formulae (1) (2) wherein R1and R2are C1-30alkyl, C2-3O-alkenyl, C2-30-alkynyl, C5-7-cycloalkyl, C6-14-aryl or 5 to 14 membered heteroaryl, wherein C1-30-alkyl, C2-3O-alkenyl and C2-3O-alkynyl can be substituted with one or more substituents selected from the group consisting of halogen, phenyl, O-C1-20-alkyl, O-C2-20-alkenyl and O- C2-2O-alkynyl, and wherein C5-7-cycloalkyl, C6-14-aryl and 5 to 14 membered heteroaryl can be substituted with one or more substituents selected from the group consisting of halogen, C1-20alkyl, C2-2O-alkenyl, C2-2O-alkynyl, O-C1-20-alkyl, O-C2-2o-alkenyl and O-C2-2o-alkynyl, Ra, Rb, Rcand Rdare independently and at each occurrence selected from the group consisting of C1-30alkyl, C2-30-alkenyl, C2-30-alkynyl, C6-14-aryl and 5 to 14 membered heteroaryl, wherein C1-30-alkyl, C2-3o-alkenyl and C2-3o-alkynyl can be substituted with one or more substituents selected from the group consisting of halogen, phenyl, O-C1-20-alkyl, O-C2-20-alkenyl and O- C2-20-alkynyl, and wherein C5-7-cycloalkyl, C6-14-aryl and 5 to 14 membered heteroaryl can be substituted with one or more substituents selected from the group consisting of halogen, C1-20alkyl, C2-2o-alkenyl, C2-20-alkynyl, O-C1-20-alkyl, O-C2-20-alkenyl and O-C2-2o-alkynyl, n and o are independently 0, 1, 2, 3, 4 or 5, and m and p are independently 0, 1, 2 or 3, and to electronic device comprising the compounds of formulae 1 or 2.

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Reference£º
Benzothiophene – Wikipedia,
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