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Simple Nickel Salts for the Amination of (Hetero)aryl Bromides and Iodides with Lithium Bis(trimethylsilyl)amide

Recent developments in the chemistry of C-N bond formation and the synthesis of anilines have allowed for the use of first-row transition metals to catalyze these transformations. Much of the progress in this area has been driven by comprehensive screening for privileged/tailored ligands, which can be costly and not readily available in a research laboratory setting. In this communication we report a protocol in which simple nickel salts catalyze the C-N cross-coupling reaction between (hetero)aryl bromides and iodides with lithium bis(trimethylsilyl)amide without the need for any additive ligand. This method is amenable to low nickel catalyst loadings (1%) as well as gram-scale reactions. Because of the good functional group tolerance and compatibility with heterocyclic moieties, this method is useful for academic laboratory settings where access to tailored ligands and noble-metal catalysts could be challenging.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Ag(I)-C-H Activation Enables Near-Room-Temperature Direct alpha-Arylation of Benzo[ b]thiophenes

The first example of near-room-temperature alpha-arylation of benzo[b]thiophenes is reported. The discovery rests on the observation of a switch in alpha-/beta-regioselectivity at different loadings of Pd2(dba)3¡¤CHCl3 in the coupling between benzo[b]thiophene and 4-iodotoluene. We show that this unprecedented regioselectivity switch is driven by a Ag(I)-mediated C-H activation at the alpha-C-H position, which becomes the dominant mode of reactivity at low concentrations of Pd. Competition experiments, kinetic studies, KIE, and D/H scrambling experiments have been carried out supporting this mechanism.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Inhibition of the Cysteine Protease Human Cathepsin L by Triazine Nitriles: Amide???Heteroarene pi-Stacking Interactions and Chalcogen Bonding in the S3 Pocket

We report an extensive ?heteroarene scan? of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate pi-stacking on the peptide amide bond Gly67?Gly68 at the entrance of the S3 pocket. This heteroarene???peptide bond stacking was supported by a co-crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the orientation of the local dipole moments of heteroarene and peptide bond could not be confirmed. Binding of benzothienyl (Ki=4 nm) and benzothiazolyl (Ki=17 nm) ligands was enhanced by intermolecular C?S???O=C interactions (chalcogen bonding) with the backbone C=O of Asn66 in the S3 pocket. The ligands were also tested for the related enzyme rhodesain.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors

(Chemical Equation Presented) A series of 4-bicyclic heteroaryl 1,2,3,4-tetrahydroisoquinoline inhibitors of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) was discovered. The synthesis and structure-activity relationship (SAR) of these triple reuptake inhibitors (TRIs) will be discussed. Compound 10i (AMR-2), a very potent inhibitor of SERT, NET, and DAT, showed efficacy in the rat forced-swim and mouse tail suspension models with minimum e ffective doses of 0.3 and 1 mg/kg (po), respectively. At efficacious doses in these assays, 10i exhibited substantial occupancy levels at the three transporters in both rat and mouse brain. The study of the metabolism of 10i revealed the formation of a significant active metabolite, compound 13.

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Benzothiophene – Wikipedia,
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Use of Benzo-Heteroaryl Sulfamide Derivatives for the Treatment of Mania and Bipolar Disorder

The present invention is a method for the treatment of mania and/or bipolar disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-heteroaryl sulfamide derivatives of formula (I) as herein defined.

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Benzothiophene – Wikipedia,
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Pd/C as a catalyst for completely regioselective c=h functionalization of thiophenes under mild conditions

The completely C3-selective arylation of thiophenes and benzo[b]thiophenes was achieved by using Pd/C as a heterogeneous catalyst without ligands or additives under mild reaction conditions. The practicability of this transformation is demonstrated by notable functional group tolerance and the insensitivity of the reaction to H2O and air. This method is also applicable to nitrogen- and oxygen-containing heterocycles, yielding the corresponding C2-arylated products. Three-phase tests along with Hg-poisoning and hot-filtration tests suggest that the catalytically active species is heterogeneous in nature. I+ can do better! Pd/C can be used without ligands or additives to catalyze the completely C3-selective arylation of diversely substituted thiophenes and benzo[b]thiophenes under mild reaction conditions. The physical nature of the catalytic species was investigated and the mechanism was studied. Relative rate data generated in a “robustness screen” were used to design a complex substrate that undergoes highly chemoselective sequential functionalization. Copyright

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Benzothiophene – Wikipedia,
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GPR40 AGONISTS IN ANTI-DIABETIC DRUG COMBINATIONS

Disclosed are compositions comprising (a) a GPR40 agonist and (b) an SGLT2 inhibitor, and methods for treating of disorders that are affected by the modulation of the GPR40 receptor and SGLT2 transporter. Such GPR40 compounds are represented by Formula (I) as follows: wherein ring W, R1, R2, R3, R5, R6, A, and Z, are defined herein.

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Benzothiophene – Wikipedia,
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USE OF BENZO-HETEROARYL SULFAMIDE DERIVATIVES FOR THE TREATMENT OF MIGRAINE

The present invention is a method for the treatment or prevention of migraine comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-heteroaryl sulfamide derivatives of formula (I) as herein defined. The present invention is directed to a method for the treatment and/or prevention of migraine, which includes mono-therapy and alternatively, co-therapy with at least anti-migraine agent

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Imidazole-containing fused three-ring compounds and uses thereof (by machine translation)

The invention discloses a formula (I) containing the structure shown as the imidazole fused three-ring compound or its pharmaceutically acceptable salt or a stereoisomer thereof or its prodrug molecule. The compound has adjusting IDO1 active role, such compounds by blocking immune checkpointing IDO1, T cell activation can be enhanced, used for the treatment of IDO1 mediated immune suppression, thus can become effective drug for the treatment of malignant tumor. With the checkpointing the antibody of the protein drug or other anti-cancer drugs share, can enhance the anti-cancer effects. At the same time also has the potential to effectively treat with IDO1 related with the immunosuppressive disease, have high application value. (by machine translation)

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Trifluoromethanesulfinyl Chloride for Electrophilic Trifluoromethythiolation and Bifunctional Chlorotrifluoromethythiolation

Trifluoromethanesulfinyl chloride (CF3SOCl) has been introduced as a new reagent for C?H trifluoromethylthiolation of indoles, thiophenes, and ketones under catalyst-free conditions and in the absence of reductant. The disproportionation of CF3SOCl to CF3SO2Cl and CF3SCl provides two pathways for the trifluoromethylthiolation. Direct trifluoromethylthiolation with CF3SCl or trifluoromethylsulfoxidation with CF3SOCl is followed by reduction with CF3SOCl. This reagent can be used to functionalize benzothiophenes, benzofurans, and indenes under the promotion of Ag2CO3. It can also be used for trifluoromethylthiolation of thiols and benzeneselenols, and 1,2-bifunctional chlorotrifluoromethylthiolation of indoles, styrenes, and alkyenes. The method can also be extended for difluorometylthiolation reactions using CF2HSOCl.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem