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A convenient synthetic method has been developed for accessing 2,6-dialkynyl-3,5-dichloropyridine derivatives in acceptable to good yields. The methodology involved ultrasound assisted site-selective alkynylation of 2,3,5,6-tetrachloropyridines under Pd/C[sbnd]Cu catalysis. A variety of terminal alkynes were employed in this C[sbnd]C coupling reaction to afford the corresponding 2,6-dialkynyl-3,5-dichloropyridine derivatives.

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Based on an established common pharmacophore of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNTTIs), a series of quinolin-2-one derivatives were synthesized and assayed for their in vitro activities against HIV-1 reverse transcriptase (RT) for the first time. Some of the tested compounds were active against HIV-1 RT. Compounds 4a2 and 4d2 showed inhibitory activities with IC50 values of 0.21 and 0.15 muM, respectively, with a mode of interaction with RT residues of the allosteric pocket similar to that of efavirenz.

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This invention is concerned with compounds of the formulaand pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are associated with the modulation of SST receptors subtype 5.

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Disclosed is an aminopyrrolidine compound represented by the formula [I] or a pharmaceutically acceptable salt thereof. The compound or the salt is useful as a prophylactic/therapeutic agent for mode disorder such as depression, anxiety disorder, anorexia, cachexia, pain and drug dependence, whose action relies on the MC4 receptor antagonistic effect.

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The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention can be useful as a medicament in the treatment and/or the decreasing and/or the prevention of fibrosis and/or fibrosis related diseases, or for use as a medicament in the treatment and/or the decreasing and/or the prevention of the autophagy and/or autophagy related diseases and for the inhibition of the autophagy flux, or for use in the inhibition of cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or cathepsins B (CTSB), L (CTSL) and/or D (CTSD) related diseases; with the proviso that said compounds are not to be used for the treatment of any forms of cancers.

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A study on the synthesis of derivatives of 4,5-bis(dimethylamino)quinoline, which is a quinoline analog of 1,8-bis(dimethylamino)naphthalene (also known by its trade name Proton Sponge) was carried out. The first two representatives of this series were obtained. Depending on the aggregate state, solvent, and structural features, these compounds may be protonated either at the quinoline heteroatom or peri-NMe2 groups.

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The adenosine receptor subfamily consists of the adenosine A1, A2A, A2B, and A3 receptors, which are localized in a variety of tissues throughout the human body. It is, therefore, a challenge to develop receptor specific ligands with improved tissue selectivity. Allosteric modulators could have these therapeutic advantages over orthosteric ligands. In the present study, a series of 2,4-disubstituted quinolines were synthesized on the basis of the structure of LUF6000 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist binding to a similar extent as 34. In addition, this new compound showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, compound 27 showed improved activity in comparison to 34, as it increased both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA at the human adenosine A 3 receptor.

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Compounds of a compound of compound of general formula (I) wherein X1, X2, A, R1R2, R3 and R4 are as defined herein; are useful as anti-mycobacterial agents, especially agents for the treatment of tuberculosis.

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In this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though pi-pi stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 muM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC 50 of 4.63±0.62 mug/mL, which was similar with that in EFV and TMC278 (IC 50 7.76±0.37 and 1.57±0.20 mug/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future.

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Phenyl substituted quinolin 4-yl derivatives and pharmaceutical compositions with activity as NMDA-receptor subtype selective blockers. The compounds of the invention modulate neuronal activity and plasticity.

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