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NOVEL 1,2-DISUBSTITUTED AMIDO-ANTHRAQUINONE DERIVATIVES, PREPARATION METHOD AND APPLICATION THEREOF

A series of novel 1,2-disubstituted amido-anthraquinone derivatives, and the preparation method and application of said derivatives. Said application includes said derivatives with therapeutically effective amount being prepared into pharmaceutical compositions for inhibition of cancer cell growth, further treating cancer.

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THIAZOLECARBOXAMIDE DERIVATIVES FOR USE AS NAMPT INHIBITORS

Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.

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Discovery and characterization of ML398, a potent and selective antagonist of the D4 receptor with in vivo activity

Herein, we report the structure-activity relationship of a chiral morpholine-based scaffold, which led to the identification of a potent and selective dopamine 4 (D4) receptor antagonist. The 4-chlorobenzyl moiety was identified, and the compound was designated an MLPCN probe molecule, ML398. ML398 is potent against the D4 receptor with IC50 = 130 nM and Ki = 36 nM and shows no activity against the other dopamine receptors tested (>20 muM against D1, D2S, D2L, D3, and D5). Further in vivo studies showed that ML398 reversed cocaine-induced hyperlocomotion at 10 mg/kg.

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Synthesis and in vitro antimycobacterial activity of B-ring modified diaryl ether InhA inhibitors

Previous structure-based design studies resulted in the discovery of alkyl substituted diphenyl ether inhibitors of InhA, the enoyl reductase from Mycobacterium tuberculosis. Compounds such as 5-hexyl-2-phenoxyphenol 19 are nM inhibitors of InhA and inhibit the growth of both sensitive and isoniazid-resistant strains of Mycobacterium tuberculosis with MIC90 values of 1-2 mug/mL. However, despite their promising in vitro activity, these compounds have Clog P values of over 5. In efforts to reduce the lipophilicity of the compounds, and potentially enhance compound bioavailability, a series of B ring analogues of 19 were synthesized that contained either heterocylic nitrogen rings or phenyl rings having amino, nitro, amide, or piperazine functionalities. Compounds 3c, 3e, and 14a show comparable MIC90 values to that of 19, but have improved Clog P values.

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ISOINDOLE-IMIDE COMPOUNDS AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed

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Structure-activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway

Wnt signaling pathway plays a critical role in numerous cellular processes, including tumor initiation, proliferation, invasion/infiltration, metastasis formation and resistance to chemotherapy. In a drug discovery project aimed at the identification of inhibitors of the canonical Wnt pathway, we selected a series of quinazoline 2,4-diones as starting point for the therapeutic treatment of glioblastoma multiforme. Despite of poor physico-chemical properties of hit compound 1, our medicinal chemistry effort allowed the discovery and characterization of lead compound 33 (SEN461), with improved ADME profile, good bioavailability and active in vitro and in vivo in glioblastoma, gastric and sarcoma tumors.

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2-(BIARYLALKYL)AMINO-3-(HETEROCYCLYLCARBONYLAMINO)-PYRIDINE DERIVATIVES

Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

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HCV INHIBITORS

The present invention relates to compounds that are useful in the treatment of viruses belonging to Flaviviridae, including flaviviruses, pestiviruses, and hepaciviruses. The invention includes compounds useful for the treatment or prophylaxis of dengue fever, yellow fever, West Nile virus, and HCV.

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Preparation of 2-heteroaryl carboxamides for the treatment and/or the prophylaxis of diseases effecting memory.

The invention relates to the novel 2-heteroaryl carboxamides according to formula (I), wherein R1 represents 1-aza-bicyclo [2.2.2]oct-3-yl, which is optionally replaced via the nitrogen atom by a group selected from the family C1-C4 alkyl, benzyl and oxy, A represents oxygen or sulfur, the ring B represents benzo or pyrido that are optionally replaced by the groups from the family of halogen, cyano, formyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C1-C6 alkyl and C1-C6 alkoxy, E represents C=C, aryl and heteroaryl, wherein aryl and heteroaryl may be replaced by groups from the family of halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C1-C6 alkoxy and C1-C6 alkyl, and to the solvents, salts or solvents of salts of said compounds. The invention also relates to the use of said compounds in the production of drugs for the treatment and/or the prophylaxis of diseases and for improving perception, power of concentration, learning power and/or retentiveness of memory.

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Method of treating a patient having precancerous lesions with quinazoline derivatives

Derivatives of Quinazoline are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.

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