- N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties
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A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT6 receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10-30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.
- Zajdel, Pawe?,Marciniec, Krzysztof,Sata?a, Grzegorz,Canale, Vittorio,Kos, Tomasz,Partyka, Anna,Jastrz?bska-Wi?sek, Magdalena,Weso?owska, Anna,Basińska-Ziobroń, Agnieszka,Wójcikowski, Jacek,Daniel, W?adys?awa A.,Bojarski, Andrzej J.,Popik, Piotr
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p. 618 - 622
(2016/07/06)
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- Substituted heterocyclic compounds and application of same to medicines
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The invention relates to substituted heterocyclic compounds and application of the same to medicines and specifically provides the novel substituted heterocyclic compounds or stereoisomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, and preparation methods thereof. The invention also relates to pharmaceutical compositions containing the compounds and application of the compounds or pharmaceutical compositions to treatment of diseases related to 5-HT6 receptors, especially Alzheimer's disease.
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Paragraph 0201; 0207; 0208; 0209; 0210; 0242; 0243- 0245
(2017/04/29)
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- Substituted heterocyclic compounds and its application on the medicament (by machine translation)
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The invention relates to substituted heterocyclic compounds and its application on the medicament, in particular to a novel class of substituted heterocyclic compounds or its isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug, and their method of preparation. The invention also relates to the compounds of the invention pharmaceutical composition, and said compound or pharmaceutical compositions for the treatment5-HT6receptor-related diseases, in particular Alzheimer's disease in the use thereof. (by machine translation)
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Paragraph 0196; 0197; 0198; 0199; 0219; 0220; 0221; 0222
(2017/06/02)
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- Pyrazole-based cathepsin S inhibitors with improved cellular potency
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High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of CatS inhibitors. Although substitutions on this heterocyclic framework
- Wei, Jianmei,Pio, Barbara A.,Cai, Hui,Meduna, Steven P.,Sun, Siquan,Gu, Yin,Jiang, Wen,Thurmond, Robin L.,Karlsson, Lars,Edwards, James P.
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p. 5525 - 5528
(2008/03/11)
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