- 2-Substituted-phenyl-oxy-5-methylsulfonyl piperazine acidamide analogue and preparation method and application thereof
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The invention discloses 2-substituted-phenyl-oxy-5-methylsulfonyl piperazine acidamide analogue and a preparation method and application thereof, and particularly, relates to 2-substituted-phenyl-oxy-5-methylsulfonyl piperazine acidamide analogue with a formula (I) compound and a preparation method and application thereof, wherein substitutions in the formula (I) compound are defined as in the description. This serial compound can inhibit the activity of glycine transport protein-1 (GlyT1), is useful in treating related diseases in central nerve and psychological fields, for example, schizophrenia (including positive symptoms, negative symptoms and cognitive symptoms), senile dementia, Parkinson's disease and other related psychological diseases, is widely applicable to the drugs for preventing and treating central nerve and psychological diseases, and is expected to be developed into new-generation GlyT1 inhibitors.
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Paragraph 0481; 0482; 0483
(2016/10/08)
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- Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition
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The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition.
- Dossetter, Alexander G.,Bowyer, Jonathan,Cook, Calum R.,Crawford, James J.,Finlayson, Jonathan E.,Heron, Nicola M.,Heyes, Christine,Highton, Adrian J.,Hudson, Julian A.,Jestel, Anja,Krapp, Stephan,MacFaul, Philip A.,McGuire, Thomas M.,Morley, Andrew D.,Morris, Jeffrey J.,Page, Ken M.,Ribeiro, Lyn Rosenbrier,Sawney, Helen,Steinbacher, Stefan,Smith, Caroline
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scheme or table
p. 5563 - 5568
(2012/09/22)
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- CYANOCYCLOPROPYLCARBOXAMIDES AS CATHEPSIN INHIBITORS
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The present invention relates to compounds of formula (I) for treating diseases associated with cysteine protease activity. The compounds are reversible inhibitors of cysteine proteases, including cathepsins B, K, C, F, H, L, O, S, W and X. Of particular interest are diseases associated with Cathepsin K.
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Page/Page column 79
(2009/03/07)
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- [4-(HETEROARYL) PIPERAZIN-1-YL]-(2,5-SUBSTITUTED -PHENYL)METHANONE DERIVATIVES AS GLYCINE TRANSPORTER 1 (GLYT-1) INHIBITORS FOR THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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The present invention relates to compounds of the general formula (I) wherein R1 is-OR1’,-SR1’ or is a heterocycloalkyl group; R1’ is lower alkyl, lower alkyl substituted by halogen or is -(CH2)n
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Page/Page column 37-38
(2008/06/13)
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