- Aromatic propionic acid derivative, preparation method and uses thereof
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The present invention discloses a compound represented by a general formula I or a tautomer, a racemate, an enantiomer, a diastereomer, a mixture and a pharmaceutically acceptable salt thereof, wherein each substituent is defined in the specification and claims. According to the present invention, the compound has obvious agonistic activity and selectivity to a GPR40 receptor in vitro, and the oral administration of the compound can significantly reduce the blood glucose concentration of rats after oral administration of glucose and increase the glucose tolerance capacity of rats in a dose-dependent manner so as to provide the good in vivo glucose lowering effect and achieve excellent pharmacokinetic properties and excellent drug-forming properties, such that the compound of the present invention can be used for the preparation of drugs for treating metabolic diseases such as diabetes and the like.
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Paragraph 0096; 0100-0102
(2019/10/01)
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- RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
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- RHO-ASSOCIATED PROTEIN KINASE INHIBITOR, PHARMACEUTICAL COMPOSITION COMPRISING THE SAME, AS WELL AS PREPARATION METHOD AND USE THEREOF
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The present invention relates to a Rho-associated protein kinase inhibitor of Formula (I), a pharmaceutical composition comprising the same, a preparation method thereof, and use thereof for the prevention or treatment of a disease mediated by the Rho-associated protein kinase (ROCK).
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- Design and optimization of 2,3-dihydrobenzo[b][1,4]dioxine propanoic acids as novel GPR40 agonists with improved pharmacokinetic and safety profiles
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GPR40 has become a new potential therapeutic target for the treatment of diabetes due to its role in mediating the enhancement of glucose-stimulated insulin secretion in pancreatic β cells with a low risk of hypoglycemia. As an effort to extend the chemical space and identify structurally distinct GPR40 agonists with improved liver safety, a novel series of fused-ring phenyl propanoic acid analogues were designed. Comprehensive structure-activity relationship studies around novel scaffolds were conducted and led to several analogues exhibited potent GPR40 agonistic activities and high selectivity against other fatty acid receptors. Further evaluation of pharmacokinetic (PK) profiles and in vivo efficacy identified compound 40a with excellent PK properties and significant glucose-lowering efficacy during an oral glucose tolerance test. In addition, compound 40a displayed lower hepatobiliary transporter inhibition and favorable druggability. All results indicate that compound 40a is a promising candidate for further development.
- Guo, Bin,Guo, Shimeng,Huang, Jing,Li, Jingya,Li, Jia,Chen, Qian,Zhou, Xianli,Xie, Xin,Yang, Yushe
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p. 5780 - 5791
(2018/11/06)
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- Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation
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Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and (R)-doxazosin·HCl.
- Yin, Xuguang,Huang, Yi,Chen, Ziyi,Hu, Yang,Tao, Lin,Zhao, Qingyang,Dong, Xiu-Qin,Zhang, Xumu
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p. 4173 - 4177
(2018/07/29)
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- 3-(Benzodioxan-2-ylmethoxy)-2,6-difluorobenzamides bearing hydrophobic substituents at the 7-position of the benzodioxane nucleus potently inhibit methicillin-resistant Sa and Mtb cell division
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Lipophilic substituents at benzodioxane C (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant Staphylococcus aureus strains to MIC values in the range of 0.2-2.5 μg/mL, whereas hydrophi
- Straniero, Valentina,Pallavicini, Marco,Chiodini, Giuseppe,Zanotto, Carlo,Volontè, Luca,Radaelli, Antonia,Bolchi, Cristiano,Fumagalli, Laura,Sanguinetti, Maurizio,Menchinelli, Giulia,Delogu, Giovanni,Battah, Basem,De Giuli Morghen, Carlo,Valoti, Ermanno
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p. 227 - 243
(2016/05/24)
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- BROMODOMAIN INHIBITORS
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The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.
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Paragraph 1518; 1519
(2015/04/28)
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- MODULATORS OF DOPAMINE NEUROTRANSMISSION
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The present invention relates to novel 1-(2,3-dihydro-1,4-benzodioxin-2-yl)- methanamine derivatives, useful as modulators of dopamine neurotransmission, and more specifically as dopaminergic stabilizers. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 50-51
(2009/12/05)
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- Synthesis and glycogen phosphorylase inhibitor activity of 2,3-dihydrobenzo[1,4]dioxin derivatives
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Novel 5-benzyl and 5-benzylidene-thiazolidine-2,4-diones carrying 2,3-dihydrobenzo[1,4]dioxin pharmacophore were synthesized and their glycogen phosphorylase inhibitor activity was also studied.
- Juhasz, Laszlo,Docsa, Tibor,Brunyaszki, Attila,Gergely, Pal,Antus, Sandor
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p. 4048 - 4056
(2008/03/12)
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- Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
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The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immunune diseases, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
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- Bispidine compounds useful in the treatment of cardiac arrythmias
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There is provided compounds of formula I, 1 wherein R1, R2, R3, R4, R5, R6, R7, R41, R42, R43 R44, R45, R46, A and B have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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- Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
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The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases and cerebral vasospasm, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
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