- Triazole naphthoquinone connected aromatic (heterocyclic) ring derivative
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The invention belongs to the field of chemical medicine, particularly relates to a micromolecule capable of resisting malignant tumor, acute leukemia and arthritis, multiple sclerosis and immunological rejection and a preparation and application of the mi
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Paragraph 0097; 0098; 0099
(2018/10/01)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0309-0310
(2017/05/14)
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- Wnt signal pathway inhibitor and use thereof
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The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.
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- Synthesis and characterization of the first inhibitor of: N -acylphosphatidylethanolamine phospholipase D (NAPE-PLD)
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N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.
- Castellani, Beatrice,Diamanti, Eleonora,Pizzirani, Daniela,Tardia, Piero,Maccesi, Martina,Realini, Natalia,Magotti, Paola,Garau, Gianpiero,Bakkum, Thomas,Rivara, Silvia,Mor, Marco,Piomelli, Daniele
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p. 12814 - 12817
(2017/12/06)
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- Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors
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The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chemical, plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.
- Dong, Yan,Li, Kehuang,Xu, Zhixiang,Ma, Haikuo,Zheng, Jiyue,Hu, Zhilin,He, Sudan,Wu, Yiyuan,Sun, Zhijian,Luo, Lusong,Li, Jiajun,Zhang, Hongjian,Zhang, Xiaohu
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p. 6855 - 6868
(2015/11/11)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present invention relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0288
(2015/05/19)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0296
(2015/08/03)
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- Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer's disease
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γ-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered Aβ42 levels in the cerebrospinal fluid (CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described.
- Chen, Jian Jeffrey,Qian, Wenyuan,Biswas, Kaustav,Yuan, Chester,Amegadzie, Albert,Liu, Qingyian,Nixey, Thomas,Zhu, Joe,Ncube, Mqhele,Rzasa, Robert M.,Chavez, Frank,Chen, Ning,Demorin, Frenel,Rumfelt, Shannon,Tegley, Christopher M.,Allen, Jennifer R.,Hitchcock, Stephen,Hungate, Randy,Bartberger, Michael D.,Zalameda, Leeanne,Liu, Yichin,McCarter, John D.,Zhang, Jianhua,Zhu, Li,Babu-Khan, Safura,Luo, Yi,Bradley, Jodi,Wen, Paul H.,Reid, Darren L.,Koegler, Frank,Dean Jr., Charles,Hickman, Dean,Correll, Tiffany L.,Williamson, Toni,Wood, Stephen
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supporting information
p. 6447 - 6454
(2013/11/19)
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- NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the mean
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Page/Page column 31
(2012/12/13)
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- NOVEL SUBSTITUTED BICYCLIC TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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The present invention is concerned with novel substituted bicyclic triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
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Page/Page column 76; 77
(2011/08/04)
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- NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma sec
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Page/Page column 66
(2011/08/04)
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- GAMMA SECRETASE MODULATORS
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The present invention provides compounds that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions conta
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Page/Page column 97-98
(2009/07/17)
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- UREA COMPOUNDS AS GAMMA SECRETASE MODULATORS
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The present invention provides compounds Formula (I) that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Page/Page column 32-33
(2010/01/29)
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