- THIOPHENE HSD17B13 INHIBITORS AND USES THEREOF
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Described herein are HSD17B13 inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of liver disease, metabolic disease, or cardiovascular disease, such as NAFLD or NASH, or drug induced liver injury (DILI).
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Paragraph 00200-00201
(2022/02/05)
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- Synthesis of novel 2-(1-adamantanylcarboxamido)thiophene derivatives. Selective cannabinoid type 2 (CB2) receptor agonists as potential agents for the treatment of skin inflammatory disease
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A set of CB2R ligands, based on the thiophene scaffold, was synthesized and evaluated in in vitro assays. Compounds 8c-i, k, l, bearing the 3-carboxylate and 2-(adamantan-1-yl)carboxamido groups together with apolar alkyl/aryl substituents at 5-position or at 4- and 5-positions of the thiophene ring possess high CB2R affinity at low nanomolar concentration, good receptor selectivity, and agonistic functional activity. The full agonist 8g, showing the best balance between receptor affinity and selectivity, was tested in vitro in an experimental model of allergic contact dermatitis and proved to be able to block the release of MCP-2 in HaCaT cells at 10 μM concentration.
- Mugnaini, Claudia,Rabbito, Alessandro,Brizzi, Antonella,Palombi, Nastasja,Petrosino, Stefania,Verde, Roberta,Di Marzo, Vincenzo,Ligresti, Alessia,Corelli, Federico
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p. 239 - 251
(2018/10/24)
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- Design, Synthesis, and SAR Studies of Heteroarylpyrimidines and Heteroaryltriazines as CB2R Ligands
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Herein we describe the design and synthesis of a new series of heteroarylpyrimidine/heteroaryltriazine derivatives on the basis of quinazoline-2,4(1H,3H)-diones as CB2R-selective ligands using a bioisosterism strategy. An acetamide group was explored to displace the enamine linker of the lead compound for the purpose of stereoisomerism elimination and hydrophilicity increase. As a result, some of the synthesized compounds showed high bioactivity and selectivity for CB2R in calcium mobilization assays, and four displayed CB2R agonist activity, with EC50 values below 30 nm. The compound exhibiting the highest agonist activity toward CB2R (EC50=7.53±3.15 nm) had a selectivity over CB1R of more than 1328-fold. Moreover, structure–activity relationship (SAR) studies indicated that the substituents on the nucleus play key roles in the functionality of a ligand, with one such example demonstrating CB2R antagonist activity. Additionally, molecular docking simulations were conducted with the aim of better understanding of these new derivatives in relation to the structural requirements for agonists/antagonists binding to CB2R.
- Qian, Hai-Yan,Wang, Zhi-Long,Chen, Li-Li,Pan, You-Lu,Xie, Xiao-Yu,Xie, Xin,Chen, Jian-Zhong
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supporting information
p. 2455 - 2463
(2018/11/23)
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- Heteroarylpyrimindinedione derivative and use thereof
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The invention provides a heteroarylpyrimindinedione derivative and use thereof. The heteroarylpyrimindinedione derivative comprises a compound with a structure shown as general formula I, and a pharmaceutically acceptable salt or hydrate thereof. The derivative is obtained by chemical synthesis, and pharmacological experiments prove that the active ligand with cannabinoid type II receptor CB2 can be used for preparation of drugs for prevention and mitigation of CB2 receptor-mediated diseases, and the drug is cannabinoid CB2 receptor agonist's agonist, partial agonist, inverse agonist or antagonist. And the general structural formula I is shown as the specification.
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Paragraph 0414; 0415; 0416
(2017/04/03)
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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- Inhibitors of histone deacetylase
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The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
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