147699-19-2Relevant articles and documents
A straightforward enantioselective synthesis of F17807
Alliot, Julien,Gravel, Edmond,Buisson, David-Alexandre,Larquetoux, Laurent,Nicolas, Marc,Doris, Eric
, p. 9383 - 9387 (2015)
An efficient approach for the enantioselective synthesis of the 1,4-benzodioxane F17807 drug is reported. The developed route relied on two key steps, namely SNAr and Mitsunobu reactions, which permitted a straightforward access to the title co
Investigating alkyl nitrates as nitric oxide releasing precursors of multitarget acetylcholinesterase-monoamine oxidase B inhibitors
Pisani, Leonardo,Iacobazzi, Rosa Maria,Catto, Marco,Rullo, Mariagrazia,Farina, Roberta,Denora, Nunzio,Cellamare, Saverio,Altomare, Cosimo Damiano
, p. 292 - 309 (2018/10/25)
Herein we envisaged the possibility of exploiting alkyl nitrates as precursors of alcohol-bearing dual inhibitors targeting acetylcholinesterase (AChE) and monoamine oxidase B (MAO B), key enzymes in neurodegenerative syndromes such as Alzheimer's disease (AD), through biotransformation unmasking an alcoholic function upon nitric oxide (NO) release. The cooperation to neuroprotection of low fluxes of NO and target enzymes’ inhibition by the alcohol metabolites might return a multitargeting effect. The in vitro screening towards ChEs and MAOs of a collection of 21 primary alcohols disclosed a subset of dual inhibitors, among which three diverse chemotypes were selected to study the corresponding nitrates. Nitrate 14 proved to be a brain permeant, potent AChE-MAO B inhibitor by itself. Moreover, it protected human SH-SY5Y lines against rotenone and hydrogen peroxide with a poor inherent cytotoxicity and showed a slow conversion profile to its alcohol metabolite 9d that still behaved as bimodal and neuroprotective molecule.
Piperidine amino derivative and application thereof in fighting schizophrenia
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, (2018/03/25)
The invention discloses a piperidine amino compound and an application thereof in fighting schizophrenia. Pharmacological experiment results show that the piperidine amino compound related to by the invention has good water solubility, has high affinity with dopamine D, D, 5-HT, and 5-HT receptors, and has good selectivity on D/D receptors. In-vivo test results show that a preferable compound has a good anti-schizophrenia effect, is relatively low in acute toxicity, high in safety and good in pharmacokinetic characteristic, and has a development value as a high-efficiency low-toxicity novel anti-schizophrenia new drug. The piperidine amino compounds are compounds represented as a structural general formula (I), or salts of the compounds, or hydrates of the salts.
Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis
He, Linhong,Pei, Heying,Zhang, Chufeng,Shao, Mingfeng,Li, Dan,Tang, Mingli,Wang, Taijing,Chen, Xiaoxin,Xiang, Mingli,Chen, Lijuan
, p. 96 - 112 (2018/01/10)
Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC50 = 21.70 ± 0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC50 values over 30 μM. Moreover, B16 showed very weak potential to block the hERG channel (IC50 = 11.10 μM) in comparison to ibrutinib (IC50 = 0.97 μM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t1/2 = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis.