- KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease
-
Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.
- An, Heeyoung,Cho, Doo-Wan,Choi, Ji Won,Han, Su-Cheol,Heo, Jun Young,Jang, Bo Ko,Jeon, Sang Ryong,Kim, Hyeon Jeong,Kim, Sangwook,Kim, Siwon,Lee, C. Justin,Lee, Hyowon,Nam, Min-Ho,Oh, Soo-Jin,Park, Jong-Hyun,Park, Ki Duk,Park, Sun Jun,Song, Hyo Jung,Yang, Young-Su,Yoon, Hyung Ho
-
p. 1729 - 1747
(2021/10/08)
-
- Gold Catalysts Can Generate Nitrone Intermediates from a Nitrosoarene/Alkene Mixture, Enabling Two Distinct Catalytic Reactions: A Nitroso-Activated Cycloheptatriene/Benzylidene Rearrangement
-
Gold-catalyzed reactions of cycloheptatrienes with nitrosoarenes yield nitrone derivatives efficiently. This reaction sequence enables us to develop gold-catalyzed aerobic oxidations of cycloheptatrienes to afford benzaldehyde derivatives using CuCl and nitrosoarenes as co-catalysts (10-30 mol %). Our density functional theory calculations support a novel nitroso-activated rearrangement, tropylium → benzylidene. With the same nitrosoarenes, we developed their gold-catalyzed [2 + 2 + 1]-annulations between nitrosobenzene and two enol ethers to yield 5-alkoxyisoxazolidines using 1,4-cyclohexadienes as hydrogen donors.
- Cheng, Mu-Jeng,Kardile, Rahul Dadabhau,Kuo, Tung-Chun,Liu, Rai-Shung,More, Sayaji Arjun
-
p. 5506 - 5511
(2021/07/31)
-
- PIPERIDINES USEFUL FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS
-
The invention relates to compounds which are substituted chiral or achiral derivatives of 3- or 4- aminopiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula I and especially their use as inhibitors of β-secretases.
- -
-
-
- SUBSTITUTED 3- AND 4- AMINOMETHYLPIPERIDINES FOR USE AS BETA-SECRETASE IN THE TREATMENT OF ALZHEIMER’S DISEASE
-
The invention relates to novel compounds, which are substituted chiral or achiral derivatives of 3- or 4- aminomethylpiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula (I) and especially their use as inhibitors of beta-secretases for the treatment of Alzheimer’s disease.
- -
-
Page/Page column 47
(2008/06/13)
-
- Comparison of the Properties of Liquid Crystals Derived from Certain Lateral Halogeno-substituted Azomethines
-
Twenty-eight 4-n-alkoxy-N-(2- and 2'-halogenobiphenyl-4-ylmethylene)anilines comprising 4,8,8,4, and 4 members derived , respectively, from 2-fluoro-, 2'-fluoro-, 2'-chloro-, 2'-bromo-, and 2'-iodo-biphenyl-4-carbaldehyde, together with six 4-p-n-alkoxy-2'-fluorobenzylideneaminobiphenyls have been prepared.The liquid crystal behaviour of these compounds has been compared with analogous azomethines with reversed CH=N linkage, previously reported.
- Brown, John W.,Butcher, Jane L.,Byron, David J.,Gunn, Elaine S.,Rees, Mark,Wilson, Robert C.
-
p. 255 - 266
(2007/10/02)
-