- Profiling the interaction of a novel toxic pyruvate dehydrogenase kinase inhibitor with human serum albumin
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To discover novel pyruvate dehydrogenase kinase (PDK) inhibitors, a new compound 2,2-dichloro-1-(4-((4-isopropylphenyl)amino)-3-nitrophenyl)ethan-1-one, namely XB-1 was identified, which inhibited PDK activity with a half maximal inhibitory concentration
- Liao, Xianjiu,Zhu, Chunlei,Huang, Ding,Wen, Xiaoqing,Zhang, Shao-Lin,Shen, Yizhong
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Read Online
- Photoinduced Iron-Catalyzed ipso-Nitration of Aryl Halides via Single-Electron Transfer
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A photoinduced iron-catalyzed ipso-nitration of aryl halides with KNO2 has been developed, in which aryl iodides, bromides, and some of aryl chlorides are feasible. The mechanism investigations show that the in situ formed iron complex by FeSO4, KNO2, and 1,10-phenanthroline acts as the light-harvesting photocatalyst with a longer lifetime of the excited state, and the reaction undergoes a photoinduced single-electron transfer (SET) process. This work represents an example for the photoinduced iron-catalyzed Ullmann-type couplings.
- Wu, Cunluo,Bian, Qilong,Ding, Tao,Tang, Mingming,Zhang, Wenkai,Xu, Yuanqing,Liu, Baoying,Xu, Hao,Li, Hai-Bei,Fu, Hua
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p. 9561 - 9568
(2021/08/06)
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- Semicarbazone compounds and application thereof
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The invention belongs to the technical field of medicines, and relates to semicarbazone compounds as shown in a general formula I and pharmaceutically acceptable salts, hydrates or prodrugs thereof, wherein the definitions of substituent groups R1, R2, R3
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Paragraph 0096-0098
(2020/07/13)
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- Design, synthesis and biological evaluation of novel aryl-acrylic derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors
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Two series of novel aryl-acrylic derivatives were designed, synthesized, and screened in enzymatic and cellular inhibitory activities. All compounds showed moderate to significant potency. The SAR analyses indicated that the semicarbazone linker is better
- Hu, Hao,Li, Ming,Wu, Di,Li, Zhiwei,Miao, Ruifeng,Liu, Yajing,Gong, Ping
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p. 3135 - 3144
(2019/06/11)
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- Thiazole derivative compounds having IDO inhibitory activity, preparation method and application thereof
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The invention relates to the technical field of medicinal chemistry, in particular to thiazole derivative compounds having IDO (indoleamine-2,3-dioxygenase) inhibitory activity, a preparation method and application thereof. The invention discloses thiazol
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Paragraph 0045; 0050-0052
(2019/01/13)
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- Dichloroacetophenones targeting at pyruvate dehydrogenase kinase 1 with improved selectivity and antiproliferative activity: Synthesis and structure-activity relationships
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Dichloroacetophenone is a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor with suboptimal kinase selectivity. Herein, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones. Structure-activity relationship analyses (SARs) enabled us to identify three potent compounds, namely 54, 55, and 64, which inhibited PDK1 function, activated pyruvate dehydrogenase complex, and reduced the proliferation of NCI-H1975 cells. Mitochondrial bioenergetics assay suggested that 54, 55, and 64 enhanced the oxidative phosphorylation in cancer cells, which might contribute to the observed anti-proliferation effects. Collectively, these results suggested that 54, 55, and 64 could be promising compounds for the development of potent PDK1 inhibitors.
- Zhang, Shao-Lin,Yang, Zheng,Hu, Xiaohui,Tam, Kin Yip
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supporting information
p. 3441 - 3445
(2018/09/29)
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- IMINOTETRAHYDROPYRIMIDINONE DERIVATIVES AS PLASMEPSIN V INHIBITORS
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A series of 2-imino-6-methyltetrahydropyrimidin-4(lH)-one derivatives, substituted in the 6-position by a phenyl moiety which in turn is meta-substituted by an optionally substituted unsaturated fused bicyclic ring system containing at least one nitrogen atom, being selective inhibitors of plasmepsin V activity, are beneficial as pharmaceutical agents, especially in the treatment of malaria.
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Page/Page column 55
(2017/07/05)
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- PHOSPHODIESTERASE 10 INHIBITORS
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The present invention if directed to certain cinnoline compounds that are PDE10 inhibitors, pharmaceutical compositions containing such compounds and processes for preparing such compounds. The invention is also directed to methods of treating diseases mediated by PDE10 enzyme, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
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Page/Page column 63-64
(2008/06/13)
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- Synthesis of fluorinated 1-(3-Morpholin-4-yl-phenyl)-ethylamines
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The synthesis of four (±)-fluorinated 1-(3-morpholin-4-yl-phenyl)-ethylamines and an enantioselective approach to these amines through reductive amination are described.
- Wu, Yong-Jin,He, Huan,Sun, Li-Qiang,Wu, Dedong,Gao, Qi,Li, Hui-Yin
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p. 1725 - 1728
(2007/10/03)
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- PROCESS FOR PRODUCING 4-SUBSTITUTED-2-NITRO-FLUOROBENZENES
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A process for selectively eliminating a compound of general formula (II) from a mixture of a compound of general formula (I) with the compound of general formula (II). This process comprises reacting the compound of general formula (II) with a tertiary am
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- Tricyclic compounds and drug compositions containing the same
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Compounds having a β-3 adrenaline receptor agonist and are useful as drugs for the treatment and prevention of diabetes, obesity, hyperlipemia, etc., represented by a general formula (I) and salts thereof, and a process for producing these, and their intermediates, wherein R represents hydrogen or methyl; R1 represents hydrogen, halogen, hydroxy, benzyloxy, amino, or hydroxymethyl; R2 represents hydrogen, hydroxymethyl, NHR3, SO2 NR4 R4', or nitro; R6 represents hydrogen or lower alkyl; and X represents nitrogen, R9 represents hydrogen, one of R7 and R8 represent hydrogen, and the other thereof represents hydrogen, amino, acetylamino, or hydroxy.
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- Synthesis and pharmacological evaluation of N-(2,5-disubstituted phenyl)-N'-(3-substituted phenyl)-N'-methylguanidines as N-methyl-D-aspartate receptor ion-channel blockers
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In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both σ receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution/pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (27b, R2 = R5 = Br, R3 = C2H5) exhibited potency at both 5 receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R2 and R5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5- (methylthio)phenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (34b, R2 = Br, R5 = SMe, R3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R3. Optimal activity in this series are afforded by 43b and 44b (R2 = Cl or Br, R5 = R3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (K(i) vs [3H]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure-activity relationships for these compounds at the NMDA receptor ion-channel site are discussed.
- Hu, Lain-Yen,Quo, Junqing,Magar, Sharad S.,Fischer, James B.,Burke-Howie, Kathleen J.,Durant, Graham J.
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p. 4281 - 4289
(2007/10/03)
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- Substituted alkylaryl ketones and methods of use as herbicides
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Ring and side chain substituted alkylaryl ketones are useful in controlling the growth of germinating and seedling weed grasses and germinating and seedling broadleaf weeds.
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