- Studies of Pendant-arm Macrocyclic Ligands. Part 5. Synthesis of Two Pyridine-containing Penta-aza Macrocycles with Single Pyrrolidinyl Pendant Arms and Characterisation of their Nickel(II) and Copper(II) Complexes. Crystal Structure of Perchlorato-3,7,...
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Two new pyridine-containing penta-aza macrocyclic ligands, 7-- and 7--3,7,11,17-tetra-azabicycloheptadeca-1(17),13,15-triene (L1 and L2 respectively) have been prepared, and their nickel(II) and copper(II) complexes of formulae 1)(OClO3)> and 3 (M = Ni or Cu, L = L1 or L2) have been isolated and characterised.In the octahedral complex 1)(OClO3)> the presence of a co-ordinated perchlorate group has been established by X-ray crystallography, and the macrocyclic ligand found to co-ordinate close to the corners of a square pyramid with the pendant pyrrolidinyl group at the apical position.
- Alcock, Nathaniel W.,Balakrishnan, Karappulli P.,Moore, Peter,Omar, Hadi A. A.
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- New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis
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Cdc2-like kinase 1 (CLK1) and dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) are involved in the regulation of alternative pre-mRNA splicing. Dysregulation of this process has been linked to cancer progression and neurodegenerative diseases, making CLK1 and DYRK1A important therapeutic targets. Here we describe the synthesis of new pyrido[3,4-g]quinazoline derivatives and the evaluation of the inhibitory potencies of these compounds toward CDK5, CK1, GSK3, CLK1 and DYRK1A. Introduction of aminoalkylamino groups at the 2-position resulted in several compounds with low nanomolar affinity and selective inhibition of CLK1 and/or DYRK1A. Their evaluation on several immortalized or cancerous cell lines showed varying degree of cell viability reduction. Co-crystal structures of CLK1 with two of the most potent compounds revealed two alternative binding modes of the pyrido[3,4-g]quinazoline scaffold that can be exploited for future inhibitor design.
- Tazarki, Helmi,Zeinyeh, Wael,Esvan, Yannick J.,Knapp, Stefan,Chatterjee, Deep,Schr?der, Martin,Joerger, Andreas C.,Khiari, Jameleddine,Josselin, Béatrice,Baratte, Blandine,Bach, Stéphane,Ruchaud, Sandrine,Anizon, Fabrice,Giraud, Francis,Moreau, Pascale
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p. 304 - 317
(2019/02/07)
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- NITROGEN-CONTAINING COMPOUNDS SUITABLE FOR USE IN THE PRODUCTION OF POLYURETHANES
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The present invention provides for the use of nitrogen compounds of formula (I) and/or of corresponding quaternized and/or protonated compounds for production of polyurethanes, compositions containing these compounds and polyurethane systems, especially polyurethane foams, which have been obtained using the compounds.
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Paragraph 0275; 0276
(2018/07/31)
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- Identification and Structure–Activity Relationship Studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1
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The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small-molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure- and ligand-based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4-aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.
- Robaa, Dina,Wagner, Tobias,Luise, Chiara,Carlino, Luca,McMillan, Joel,Flaig, Ralf,Schüle, Roland,Jung, Manfred,Sippl, Wolfgang
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supporting information
p. 2327 - 2338
(2016/10/24)
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- Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents
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A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD.
- Luo, Wen,Wang, Ting,Hong, Chen,Yang, Ya-Chen,Chen, Ying,Cen, Juan,Xie, Song-Qiang,Wang, Chao-Jie
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supporting information
p. 17 - 26
(2016/07/06)
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- Synthesis and antitumor activity of 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety
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We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds exhibit broad-spectrum antitumor potency, and the most active compound 23p (IC50: 2.357-3.012 μM) was found more potent than Sunitinib (IC50: 31.594-49.036 μM) against HepG2, A549 and Skov-3, respectively.
- Zhang, Jun,Shen, Weiyi,Li, Xiaoning,Chai, Yun,Li, Senjun,Lv, Kai,Guo, Huiyuan,Liu, Mingliang
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- Novel n(phenylsulphonyl)glycine derivatives and their therapeutic use
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The present invention relates to novel N-(phenylsulphonyl)glycyl-glycine compounds, which are defined by formula I and the description, as well as their method of preparation and their use in therapeutics
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- A new class of histamine H3-receptor antagonists: Synthesis and structure - Activity relationships of 7,8,9,10-Tetrahydro-6H-cyclohepta[b]quinolines
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The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H3 receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and the effect of conformational restraints are described. Several compounds with high affinity and selectivity for the H3 receptor were discovered.
- Turner, Sean C.,Esbenshade, Timothy A.,Bennani, Youssef L.,Hancock, Arthur A.
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p. 2131 - 2135
(2007/10/03)
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- 2-aminobenzoxazole derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminobenzoxazole derivative compounds of the following formula: wherein R1 to R4 and Z have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminobenzoxazole derivative compounds.
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- N-SUBSTITUTED-N'-SUBSTITUTED UREA DERIVATIVE AND USE THEREOF AS TNF-γ(a) PRODUCTION INHIBITOR
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N-Substituted-N'-substituted urea derivatives represented by the following formula, analogs thereof or pharmaceutically acceptable salts thereof are herein provided. These compounds show a TNF- α production inhibitory activity.
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- Pancreatic imaging agents
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A novel group of radiolabelled diamines are provided, effective for pancreatic imaging and represented by the formula STR1 wherein n is 1 to 10; R1 and R2 are the same or different and are hydrogen, hydroxyl or lower alkyl having 1 to 6 carbon atoms; R3 is lower alkyl having 1 to 6 carbon atoms; and N' is a nitrogen atom forming part of a 4- to 8-membered heterocyclic ring containing one or two hetero atoms, one of which is said nitrogen, said heterocyclic ring being unsubstituted or substituted with one or more lower alkyl groups and pharmaceutically acceptable acid addition salts thereof.
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- POTENTIAL ANTIDEPRESSANTS: 10-AMINO-2-CHLORO-10,11-DIHYDRODIBENZOTHIEPINS
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Reduction of N-(2-chloro-10,11-dihydrodibenzothiepin-10-yl)formamide with lithium aluminium hydride resulted in the methylamino compound IV.The dimethylamino compound V was obtained by methylation of 10-amino-2-chloro-10,11-dihydrodibenzothiepin with formic acid and aqueous formaldehyde.Substitution reactions of 2,10-dichloro-10,11-dihydrodibenzothiepin with a series of primary and secondary amines afforded the title compounds VI to XXVIII.The bases were transformed to salts and pharmacologically tested.Only the pyrrolidino compound IX (hydrogen succinate VUFB-15551) showed a clear pharmacological profile of a potential antidepressant.
- Valenta, Vladimir,Vlkova, Marie,Holubek, Jiri,Metysova, Jirina,Protiva, Miroslav
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p. 1979 - 1994
(2007/10/02)
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