- The reactions of N3P3Cl6 with monodentate and bidentate ligands: the syntheses and structural characterizations, in vitro antimicrobial activities, and DNA interactions of 4-fluorobenzyl(N/O)spirocyclotriphosphazenes
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The Cl replacement reactions of 4-fluorobenzyl(N/O)spirocyclotriphosphazene (2) with excess monoamines led to the formation of 4-fluorobenzylspiro(N/O)tetraaminocyclotriphosphazenes (2a–2d). The partly substituted dispiro 3b and dispiro 3c and fully substituted trispirocyclotriphosphazenes (trans 4a, cis 4c, 4d, and 4e) were obtained, respectively, from the reactions of 2 with one equimolar and two equimolar amounts of diamines, aminoalcohol, and diols. Although efforts were made for the separation of the cis/trans and optical isomers of the dispiro phosphazenes, only one set of diastereomers (RR/RS or SS/SR) of dispiro 3b and dispiro 3c was isolated, respectively. The31 P NMR spectral data of the other dispiro phosphazenes were evaluated from the31 P NMR spectra of the reaction mixtures. The reactions of 2 with excess N-methylethylenediamine gave trans 4a as a racemic mixture. While trans 4b (racemic) and cis 4b (meso) occurred from the reaction of 2 with excess N-methyl-1,3-propanediamine, they were not isolated separately. Some of the phosphazenes were screened against bacteria and fungi. The activities of the compounds against anaerobic and microaerophilic gram-negative bacteria were evaluated. It was found that compounds 2, 2b, and trans 4a exhibited tolerable toxic effects on fibroblast cells and had the highest toxicity against MCF-7 cells.
- Okumu?, Aytu,Elmas, Gamze,Kili?, Zeynel,RAMAZANOGLU, Nagehan,A?ik, Leyla,Türk, Mustafa,Ak?a, Gül?in
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- Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition
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Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.
- Berglund, Susanne,Egner, Bryan J.,Graden, Henrik,Graden, Joakim,Morgan, David G.A.,Inghardt, Tord,Giordanetto, Fabrizio
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scheme or table
p. 4268 - 4273
(2010/04/30)
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- FUSED BICYCLIC PYRIMIDINE DERIVATIVES
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A novel fused bicyclic pyrimidine derivative or a salt thereof that acts as a tachykinin receptor antagonist and, in particular, as an NK1 receptor antagonist is represented by the following general formula (1): wherein the rings A and B are each a benzene ring having 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring); the ring C is a nitrogen-containing ring; m is 1 or 2; and n is 2 or 3.
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