- Heterogeneous Catalyzed Chemoselective Reductive Amination of Halogenated Aromatic Aldehydes
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The chemoselective conversion of a specific functional group in a multifunctional substrate is of great importance in the chemical industry to obtain cost efficient, sustainable and waste free processes. This work focuses on the chemoselective amination of halogenated aromatic aldehydes with dimethyl amine towards halogenated aromatic amines, a raw material used in the production of for example agrochemical active ingredients. It was found that by combining palladium, a metal known for dehalogenation reactions, and copper, known for its direct hydrogenation of aldehydes to alcohols, in one heterogeneous bimetallic catalyst, a synergistic effect is obtained. By depositing copper onto a palladium on carbon catalyst with a Cu/Pd ratio of at least 1 : 1, the yield could be increased from 66 % (Pd/C) to 98 % (PdCu/C). Moreover, this highly active and stable catalyst also showed suppressed dehalogenation side-reactions in several other chemical conversions such as hydrogenation of nitro functional groups and hydrogenation of aldehydes.
- Dumoleijn, Kim N. R.,Villa, Alberto,Marelli, Marcello,Prati, Laura,Moonen, Kristof,Stevens, Christian V.
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p. 3021 - 3026
(2021/05/18)
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- Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome
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On the basis of its essential role in driving inflammation and disease pathology, cell necrosis has gradually been verified as a promising therapeutic target for treating atherosclerosis, systemic inflammatory response syndrome (SIRS), and ischemia injury, among other diseases. Most necrosis inhibitors targeting receptor-interacting protein 1 (RIP1) still require further optimization because of weak potency or poor metabolic stability. We conducted a phenotypic screen and identified a micromolar hit with novel amide structure. Medicinal chemistry efforts yielded a highly potent, selective, and metabolically stable drug candidate, compound 56 (RIPA-56). Biochemical studies and molecular docking revealed that RIP1 is the direct target of this new series of type III kinase inhibitors. In the SIRS mice disease model, 56 efficiently reduced tumor necrosis factor alpha (TNFα)-induced mortality and multiorgan damage. Compared to known RIP1 inhibitors, 56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies.
- Ren, Yan,Su, Yaning,Sun, Liming,He, Sudan,Meng, Lingjun,Liao, Daohong,Liu, Xiao,Ma, Yongfen,Liu, Chunyan,Li, Sisi,Ruan, Hanying,Lei, Xiaoguang,Wang, Xiaodong,Zhang, Zhiyuan
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p. 972 - 986
(2017/02/19)
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- Antimycobacterial activity of new 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-one derivatives. Molecular modeling investigations
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3H-1,3,4-Oxadiazol-2-one derivatives were synthesized and tested for their in vitro antimycobacterial activity. Oxadiazolone derivatives showed an interesting antimycobacterial activity against the reference strain of Mycobacterium tuberculosis H37Rv. Molecular modeling investigations were performed and showed that the active compounds possess all necessary features to target the protein active site of the mycobacterial cytochrome P450-dependent sterol 14α-demethylase in the sterol biosynthesis pathway as the calculated free energy of binding were in agreement with the corresponding MIC values.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Fermeglia, Maurizio,Posocco, Paola,Pricl, Sabrina,Banfi, Elena,Scialino, Giuditta,Vio, Luciano
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experimental part
p. 4693 - 4707
(2009/10/24)
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- Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-ones
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In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.
- Piazzi, Lorna,Belluti, Federica,Bisi, Alessandra,Gobbi, Silvia,Rizzo, Stefano,Bartolini, Manuela,Andrisano, Vincenza,Recanatini, Maurizio,Rampa, Angela
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p. 575 - 585
(2008/03/12)
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- Intramolecular addition of stabilized enolates to (η6-arene)ruthenium complexes: Synthesis of Ru-coordinated azaspirocycles
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(formula presented) Stabilized enolates attached to cationic (arene)RuIICp complexes via an amide linkage were found to participate in nucleophilic aromatic addition reactions resulting in the formation of novel cyclohexadienyl-Ru azaspirocycles. Enolate addition to the activated arene ring was found to proceed with complete stereoselectivity.
- Pigge, F. Christopher,Fang, Shiyue,Rath, Nigam P.
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p. 1851 - 1854
(2008/02/11)
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- Oxidations with Cerium(IV) Sulfate: Intramolecular Cyclization of N-Benzyl-&β-aminoketones Yielding 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines
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Preparation and regiospecific cerium(IV) sulfate of the substituted N-benzyl-β-aminoketones 3 are described. 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines 4 so obtained are reduced by sodium borohydride.
- Holzgrabe, Ulrike
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p. 647 - 654
(2007/10/02)
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- Benzylamines: Synthesis and evaluation of antimycobacterial properties
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The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (MIC 10.2 μg/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 μg/mL), and N-butyl-3,5-difluorobenzylamine (MIC 6.4 μg/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combination of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.
- Meindl,Von Angerer,Schonenberger,Ruckdeschel
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p. 1111 - 1118
(2007/10/02)
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