- Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
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A new manganese catalyzed heterocyclization of aminoalcohols has been accomplished. A wide range of heterocycles were synthesized, including 1,2,3,4-tetrahydroquinolines, dihydroquinolinones, and 2,3,4,5-tetrahydro-1H-benzo[b]azepines. The reaction is performed under mild reaction conditions using air and moisture stable manganese catalysts. The desired heterocycles were obtained in good to excellent yields.
- Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
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supporting information
(2022/03/17)
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- Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives
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The transition metal-catalyzed reductive cyclization of o-nitrostyrene in the presence of carbon monoxide (CO) has been developed to be a general synthetic route to an indole skeleton, wherein CO was used as a reductant to deoxidize nitroarene into nitrosoarene and/or nitrene with CO2 release, but the selective insertion of CO into the heterocyclic product with higher atom economy has not yet been realized. Herein, the Pd-catalyzed reduction of o-nitrostyrene by CO and its regioselective insertion were efficiently achieved to produce synthetically useful five- and six-membered benzo-fused lactams. Detailed investigations revealed that the chemoselectivity to indole or lactam was sensitive to the nature of the counteranions of Pd2+ precursors, whereas ligands significantly decided the carbonylative regioselectivity by different reaction pathways. Using PdCl2/PPh3/B(OH)3 (condition A), an olefin hydrocarboxylation was primarily initiated followed by partial reduction of the NO2 moiety and cyclization reaction to give N-hydroxyl indolin-2-one, which was further catalytically reduced by CO to afford the indolin-2-one as the final product with up to 95% yield. When the reaction was conducted under the Pd(TFA)2/BINAP/TsOH·H2O system (condition B), complete deoxygenation and carbonylation of the NO2 group occurred initially to yield the corresponding isocyanate followed by internal hydrocyclization to generate 3,4-dihydroquinolin-2-one with up to 98% yield. Importantly, the methodology could be efficiently applied in the synthesis of marketed drug Aripiprazole.
- Yang, Li,Shi, Lijun,Xing, Qi,Huang, Kuo-Wei,Xia, Chungu,Li, Fuwei
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p. 10340 - 10348
(2018/10/20)
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- 2-Aminopyridine Derivatives as Potential σ2 Receptor Antagonists
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σ2 Receptor research is receiving increasing interest with regard to the potential of σ2 proteins as targets for tumor therapy and diagnosis. Nevertheless, knowledge about the σ2 receptor is far from conclusive. The paucity and modest affinity of known σ2 antagonists represent one of the limitations to σ2 receptor research. Previous studies of the high-affinity σ2 agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine 4 (PB28) suggested that a decrease in lipophilicity might lead to σ2 ligands devoid of antiproliferative activity (potential σ2 antagonists). With the aim of producing σ2 receptor antagonists, we replaced the tetralin nucleus of compound 4 with a 2-aminopyridine moiety. A series of compounds with high affinity for both σ subtypes and with no antiproliferative activity in various cells (mouse HT-22, human SK-N-SH, MCF-7wt, and MCF-7σ1) were obtained. The effect on Ca2+ mobilization was investigated for high-affinity compounds 18 and 4, which showed opposite effects. All of the data support the new 2-aminopyridines as high-affinity σ ligands with σ2 antagonist and σ1 agonist activity, and, despite the lack of significant σ2 versus σ1 selectivity, these novel compounds may be better tools for σ receptor research than the known low-affinity σ2 antagonists.
- Abate, Carmen,Ferorelli, Savina,Niso, Mauro,Lovicario, Cesarea,Infantino, Vittoria,Convertini, Paolo,Perrone, Roberto,Berardi, Francesco
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p. 1847 - 1857
(2012/10/30)
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- CYCLIC COMPOUNDS CONTAINING ZINC BINDING GROUPS AS MATRIX METALLOPROTEINASE INHIBITORS
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This invention provides compounds defined by Formula I Z-L-R1-Q-D-(V1)m-R2 I or a pharmaceutically acceptable salt thereof, wherein Z, L, R1, Q, D, V1, m, and R2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification.
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Page/Page column 256; 264
(2010/02/06)
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