- A Fluorinated Ligand Enables Room-Temperature and Regioselective Pd-Catalyzed Fluorination of Aryl Triflates and Bromides
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A new biaryl monophosphine ligand (AlPhos, L1) allows for the room-temperature Pd-catalyzed fluorination of a variety of activated (hetero)aryl triflates. Furthermore, aryl triflates and bromides that are prone to give mixtures of regioisomeric aryl fluorides with Pd-catalysis can now be converted to the desired aryl fluorides with high regioselectivity. Analysis of the solid-state structures of several Pd(II) complexes, as well as density functional theory (DFT) calculations, shed light on the origin of the enhanced reactivity observed with L1.
- Sather, Aaron C.,Lee, Hong Geun,De La Rosa, Valentina Y.,Yang, Yang,Müller, Peter,Buchwald, Stephen L.
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supporting information
p. 13433 - 13438
(2015/11/09)
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- Compounds
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Compounds of Formula (I), compositions containing them, their use in therapy, including their use as antibacterials, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 41
(2009/08/14)
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- Piperazine derivatives
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This invention relates to piperazine derivatives of the formula: wherein each symbol is as defined in the description, and its pharmaceutically acceptable salt, to processes for preparation thereof, to pharmaceutical composition comprising the same, and to a use of the same for treating or preventing Tachykinin-mediated diseases in human being or animals.
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Page/Page column 25
(2010/02/15)
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- Method for producing halogen-substituted aromatic aldehyde
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In the production method of the invention, a halogen-substituted aromatic compound is reacted with carbon monoxide in the presence of hydrogen fluoride and boron trifluoride into a corresponding halogen-substituted aromatic aldehyde. By the use of hydrogen fluoride and boron trifluoride, the para position to halogen atom is selectively formylated to provide the halogen-substituted aromatic aldehyde in high yields in a short reaction time even at temperatures lower than room temperature.
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Page/Page column 5-6
(2008/06/13)
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- Process for preparing benzyl alcohols and their use
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Benzyl alcohols, particularly those which bear fluorine substituents or fluoroalkyl substituents on the benzyl ring, can be obtained by formylation of corresponding aryl bromides to form benzaldehydes and reduction of the latter using further formate, wherein the benzaldehydes formed do not have to be isolated.
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- Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1
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A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC50 = 3.5 μM) shows inhibitory activity comparable to cariporide (IC50 = 3.4 μM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC50 = 0.003 μM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.
- Ahmad,Doweyko,Dugar,Grazier,Ngu,Wu,Yost,Chen,Gougoutas,DiMarco,Lan,Gavin,Chen,Dorso,Serafino,Kirby,Atwal
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p. 3302 - 3310
(2007/10/03)
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- 1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active antiinflammatory agents
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Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mpk for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mpk) and hyperalgesia (ED50 = 11- 40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.
- Khanna, Ish K.,Weier, Richard M.,Yu, Yi,Xu, Xiang D.,Koszyk, Francis J.,Collins, Paul W.,Koboldt, Carol M.,Veenhuizen, Amy W.,Perkins, William E.,Casier, Jacquelen J.,Masferrer, Jaime L.,Zhang, Yan Y.,Gregory, Susan A.,Seibert, Karen,Isakson, Peter C.
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p. 1634 - 1647
(2007/10/03)
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- Synthesis of fluorobenzaldehydes
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4-fluorobenzaldehydes are formed from compounds of the formula (I) STR1 wherein R1, R2, R3 and R4 are the same or different, and represent H, halogen, or an alkyl group of from 1 to about 10 carbon atoms, wherein, when at least one of R1, R2, R3 or R4 is halogen, at least one of remaining R1, R2, R3 or R4 is alkyl. the compound of formula of (I) is reacted with a formylating agent in the presence of FeCl3 in a reaction mixture, from which is separated a compound of the formula (II) STR2 wherein R1, R2 , R3 and R4 are as defined above.
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