- Substrate and Catalyst Effects in the Enantioselective Copper-Catalysed C–H Insertion Reactions of α-Diazo-β-oxo Sulfones
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Excellent enantioselectivities of up to 98 % ee are achieved by employing the copper-bis(oxazoline)-NaBARF catalyst system in the C–H insertion reactions of α-diazo-β-oxo sulfones. The influence of variation of the bis(oxazoline) ligand, copper salt, additive and substrate on both the efficiency and the enantioselectivities of these intramolecular C–H insertion reactions has been explored. Optimum enantioselectivities are achieved with phenyl and diphenyl ligands across the substrate series.
- Shiely, Amy E.,Clarke, Leslie-Ann,Flynn, Christopher J.,Buckley, Aoife M.,Ford, Alan,Lawrence, Simon E.,Maguire, Anita R.
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supporting information
p. 2277 - 2289
(2018/06/04)
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- INHIBITORS OF SPHINGOSINE KINASE 1
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The invention relates to compounds of Formula (I). Compounds of the present invention are inliibitors of sphingosine kinase 3, and are useful in the treatment of various disorders and conditions, such as inflammatory disorders
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Page/Page column 82
(2010/04/25)
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- M-AMIDINO PHENYL ANALOGS AS FACTOR Xa INHIBITORS
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The present application describes m-amidino phenyl analogs of formula (I), wherein D can be amidino and E can be phenyl, which are useful as inhibitors of factor Xa.
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- Vitronectin Receptor Antagonists
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Compounds of the formula (1) are disclosed which are vitronectin receptor antagonists and are useful in the treatment of osteoporosis:
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- Novel tropane-based irreversible ligands for the dopamine transporter
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3α-(Diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4′-azido-3′-iodophenyl)butyl]- 3α-[bis(4′-fluorophenyl)methoxy]tropane, [125I]1, that covalently attached to the 1-2 transmembrane spanning region of the dopamine transporter (DAT). This was in contrast to the 4-7 transmembrane spanning region labeled by a cocaine-based photoaffinity label, [125I] 2 (RTI 82). To characterize further these different binding domains, photoaffinity ligands that had the 4′-azido-3′-iodophenyl substituent extended from the same position on the tropane ring were desirable. Thus, identification of the optimal alkyl linker between this substituent and the tropane nitrogen in the benztropine series was investigated to ultimately prepare the identical N-substituted analogue of 2. In this pursuit, the N-[4-(4′-azido-3′-iodophenyl)propyl] analogue of 3α-[bis(4′-fluorophenyl)methoxy]tropane (9a) was synthesized as well as two isothiocyanate analogues that do not require photoactivation (10a,b) for irreversible binding. The synthesis of these target compounds was achieved using a modification of the strategy developed for 1. Evaluation of these compounds for displacing [3H]WIN 35 428 binding at DAT in rat caudate putamen revealed that the 4′-azido-3′-iodophenylbutyl substituent, found in 1, provided optimal binding affinity and was chosen to replace the N-CH3 group on 2. Both the 4′-azido-3′-iodophenyl- and the 4′-isothiocyanatophenylbutyl analogues of 2 (25 and 26, respectively) were synthesized. Both products bound to DAT with comparable potency (IC50 = 30 nM) to RTI 82 (2). In addition, compound 26 demonstrated wash-resistant displacement of [3H]WIN 35 428 in HEK 293 cells stably transfected with hDAT. These ligands will provide important tools for further characterizing the binding domains for tropane-based dopamine uptake inhibitors at the DAT.
- Zou,Kopajtic,Katz,Wirtz,Justice Jr.,Newman
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p. 4453 - 4461
(2007/10/03)
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- α-branched anilines, toluenes, and analogs thereof as factor Xa inhibitors
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The present application describes m-amidino phenyl analogs of formula I: wherein D can be amidino and E can be phenyl, which are useful as inhibitors of factor Xa.
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- Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides
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A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the CHRC/5 cell line.Among them the acridone derivatives were the most potent.A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain.Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone.On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy-9-oxo-N-phenyl>-4-acridinecarboxamide (84) has been selected for further development.
- Dodic, Nerina,Dumaitre, Bernard,Daugan, Alain,Pianetti, Pascal
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p. 2418 - 2426
(2007/10/02)
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