The synthesis and characterization of BMS-204352 (MaxiPost™) and related 3-fluorooxindoles as openers of maxi-K potassium channels

Hewawasam, Piyasena; Gribkoff, Valentin K.; Pendri, Yadagiri; Dworetzky, Steven I.; Meanwell, Nicholas A.; Martı́nez, E.; Boissard, Christopher G.; Post-Munson, Debra J.; Trojnacki, Joanne T.; Yeleswaram, Krishnaswamy; Pajor, Lorraine; Knipe, Jay O.; Gao, Qi; Perrone, Robert; Starrett, John E.

doi:10.1016/s0960-894x(02)00101-4

Cited by 172 publications

(111 citation statements)

References 8 publications

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“…But, conversion to the corresponding acids has not been demonstrated in the literature, probably due to instability of a-fluoroaldehydes.12 Thus, the present methodology is expected to be useful to provide a variety of optically active fluorine-containing compounds. 7. enantioselective manner (up to 99% ee).…”

Section: Fluorination Of N-boc Oxindoles26mentioning

confidence: 90%

“…Otherwise, the reaction did not proceed to completion. The catalyst amount could be reduced to 5 mol % without problem, although a drop in the selectivity was finally observed when 2.5 mol % of 32b was used (entries [6][7][8]. It is interesting that no formation of a difluorinated compound and no racemization of the monofluorinated product were observed under these reaction conditions.…”

Section: Fluorination Of N-boc Oxindoles26mentioning

confidence: 99%

“…4 The efficacy of the fluorine-substitution at chiral sp3 carbon centers has been demonstrated by the development of medicinally important compounds 1-4 (Chart 2). 5,6,7,8 In addition to the development of chiral electrophilic fluorinating reagents,9 catalytic enantioselective fluorination reactions have been attracting increasing attention.4 Before our work, there had been only two reported examples using a chiral Ti complex and a chiral phase transfer catalyst, where pioneering, but limited success was achieved in respect to both substrate-generality and enantioselectivity.1° In the past fivc years, great pi ogress has been made in this field with the development of novel metal catalysts" and organocatalysts,12 and not only active methine compounds but also primary …”

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confidence: 99%

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Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

Hamashima

Sodeoka

2007

J. Syn. Org. Chem., Jpn.

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: Two catalytic systems were developed for efficient catalytic enantioselective a-fluorination reactions of carbonyl compounds. Cationic Pd complexes were found to be effective for fluorination of active methine and methylene compounds, and various substrates including B-ketoesters, B-ketophosphonates, and other related compounds were fluorinated in environmentally friendly alcoholic solvents (up to 99% ee). This system was also applicable to the reaction of 3-substituted oxindole derivatives. In addition, we succeeded in developing a novel trinary system NiCl2-binap/R3SiOTf/2,6-lutidine for the reaction of less acidic a-aryl acetic acid derivatives, and the desired reaction proceeded smoothly to give the corresponding monofluorinated compounds in a highly enantioselective manner (up to 88% ee). Our fluorination reactions are versatile, being applicable to stereoselective synthesis of chiral fluorinated analogues of fundamental building blocks and catalytic asymmetric synthesis of BMS204352, a promising agent for the treatment of stroke.

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Section: Fluorination Of N-boc Oxindoles26mentioning

confidence: 90%

Section: Fluorination Of N-boc Oxindoles26mentioning

confidence: 99%

mentioning

confidence: 99%

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Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

Hamashima

Sodeoka

2007

J. Syn. Org. Chem., Jpn.

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“…Introduction of fluorinated amino acids such as 6 into peptides often changes the original conformation and biological properties [12]. Moreover, clinical application of BMS-204532 (Maxipost, 7) as a potassium channel opener [13] further encouraged us to pursue the synthesis the fluorinated tryptophan analog 6 as a potential building block for drug development.…”

Section: Introductionmentioning

confidence: 99%

Synthetic studies of 3-(3-fluorooxindol-3-yl)-l-alanine

Fujiwara

Yin

Jin

et al. 2008

Journal of Fluorine Chemistry

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Oxidative fluorination of several protected tryptophans 8b-g with Selectfluor™ proceeded smoothly in aqueous media to give a diastereomeric mixture of the corresponding 3-fluorooxindoles 9b-g. Attempted deprotection of the 3-fluorooxindoles 9b-g under various conditions did not afford 3-(3-fluorooxindol-3-yl)-L-alanine (6). Reaction of the suitably protected tryptophan derivative 16 with Selectfluor™ produced the fluorinated product 17. Simultaneous cleavage of all protective groups of 17 under acidic conditions successfully gave the target compound 6 in excellent yield.

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“…3C) is a chiral candidate drug for post stroke neural protection [31], and blocks the calcium-dependent potassium current [32]. Given its possible interaction with other K + channels [33,34,35,36], we explored its potential as an antiepileptic agent by increasing the IK DR conductance (from 0.001 pS/μm 2 to 0.002 pS/ μm 2 ). Moreover, we also tested the putative combined effect of lamotrigine and flindokalner by simultaneously changing both sets of simulation parameters.…”

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confidence: 99%

Computational Models of Neuronal Biophysics and the Characterization of Potential Neuropharmacological Targets

Ferrante¹,

Blackwell²,

Migliore³

et al. 2008

CMC

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The identification and characterization of potential pharmacological targets in neurology and psychiatry is a fundamental problem at the intersection between medicinal chemistry and the neurosciences. Exciting new techniques in proteomics and genomics have fostered rapid progress, opening numerous questions as to the functional consequences of ligand binding at the systems level. Psycho- and neuro-active drugs typically work in nerve cells by affecting one or more aspects of electrophysiological activity. Thus, an integrated understanding of neuropharmacological agents requires bridging the gap between their molecular mechanisms and the biophysical determinants of neuronal function. Computational neuroscience and bioinformatics can play a major role in this functional connection. Robust quantitative models exist describing all major active membrane properties under endogenous and exogenous chemical control. These include voltage-dependent ionic channels (sodium, potassium, calcium, etc.), synaptic receptor channels (e.g. glutamatergic, GABAergic, cholinergic), and G protein coupled signaling pathways (protein kinases, phosphatases, and other enzymatic cascades). This brief review of neuromolecular medicine from the computational perspective provides compelling examples of how simulations can elucidate, explain, and predict the effect of chemical agonists, antagonists, and modulators in the nervous system.

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The synthesis and characterization of BMS-204352 (MaxiPost™) and related 3-fluorooxindoles as openers of maxi-K potassium channels

Cited by 172 publications

References 8 publications

Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

Catalytic Enantioselective .ALPHA.-Fluorination of Carbonyl Compounds Using Chiral Transition Metal Complexes

Synthetic studies of 3-(3-fluorooxindol-3-yl)-l-alanine

Computational Models of Neuronal Biophysics and the Characterization of Potential Neuropharmacological Targets

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