- Efficient Diastereoselective Three-Component Synthesis of Pipecolic Amides
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An efficient Ugi-type three-component reaction (U-3CR) for the synthesis of pipecolic amides is reported. The U-3CR between electronically diverse isocyanides, carboxylic acids and 4-substituted Δ1-piperideines proceeds in a highly diastereoselective fashion. The Δ1-piperideines are obtained by NCS-mediated oxidation of the corresponding 4-substituted piperidines, which in turn are generated by an efficient two-step procedure involving the alkylation of 4-picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U-3CR, in combination with the convertible isocyanide 2-bromo-6-isocyanopyridine, in the synthesis of the anticoagulant argatroban.
- van der Heijden, Gydo,van Schaik, Timo B.,Mouarrawis, Valentinos,de Wit, Martin J. M.,Velde, Christophe M. L. Vande,Ruijter, Eelco,Orru, Romano V. A.
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supporting information
p. 5313 - 5325
(2019/06/10)
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- METHOD FOR PREPARING ARGATROBAN MONOHYDRATE
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A method is described for preparing argatroban monohydrate obtained from (2R,4R)-1-[NG-nitro-N2-(3-methyl-8-quinolinesulphonyl)-L-arginyl]-4-methyl-2- piperidine carboxylic acid by suitably treating crude argatroban. The method either comprises preparation of argatroban monohydrate in a continuous step or an intermediate step of isolating a purified argatroban. Also obtainable from argatroban monohydrate is anhydrous argatroban, shown to have new physico- chemical characteristics. The described argatroban synthesis and purification process hence enables three different forms of argatroban, not previously described, to be obtained, each with distinctive physico-chemical characteristics and in particular enables argatroban monohydrate to be obtained with high yield and with high purity, being therefore a product suitable for use as active principle in proprietary medicines.
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Page/Page column 20-21
(2009/11/29)
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- A short synthesis of argatroban: A potent selective thrombin inhibitor
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Argatroban was synthesized in seven steps from 4-methylpiperidine. The condensation of (±)-trans-benzyl 4-methylpipecolic acid ester with Nα-Boc-Nω-nitro-L-arginine led to two diastereomers that were separated. One of them is the precursor of argatroban.
- Cossy, Janine,Belotti, Damien
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p. 1989 - 1992
(2007/10/03)
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- METHOD FOR INHIBITING THROMBOSIS
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A method for inhibiting the formation of a thrombis is disclosed wherein an antithrombin composition is topically administered in the form of an emulsion which comprises, together with a solvent, a diluent, and an emulsifier, N. sup.2-arylsulfonyl-L-arginineamide represented by the general formula (I): STR1 wherein R 1 represents (2R,4R)-4-alkyl-2-carboxypiperidino group, R. sup.2 represents phenyl group or a condensed polycyclic compound residue as defined below, and said R 2 optionally has one or more substituents selected from lower alkyl group, lower alkoxy group or amino group substituted by lower alkyl group, said condensed polycyclic compound residue being a condensed polycyclic compound residue including a benzene ring, said benzene ring being bound to the sulfur atom of the sulfonyl group in the general formula (I) and said benzene ring being condensed with other ring which may be a heterocyclic ring, and said polycyclic compound residue having 7-14 carbon atoms in total, its hydrate and/or its salt.
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- Compositions containing argatroban analogs
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An antithrombin composition in the form of a lipid emulsion which comprises, together with unsaturated fatty acid and an emulsifier, N2-arylsulfonyl-L-arginineamide of the following general formula (I): wherein R1 represents (2R,4R)-4-alkyl-2-carboxypiperidino group, R2 represents phenyl group or condensed polycyclic compound residue as defined below, said R2 optionally having one or more substituents selected from lower alkyl group, lower alkoxy group, or amino group substituted by lower alkyl group, said condensed polycyclic compound residue being a condensed polycyclic compound residue including a benzene ring, said benzene ring being bound to the sulfur atom of the sulfonyl group in the general formula (I), and said benzene ring being condensed with other ring which may be a heterocyclic ring, and said polycyclic compound residue having 7 - 14 carbon atoms in total,its hydrate and/or its salt is provided.
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- Method for dissolving arginineamides and pharmaceutical compositions containing them
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A method for dissolving an arginineamide of the invention comprising dissolving N2 -arylsulfonyl-L-arginineamide having the general formula (I) STR1 wherein R1 represents a (2R, 4R)-4-alkyl-2-carboxypiperizino group and R2 represents a phenyl group or a condensed polycyclic compound residue which may be substituted with one or more substituents selected from lower alkyl groups, lower alkoxy groups and lower alkyl-substituted amino groups, said condensed polycyclic compound residue including a benzene ring which binds to sulfur atom of the sulfonyl group in the general formula (I) and is condensed with one or more other rings which may be heterocyclic and having 7 to 14 carbon atoms as the ring-constituent atoms; and/or its salt in a solvent of alcohol and water is disclosed herein. And, the pharmaceutical composition comprising N2 -arylsulfonyl-L-arginineamide having the general formula (I), an alcohol and water is disclosed herein.
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- N2 -Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof
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N2 -Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof have been found to be effective as pharmaceutical agents for the inhibition and suppression of thrombosis in mammals.
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