Abstract:Die aus den Cyanphenylalaninen (II) mit den N‐Arylsulfonylglycinen (I) zugänglichen Peptide (III) lassen sichgmit p‐Nitrophenol (IV)/ DCC in die Nitrophenylester (V) überführen, die mit den Aminen (VI) die Peptidamide (VII) ergeben.
“…For this purpose glycine was acylated with 4-cyanobenzenesulfonyl chloride, and the resulting N α -(4-cyanobenzenesulfonyl)glycine was then converted to the N -hydroxysuccinimide ester which in turn was used to acylate d , l -4- and d , l -3-cyanophenylalanine as well as the related ethyl esters. The two cyanophenylalanine derivatives were prepared following essentially known procedures, whereas d , l -4- and d , l -3-cyanophenylalanine ethyl esters were obtained by catalytic phase-transfer alkylation of the dibenzophenone imine of glycine ethyl ester with 3- and 4-cyanobenzyl bromide according to the method described by O‘Donnell and Bennett, followed by mild acid hydrolysis of the Schiff base. 1 Syntheses of Bis-Substituted Derivatives of Racemic N α -Benzenesulfonyl-glycyl-phenylalanine Ethyl Esters a a (a) TEA, DMF; (b) H 2 S, TEA, pyridine; (c) CH 3 I, acetone; (d) NH 4 OAc, MeOH, Δ; HPLC. …”
A series of derivatives of rac-benzenesulfonyl-glycyl-phenylalanine or its ethyl ester with a combination of thioamido/amidino or amidino/amidino substituents in the benzene rings was synthesized as potential inhibitors of factor Xa (fXa). Among these, the racemic 4'-amidinobenzenesulfonyl-glycyl-4-amidinophenylalanine ethyl ester was found to exhibit the highest affinity for fXa despite the unfavored location of the amidino substituent in the para position. X-ray structural analysis of the trypsin complex with this bis-benzamidine compound revealed a retro-binding mode if compared to those of similar compounds, so far analyzed in complexes with trypsin or fXa. This noncanonical binding mode as well as its slow plasma clearance rates in rats, if compared to those of other benzamidine derivatives, suggests this compound as an interesting new lead structure for the design of fXa inhibitors.
“…For this purpose glycine was acylated with 4-cyanobenzenesulfonyl chloride, and the resulting N α -(4-cyanobenzenesulfonyl)glycine was then converted to the N -hydroxysuccinimide ester which in turn was used to acylate d , l -4- and d , l -3-cyanophenylalanine as well as the related ethyl esters. The two cyanophenylalanine derivatives were prepared following essentially known procedures, whereas d , l -4- and d , l -3-cyanophenylalanine ethyl esters were obtained by catalytic phase-transfer alkylation of the dibenzophenone imine of glycine ethyl ester with 3- and 4-cyanobenzyl bromide according to the method described by O‘Donnell and Bennett, followed by mild acid hydrolysis of the Schiff base. 1 Syntheses of Bis-Substituted Derivatives of Racemic N α -Benzenesulfonyl-glycyl-phenylalanine Ethyl Esters a a (a) TEA, DMF; (b) H 2 S, TEA, pyridine; (c) CH 3 I, acetone; (d) NH 4 OAc, MeOH, Δ; HPLC. …”
A series of derivatives of rac-benzenesulfonyl-glycyl-phenylalanine or its ethyl ester with a combination of thioamido/amidino or amidino/amidino substituents in the benzene rings was synthesized as potential inhibitors of factor Xa (fXa). Among these, the racemic 4'-amidinobenzenesulfonyl-glycyl-4-amidinophenylalanine ethyl ester was found to exhibit the highest affinity for fXa despite the unfavored location of the amidino substituent in the para position. X-ray structural analysis of the trypsin complex with this bis-benzamidine compound revealed a retro-binding mode if compared to those of similar compounds, so far analyzed in complexes with trypsin or fXa. This noncanonical binding mode as well as its slow plasma clearance rates in rats, if compared to those of other benzamidine derivatives, suggests this compound as an interesting new lead structure for the design of fXa inhibitors.
The effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III, fibrinogen and platelets was studied in a rat model of disseminated intravascular coagulation (DIC) induced by thrombin infusion. Antithrombin III is consumed during thrombin infusion to a limited degree. Simultaneous administration of exogenous thrombin inhibitors ameliorates the consumption of fibrinogen and platelets. At high thrombin doses, tolerated only during additional administration of thrombin inhibitors, heparin leads to increased consumption of antithrombin III, whereas hirudin and the synthetic inhibitor do not. In every case, the thrombin effect on fibrinogen and platelets is inhibited.
“…We used allyl benzamidine-4-carboxylate (7), synthesised from 4-cyanobenzoic acid by the thioimidate route. [19] Once the allyl ester was cleaved, the carboxylic function could be straightforwardly elaborated to give rise to a wide variety of compounds. The cleavage could be performed under very mild, neutral conditions [20] , with Nmethylmorpholine/acetic acid and Pd(PPh 3 ) 4 in DCM.…”
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