121912-29-6Relevant articles and documents
POLYMER BOUND 4-DIALKYLAMINO PYRIDINES: SYNTHESYS, CHARACTERIZATION AND CATALYTIC EFFICIENCY.
Guendouz, Farida,Jacquier, Robert,Verducci, Jean
, p. 7095 - 7108 (1988)
This work describes the synthesis of 4-carboxy-N-(4'-pyridino) piperidine (CPP), a functionalized analogue of the 4-dialkylamino pyridines, and its anchorage to various polymers by means of an amide bond.Some methods of titration of these supported CPP are pointed out.The efficiency of various supported CPP in the acetylation reaction of 1-methyl cyclohexanol are compared with DMAP as standard.The influence of various factors (polymer type, spacer, loading and temperature) are interpreted in relation to the nature of the microenvironment.An important decrease of the apparent pK of supported CPP as compared to DMAP (about 2 pK units) is assessed.
Synthesis and biological evaluation of direct thrombin inhibitors bearing 4-(piperidin-1-yl)pyridine at the P1 position with potent anticoagulant activity
De Candia, Modesto,Fiorella, Filomena,Lopopolo, Gianfranco,Carotti, Andrea,Romano, Maria Rosaria,Lograno, Marcello Diego,Martel, Sophie,Carrupt, Pierre-Alain,Belviso, Benny D.,Caliandro, Rocco,Altomare, Cosimo
, p. 8696 - 8711 (2013/12/04)
The design and synthesis of a new class of nonpeptide direct thrombin inhibitors, built on the structure of 1-(pyridin-4-yl)piperidine-4-carboxamide, are described. Starting from a strongly basic 1-amidinopiperidine derivative (6) showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa activity and artificial membrane permeability were considerably improved by optimizing the basic P1 and the X-substituted phenyl P4 binding moieties. Structure-activity relationship studies, usefully complemented with molecular modeling results, led us to identify compound 13b, which showed excellent fIIa inhibition (Ki = 6 nM), weak anti-Xa activity (K i = 5.64 μM), and remarkable selectivity over other serine proteases (e.g., trypsin). Compound 13b showed in vitro anticoagulant activity in the low micromolar range and significant membrane permeability. In mice (ex vivo), 13b demonstrated anticoagulant effects at 2 h after oral dosing (100 mg·kg-1), with a significant 43% prolongation of the activated partial thromboplastin time (aPTT), over controls (P 0.05).
Investigation of factor Xa inhibitors containing non-amidine S1 elements
Franciskovich, Jeffry B.,Masters, John J.,Tinsley, Jennifer M.,Craft, Trelia J.,Froelich, Larry L.,Gifford-Moore, Donetta S.,Klimkowski, Valentine J.,Smallwood, Jeffrey K.,Smith, Gerald F.,Smith, Tommy,Towner, Richard R.,Weir, Leonard C.,Wiley, Michael R.
, p. 4838 - 4841 (2007/10/03)
Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their
Benzamidine derivatives
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, (2008/06/13)
Benzamidine derivatives of the following formula, analogs thereof and pharmaceutically acceptable salts thereof are provided. These compounds have an effect of inhibiting activated blood-coagulation factor X, and they are useful as agents for preventing or treating various diseases caused by thrombi or emboli.
