Biomedical subjects

Xavier de Leval

Publications and source records attributed to Xavier de Leval.

24 records · Page 2Linked to original sources

PubMed2002

Spectral and crystallographic study of pyridinic analogues of nimesulide: determination of the active form of methanesulfonamides as COX-2 selective inhibitors.

Compound 7, N-(3-phenoxy-4-pyridinyl)trifluoromethanesulfonamide, showed in vitro (whole blood assay) a strong inhibitory activity on the two cyclooxygenase (COX) enzymes (IC(50)(COX-1) = 2.2 microM and IC(50)(COX-2) = 0.4 microM), being more active but less COX-2-selective than nimesulide. Physicochemical studies and structural analyses indicated that the anionic sulfonamidate species seemed to be the active form of methanesulfonamides, which optimally interacted with the COX enzymes' active sites.

Aminopyridines↗

PubMed2002

N-(3-Phenoxy-4-pyridinio)methanesulfonamidate.

The title compound, C(12)H(12)N(2)O(3)S, is a strict pyridine analogue of nimesulide, a selective inhibitor of cyclooxygenase-2. The structure is characterized by a pyridinium ring with a deprotonated sulfonamide group. An intermolecular charge-assisted hydrogen bond between these two groups is observed within the crystal packing, linking the molecules into an infinite chain running along the b-axis direction.

Aminopyridines↗

PubMed2002

Thromboxane A2 inhibition: therapeutic potential in bronchial asthma.

Bronchial asthma is a disease defined by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. In addition to histamine and acetylcholine, recent studies have emphasized the role of arachidonic acid metabolites (leukotrienes, prostaglandins and thromboxane A(2)) in the pathogenesis of asthma. Among these mediators, thromboxane A(2) (TXA(2)) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A(2) is believed to be involved not only in late asthmatic responses but also in bronchial hyperresponsiveness, a typical feature of asthma. Strategies for inhibition of TXA(2) include TXA(2) receptor antagonism and thromboxane synthase inhibition. Results of double-blind, placebo-controlled clinical trials have proven the efficacies of the thromboxane receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in the treatment of patients with asthma. Seratrodast and ozagrel are available in Japan for the treatment of asthma. Ramatroban, another thromboxane receptor antagonist, is currently under phase III clinical evaluation in Europe and Japan for the treatment of asthma. The pharmacological profiles of the thromboxane modulators may be improved by combination with leukotriene D(4) receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D(4) and thromboxane A(2 )receptors, may have potent therapeutic effects in the treatment of bronchial asthma. Large scale clinical trials are necessary to further define the role of thromboxane modulators in the treatment of patients with asthma.

Anti-Asthmatic Agents↗

PubMed2002

Therapeutic potential of thromboxane inhibitors in asthma.

This paper reviews the role of thromboxane A(2) (TXA(2)) in the pathogenesis of pulmonary allergies, particularly asthma. The potential of TXA(2) modifiers in the prevention and/or treatment of pulmonary allergies is also discussed. Bronchial asthma is characterised by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. Several studies have elucidated the role of arachidonic acid metabolites (leukotrienes, prostaglandins and TXA(2)) in the pathogenesis of asthma. Among those mediators, TXA(2) has attracted attention due to its strong physiological activity. Indeed, TXA(2) demonstrates not only potent bronchoconstrictive activity but is also believed to be involved both in late asthmatic responses and in bronchial hyperresponsiveness, a typical feature of this disease. Several thromboxane receptor antagonists (TXRAs) and thromboxane synthase inhibitors (TXSIs) have been studied with the aim of reducing or preventing asthma. As double-blind, placebo-controlled clinical trials have proven the efficiency of some TXA(2) modifiers in treating asthma, the TP receptor antagonist seratrodast (AA-2414) and the thromboxane synthase inhibitor ozagrel hydrochloride (OKY-046) are now available as anti-asthmatic agents in Japan. Moreover, seratrodast and ramatroban (BAY-U-3405), another thromboxane receptor antagonist, are currently under Phase III clinical evaluation in the US for the treatment of asthma.

Asthma↗

PubMed2002

New trends in dual 5-LOX/COX inhibition.

Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic pathways. The interest of developing such compounds is supported by a large number of pharmacological studies. Compared to COX or LOX pathways single inhibitors, dual inhibitors present at least two major advantages. First, dual inhibitors, by acting on the two major arachidonic acid metabolic pathways, possess a wide range of anti-inflammatory activity. Secondly, dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of COX inhibitors. The mechanism of their gastric-sparing properties is not completely understood, although it has been demonstrated that leukotrienes significantly contribute to the gastric epithelial injury. Finally, both COX and LOX derivatives (prostanoids and leukotrienes, respectively) are involved in other diseases than inflammation such as cancer proliferation where the use of dual inhibitors could be an interesting approach.

Animals↗

PubMed2002

Recent advances in antiplatelet agents.

Platelet aggregation plays a key role in the pathogenesis of thromboembolic diseases such as myocardial infarction, stroke, unstable angina and peripheral artery disease. Until recently, aspirin was the only antiplatelet agent available to prevent or treat these events. Over the past several years, there has been a substantial expansion in the antiplatelet armamentarium as well as in the understanding of the clinical importance of antiplatelet therapy in limiting the complications of thrombosis. Aspirin was one of the first agents to be adopted and it remains as the standard therapy with the higher amount of available clinical information. Following aspirin, ADP receptor antagonists like ticlopidine and clopidogrel as well as phosphodiesterase inhibitors dipyridamole and cilostazol have been introduced. Glycoprotein (GP) IIb/IIIa receptor antagonists like eptifibatide, tirofiban and abciximab are the newer antiplatelet agents which act at the end of the common pathway of platelet aggregation. Although results of clinical studies with the first oral GPIIb/IIIa antagonists were disappointing, agents of the new generation might expand the potential application of GPIIb/IIIa targeted therapy. This review will highlight recent advances in the development of aspirin, phosphodiesterase inhibitors, ADP receptor antagonists and the platelet glycoprotein IIb/IIIa inhibitors. The emphasis of this paper has been placed on the chemical aspects of these agents.

Animals↗