Showing papers by "Pascal De Tullio published in 2000"
TL;DR: Observations that COX-1, involved in several homeostatic processes, played a housekeeping role while COx-2 expression was associated with inflammation and other pathologies such as cancer proliferation have led to the development ofCOX-2 selective inhibitors in order to reduce the classical side-effects, of which gastric irritation is the most common, associated with the use of conventional NSAIDs.
Abstract: Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances that are involved in several physiological processes but also in pathological conditions such as inflammation. Since ten years now, it is well known that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional nonsteroidal antiinflammatory drugs (NSAIDs). Observations that COX-1, involved in several homeostatic processes, played a housekeeping role while COX-2 expression was associated with inflammation and other pathologies such as cancer proliferation have led to the development of COX-2 selective inhibitors in order to reduce the classical side-effects, of which gastric irritation is the most common, associated with the use of conventional NSAIDs.
49 citations
TL;DR: The main biological role of CCK, the therapeutic potential ofCCK-A and CCK-B receptor agonists and antagonists and the common compounds from the different families of ligands are reviewed.
Abstract: Cholecystokinin (CCK) is an important ‘brain-gut’ hormone located both in the gastrointestinal (GI) system and in the CNS. At least two different G-coupled high affinity receptors have been identified: the CCK-A and the CCK-B receptors. Although the complex biological role of CCK is, as yet, not fully understood, its connection with many different physiological processes both at the GI level and at the CNS level is now well established. There is much potential for therapeutic use of CCK receptor ligands, however, clear investigations have yet to be completed. Several chemical families have been investigated over the last 20 years to find potent, subtype selective and stable CCK receptor agonists and antagonists. The main goal was to discover new therapeutic drugs acting on GI and/or on CNS diseases and also, to obtain powerful pharmacological tools that could permit a better understanding of the biological role of CCK. Despite promising results from investigations into medicinal chemistry of CCK receptor ...
46 citations
TL;DR: It is suggested that 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1, 1-dioxides may be considered as new examples of K(ATP) channel openers expressing a pharmacological profile similar to that of pinacidil and diazoxide.
Abstract: A series of 3-alkylamino-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to diazoxide and pinacidil were synthesized and tested as possible KATP channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. In contrast to previously described 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides, most of the new compounds were found to be poorly active on B-cells but exhibited clear vasorelaxant properties. 3-(3,3-Dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (4d) and 7-chloro-3-(3,3-dimethyl-2-butylamino)-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxide (5d), two compounds bearing the alkyl side chain of pinacidil, were found to be the most active representatives of their respective series on rat aorta rings. 3-Cycloalkylalkylamino- and 3-aralkylamino-7-chloro-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides also expressed myorelaxant activity on electrically stimulated guinea pig ileum and ...
43 citations
Patent•
28 Nov 2000TL;DR: In this paper, a compound of formula (I) is defined, where X represents a fluorine, bromine or iodine atom or a methyl group; R 1 and R 2 represent each a hydrogen atom or an alkyl group; their isomers when they exist, as well as their additive salts to a pharmaceutically acceptable acid.
Abstract: The invention concerns a compound of formula (I) wherein: X represents a fluorine, bromine or iodine atom or a methyl group; R1 and R2, identical or different, represent each a hydrogen atom or an alkyl group; their isomers when they exist, as well as their additive salts to a pharmaceutically acceptable acid.
17 citations
TL;DR: 3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides with nitro, amino or acetylamino groups in the 7-position have been synthesized in an attempt to discover new tissue-selective KATP-channel openers.
Abstract: 3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides with nitro, amino or acetylamino groups in the 7-position have been synthesized in an attempt to discover new tissue-selective KATP-channel openers.
The compounds were tested as putative pancreatic β-cells KATP-channel openers by measuring their inhibitory activity on the insulin releasing process. The influence of the substituent in the 7-position on the acidic character (pKa) and on biological activity is discussed.
The nitrobenzene derivatives were biologically active, but less so than the un-derivatized parent pyridothiadiazine dioxides.
3 citations