1,721,016 research outputs found
3-Aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones: A New Class of Selective A1 Adenosine Receptor Antagonists.
No full textRadioligand binding assays using bovine cortical membrane preparations and biochemical in vitro studies revealed that various 3-aryl[1,2,4]triazino[4,3-α]benzimidazol-4(10H)-one (ATBI) derivatives, previously reported by us as ligands of the central benzodiazepine receptor (BzR) (Primofiore, G.; et al. J. Med. Chem. 2000, 43, 96-102), behaved as antagonists at the A1 adenosine receptor (A1AR). Alkylation of the nitrogen at position 10 of the triazinobenzimidazole nucleus conferred selectivity for the A1AR vs the BzR. The most potent ligand of the ATBI series (10-methyl-3-phenyl[1,2,4]triazino[4,3-α]benzimidazol-4(10H)-one 12) displayed a Ki value of 63 nM at the A1AR without binding appreciably to the adenosine A2A and A3 nor to the benzodiazepine receptor. Pharmacophore-based modeling studies in which 12 was compared against a set of well-established A1AR antagonists suggested that three hydrogen bonding sites (HB1 acceptor, HB2 and HB3 donors) and three lipophilic pockets (L1, L2, and L3) might be available to antagonists within the A1AR binding cleft. According to the proposed pharmacophore scheme, the lead compound 12 engages interactions with the HB2 site (via the N2 nitrogen) as well as with the L2 and L3 sites (through the pendant and the fused benzene rings). The results of these studies prompted the replacement of the methyl with more lipophilic groups at the 10-position (to fill the putative L1 lipophilic pocket) as a strategy to improve A1AR affinity. Among the new compounds synthesized and tested, the 3,10-diphenyl[1,2,4]-triazino[4,3-α]benzimidazol-4(10H)-one (23) was characterized by a Ki value of 18 nM which represents a 3.5-fold gain of A1AR affinity compared with the lead 12. A rhodopsin-based model of the bovine adenosine A1AR was built to highlight the binding mode of 23 and two well-known A1AR antagonists (III and VII) and to guide future lead optimization projects. In our docking simulations, 23 receives a hydrogen bond (via the N1 nitrogen) from the side chain of Asn247 (corresponding to the HB1 and HB2 sites) and fills the L1, L2, and L3 lipophilic pockets with the 10-phenyl, 3-phenyl, and fused benzene rings, respectively
Synthesis and anti-infiammatory properties of 2-aminobenzimidazole derivatives
No full textSeveral 1-alkyl or 1-aralkyl substituted 2-aminobenzimidazole derivatives, bearing an acetic or acetohydroxamic group at 3-position, were synthesized. Some of these products were tested for their antiinflammatory and analgesic properties. These compounds exhibited an antiinfammatory activity lower than that of reference drug Indomethacin. Compound 2e showed the highest efficacy, but not in a dose-related manner. Only compounds 3a and 16 exhibited some analgesic activity, but at a very high dose
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Specific inhibition of benzodiazepine receptor binding by some 6H-indolo[2,3-b] [1,8]naphthyridines and 11H-indolo [3,2-c] [1,8]naphthyridines.
No full textThe reactivity of some 6H-indolo[2,3-b] [1,8]naphthyridines (II) and 11H-indolo[3,2-c] [1,8]naphthyridines (III) in displacing specific [3H] diazepam binding from bovine brain membranes was examined. All the indolonaphthyridines tested are active and show a higher activity than indole and tryptophan. The inhibition is due to direct interaction with the benzodiazepine binding sites. Some structure-activity relationships are discussed
Benzodiazepine receptor affinity and interaction of new indole derivatives.
No full textRecently, several derivatives, in which tryptamine, tyramine, and dopamine moieties are linked to the indole nucleus by an oxalyl bridge, were tested for their affinity and efficacy at the benzodiazepine receptor (BzR). To better define the structure-activity relationships (SAR) several phenylethylamine derivatives were also synthesized and tested for their affinity at the BzR. Compounds bearing a protic group on the aromatic system of the side chain show a pharmacological profile of inverse agonist, while the products lacking this group behave as partial agonist. We now report the affinity data at the BzR of new compounds in which the distance between the phenyl ring and the amide group of the side chain has been changed. The benzylamine derivatives showed a good affinity at the BzR, generally higher than that of the phenylethylamine dervatives. In this series the pharmacological profile showed to be opposite to that of the corresponding phenylethylamine derivatives, since the compounds substituted with protic groups on the phenyl ring behaved as partial agonists. Moreover, a probable interaction with the receptor site is hypothesized
Synthesis of novel 1-aryl[1]benzoxepino[5,4-c]pyrazole and [1]benzoxepino[5,4-d]pyrimidine derivatives
No full textSeveral 1-aryl[1]benzoxepinopyrazoles were prepared by reaction of 4- hydroxymethylene[1]benzoxepinones with appropriate phenylhydrazine hydrochlorides. The direct condensation of hydroxymethylenebenzoxepinones with variously substituted amidines failed to give benzoxepinopyrimidines. These compounds were obtained via the key intermediates morpholine enaminobenzoxepinones
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Synthesis of new 6H-indolo[2,3-b] [1,8]naphthyridines and their specific inhibition of benzodiazepine receptor.
No full textSome 3-amino- and 3-hydroxy-8-halosubstituted 6H-indolo[2,3-b] [1,8]naphthyridines were synthesized and tested for their affinity for the benzodiazepine receptor in bovine cortical membranes. All prepared compounds were more active than the corresponding 8-unsubstituted derivatives. Moreover, among these compounds the 8-chloroindolonaphthyridines were clearly the most potent
- …
