Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

VARIATIONS OF CLIMATE PARAMETERS AND THEIR IMPACT ON CABERNET SAUVIGNON AND SAUVIGNON BLANC PHENOLOGY IN CONDITIONS OF CENTRAL SERBIA

Research carried out in vineyard of King Peter I Karadjordjevic-Royal Winery at Oplenac-Topola municipality, on Sauvignon blanc and Cabernet sauvignon. Vineyard planted with Sauvignon blanc is geographically positioned at GPS coordinates N 44° 14' 4" and E 20° 41' 15" and Cabernet sauvignon is geographically positioned at GPS coordinates N 44° 14' 35" and E 20° 41' 22". Climat parameters (series from 1982-2011 year) included following parameters: mean monthly, vegetation (april-october) and annual temperature, active and effective temperature, precipitation distribution (annual and vegetation) and wind direction. Phenological observation included beginning and end of following phenophases: bleeding, budbreakt, shoot growing, flowering, berry development and ripening. The greatest variation Sauvignon blanc manifested in duration of grape ripening which is in 2010. lasted 46 days while in 2011. lasted 34 days. Cabernet sauvignon in 2011. had a lower number of days that have passed from bleeding to full maturity (209 days) compared to 2010., when it passed 217 days

YIELD AND QUALITY OF MÜLLER-THURGAU CLONE GM11 OF NIS GRAPE GROWING REGION

This paper presents the results of research variety Müller-Thurgau, clone 11 Gm, in order to determine quality indicators and the possibility of expansion in the vineyards of Southern Serbia. In terms of Nis grape growing region of the test are the most important agro technological and economic characteristics of the clone 11 Gm compared to the standard variety Müller-Thurgau. The test clone exhibited significant differences in yield and quality of grapes

Strukturni pokazatelji grozda i bobice klonova sorte Burgundac crni i njihov uticaj na hemijske karakteristike vina

Research were carried out in the vineyard of Experimental field “Radmilovac” at Faculty of Agriculture in Belgrade and included 3 Pinot Noir clones: R4, 115 and 667. For the purpose of research the structural indicators of grape and berries by are selected ten vines of each clone. Wine of the clones was prepared by procedure microvinification. Of all the tested clones, clone R4 had the best relationship structure of the bunch (bunch stem - 3.91%, and berries - 96.09%) and the highest concentration of total phenolic compounds. A strong correlation between the skin in the berries and the total phenolic compounds in all wine was founded.Istraživanja su obavljena na OD “Radmilovac” Poljoprivrednog fakulteta Univerziteta u Beogradu i obuhvatila su tri klona sorte Burgundac crni: R4, 115 i 667. Za ispitivanja strukturnih pokazatelja grozda i bobice odabrano je po 10 čokota svakog klona. Vino od klonova je spravljeno postupkom mikrovinifikacije. Od svih ispitivanih klonova, klon R4 je imao najpovoljniji odnos strukture grozda (ogrozdina - 3,91%; bobice - 96,09%), kao i najveću koncentraciju ukupnih fenolnih jedinjenja u vinu. Kod ispitivanih klonova je utvrđena jaka korelaciona zavisnost između udela pokožice u bobici i količine ukupnih fenolnih jedinjenja u vinu

QUALITY AND ANTIOXIDANT PROPERTIES OF PINOT NOIR GRAPEVINE VARIETY UNDER AGROECOLOGICAL CONDITIONS OF VRŠAC IN SERBIA

This research was focused on the antioxidant properties of grape variety Pinot Noir in the period from 2009-2011 in Vojvodina (location Vršac - 45o 8' 40,80" N; 21º 24' 7,97" E, 199 m a. s. l.). Pinot Noir variety was grown on Berlandieri x Riparia Kober 5BB rootstock, at a distance of 3 x 0.8 m. Mechanical properties of bunch and berry, quality and chemical properties of grapes were analyzed. The contents of monomeric and polymeric anthocyanins in grape berry skin were 11.68 and 94.67 mg of malvidin-3-glucoside/g. Correlative relationship between phenolic content and antioxidant activity of berry skin was r = 0.754, n = 18, p <0.0005. Quality and antioxidant activity of Pinot Noir grape variety was determined to be high under the agroecological conditions of Vršac in Serbia

INFLUENCE OF CULTIVAR CHARACTERISTICS OF MUSCAT TABLE GRAPEVINE CULTIVARS (VITIS VINIFERA L.) ON GRAPE BRANDY COMPOSITION AND QUALITY

The goal of this paper has been to examine influence of a cultivar on the quality of a grape brandy produced from the muscat table cultivars: Demir kapija, Early muscat, Radmilovacki muskat, Banatski muskat, Muscat Hamburg, Smederevski muskat, Italy and Afuz-ali. In terms of the content of methyl alcohol as well as of the total evaporable ingredients, grape brandies made of the fermented grape mash of investigated cultivars meet the prescribed standards stipulated by the Rulebook on the Quality of Alcoholic Beverages

A novel series of positive modulators of the AMPA receptor : discovery and structure based hit-to-lead studies

Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor

Structure based evolution of a novel series of positive modulators of the AMPA receptor

Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotyope with a promising overall profile, exemplified by

CNS Drug Design: Balancing Physicochemical Properties for Optimal Brain Exposure

The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major challenge for medicinal chemists working in CNS drug discovery. Analogous to the now widely accepted rule of 5 in the design of oral drugs, the physicochemical properties required for optimal brain exposure have been extensively studied in an attempt to similarly define the attributes of successful CNS drugs and drug candidates. This body of work is systematically reviewed here, with a particular emphasis on the interplay between the most critical physicochemical and pharmacokinetic parameters of CNS drugs as well as their impact on medicinal chemistry strategies toward molecules with optimal brain exposure. A summary of modern CNS pharmacokinetic concepts and methods is also provided

CNS Physicochemical Property Space Shaped by a Diverse Set of Molecules with Experimentally Determined Exposure in the Mouse Brain

Understanding the “limits and boundaries” of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward “traditional” aminergic targets and commonly described as small lipophilic amines. This miniperspective describes the statistical analysis of the calculated physicochemical properties for a diverse set of ligands for mostly “nontraditional” CNS targets and classified as either “brain penetrant” or “peripherally restricted” on the basis of the experimental mouse brain exposure. The results suggested that (a) the physicochemical property space conducive to brain exposure is larger than the one defined by the marketed CNS drugs and (b) the most critical brain exposure determinants are descriptors of the molecular size and hydrogen bond capacity. These findings led to a modified version of the CNS MPO scoring algorithm, termed CNS MPO.v2