scholarly journals Solution Phase Synthesis of Chemical Libraries for Lead Discovery

1996 ◽  
Vol 1 (4) ◽  
pp. 179-186 ◽  
Author(s):  
Cheryl D. Garr ◽  
John R. Peterson ◽  
Lauri Schultz ◽  
Amy R. Oliver ◽  
Ted L. Underiner ◽  
...  

By integrating advanced computational design and synthesis, a series of structurally diverse reaction products based on three core scaffolds were prepared by a propietary high throughput synthesis method. Incorporation of auto-mated work stations and sample handling techniques allowed for the production of more than 20,000 compounds in a relatively short time. A method to efficiently obtain quantitative and qualitative analytical data on these compounds was developed. Structural comparison of the individual members of this library with a database of clinical drug candidates revealed a significant degree of similarity based on Tanimoto coefficients.

Author(s):  
Наталія Юріївна Бондар

The article deals with the influence of the archetype of the way on the formation of the personality in the novel Paper Towns by John Green. The purpose of this article is to determine the originality of the image of an American teenager and to identify the influence of the archetype of the way on the formation of the personality, as well as to consider the archetype of the way as a real path of the character in the novel Paper Towns by John Green, taking into account the individual author’s interpretation. This object of research has been chosen because through it one can comprehend the specifics of the psychology of a teenager and define the artistic features that distinguish the author’s stylistics and worldview. The comprehensive research methodology has been used in the work: the synthesis of the comparative historical method, holistic analysis, elements of mythopoetic and hermeneutic methods. In the novel Paper Towns by John Green mythopoetic consciousness presupposes ontological ambivalent intentions in the archetype of the child / teenager (good and evil children). The metaphorical extension of the archetype of the child / teenager has been revealed in this article. All the images of teenagers are given in the development, on the way to growing up. The originality of the archetype of the way here lies in the fact that it merges with the concepts of Space and Chaos, confirming the idea of the unity of mankind. The metaphors themselves are also peculiar, associated with the archetype of the way: inanimate strings, gradually turning into living blades of grass, intertwined with roots with all that exists. During the search for Margo, Quentin grows up significantly, becomes more tolerant to their friends, and he learns to take responsibility for him. The image of Margo is the image of a rebel against any lack of freedom that it is inevitable in the “golden cage”. It is also revealed how Quentin is influenced by the new world opened during his trips, and his personal environment: for example, Radar opens his eyes to the fact that he does not need to demand too much from others. Both Margo is changed (from a “paper” girl – to a real one) and Ben and Radar are changed (false interests go into the background; everyone learns to expose himself to risks and troubles for the sake of friendship and human salvation). Ben and Radar are also shown in the development, in a short time they learn to understand each other and distinguish false values from true ones. These changes occur with all the teenagers, regardless of their skin color and nationality, and such an interpretation of the insignificance of formal differences is also a new word of the author.


1983 ◽  
Vol 73 (3) ◽  
pp. 135-149 ◽  
Author(s):  
F. Debon ◽  
P. Le Fort

ABSTRACTA classification is proposed, based mainly on major element analytical data plotted in a coherent set of three simple chemical-mineralogical diagrams. The procedure follows two complementary steps at two different levels. The first is concerned with the individual sample: the sample is given a name (e.g. granite, adamellite, granodiorite) and its chemical and mineralogical characteristics are determined. The second one is more important: it aims at defining the type of magmatic association (or series) to which the studied sample or group of samples belongs. Three main types of association are distinguished: cafemic (from source-material mainly or completely mantle-derived), aluminous (mainly or completely derived by anatexis of continental crust), and alumino-cafemic (intermediate between the other two types). Subtypes are then distinguished among the cafemic and alumino-cafemic associations: calc-alkaline (or granodioritic), subalkaline (or monzonitic), alkaline (and peralkaline), tholeiitic (or gabbroic-trondhjemitic), etc. In the same way, numerous subtypes and variants are also distinguished among the aluminous associations using a set of complementary criteria such as quartz content, colour index, alkali ratio, quartz–alkalies relationships and alumina index.Although involving a new approach using partly new criteria, this classification is consistent with most of the divisions used in previous typologies. The method may also be used in the classification of the volcanic equivalents of common plutonic rocks.


2021 ◽  
Vol 11 (6) ◽  
pp. 16-24
Author(s):  
Hemant U Chikhale

Humans are now in a bioinformatics and chemo informatics century, where we can foresee data across domains like as healthcare, the environmental, technology, and public health. The use of information sharing in silico methodologies has impacted sickness administration by predicting the absorption, distribution, metabolism, excretion, and toxicity (ADMET) patterns of synthetic compounds and efficient and environmentally succeeding pharmaceuticals upfront. The purpose of lead discovery and design is to create the appearance of novel drug candidates that can attach to a specific illness cause. The lead investigative process starts with the recognition of the lead structure, which is followed by the synthesis of its analogs and their estimation in order to produce a candidate for lead improvement. The finding of the proper lead exact is the fundamental and primary worked in the traditional lead discovery progression, and the use of computer (in silico) approaches is widely used in lead innovation. A medicinal chemist's passion for building lead structure is piqued by biomolecules, which are often made up of DNA, RNA, and proteins (such as enzymes, receptors, transporters, and ion channels). The underlying principle of such nuts and bolts is noteworthy to be acquainted with their pharmacological implication to the disease under examination. The motive of this review piece of writing is to emphasize several of the in silico methods that are used in lead discovery and to express the applications of these computational methods.


2019 ◽  
pp. 128-148 ◽  
Author(s):  
Miriam Noël Haidle

Cumulative culture is widely seen as a uniquely human characteristic involving distinct cognitive and behavioral performances. In searching for its origin, different factors have been suggested as crucial, based on comparative studies, and dates proposed as to when cumulative culture may have emerged in human evolution. This chapter reviews possible factors, suggesting that several are necessary, not only in the social sphere but also in the individual and environmental spheres. These interdependent factors have developed in three developmental dimensions (evolutionary-biological, ontogenetic-individual, and historical-social) in interaction with the specific environment. The interplay of basic factors and developmental dimensions shows a slow and gradual development of cumulative culture from its basis to simple and advanced donated culture. The onset of cumulative culture is concluded not to have been a single-trait event that occurred in a relatively short time but rather, the result of multifactorial and gradual processes that unfolded over millions of years.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2261 ◽  
Author(s):  
Kenneth Smith ◽  
Devin G. Peterson

Differences in the aroma profiles of extruded maize puffs made from refined grain and whole grain flour were investigated. Gas chromatography/mass spectrometry/olfactometry (GC/MS/O) analysis reported 13 aroma compounds with a flavor dilution (FD) value ≥16. Quantitative analysis identified eight compounds as statistically different, of which seven compounds were higher in concentration in the whole grain sample. Sensory recombination and descriptive analysis further supported the analytical data, with higher mean aroma intensities for cooked, corn chip, roasted, and toasted attributes for the whole grain sample. Generally, the compounds responsible for perceived differences in whole grain maize extruded puffs were associated with increased levels of Maillard reaction products, such as 2-ethyl-3,5-dimethylpyrazine and 2-acetyl-2-thiazoline.


Chemistry ◽  
2020 ◽  
Vol 2 (4) ◽  
pp. 837-848
Author(s):  
Csilla Sepsey Für ◽  
Hedvig Bölcskei

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and synthesis of a new compound library, important points are in focus nowadays: Lipinski’s rule of five (RO5); the high Fsp3 character; the use of bioisosteric heterocycles instead of aromatic rings. With said aim in mind, we have synthesized a small compound library of new spiro[cycloalkane-pyridazinones] with 36 members. The compounds with this new scaffold may be useful in various drug discovery projects.


2019 ◽  
Vol 116 (26) ◽  
pp. 12793-12797 ◽  
Author(s):  
Yoobin Park ◽  
Geoff MacDonald

Do people have a “type” when it comes to their romantic partners’ personalities? In the present research, we used data from a 9-y longitudinal study in Germany and examined the similarity between an individual’s ex- and current partners using the partners’ self-reported personality profiles. Based on the social accuracy model, our analyses distinguished similarity between partners that was attributable to similarity to an average person (normative similarity) and resemblance to the target participant himself/herself (self-partner similarity) to more precisely examine similarity from partner to partner (distinctive similarity). The results revealed a significant degree of distinctive partner similarity, suggesting that there may indeed be a unique type of person each individual ends up with. We also found that distinctive partner similarity was weaker for people high in extraversion or openness to experience, suggesting that these individuals may be less likely to be in a relationship with someone similar to their ex-partner (although the individual difference effects were not mirrored in an alternative analytic approach). These findings provide evidence for stability in distinctive partner personality and have important implications for predicting future partnering behaviors and actions in romantic relationships.


2019 ◽  
Vol 13 ◽  
pp. 117822181882297 ◽  
Author(s):  
Megan E Patrick ◽  
Yvonne M Terry-McElrath

High-intensity drinking (HID; ie, having 10+ drinks in a row) is a recognized public health concern due to the individual and public risks (eg, alcohol-related injuries, alcohol poisoning, memory loss, sexual risk) associated with consumption of a large quantity of alcohol over a relatively short time period. Using nationally representative samples of US 8th, 10th, and 12th grade students, and follow-up of subsamples of 12th graders, we present overall and sex-specific prevalence estimates of past 2-week HID from 29 966 individuals at the modal ages of 14 to 30 in 2016-2017. Similar data for the more commonly studied measure of binge drinking (having 5+ drinks in a row) is provided for comparison. HID prevalence ranged from 1% to 11.5% and was significantly higher for males than females at all ages other than modal age 14 (8th grade). Binge drinking prevalence ranged from 3.5% to 32.5%; males reported a higher prevalence than females at approximately half of the ages examined. Peak binge drinking and HID age for males was earlier (modal age 21/22) than that for females (modal age 21-24 for binge drinking and 25/26 for HID). The observed rapid increase in HID from adolescence through the early to mid-20s highlights the importance of prevention and intervention efforts targeted to these ages.


2015 ◽  
Vol 3 (16) ◽  
pp. 3141-3149 ◽  
Author(s):  
Rong Chen ◽  
Haibo Qu ◽  
Shaoyun Guo ◽  
Paul Ducheyne

The controlled release of large molecules (such as proteins) in a very short time (several days) was achieved through the co-hydrolysis and co-condensation of different precursors.


2013 ◽  
Vol 2 (2) ◽  
pp. 70-75 ◽  
Author(s):  
Kwai S. Chan ◽  
Michael A. Miller ◽  
Wuwei Liang ◽  
Carol Ellis-Terrell

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