TY - JOUR. T1 - Pharmacophore based three dimensional structure activity relationship studies on a novel series of pyrimidine-7-ones as selective inhibitors of cdk4. AU - Pai, Aravinda. AU - Jayashree, B. S.. AU - Jeyaprakash, R. S.. AU - Kini, Suvarna G.. AU - Lobo, Richard. PY - 2017/1/1. Y1 - 2017/1/1. N2 - Drug discovery based on the pharmacophore searching is used in the leading modification and searching programmes. In this context, it was thought appropriate to extensively perform pharmacophoric searching in our laboratory for identifying an ideal scaffold for designing an anticancer candidate that eventually could emerge out to become a CDK inhibitor. Four feature pharmacophores consisting of a dual hydrogen bond acceptor site, a hydrogen bond donor site and a positive ionic group as characteristic pharmacophoric features were developed for a novel series of pyrimidin-7-ones for the selective inhibition of CDK4. The hypothesis AADP20 resulted in a statistically reliable 3D QSAR model ...
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TY - JOUR. T1 - Effects of alkyl side chain modification of coenzyme Q10 on mitochondrial respiratory chain function and cytoprotection. AU - Fash, David M.. AU - Khdour, Omar M.. AU - Sahdeo, Sunil J.. AU - Goldschmidt, Ruth. AU - Jaruvangsanti, Jennifer. AU - Dey, Sriloy. AU - Arce, Pablo M.. AU - Collin, Valérie C.. AU - Cortopassi, Gino A. AU - Hecht, Sidney M.. PY - 2013/4/15. Y1 - 2013/4/15. N2 - The effect of the alkyl side chain length of coenzyme Q10 on mitochondrial respiratory chain function has been investigated by the use of synthetic ubiquinone derivatives. Three analogues (3, 4 and 6) were identified that exhibited significantly improved effects on mitochondrial oxygen consumption and mitochondrial membrane potential, and also conferred significant cytoprotection on cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. The analogues also exhibited lesser inhibition of the electron transport chain than idebenone. The results obtained ...
Inhibition of 15-lipoxygenases by flavonoids: structure-activity relations and mode of action. Biochem Pharmacol. 2003 Mar 01; 65(5):773-81 ...
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div class=citation vocab=http://schema.org/,,i class=fa fa-external-link-square fa-fw,,/i, Data from ,span resource=http://link.lib.byu.edu/resource/elrIjMIuaD0/ typeof=Organization http://bibfra.me/vocab/lite/Meeting,,span property=name http://bibfra.me/vocab/lite/label,,a href=http://link.lib.byu.edu/resource/elrIjMIuaD0/,ACS Symposium on Structure-Activity Relationships in Heterogeneous Catalysis, 1990,/a,,/span, - ,span property=potentialAction typeOf=OrganizeAction,,span property=agent typeof=LibrarySystem http://library.link/vocab/LibrarySystem resource=http://link.lib.byu.edu/,,span property=name http://bibfra.me/vocab/lite/label,,a property=url href=http://link.lib.byu.edu/,Brigham Young University,/a,,/span,,/span,,/span,,/span,,/div ...
The most active analogues were identified at the greatest concentration of even with having an additional benzyl ring to its parent compound T837
TY - JOUR. T1 - Structure-activity profiles of eleutherobin analogs and their cross- resistance in Taxol-resistant cell lines. AU - McDaid, Hayley M.. AU - Bhattacharya, Samit K.. AU - Chen, Xiao Tao. AU - He, Lifeng. AU - Shen, Heng Jia. AU - Gutteridge, Clare E.. AU - Horwitz, Susan Band. AU - Danishefsky, Samuel J.. N1 - Funding Information: This research was supported by grants from the National Institutes of Health (CA 39821 to S.B.H and CA 28824 to S.J.D.) H.M. McDaid á L. He á H.-J. Shen á S.B. Horwitz (&) Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA Tel. +1-718-430-2163; Fax +1-718-430-8922. PY - 1999. Y1 - 1999. N2 - Purpose: Eleutherobin, a natural product, is an antimitotic agent that promotes the polymerization of stable microtubules. Although its mechanism of action is similar to that of Taxol, its structure is distinct. A structure- activity profile of synthetic eleutherobin derivatives that have ...
Trebert-Haeberlin, S., Lux, F., Karl, J., Spruss, Thilo und Schönenberger, Helmut (1987) Determination of platinum and biologically important trace elements in structure-activity relationship studies on platinum-containing anti-cancer drugs. Special procedures for removing phosphorus-32 as well as for the estimation of molybdenum-99 and gold-199. Journal of radioanalytical and nuclear chemistry 113 (2), S. 461-467 ...
Title: Flavonoids as Promising Lead Compounds in Type 2 Diabetes Mellitus: Molecules of Interest and Structure-Activity Relationship. VOLUME: 18 ISSUE: 17. Author(s):E. Nicolle, F. Souard, P. Faure and A. Boumendjel. Affiliation:Universite de Grenoble I/CNRS, UMR 5063, Departement de Pharmacochimie Moleculaire, BP 53 F-38041 Grenoble Cedex 9, France.. Keywords:Flavonoids, antioxidants, antidiabetic, inhibitors, α-glycosidase, glucose transport, aldose reductase, structure-activity relationship, mechanism of action, hyperglycemia. Abstract: There is evidence that hyperglycemia results in the generation of reactive oxygen species, leading to oxidative stress in various tissues, including vascular system. An important link between oxidative stress, inflammatory response and insulin activity is now well established. The ability of antioxidants to protect against the deleterious effects of hyperglycemia and also to improve glucose metabolism and intake must be considered as leads of choice in ...
TY - JOUR. T1 - Highly stable, anion conductive, comb-shaped copolymers for alkaline fuel cells. AU - Li, Nanwen. AU - Leng, Yongjun. AU - Hickner, Michael A.. AU - Wang, Chao Yang. PY - 2013/7/10. Y1 - 2013/7/10. N2 - To produce an anion-conductive and durable polymer electrolyte for alkaline fuel cell applications, a series of quaternized poly(2,6-dimethyl phenylene oxide)s containing long alkyl side chains pendant to the nitrogen-centered cation were synthesized using a Menshutkin reaction to form comb-shaped structures. The pendant alkyl chains were responsible for the development of highly conductive ionic domains, as confirmed by small-angle X-ray scattering (SAXS). The comb-shaped polymers having one alkyl side chain showed higher hydroxide conductivities than those with benzyltrimethyl ammonium moieties or structures with more than one alkyl side chain per cationic site. The highest conductivity was observed for comb-shaped polymers with benzyldimethylhexadecyl ammonium cations. The ...
Date Published: Saturday, March 1, 2003 Biochem Pharmacol 2003, 65 (5), 773-81. Authors: ​Sadik, C. D.; Sies, H.; Schewe, T. Brief:
Positions A and B. Exocyclic substituents on AcF-[OPdChaWR]. Three analogs (16-18) simultaneously varied substituents at positions A and B on the cyclic scaffold (Table 1). Complete removal of the acetylated Phe (16), leaving only the cyclic component, diminished receptor affinity to undetectable levels. Attaching a cinnamoyl substitutent (17) to the macrocycle reduced (26-fold) receptor affinity, but hydrocinnamyl (18) did not alter C5aR affinity or antagonist potency. The negligible affinity of the cyclic scaffold [OPdChaWR] reveals how important the exocyclic component is for high affinity with C5aR. Because the substituent at position A is not crucial for binding, the Phe side chain contributes substantially to receptor affinity. Flexibility in the exocyclic appendage is important, the trans double bond of the cinnamoyl group has low affinity for the receptor, whereas the more flexible saturated hydrocinnamoyl appendage has affinity and potency comparable with 1.. Position C. Substitution of ...
In addition to inversion of the stereochemistry of the 15S-hydroxyl group of PGD2, various other modifications of the substituents at C15 of PGD2 have little effect on DP2-mediated responses. For example, oxidation of the hydroxyl group to a keto group, as in 13,14-dihydro-15-keto-PGD2, only slightly reduces DP2 agonist activity but completely abolishes DP1 agonist activity (Gervais et al., 2001; Hirai et al., 2001; Monneret et al., 2001). Likewise, removal of the 15-hydroxyl group coupled with the addition of a double bond to the alkyl side chain of PGD2 (15-deoxy-Δ12,14-PGD2) does not affect DP2 activity (Monneret et al., 2002) but dramatically reduces DP1-mediated responses (Bundy et al., 1983). As noted above, inversion of the stereochemistry at C15 coupled with addition of a methyl group increases potency at the DP2 receptor and nearly completely eliminates it at the DP1 receptor (Monneret et al., 2003). These findings might be interpreted to suggest that the alkyl side chain of PGD2 does ...
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The duocarmycins are potent antitumor agents with potential for use in the development of antibody-drug conjugates (ADCs) as well as being clinical candidates…
Hereunder, we highlight bacterial membrane anionic lipids as attractive targets in the design of antibacterial drugs which can be effective against both Gram-positive and Gram-negative resistant bacteria. In this approach, first, molecular foundations and structure-activity relationships are laid out for membrane-targeting drugs and drug candidates from the structure and physicochemical properties of the main membrane targets, describing, as well, the corresponding identified resistances. Second, this approach is illustrated by the history of the emergence of antibacterial and antifungal amphiphilic aminoglycosides (AAGs) which are active against Gram-positive and Gram-negative resistant bacteria. AAGs have resulted from intensive medicinal chemistry development of a group of old antibiotic drugs known as aminoglycosides (AGs), which target ribosomal RNA. The aforementioned AAGs are being used towards discovering new antibiotics which are less toxic and less susceptible to resistance. The ...
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The protein kinases are a large family of enzymes that play a fundamental role in propagating signals within the cell. Because of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and physicochemical properties of key binding site residues, referred to here as substructures, have been shown to be informative of inhibitor selectivity. This thesis introduces two fundamental approaches for the comparative analysis of substructure similarity and demonstrates the importance of each method on a variety of large protein structure datasets for multiple biological applications. The Family-wise Alignment of SubStructural Templates Framework (The FASST Framework) provides an unsupervised learning approach for identifying substructure clusterings. The substructure clusterings identified by FASST allow for the automatic ...
Adrenodoxin, Escherichia Coli, Kinetics, Molecular Cloning, Point Mutation, Polymerase Chain Reaction, Protein Binding, Recombinant Proteins, Structure-Activity ...
0041] In reference to chemicals, such as organic chemicals, analog or derivative relates to a chemical molecule that is similar to another chemical substance in structure and function, often differing structurally by a single element or group, but may differ by differ by modification of more than one group (e.g., 2, 3, or 4 groups) if it retains the same function as the parental chemical. Such modifications are routine to persons skilled in the art, and include, for example, additional or substituted chemical moieties, such as esters or amides of an acid, protecting groups such as a benzyl group for an alcohol or thiol, and tert-butoxylcarbonyl groups for an amine. Also included are modifications to alkyl side chains, such as alkyl substitutions (e.g., methyl, dimethyl, ethyl, etc.), modifications to the level of saturation or unsaturation of side chains, and the addition of modified groups such as substituted phenyl and phenoxy. Derivatives may also include conjugates, such as biotin or ...
1AAQ: Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays.
Mokrosz, M. J.; Mokrosz, J. L.; Duszyńska, B.; Dereń-Wesołek, A.; Kłodzińska, A.; Kowalski, P.; Charakchieva-Minol, S.; Tatarczyńska, E.; Kowalska, T.; Majka, Z.; Chojnacka-Wójcik, E.; Misztal, S. 5-HT1A and 5-HT2A receptor affinity and functional profile of some N-[3-(4-aryl-1-piperazinyl)propyl] derivatives of indolin-2(1H)-one, quinolin-2(1H)-one and isoquinolin-1(2H)-one. Part 30: Structure-activity relationship studies of CNS agents. Pharmazie 1997, 52, 423-428 (http://www.ncbi.nlm.nih.gov/pubmed/9260266 ...
A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has been synthesized by the Grignard reaction and subsequent esterification. These compounds were screened for their antimicrobial activities in an agar diffusion assay. The compounds with C10 to C12-alkyl side chains displayed significant antimycotic activity.
The present invention provides novel pharmaceutical compositions comprising aminoalkyl phosphorothioate compounds in combination with surfactants, hydrotropes and chelating agents. The compositions are well-suited for subcutaneous administration.
1EET: Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues.
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The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.. Year introduced: 1972. PubMed search builder options. Subheadings: ...
The synthesis and thermotropic properties of four homologous series of salicylaldimine-based dimer liquid crystals are reported. Two 4-(4-alkoxy-2-hydroxybenzylideneamino) benzoyloxy groups are connected to a central part consisting of a 1,3-phenylene, 1,5-pentylene, 2,2-dimethyl- 1,5-pentylene or 3,3-dimethyl-1,5-pentylene unit. The terminal alkoxy chains have been varied from 4 to 16 carbon atoms in length. All the compounds exhibit liquid crystalline phases whose behaviour depends on the nature of the central part and the length of the alkoxy terminal chains. All compounds of the series with the central phenyl part exhibit enantiotropic B-phases, and the sequence B-6 - B-1 - B-2 on increasing terminal chain length was observed. Replacement of the phenyl group with a pentyl central group partly suppresses the formation of B-phases. The longer homologues of this series show the B1 phase, while the shorter exhibit an intercalated SmCc mesophase. The introduction of methyl substituents to the ...
In the present study, we have evaluated the impacts of point mutations on structural and functional evolution of hypothetical proteins identical to bacterial AD
The Medicinal chemistry course deals with the drug discovery, design and development. Attention is paid to the description of the mechanism of action of drugs, to interactions of drugs with their molecular targets (e.g. enzymes and receptors), and to the study of physico-chemical properties of compounds. The relationship between biological properties (activity) of the compounds and their chemical structure (structure-activity relationship (SAR) study) is discussed as well. During the course, common classes of drugs (e.g. antibiotics, antivirals, anticancer agents) and the basics of pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body does to the drug), including ADMET (absorption, distribution, metabolism, excretion, toxicity) are also discussed. An excursion to IOCB (medicinal chemistry, virology, biochemical pharmacology) will also be part of the course ...
Fingerprint Dive into the research topics of Nonlinear Optical Properties of the Linear Quadrupolar Molecule: Structure-Function Relationship Based on a Three-State Model. Together they form a unique fingerprint. ...
Structure-activity studies of a series of dipyrazolo[3,4-b:3,4-d]pyridin-3-ones binding to the immune regulatory protein B7.1 ...
Ceccarelli, SM; Jaeschke, G; Buettelmann, B; Huwyler, J; Kolczewski, S; Peters, JU; Prinssen, E; Porter, R; et al. (2007). „Rational design, synthesis, and structure-activity relationship of benzoxazolones: New potent mglu5 receptor antagonists based on the fenobam structure. Bioorganic & medicinal chemistry letters. 17 (5): 1302-6. PMID 17189691. doi:10.1016/j.bmcl.2006.12.006 ...
Mologni, L. and Rostagno, R. and Brussolo, S. and Knowles, P.P. and Kjaer, S. and Murray-Rust, J. and Rosso, E. and Zambon, A. and Scapozza, L. and McDonald, Neil Q. and Lucchini, V. and Gambacorti-Passerini, C. (2010) Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorganic & Medicinal Chemistry 18 (4), pp. 1482-1496. ISSN 1464-3391. ...
The synthesis and structure-activity relationship of a novel series of compounds with combined effects on 5-HT3A and 5-HT1A receptors and on the serotonin ...
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Is it ALWAYS the case that when there are substituents in a cyclic molecule, the equatorial position is more stable? (Even when the substituents are right next to each other so that one would be placed down and another up towards each other ...
Drugs that block pro-inflammatory cytokines or their receptors such as Enbrel (a soluble TNF1 receptor) or Anakinra (a soluble IL-1 receptor antagonist) have be...
It will help you to easily restore your male power and sexual abilities and regain your self-confidence. It is a generic of the world-famous brand, so that it costs much less than the original drug.. Now there are many medications with a similar effect on the mans body. Lets look at the main characteristics of Sildalis and its differences from the other analogs ...
Understanding the structure-function relationships at cellular, circuit, and organ-wide scale requires 3D anatomical and phenotypical maps, currently unavailable for many organs across species. At the root of this knowledge gap is the absence of a method that enables whole-organ imaging. Herein, we …
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A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is… Expand ...
Structure-Based and Multiple Potential Three-Dimensional Quantitative Structure-Activity Relationship (SB-MP-3D-QSAR) for Inhibitor Design
According to our new market research study on Quantitative Structure-Activity Relationship (QSAR) Market Forecast to 2027 - COVID-19 Impact and Global Analysis - by Application and Industry, the market is expected to reach US$ 1,888.5 million in 2027 from US$ 1,388.1 million in 2019; it is estimated to grow at a CAGR of 4.0% from 2020 to 2027. The market growth is mainly attributed to the increasing adoption rate of modeling tools in drug discovery and rising investments for drug discovery. However, low adoption rate of the technique in emerging countries is hindering the quantitative structure-activity relationship market growth.. Based on application, the quantitative structure-activity relationship market is segmented into drug discovery, molecular modeling, chemical screening, regulatory and decision-making, and other applications. In 2019, the drug discovery segment accounted for the largest share, and it is further expected to register the highest CAGR in the market during the forecast ...
Method for developing a quantitative structure activity relationship that includes obtaining a training set of chemical compounds with molecular descriptors consisting of a number of multidimensional vectors with an activity class for each of the vectors; partitioning the multidimensional vectors into groups having interdependence; transforming the descriptors such that the interdependence of the groups is lessened; estimating a probability distribution of the descriptors by assuming that a probability distribution of a product of each of the groups is approximately equal to the probability distribution of the molecular descriptors; performing the partitioning, transforming and estimating steps for each of the activity classes; and, developing a probability distribution for the activity classes.
Diarylquinolines, synthesis pathways and quantitative structure-activity relationship studies leading to the discovery of TMC207 ...
TY - JOUR. T1 - In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationships. AU - Iwatsuki, Masato. AU - Otoguro, Kazuhiko. AU - Ishiyama, Aki. AU - Namatame, Miyuki. AU - Nishihara-Tukashima, Aki. AU - Hashida, Junko. AU - Nakashima, Takuji. AU - Masuma, Rokuro. AU - Takahashi, Yoko. AU - Yamada, Haruki. AU - Ömura, Satoshi. N1 - Funding Information: This work was supported, in part, by funds from the Drugs for Neglected Diseases initiative (DNDi), Quality Assurance Framework of Higher Education from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), and the All Kitasato Project Study (AKPS). We are grateful to Ms H Sekiguchi and Mr T Furusawa for their technical assistance.. PY - 2010/10. Y1 - 2010/10. KW - Antitrypanosomal. KW - low-molecular-weight antibiotics. KW - structure/activity relationships. UR - http://www.scopus.com/inward/record.url?scp=78049283272&partnerID=8YFLogxK. UR - ...
Title:Chalcones as Scavengers of HOCl and Inhibitors of Oxidative Burst: Structure-Activity Relationship Studies. VOLUME: 17 Author(s):Thaise Martins, Vera L.M. Silva, Artur M.S. Silva, José L.F.C. Lima, Eduarda Fernandes* and Daniela Ribeiro*. Affiliation:LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, LAQV, REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, LAQV, REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto. Keywords:Chalcones, hypochlorous acid, scavenging activity, reactive species, human ...
The natural product aigialomycin D (1) is a member of the resorcylic acid lactone (RAL) family possessing protein kinase inhibitory activities. This paper describes the synthesis of aigialomycin D and a series of its analogues and their activity for the inhibition of protein kinases related to cancer pathways. A preliminary study of these compounds in the inhibition of CDK2/cyclin A kinase has found that aigialomycin D and analogues 11 and 23 are moderate CDK2/cyclin A inhibitors with IC 50 values of ca. 20 μM. Kinase profiling of aigialomycin D against a panel of kinases has led to the identification of MNK2 as a promising target (IC 50 = 0.45 μM), and preliminary structure-activity relationship studies have been carried out to identify the essential functional groups for activity. © 2011 American Chemical Society ...
TY - JOUR. T1 - A conformational and structure-activity relationship study of cytotoxic 3,5-bis(arylidene)-4-piperidones and related N-acryloyl analogues. AU - Dimmock, J. R.. AU - Padmanilayam, M. P.. AU - Puthucode, R. N.. AU - Nazarali, A. J.. AU - Motaganahalli, N. L.. AU - Zello, G. A.. AU - Quail, J. W.. AU - Oloo, E. O.. AU - Kraatz, H. B.. AU - Prisciak, J. S.. AU - Allen, T. M.. AU - Santos, C. L.. AU - Balzarini, J.. AU - De Clercq, E.. AU - Manavathu, E. K.. PY - 2001/2/15. Y1 - 2001/2/15. N2 - A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds ...
TY - JOUR. T1 - Design, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer. AU - Ashraf-Uz-Zaman, Md. AU - Shahi, Sadisna. AU - Akwii, Racheal. AU - Sajib, Md Sanaullah. AU - Farshbaf, Mohammad Jodeiri. AU - Kallem, Raja Reddy. AU - Putnam, William. AU - Wang, Wei. AU - Zhang, Ruiwen. AU - Alvina, Karina. AU - Trippier, Paul C.. AU - Mikelis, Constantinos M.. AU - German, Nadezhda A.. N1 - Funding Information: K i determinations and receptor binding profiles were generously provided by the National Institute of Mental Healths Psychoactive Drug Screening Program , Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, Ph.D. at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. Funding Information: This work is supported by the NIH 1R15CA231339-0 to N.G. and C.M., CPRIT RP170003 to T.P. and N.G, NIH R01 ...
A quantitative structure-activity relationship study on 6-aryl-pyrazolo (3,4-b) pyridines was performed to gain structural insight into the binding mode of the molecules to the glycogen synthase kinase -3α, an enzyme phosphorylate and inhibit Glycogen Synthase (GS) which is the rate limiting enzyme in the glycogen biosynthesis. The molecular modeling studies were performed using CS Chem. Office 2001 molecular modeling software version 6.0. Allinger`s MM2 force field by fixing Root Mean Square Gradient (RMS) to 0.1 Kcal mol-1 and semiemperical AM1 Hamiltonian method (MOPAC module) were used to minimize the energy and calculate descriptors. The thermodynamic and steric features of 6-aryl-pyrazolo (3,4-b) pyridines are highly correlated with GSK-3α inhibitory activity. The results of the study suggests that introduction of bulky groups at C-5 position of the pyrazolopyridine ring will increase the GSK-3α inhibitory potency as it may involve in hydrophobic interaction with the ATP binding site of ...
Looking for online definition of methoxyl in the Medical Dictionary? methoxyl explanation free. What is methoxyl? Meaning of methoxyl medical term. What does methoxyl mean?
TY - JOUR. T1 - Structure-function correlations in stroke. AU - Sathian, K.. AU - Crosson, Bruce. N1 - Publisher Copyright: © 2015 Elsevier Inc.. PY - 2015/3/4. Y1 - 2015/3/4. N2 - A variety of behavioral deficits can result from stroke. In this issue of Neuron, Corbetta etal. (2015) report that the deficits tend to cluster into just a few sets and are mostly associated with subcortical damage disrupting inter-regional connectivity.. AB - A variety of behavioral deficits can result from stroke. In this issue of Neuron, Corbetta etal. (2015) report that the deficits tend to cluster into just a few sets and are mostly associated with subcortical damage disrupting inter-regional connectivity.. UR - http://www.scopus.com/inward/record.url?scp=84924265168&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84924265168&partnerID=8YFLogxK. U2 - 10.1016/j.neuron.2015.02.031. DO - 10.1016/j.neuron.2015.02.031. M3 - Short survey. C2 - 25741715. AN - SCOPUS:84924265168. VL - 85. SP - ...
NMR (Nuclear Magnetic Resonance) Spectroscopy has found significant applications in drug discovery based on its capacity to map molecular interactions at the atomic level. Chemical shifts, cross relaxation, and exchange of protons are among the NMR parameters which are highly sensitive to the exact environment of the molecules, and therefore yield information about whether a small molecule (candidate compound) binds to a target protein (receptor) or to other macromolecules. These NMR parameters are also used to exactly map the part of the macromolecular target to which the ligand is bound. Spectacular advances in the use of NMR spectroscopy in drug discovery and development have been triggered by a greater understanding of the disease process at the molecular level. Structure - Activity Relationship Studies in Drug Development by NMR Spectroscopy presents comprehensive reviews on NMR spectroscopic drug development written by leading experts in the field ...
TY - JOUR. T1 - Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors. AU - Sharma, Sahil. AU - Singh, Jagjeet. AU - Ojha, Ritu. AU - Singh, Harbinder. AU - Kaur, Manpreet. AU - Bedi, P. M.S.. AU - Nepali, Kunal. PY - 2016/4/13. Y1 - 2016/4/13. N2 - Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article ...
Bioisosteric replacement and scaffold hopping are twin methods used in drug design to improve the synthetic accessibility, potency and drug like properties of a compound and to move into novel chemical space. Bioisosteric replacement involves swapping functional groups of a molecule with other functional groups that have similar biological properties. Scaffold hopping is the replacement of the core framework of a molecule with another scaffold that will improve the properties of the molecule or to find similar potent compounds that exist in novel chemical space. This review outlines the key concepts, importance and challenges of both methods using examples and comparisons of techniques available for finding bioisosteric replacements and scaffold hops. There are many methods available for bioisosteric replacement and scaffold hopping, all with their own advantages and disadvantages. Drug design projects would benefit from a combination of these methods to retrieve diverse and complimentary ...
The structure-activity relationship studies that have been reported for cannabinoids suggest that 1) the conformation of the C-ring at the C9 position, 2) the A-ring phenolic hydroxyl, and 3) the hydrophobic side chain are important determinants for the production of analgesia, as well as other cannabinoid effects. However, either these previous structure-activity studies described for cannabinoid compounds have not been quantitative in nature or the prediction of the activity of known and unknown compounds based on molecular structure has not been tested in a comprehensive manner. In this study we describe a three-dimensional molecular modeling program using comparative molecular field analysis to derive quantitative structure-activity relationships fitting pharmacological potencies and binding affinities of cannabinoids. The analysis has proven to accurately fit the pharmacological activity of cannabinoid analogs, with cross-validated r2 values of greater than 0.3 and final analysis r2 values ...
Hall, Brian, Ph.D., May 2008 Pharmacology/Pharmaceutical Sciences Structure Activity Relationships for Intracellular Loop 2 of the 5HT1A Serotonin Receptor Chairperson: Dr. Keith Parker The human (H) serotonin (5-hydroxytrptamine; 5HT) 1a receptor (R) has been implicated in various physiological processes such as mood regulation, vascular and temperature control, anxiety, depression, and migraine headache. This seven transmembrane domain (7TMD), G protein-coupled receptor (GPCR) is negatively coupled to adenylyl cyclase (AC). This work was designed to better understand the coupling and activation requirements of intracellular loop 2 (ic2) with Gi in Chinese Hamster Ovary (CHO) cells. 10 MER peptides that are derived from the known sequence of the cloned receptor have been used as probes and the current study includes peptides P21 to P27 of ic2 (LDRYWAITDPIDYVNKRTPRPR), approaching the ic2 carboxy terminus of TMD4 two residues per 10 MER. Peptide ability to uncouple receptor from G protein was
To develop a predictive instrument for the assessment of environmental risks of chemical substances based on their structure-activity relationships
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Principal Component Analysis (PCA) and Artificial Neural Network (ANN) were used to analyze the relationship between the structure and the activities of a series of nine biphenylphenyl methanone derivatives against Mycobacterium tuberculosis in vitro. Both PCA and ANN were able to classify these derivatives in two categories: low active and highly active compounds. Empirical and theoretical descriptors were used in the classification process. The descriptors selected by PCA indicated that the reactivity plays an important role in the determination of antimycobacterial activity of biphenylphenyl methanone derivatives (BPM). The BPM showed a moderate activity against the M. tuberculosis strain tested with the exception of chloride-, bromide- and nitroderivatives (when X = Cl, Br, NO2) which were the most actives against M. tuberculosis in vitro among all the methanones studied ...
In November 2004, the OECD member countries agreed on the principles for validating (quantitative) structure-activity relationship [(Q)SAR] models for their use in regulatory assessment of chemical safety. (Q)SARs are methods for estimating the toxicity and other properties of a chemical from its molecular structure.
Quantitative Structure-Activity Relationship (QSAR) Models of Mutagens and Carcinogens von Romualdo Benigni und Buchbewertungen gibt es auf ReadRate.com. Bücher können hier direkt online erworben werden.
TY - JOUR. T1 - Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 2. T2 - SAR studies on the pyridine ring 3-substituent. AU - Luo, Qun Li. AU - Li, Jing Ya. AU - Chen, Ling Ling. AU - Li, Jia. AU - Ye, Qizhuang. AU - Nan, Fa Jun. PY - 2005/2/1. Y1 - 2005/2/1. N2 - Systematic SAR studies on the pyridine ring 3-substituent of PCAT, an inhibitor of EcMetAP1 and ScMetAP1, revealed that 3-substituents have different selectivity for EcMetAP1 and ScMetAP1. The selective inhibitors of type I MetAP are useful tools for investigating the detailed interactions between the enzymes and their inhibitors. In addition, these findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.. AB - Systematic SAR studies on the pyridine ring 3-substituent of PCAT, an inhibitor of EcMetAP1 and ScMetAP1, revealed that 3-substituents have different selectivity for EcMetAP1 and ScMetAP1. The selective inhibitors of type I MetAP are ...
Diacylglycerol lipase α (DAGLα) is responsible for the formation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα inhibitors are required to study the physiological role of 2-AG. Previously, we identified the α-ketoheterocycles as potent and highly selective DAGLα inhibitors. Here, we present the first comprehensive structure-activity relationship study of α-ketoheterocycles as DAGLα inhibitors. Our findings indicate that the active site of DAGLα is remarkably sensitive to the type of heterocyclic scaffold with oxazolo-4N-pyridines as the most active framework. We uncovered a fundamental substituent effect in which electron-withdrawing meta-oxazole substituents increased inhibitor potency. (C6-C9)-acyl chains with a distal phenyl group proved to be the most potent inhibitors. The integrated SAR data was consistent with the proposed binding pose in a DAGLα homology model. Altogether, our results may guide the design of future DAGLα inhibitors as ...
J. O. Midiwo, A. Yenesew, B. F. Juma, S. Dereses, J. A. Ayoo, A. Aluoch and S. Guchu There are several described medicinal plants in Kenya from a flora of approximately 10,000 members. Strong cross-medical information from the 42 ethnic groups points to the high potential of some of these species. The Myrsinaceae are well established ethno-anthelmintics and anti-bacterials. They are harbingers of long alkyl side chain benzoquinones which clearly have a protective function from their histochemical disposition. The main benzoquinone in the sub-family Myrsinodae is embelin while for the Maesodae it is maesaquinone together with its 5-acetyl derivative; the distribution of these benzoquinones by their alkyl side chain length or the presence/absence of a 6-methyl group is in accord with morphological sub-family de-limitation. The benzoquinones showed anti-feedant, anti-microbial, phytotoxic, acaricidal, insecticidal and nematicidal activity. Many other benzoquinones of medium and minor concentration ...
Indolealkylamines and prolactin secretion a structure-activity study in the central nervous system of the rat Academic Article ...
Inductive Logic Programming (ILP) becomes interesting when the expressive power of first-order representation provides comprehensibility to learning result and capability to handle more complex data consisting of their relations. Nevertheless, the bottleneck for learning first-order theory is enormous hypothesis search space which causes inefficient performance by the existing learning approaches compared to the propositional approaches. This paper introduces an improved ILP approach capable of handling more efficiently a kind of data called multiple-part data, i.e., one instance of data consists of several parts as well as relations among parts. This approach tries to find hypothesis describing class of each training example by using both individual and relational characteristics of its part which is similar to finding common substructures among the complex relational instances. The multiple-part data can be found in various domains especially on Structure-Activity Relationship (SAR) studies ...
TY - JOUR. T1 - Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin. AU - Fischer, Peter M.. AU - Zhelev, N. Z.. AU - Wang, S.. AU - Melville, J. E.. AU - Fåhraeus, R.. AU - Lane, D. P.. PY - 2000/2. Y1 - 2000/2. N2 - Peptides derived from the third α-helix of the homeodomain (residues 43-58; Penetratin) of Antennapedia, a Drosophila homeoprotein, were prepared by simultaneous multiple synthesis. Sets of N- and C-terminally truncated peptides, as well as a series of alanine substitution analogues, were studied. Cell penetration assays using human cell cultures with these peptides revealed that the C-terminal segment 52Arg-Arg-Met-Lys-Trp-Lys- Lys58 of the parent sequence was necessary and sufficient for efficient cell membrane translocation. Individual Ala substitutions of the peptides basic residues led to markedly decreased cell internalization ability, whereas replacement of hydrophobic residues was tolerated surprisingly ...
5-Methylcytosine (MeC) is an endogenous modification of DNA that plays a crucial role in DNA-protein interactions, chromatin structure, epigenetic regulation, and DNA repair. MeC is produced via enzymatic methylation of the C-5 position of cytosine by DNA-methyltransferases (DNMT) which use S-adenosylmethionine (SA Nucleic Acid Modifications
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TY - JOUR. T1 - Structure-activity relationships of endothelin. T2 - Importance of the C-terminal moiety. AU - Kimura, Sadao. AU - Kasuya, Yoshitoshi. AU - Sawamura, Tatsuya. AU - Shinmi, Osamu. AU - Sugita, Yoshiki. AU - Yanagisawa, Masashi. AU - Goto, Katsutoshi. AU - Masaki, Tomoh. N1 - Funding Information: ACKNOWLEDGMENTS: We thank Ms. Lisa G. Bond for reading the manuscript, and Drs S. Sakakibara, M. Fujino and C. Kitada for the synthesis of ET. This work was supported in part by grants from the University of Tsukuba Project Research and the Ministry of Education, Science and Culture of Japan. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 1988/11/15. Y1 - 1988/11/15. N2 - The vasoconstrictor activities of various forms of derivatives of endothelin (ET) were characterized in vitro by measuring the contraction of porcine coronary artery strips. The removal of the C-terminal Trp21 reduced the molar potency of the peptide by nearly 3 orders of magnitude. The removal of ...
A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B ...
Synthesis and structure-activity relationships of 7.BETA.-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporin derivatives. III. Synthesis and antibacterial activity of 7.BETA.-[2-amino-2-(2-aminothiazol-4-yl)acetamido]cephalosporins.:III. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7β-[2-AMINO- 2-(2-A MINOTHIAZOL-4-YL)ACETAMIDO]CEPHALOSPORINS (1980 ...
Figure 2: LTX-315 induces immunogenic cell death in cancer cells. When treated with LTX-315, dying cancer cells release damage-associated molecular patterns (DAMP) such as calreticulin, ATP, HMGB1, mitochondria-derived DNA (mtDNA) and formyl peptides (FMIT). DAMPs bind to specific receptors on antigen-presenting cells such as dendritic cells (DC) and promotes their maturation and engulfment of tumor-antigens with subsequent presentation to T cells and execution of effective immune response (Zhou et al, and Eike et al, Oncotarget, 2015, Zhou et al, Cell Death and Disease, 2016, Sveinbjørnsson et al, Future Medicinal Chemistry, 2017) ...
Scientists who want to keep competitive, increase their productivity and enhance decision making should take a look at PerkinElmers just-released new edition of their powerhouse informatics suite, ChemBioOffice 13.. The latest version offers powerful new toolbars, calculations and cloud-based collaboration tools for secure sharing of structures, reactions and drawings with other scientists around the world. Additional biology functionality allows for easier correlation between biological activity and chemical structures.. There are also enhancements to ChemBio3D enabling synthetic chemists and biologists to generate three-dimensional models to assess the shape and properties of compounds, polymers, proteins in a manner accessible to both chemists and biologists alike. Meanwhile, ChemBioFinder helps scientists organise their compounds effectively, search for them and transform data into graphs for structure-activity relationship analysis.. Download our top ten new features in ChemBioOffice 13 ...
The cardiac toxicity of arsenic trioxide (ATO) was studied in chick embryos. Fertilized eggs of White Leghorns were incubated and investigated. The chick embryonic heart has been often used in pharmacologic and toxicologic experiments. After ATO at 0.25, 0.5 or 1.0 mg/egg was injected into fertilized eggs, heart rates (HRs) were measured by electrocardiogram. After low dosing of ATO, the heart rate was not different compared with control. However, HRs significantly decreased in a dose- and time-dependent manner ( ...
Comparison of staurosporine and four analogues: Their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr ...
Thomas Peyret joined Certara Strategic Consulting as an associate scientist in January 2012. His modeling experience includes population PK/PD and physiological modeling. He has performed modeling and simulation and reporting for regulatory consultancy and drug development across a range of therapeutic areas including genetic diseases and oncology. Dr. Peyret has a PhD in Public Health, from the University of Montreal (Canada). His PhD research focused on the development of tools for predicting the pharmacokinetics of environmental chemicals. His PhD modeling experience includes physiologically based pharmacokinetic and quantitative structure activity relationships.
387509240 - EP 1003747 A4 2002-11-06 - CARBAPENEMS WITH NAPHTHOSULTAM DERIVATIVE LINKED VIA METHYLENE - [origin: WO9909032A1] The present invention relates to carbapenem antibacterial agents in which the carbapenem nucleus is substituted at the 2-position with a naphthosultam linked through a CH2 group. The napththosultam is further substituted with various substituent groups including at least one cationic group.[origin: WO9909032A1] The present invention relates to carbapenem antibacterial agents in which the carbapenem nucleus is substituted at the 2-position with a naphthosultam linked through a CH2 group. The napththosultam is further substituted with various substituent groups including at least one cationic group.
As you can imagine, I couldnt do all this without offering the chemistry behind some thoughts. Pectin chemistry is quite complicated though and there are several types available (low methoxyl, high methoxyl and amidated - so far Ive only included the two first in Texture - A hydrocolloid recipe collection). Commercial packs of pectin for home use do normally not specify which type of pectin they contain, but I assume that it is the high methoxyl which gels in the presence of sugar and at low pH (as opposed to the low methoxyl which requires calcium ions to gel). The easiest is probably to follow the instructions that come with the pack you chose. Always add pectin before you add sugar (unless you premix them). The reason for this is that the gelling of high methoxyl pectins is promoted by sugar. If you add sugar before pectin, it will be very diffult to get the pectin properly dispersed and dissolved (it can be done with an immersion blender though - Ive tried that once). Ready to use ...
A rapid and versatile method has been developed for the synthesis of oligonucleotides which contain an aliphatic amino group at their 5 terminus. This amino group reacts specifically with a variety of electrophiles, thereby allowing other chemical species to be attached to the ohgonucleotide. This chemistry has been utilized to synthesize several fluorescent derivatives of an oligonucleotide primer used in DNA sequence analysis by the dideoxy (enzymatic) method. The modified primers are highly fluorescent and retain their ability to specifically prime DNA synthesis. The use of these fluorescent primers in DNA sequence analysis will enable DNA sequence analysis to be automated. ...
A test on water solubility is not required. The substance is manufactured and marketed as 40% aqueous solution. Thus, the substance is highly soluble in water (at least 400 g/L). Amphopropionates C12-18 is a UVCB substance containing C8-, C10-, C12-, C14-, C16-, and C18-alkyl side chains. Based on this and the variable composition of the compound (alkyl chain distribution dependent on origin of the coco fatty acid) the calculation of physico-chemical properties for the mixture is not feasible. To get a hint on the physico-chemical data, the EPIWIN calculation was conducted for the C8 and the C18 derivatives. The water solubilities were calculated using EPIWIN v3.20, WSKOW v1.41. The calculation yielded water solubilities of 1000000 mg/L and 1396 mg/L (at 25°C each) for the C8 and C18 derivatives, respectively, taking into account the log Kow values estimated via EPIWIN (C8: log Kow=-6.53; C18: log Kow=-1.62). Based on these results and the classification scheme the C8-derivative can be regarded ...
With the increasing availability of small molecules, drug-like libraries, and robotic automation, the search for sortase inhibitors has now entered the era of high-throughput screening. A screen of 1000 diverse compounds for inhibition of sortase yielded a diarylacrylnitrile with an IC50 of 231 μM (Oh et al., 2004). Examination of the structure-activity relationships of this compound indicated placing the two benzene rings in the trans-orientation as a (Z)-diarylacrylonitrile lowered the IC50 to 28 μM. Further structure-activity relationship indicated that a 2,5-dimethoxy configuration was the most potent with a competitive inhibition profile. Dialysis and activity recovery experiments suggested that inhibition was reversible. Modeling studies suggested further that the phenyl rings of the inhibitor may interact with lipophilic residues of the sortase substrate binding pocket. Future work on this class of inhibitors will be needed to achieve a structural appreciation of sortase ...
in Bioorganic & Medicinal Chemistry (2011), 19(4), 1550-61. Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships ... [more ▼]. Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC(50) values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual ...