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801.
López-Rodríguez ML Benhamú B Murcia M Alvaro E Campillo M Pardo L 《Journal of computer-aided molecular design》2003,17(8):515-524
We report a structure-affinity analysis of an important element in the pharmacophore model for the recognition of 5-HT4 receptor antagonists: the voluminous substituent attached to the basic nitrogen of the ligand. We have designed, synthesized and pharmacologically evaluated a series of benzimidazole derivatives 1 containing a common molecular skeleton formed by N-[(4-piperidyl)methyl]-6-chlorobenzimidazole-4-carboxamide and four different substituents (R = butyl, 2-[(methylsulfonyl)amino]ethyl, 5-[(phenylacetyl)amino]pentyl, and 5-[(benzylsulfonyl)amino]pentyl). These compounds possess binding affinities in the nM range (Ki = 0.11-1.50 nM). Moreover, a ligand that contains a hydrogen atom attached to the basic nitrogen (R = H; Ki = 150 nM) is used as a control for structure-affinity relationships. 相似文献
802.
Compounds that bind with significant affinity to the opioid receptor types, , , and , with different combinations of activation and inhibition at these three receptors could be promising behaviorally selective agents. Working on this hypothesis, the chemical moieties common to three different sets of opioid receptor agonists with significant affinity for each of the three receptor types , , or were identified. Using a distance analysis approach, common geometric arrangements of these chemical moieties were found for selected , , or opioid agonists. The chemical and geometric commonalities among agonists at each opioid receptor type were then compared with a non-specific opioid recognition pharmacophore recently developed. The comparison provided identification of the additional requirements for activation of , , and opioid receptors. The distance analysis approach was able to clearly discriminate -agonists, while global molecular properties for all compounds were calculated to identify additional requirements for activation of and receptors. Comparisons of the combined geometric and physicochemical properties calculated for each of the three sets of agonists allowed the determination of unique requirements for activation of each of the three opioid receptors. These results can be used to improve the activation selectivity of known opioid agonists and as a guide for the identification of novel selective opioid ligands with potential therapeutic usefulness. 相似文献
803.
Novel medium- and macro-sized heterocyclic compounds were assessed for their potential as subtype-selective adrenergic ligands. Their conformational flexibilities were investigated and their geometric shapes were compared to rigid lead compounds of known selectivity. In the case of 1A selective antagonists, interesting potential targets for synthesis and evaluation were identified by 'opening up' various rings of the fused-ring lead compound 1 by shared-bond cleavage. For 2 selective ligands, compound 6 was the lead compound and the possibility of mimicking the fused-ring system via intramolecular hydrogen bonding was investigated. None of the potential targets were closely enough related in this case to the lead compound to warrant synthesis. 相似文献
804.
Tetsuo MuranoYoko Yuasa Hirokuni KobayakawaTsutomu Yokomatsu Shiroshi Shibuya 《Tetrahedron》2003,59(51):10223-10230
A synthetic approach to a new type of acyclic nucleotide analogues 8 and 9 was examined. The design was based on acyclic modification of MRS 2179, a P2Y1-antagonist, and replacement of one of two phosphate groups characterized by MRS 2179 with an isosteric difluoromethylenephosphonyl group. The nucleotide analogues 8 and 9 were enantio-divergently prepared as their ester-protecting derivatives from a highly differentiated 1,5-pentanediol derivative possessing a difluoromethylenephosphonyl group at the 3-position. 相似文献
805.
Synthesis of ferrocene‐based dipeptide receptors FcL1 , FcL2 , FcL3 , FcL4 , FcL5 was carried out by the acylation reaction of ferrocenecarboxylic acid with dipeptide esters. Compounds were characterized by IR, 1H NMR, 13C NMR and elemental analysis. Single‐crystal X‐ray analysis of FcL3 showed it has two independent chiral molecules and the two chiral atoms (C12 and C35) are in R configuration. Their cyclic voltammetric behaviors showed a pair of well‐defined and stable redox waves in the potential range 0.00–1.00 V. The configuration of the metals influenced the receptor's characteristics greatly, and at the same time the FcL compounds could selectively sense group IIB metal ions Zn2+, Cd2+ and Hg2+. The biological activities of FcL1 , FcL2 , FcL3 , FcL4 , FcL5 were studied against the tested bacteria; among them, FcL4 showed significant activity against all five bacterial strains tested. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
806.
Self‐Controlled Monofunctionalization of Quantum Dots for Multiplexed Protein Tracking in Live Cells
Changjiang You Dr. Stephan Wilmes Oliver Beutel Sara Löchte Yulia Podoplelowa Friedrich Roder Christian Richter Thomas Seine Dirk Schaible Gilles Uzé Dr. Samuel Clarke Dr. Fabien Pinaud Dr. Maxime Dahan Dr. Jacob Piehler Prof. Dr. 《Angewandte Chemie (International ed. in English)》2010,49(24):4108-4112
807.
808.
N. E. Kuz’mina E. S. Osipova V. S. Kuz’min V. B. Sitnikov 《Russian Chemical Bulletin》2006,55(9):1523-1529
By superposition of the molecules of opiate receptor ligands of various structural classes, three regions responsible for
the nonselective ligand affinity were distinguished in the opiate pharmacophore. Spatial arrangement features, electronic
properties, the capability of H-bonding and hydrophobic and electrostatic interactions of these regions were determined. The
set of geometric parameters found can be used as a criterion for estimation of the opiate activity in simulation of new types
of ligands.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1469–1475, September, 2006. 相似文献
809.
Hyeong-Won Ryu Young Cho Dae-Young Kim Thong-Sung Ko 《Reaction Kinetics and Catalysis Letters》1999,66(1):127-132
Phosphodiester cleavage of BNPP can be accelerated by various degradative receptors including enzymes. In the hydrolytic cleavage
of BNPP, a bell-shaped receptor concentration-rate profile composed of a positive-catalysis phase at low receptor concentrations
and a negative-catalysis phase at excess receptor concentration was observed. The negative catalysis can be explained by nonproductive
binding, leading to an increase of the activation energy barrier and a decrease of the reaction rate. 相似文献
810.
Agnieszka Adamczyk‐Woźniak Zbigniew Brzózka Michał K. Cyrański Alicja Filipowicz‐Szymańska Paulina Klimentowska Anna Żubrowska Kamil Żukowski Andrzej Sporzyński 《应用有机金属化学》2008,22(8):427-432
A series of ortho‐(aminomethyl)phenylboronic acids was synthesized and their structures were determined by single‐crystal X‐ray diffraction. The structures are stabilized by the inter‐ and intramolecular hydrogen bonds. The sugar‐binding ability of these compounds was evaluated for D ‐glucose, D ‐fructose and D ‐galactose by the competition assay with Alizarin Red S (ARS). The results indicate that the sugar binding ability and selectivity towards sugars depend on the substituents in amino group. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献