Search results for "heterocyclic"
showing 10 items of 490 documents
Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.
1993
1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human…
Evaluation of carpal tunnel syndrome in patients with polyneuropathy
1997
The difference between the median nerve latency to the second lumbrical muscle and the ulnar nerve latency to the second interosseous muscle (L-I DIFF) was tested in a prospective study to discriminate whether prolonged distal motor latency of the median nerve in patients with polyneuropathy (PNP) reflects an additional carpal tunnel syndrome (CTS). We investigated 92 patients (107 hands) with CTS, 30 patients (34 hands) with PNP, 22 patients (27 hands) with CTS and coexisting PNP (PNP+CTS), and 77 controls (87 hands). L-I DIFF was significantly prolonged in both the CTS and PNP+CTS patients as compared to PNP patients and controls. It proved to be the most specific test to differentiate be…
Coupling between agonist and chloride ionophore sites of the GABA(A) receptor: agonist/antagonist efficacy of 4-PIOL.
2000
Eight gamma-aminobutyric acid (GABA) mimetics were tested on their ability to differentiate native GABA(A) receptor subtypes present in various rat brain regions. In rat brain cryostat sections, little regional variations by the agonistic actions of muscimol, thiomuscimol, 4,5,6,7-tetrahydroisoazolo(5,4-c)pyridin-3-ol, piperidine-4-sulphonic acid, taurine and beta-alanine on [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABA(A) receptor channels were found. They were very similar to those found for GABA itself and indicated no direct correlation with single subunit distributions for any of these compounds. Only the low-efficacy GABA mimetic 5-(4-piperidyl)isoxazol-3-ol (4-PIOL…
Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum.
2011
We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y(6) receptor antagonist, and mimicked by PSB 0474, P2Y(6)-receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin,…
Exploring kainate receptor pharmacology using molecular dynamics simulations.
2010
Ionotropic glutamate receptors (iGluRs) are enticing targets for pharmaceutical research; however, the search for selective ligands is a laborious experimental process. Here we introduce a purely computational procedure as an approach to evaluate ligand–iGluR pharmacology. The ligands are docked into the closed ligand-binding domain and during the molecular dynamics (MD) simulation the bi-lobed interface either opens (partial agonist/antagonist) or stays closed (agonist) according to the properties of the ligand. The procedure is tested with closely related set of analogs of the marine toxin dysiherbaine bound to GluK1 kainate receptor. The modeling is set against the abundant binding data …
Altered atypical coupling of γ-aminobutyrate type A receptor agonist and convulsant binding sites in subunit-deficient mouse lines
2001
We searched for subunit correlations for GABA(A) receptor-associated atypically GABA-insensitive [35S]TBPS binding. The homomeric beta3 subunit receptors could be excluded, as GABA-insensitive [35S]TBPS binding was present in beta3-/- mice. Localization of GABA-insensitive [35S]TBPS binding correlated best with those of delta, alpha4 and alpha6 subunit mRNAs. The amounts of GABA-insensitive [35S]TBPS binding components were increased in delta-/- mice, but dramatically reduced in alpha6-/- mice, suggesting a role for alpha6 but excluding delta subunits.
Catalytic Enantioselective Aza-Reformatsky Reaction with Cyclic Imines
2016
A catalytic highly enantioselective aza-Reformatsky reaction with cyclic aldimines and ketimines for the synthesis of chiral b-amino esters with good yields and excellent enantioselectivities is reported.Areadily available diaryl prolinol is used as a chiral ligand, ZnMe2 as a zinc source and ethyl iodoacetate as reagent in the presence of air atmosphere. The reaction with cyclic ketimines generates a quaternary stereocenter with excellent levels of enantioselectivity. Furthermore, five-membered N-sulfonyl ketimines were used as electrophiles with good enantiomeric excesses, under the optimized reaction conditions. Moreover, several chemical transformations were performed with the chiral b-…
A multifunctional bioconjugate module for versatile photoaffinity labeling and click chemistry of RNA
2011
A multifunctional reagent based on a coumarin scaffold was developed for derivatization of naive RNA. The alkylating agent N3BC [7-azido-4-(bromomethyl)coumarin], obtained by Pechmann condensation, is selective for uridine. N3BC and its RNA conjugates are pre-fluorophores which permits controlled modular and stepwise RNA derivatization. The success of RNA alkylation by N3BC can be monitored by photolysis of the azido moiety, which generates a coumarin fluorophore that can be excited with UV light of 320 nm. The azidocoumarin-modified RNA can be flexibly employed in structure-function studies. Versatile applications include direct use in photo-crosslinking studies to cognate proteins, as dem…
N‐Heterocyclic Carbene Catalyzed [4+2] Annulation of Enals via a Double Vinylogous Michael Addition: Asymmetric Synthesis of 3,5‐Diaryl Cyclohexenones
2017
A strategy for the N-heterocyclic carbene (NHC) catalyzed asymmetric synthesis of 3,5-diaryl substituted cyclohexenones has been developed via oxidative [4+2] annulation of enals and alkenylisoxazoles. It is the first example of using NHC organocatalysis in a double vinylogous Michael type reaction, a challenging but highly desirable topic. This unprecedented protocol affords good yields as well as high to excellent diastereo- and enantioselectivities.
Switchable Access to Different Spirocyclopentane Oxindoles by N-Heterocyclic Carbene Catalyzed Reactions of Isatin-Derived Enals and N-Sulfonyl Ketim…
2017
A novel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important β-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters, including two quaternary carbon centers, was developed. Alternatively, spirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials, isatin-derived enals, and N-sulfonyl ketimines, in the presence of a slightly different NHC catalytic system. This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for a broad range of substrates.