Search results for "pyrrolidine"
showing 10 items of 151 documents
Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine
1976
The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetyl…
Does concomitant diabetes affect treatment responses in overactive bladder patients?
2013
Summary Aims To compare the efficacy and tolerability of a muscarinic receptor antagonist, darifenacin, in the treatment of overactive bladder (OAB) patients with concomitant diabetes as compared with those without comorbidities. Methods Post hoc exploratory analysis of a published, large, non-interventional study in OAB patients treated with darifenacin including 532 diabetics and 1315 controls. Associations of diabetes with treatment responses were evaluated by multiple regression models. Results Diabetics (largely type 2 patients) and controls differed in baseline age, body weight, duration of OAB symptoms and presence of comedications. However, they exhibited similar OAB symptom episode…
Formation and release of acetylpyrrolidinecholine (N-methyl, N-acetoxyethylpyrrolidinium) as a false cholinergic transmitter in the myenteric plexus …
1977
1. Longitudinal muscle strips of the guineapig small intestine were incubated with Tyrode solution containing the choline analogue pyrrolidinecholine. At the end of the incubation the concentrations of acetylcholine and its analogue acetylpyrrolidinecholine were determined in the strips by gas chromatography. 2. After 120 min of incubation with 1 mM pyrrolidinecholine, acetylpyrrolidinecholine comprised about 15% of the total amount of acetylcholine plus acetylpyrrolidinecholine. Electrical stimulation (1 Hz) of the strips during the incubation slightly increased the proportion of acetylpyrrolidinecholine to 21%. 3. The acetylcholine content of control strips increased significantly during …
Postischemic application of lipid peroxidation inhibitor U-101033E reduces neuronal damage after global cerebral ischemia in rats.
1998
Background and Purpose —The lipid peroxidation inhibitor U-101033E was examined for effects on cerebral blood flow (CBF), cortical tissue hemoglobin oxygen saturation (HbS o 2 ), and neuronal damage. Methods —Fifteen minutes of global cerebral ischemia was induced by two-vessel occlusion and hypobaric hypotension. Wistar rats (n=25) were randomized to receive vehicle (n=9) or 40 mg/kg U-101033E (n=9) intraperitoneally during 2 hours of reperfusion. A sham group (n=7) had neither ischemia nor therapy. Histology was evaluated 7 days after ischemia. Results —During late hyperperfusion (at 17 minutes), vehicle-treated animals had a higher ( P =0.044) cortical tissue HbS o 2 (72.0±1.4%) than di…
Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta-peptides via nucleophilic ring-opening of beta-lactams.
2006
The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by resolution with D- and L-Boc phenylalanine is described. The potential of these optically active spiro beta-lactams on the synthesis of peptidomimetics as analogues of melanostatin is evaluated. Theoretical studies of several models, at the Becke3LYP/6-31+G* level of theory, together with previous experimental evidences from our group, gathered by NMR, allow us to design structures that can efficiently mimic some biologically active peptide-type molecules. On the other hand, the spiro beta-lactams have shown their utility in the preparation of beta-peptides. As an example, a homo-tetra-beta-peptide was synthes…
A Fluorine Scan at the Catalytic Center of Thrombin: CF, COH, and COMe Bioisosterism and Fluorine Effects on pKa and logD Values
2006
A series of 16 tricyclic thrombin inhibitors was prepared by using the 1,3-dipolar cycloaddition of azomethine ylides derived from 3- or 4-hydroxyproline and 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide as the key step. The terminal pyrrolidine ring of the inhibitors was systematically substituted to explore the potential bioisosteric behavior of C-F, C-OH, and C-OMe residues pointing into the environment of the catalytic center of a serine protease. X-ray crystal structure analyses revealed a distinct puckering preference of this ring. Substitution by F, HO, and MeO has a strong effect on the basicity of the adjacent pyrrolidine nitrogen center which originates from two sigma-indu…
In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of tran…
1996
Transcription factor NF-kappaB is essential for the induction of nitric oxide synthase (NOS) II (iNOS) by bacterial lipopolysaccharide in murine macrophages (Xie, Q. W., Kashiwabara, Y., and Nathan, C. (1994) J. Biol. Chem. 269, 4705-4708). In 3T3 fibroblasts, agents other than cytokines are efficacious inducers of NOS II expression. In addition to cytokines such as interferon-gamma or tumor necrosis factor-alpha, protein kinase C-stimulating agents such as tetradecanoylphorbol-13-acetate, or cyclic AMP-elevating agents such as forskolin and 8-bromo-cAMP markedly increased NOS II mRNA (measured by Sl nuclease and RNase protection analyses), NOS II protein (determined by Western blotting), a…
Study of aromatic nucleophilic substitution with amines on nitrothiophenes in room-temperature ionic liquids: are the different effects on the behavi…
2006
The kinetics of the nucleophilic aromatic substitution of some 2-L-5-nitrothiophenes (para-like isomers) with three different amines (pyrrolidine, piperidine, and morpholine) were studied in three room-temperature ionic liquids ([bmim][BF4], [bmim][PF6], and [bm(2)im][BF4], where bmim = 1-butyl-3-methylimidazolium and bm(2)im = 1-butyl-2,3-dimethylimidazolium). To calculate thermodynamic parameters, a useful instrument to gain information concerning reagent-solvent interactions, the reaction was carried out over the temperature range 293-313 K. The reaction occurs faster in ionic liquids than in conventional solvents (methanol, benzene), a dependence of rate constants on amine concentration…
Trifluridine/tipiracil in earlier lines of chemotherapy for advanced colorectal cancer
2020
Retrospective Study of Regorafenib Versus TAS-102 Efficacy and Safety in Chemorefractory Metastatic Colorectal Cancer (mCRC) Patients: A Multi-instit…
2021
INTRODUCTION: There have been significant developments in colorectal cancer (CRC) research over the last few years, with the introduction of new agents that have been prolonged median overall survival of metastatic colorectal cancer (mCRC). These therapies have improved patient outcomes; however, despite significant progress in strategies for cancer treatment, their use is limited by development of resistant mechanism. Almost 30% of patients with refractory mCRC will remain good candidates for further treatment. Regorafenib and TAS-102 are novel antitumor agents for patients with refractory mCRC. However, it is unclear which patients may derive a survival benefit from these drugs in real-li…