Search results for "Tertiary amine"
showing 10 items of 46 documents
Chromone and phenanthrene alkaloids from Dennettia tripetala.
2002
Dennettine, a new 2,6-dimethoxychromone and three known phenanthrene alkaloids (uvariopsine, stephenanthrine and argentinine) in addition to the phenolic and known compound vanillin were isolated from the roots of Dennettia tripetala. Their structures were determined by physical and spectroscopical one dimensional (1D) and 2D-NMR analysis, including heteronuclear multiple bond correlation and nuclear Overhauser enhancement spectroscopy.
Regioisomeric 5(3)-aminomethyl-3(5)-phenylisoxazoles: synthesis, spectroscopic discrimination, and muscarinic activity.
1995
The regioselective synthesis of isomeric 5(3)-aminomethyl-3(5)-phenyl isoxazoles using different methods is described. Spectroscopic data, especially mass spectrometric fragmentation, were used to identify and characterize the regioisomers. The muscarinic activity of these isoxazoles was assayed on isolated guinea-pig ileum and atria as well as on isolated rabbit vas deferens. Regioisomere 5(3)-Aminomethyl-3(5)-phenyl-isoxazole: Synthese, spektroskopische Unterscheidung und muskarinische Aktivitat Es werden verschiedene Verfahren zur regioselektiven Darstellung von 5(3)-Aminomethyl-3(5)-phenyl-isoxazolen beschrieben, die anhand ihrer spektroskopischen Daten, insbesondere der massenspektrosk…
Mechanism of Block by 4-Aminopyridine of the Transient Outward Current in Rat Ventricular Cardiomyocytes
1998
The effects of 4-aminopyridine (4-AP) on the transient outward current (I to ) were investigated in rat ventricular cardiomyocytes at different values of intracellular pH (pH i ) and extracellular pH (pH o ). The 4-AP was administered either extracellularly (bath application) or intracellularly (diffusion from the intrapipette solution). The 4-AP diminished I to given either from inside or outside the cell membrane. The block by extracellularly applied 4-AP (4-AP o ) of the peak amplitude of I to was decreased by external acidification but increased by external alkalinization: conversely. the block by 4-AP o was decreased by internal alkalinization but increased by internal acidification. I…
Molecular Pacman: Folding, Inclusion, and X-ray Structures of Tri- and Tetraamino Piperazine Cyclophanes
2008
Reaction of piperazine and 1,3-bis(bromomethyl)-2-nitrobenzene under high-dilution conditions yields cyclic trimeric trinitro, tetrameric tetranitro, and pentameric pentanitro piperazine cyclophanes. Reduction of the nitro groups with SnCl(2) under acidic conditions produces the corresponding triamino and tetraamino piperazine cyclophanes. The solution studies of both nitro and amino piperazine cyclophanes at 30 degrees C by (1)H NMR spectroscopy shows symmetrical structures owing to the fast conformational exchange, whereas the low temperature studies of the tetraamino piperazine cyclophane reveals interesting dynamic behavior that indicates additional intramolecular interactions. Careful …
Hydrogen-bond-mediated self-assembly of 26-membered diaza tetraester crowns of 3,5-disubstituted 1 h -pyrazole. Dimerization study in the solid state…
2011
By using an improved synthetic method reported earlier, the cyclic stannoxanes obtained from RN-diethanolamine (R = Me, Bu) and dibutyltin oxide have been reacted with 1H-pyrazole-3,5-dicarbonyl dichloride to afford 26-membered diaza tetraester crowns (1, R = Me; 3, R = Bu) and 39-membered triaza hexaester crowns (2, R = Me; 4, R = Bu). The new structures were identified from their analytical and spectroscopic (1H and 13C NMR, FAB-MS, and/or ESI-MS) data. Both diaza tetraester crowns (1 and 3), containing two 1H-pyrazole units, self-assemble into dimeric species through the formation of four hydrogen bonds involving the two NH pyrazole groups and the two tertiary amine groups of both crowns…
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…
3D-QSAR pharmacophore modeling and in silico screening of new Bcl-xl inhibitors.
2010
Bcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finall…
Predicting and Tuning Physicochemical Properties in Lead Optimization: Amine Basicities
2007
This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivativ…
Stimuli-Responsive Tertiary Amine Functional PEGs Based on N,N-Dialkylglycidylamines
2014
Amine-functional poly(ethylene glycol) (PEG) copolymers have been prepared that exhibit thermo- and pH- responsive behavior in aqueous solution. Three novel tertiary di(n-alkyl)glycidylamine monomers have been introduced for anionic ring-opening copolymerization (AROcP) with ethylene oxide (EO): N,N-di(n-butyl)glycidylamine (DButGA), N,N-di(n-hexyl)glycidylamine (DHexGA), and N,N-di(n-octyl)glycidylamine (DOctGA). Via controlled AROcP we synthesized well-defined (Mw/Mn = 1.05–1.14), water-soluble block- and gradient-type PEG copolymers, containing up to 25 mol % of the respective dialkylglycidylamine comonomer. Molecular weights ranged from 4900 to 12 000 g mol–1. Detailed in-situ 1H NMR ki…
Synthesis of Novel Folic Acid-Functionalized Biocompatible Block Copolymers by Atom Transfer Radical Polymerization for Gene Delivery and Encapsulati…
2005
Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)- ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino) ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previou…