China
Africa
Explore chapters and articles related to this topic
Cholinergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Vishal S. Gulecha, Manoj S. Mahajan, Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
The drugs such as hexamethonium, trimethaphan, and mecamylamine cause blockade of autonomic ganglia without causing their stimulation. In 1913, Marshall had coined the term “nicotine-paralyzing” to describe the action of TMA on ganglia. Also, Acheson and Moe had explained in detail the correlation between effects of TMA on the cardiovascular system (CVS) and autonomic ganglia. Later, bisquaternary ammonium salts were developed by Baelow and coworkers. The drug-like hexamethonium consists of six methylene groups between the two quaternary nitrogen atoms with least neuromuscular and muscarinic blocking activities. Another drug, trimethylsulfonium, similar to quaternary and bisquaternary ammonium ions, possesses ganglionic blocking actions and is a hallmark in the development of sulfonium ganglionic blocking agents, for example, trimethaphan. In 1950, secondary amine compounds as mecamylamine were introduced into therapy for hypertension (Brunton et al., 2011).
Asymmetric Reduction of C=N Bonds by Imine Reductases and Reductive Aminases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Matthias Höhne, Philipp Matzel, Martin Gand
Reductive amination is the most atom-efficient synthesis to prepare a desired secondary amine (Fig. 14.5, green path). The elegance of the enzymatic reductive amination lies in its atom economy: It is a one-step reaction, compared to the established multi-step procedures of chemical synthesis (Fig. 14.5, red path). Other established enzymatic routes (Fig. 14.5, blue paths) are restricted to the synthesis of primary amines only. Only monoamine oxidases (MAO) were evolved to access a comparable product scope (Batista et al., 2018): They require the amine racemate as substrates and arrive at the enantiopure amine via deracemization. IREDs allow a one-step synthesis of secondary and tertiary amines (green path), compared to multi-step approaches of chemical or alternative enzymatic routes (shown in red or blue, respectively).
Pharmacokinetics of Amphetamines: In Vivo and in Vitro Studies of Factors Governing Their Elimination
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Measuring the difference spectra of microsomes in the presence of a wide range of concentrations of D-(+)-N-methylamphetamine and cytochrome P-450 (a type I binding spectrum)74 reveals a complex Lineweaver Burke plot,75 which can be explained by the presence of distinctly binding sites, each with its own affinity (Ks value). D-(+)-N-dimethylamphetamine on the contrary shows a linear Lineweaver Burke plot, indicating one binding site. These data are confirmed by the results of measurements of metabolic rates at different substrate concentrations. For the N-dimethylamphetamines normal Lineweaver Burke plots were found, while N-methylamphetamines show a complex Lineweaver Burke plot (Figures 9A and 9B). The N-demethylation of the secondary amine, N-methylamphetamine, shows a manifest stereoselectivity, in contrast to the tertiary amine, N-dimethylamphetamine (Figure 9). The complex Lineweaver Burke plots seen for the secondary amines may be the result of (1) a negative cooperativity which means that at higher substrate concentrations the conversion is facilitated, (2) two different binding sites, or (3) binding sites on two different enzymes. Studies of the in vitro metabolism of these compounds in subcellular preparations have revealed that amphetamines are metabolized by different enzyme identities.
Fluorescent melamine-formaldehyde/polyamine coatings for microcapsules enabling their tracking in composites
Published in Journal of Microencapsulation, 2022
Christian Neumann, Sophia Rosencrantz, Andreas Schmohl, Latnikova Alexandra
The ratio of the reactive groups is known to have a great influence on the formation of the MF condensates. Therefore, the influence of the ratio between the reactive (primary + secondary) amine groups of the polyamine [AMINE] and the hemiaminal ether groups [HAE] was systematically investigated. The polymerisation of the MF prepolymer and the PEI (Mw = 2000 g/mol) was carried out with a deficit of reactive amine groups (1:0.1) up to an excess of amines (1:2) as shown in Table 1. All synthesised MF/PEI polymers precipitated in the form of particulate condensates from the aqueous phase. The [HAE]:[AMINE] ratio of 1:0.1 to 1:0.5 led to higher yields (75–85% w/w) while MF/PEI (1:1)* and MF/PEI (1:2)* led to considerably lower yields. It can be assumed that the loss in yield with excess of amines is caused by the lower cross-linking density, the increase of the water solubility of the polycondensates and the high polymer concentration that could affect the polycondensation.
A patent review of adenosine A2B receptor antagonists (2016-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Beatrice Francucci, Diego Dal Ben, Catia Lambertucci, Andrea Spinaci, Rosaria Volpini, Gabriella Marucci, Michela Buccioni
In 2020, Vernalis (R&S) Ltd., published a patent related to novel thienopyrimidine derivatives with high A2BAR antagonist activities [76]. Synthetic schemes, pharmaceutical compositions, and the use of these compounds for the treatment, prevention, or suppression of disorder mediates by A2BAR are reported. All compounds were tested determining intracellular calcium flux triggered by receptor activation, which was measured through the fluorescence of an incorporated calcium sensitive dye. Results showed that the affinity of these compounds is from 12 to 198 folds higher for the A2BAR respect A2AAR, and they also are selective respect to A1 and A3ARs (Table 2). Compounds 1 and 3 are characterized by a secondary amminein the sixth position which plays an important role in selectivity toward A2BAR. In fact, compound 2 with a tertiary ammine in the same position showed a diminution in terms of selectivity for A2BAR respect to compound 1. Compound 4, possessing a primary ammine group in six position, showed a decrease in affinity vs. A2BAR, nevertheless the selectivity vs. this receptor increases due to the less affinity for the other receptor subtypes. A secondary amine group characterizes compound 5, which respect to the secondary amines present in the compounds listed above, is sterically bulky and this leads to a decrease in selectivity and affinity toward all receptor subtypes.
PDE1 inhibitors: a review of the recent patent literature (2008-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Mei-Ling Le, Mei-Yan Jiang, Chuan Han, Yi-Yi Yang, Yinuo Wu
In 2015, Kehler and coworkers disclosed a series of PDE1 inhibitors with quinazoline scaffold (Figure 27). The X group on the quinazoline was a halogen atom in the first patent. The IC50 values of these compounds against PDE1 ranged from 7 nM to 2800 nM. Most compounds in this patent had two or more stereoisomers and one showed better inhibitory activities than others [79]. For the representative compound 86, stereoisomer 1 gave the IC50 value of 9.9 nM, while stereoisomer 2 gave the IC50 value of 65 nM against PDE1B. However, no configuration was provided for each stereoisomer. In another patent by Kehler, the X group on the quinazoline was instead by the methoxy group. The amine can be primary amine, secondary amine, or cyclic aliphatic amine [80]. The configuration had a significant impact on the inhibitory activities. For example, the (S)-87 was 30-fold more potent against PDE1B than (R)-87 [81].