- Synthesis, β-adrenoceptor pharmacology and toxicology of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl) ethylamino)propane hydrochloride, a short acting β1-specific antagonist
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The synthesis of S-(-)-1-(4-(2-ethoxyethoxy)phenoxy)-2-hydroxy-3-(2-(3,4-dimethoxyphenyl) ethylamino)propane hydrochloride (D140S·HCl 6), a novel short acting β1-specific adrenoceptor antagonist, has been described. The antagonist potency for D140S·HCl 6 has been compared with esmolol, another short acting agent, and other well known β-adrenoceptor antagonists in isolated rat tissue preparations. The pharmacokinetics of D140S·HCl 6 in 7 day continuous intravenous infusions and 4 weeks intravenous bolus injection studies in conscious rats and dogs have been examined in toxicology studies. The effect on the isoprenaline-induced heart rate increase and the pharmacodynamic half-life of D140S·HCl 6 has been compared with esmolol in a conscious rat model. In addition, the results of a range of toxicological studies are presented. The results indicate that D140S·HCl 6 is a highly specific β1-adrenoceptor antagonist (pA2=8.15±0.22, β1/β2 selectivity>4400). The in vitro studies suggest D140S·HCl is ca. ten times more potent and 60 times more β1-specific than racemic esmolol. Pharmacokinetic non-linearity was seen when given as a 7 day intravenous infusion at toxicological doses above 10 mg kg-1 h-1 in the rat and 2.5 mg kg-1 h-1 in the dog. Both D140S·HCl 6 and esmolol have very short durations of action after intravenous infusion in the rat (pharmacodynamic half-life is 15 min for D140S·HCl and 10 min for esmolol). The toxicological tests indicate that D140S·HCl 6 shows no unexpected toxicity and none of the tissue irritancy problems reported for esmolol formulations.
- Jackman, Graham P.,Iakovidis, Dimitri,Nero, Tracy L.,Anavekar, Nagesh S.,Rezmann-Vitti, Linda A.,Louis, Simon N.S.,Mori, Masanori,Drummer, Olaf H.,Louis, William J.
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- A simple route to 1,4-addition reactions by Co-catalyzed reductive coupling of organic tosylates and triflates with activated alkenes
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An efficient Co-catalyzed 1,4-addition reaction of alkyl/aryl triflates and tosylates with activated alkenes is described. In this reaction, an air-stable cobalt(ii) complex, a mild reducing agent Zn and a simple proton source (H2O) are used. A radical mechanism for the addition of alkyl tosylates to activated alkenes is likely involved.
- Hsieh, Jen-Chieh,Chu, Yi-Hua,Muralirajan, Krishnamoorthy,Cheng, Chien-Hong
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supporting information
p. 11584 - 11587
(2017/10/27)
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- Glucopyranosyl derivative and application thereof in medicines
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The invention relates to a glucopyranosyl derivative used as a sodium-dependent glucose transporter (SGLT) inhibitor, a medicinal composition containing the derivative, and an application of the derivative and the medicinal composition in medicines, and especially relates to the glucopyranosyl derivative represented by formula (I) or a pharmaceutically acceptable salt or all stereoisomers thereof, or the medicinal composition containing the derivative, and a use of the derivative and the medicinal composition in the preparation of medicines for treating diabetes and diabetes related diseases.
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Paragraph 0599; 0600; 0601; 0602; 0603
(2016/10/08)
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- Synthesis and radical polymerisation of methacrylic monomers with crown ethers or their dipodal counterparts in the pendant structure
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The synthesis and radical polymerisation of methacrylic monomers with benzo-12-crown-4, benzo-15-crown-5, benzo-18-crown-6, and their dipodal counterparts in the ester residue is described. The radical polymerisation of the monomers in solution was carried out at different temperatures, and the polymerisation kinetics curves were obtained by direct measurement of the instantaneous monomer concentrations by nuclear magnetic resonance spectroscopy (NMR). Thus, the polymerisation rate parameter (2fkp/〈k t〉1/2), along with the polymer stereoregularity, were obtained in terms of the molar fractions of meso and racemo diads and of syndiotactic, isotactic and heterotactic triads. The interaction of the polymers with cations was studied using polymer networks as solid phases in the solid-liquid extraction of lanthanide cations from both organic and aqueous media.
- Rey, Jimena,Garcia, Felix Clemente,Garcia, Jose Miguel
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scheme or table
p. 948 - 957
(2012/03/27)
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- Synthesis and Biological Activity of Furanyl Anti-Juvenile Hormonal Compounds
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Twenty-one synthetic compounds, containing one or more furan rings, were demonstrated to possess anti-juvenile hormone (AJH) activity as evidenced by their induction of premature metamorphosis in the milkweed bug, Oncopeltus fasciatus (Dallas) by contact, topical application or fumigation. The ED 50 of the four most active analogs required to induce precocious metamorphosis from 3rd-instar nymphs by residue contact in a Petri dish compared favorably with that of precocene II (6,7-dimethoxy-2,2-dimethyl 2H-chromene) a naturally occurring phytochemical AJH. Precocious metamorphosis was fully reversible by co-treatment with juvenile hormone (JH III) or JH analogs, demonstrating that the observed AJH activity resulted from an induced deficiency of juvenile hormone.
- Bowers, William S.,Unnithan, Gopalan C.,Fukushima, Jun-ichi,Toda, Jun,Sugiyama, Takeyoshi
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- New 5-nitroimidazoles bearing lactame nucleus: Synthesis and antibacterial properties
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New 5-nitroimidazoles bearing a trisubstituted ethylenic double bond in position 2 were prepared by reacting various 1-alkyl-2-chloromethyl-5-nitroimidazole with 3-nitrolactam anions by S(RN)1 mechanism in phase-transfer catalysis conditions. These compounds showed in vitro and in vivo antianaerobic activity which was clearly greater than that of metronidazole. Structure-activity relationships have been discussed.
- Jentzer,Vanelle,Crozet,Maldonado,Barreau
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p. 687 - 697
(2007/10/02)
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