- Preparation method and application of tetrahydrobenzothiophene compound and pharmaceutical composition
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The invention belongs to the field of medicines, and particularly relates to a tetrahydrobenzothiophene compound as well as a pharmaceutical composition and a preparation method and application thereof. The tetrahydrobenzothiophene compound is a compound I as shown I. In-flight R1 And R2 The C1 -4 is a saturated/unsaturated hydrocarbon group. - OCH3 , OCH2 CH3 Phenyl, substituted phenyl, NO2 One - COR of - OH - F, Cl - Br. I - H R1 AND R2 Or different. R3 It is-F. - Cl, Br, I, OH, Amino, C1 -4 saturated/unsaturated hydrocarbon group, OCH3 , OCH2 CH3 , H, Wherein one of them is, n ≥ 5, n Being an integer. The compound effectively inhibits salmonella by inhibiting the synthesis of ATP-dependent transporter in the lipopolysaccharide synthesis pathway. Aeruginosa, escherichia coli and staphylococcus aureus.
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- In vitro and in vivo evaluation of the antimalarial MMV665831 and structural analogs
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Antimalarial candidates possessing novel mechanisms of action are needed to control drug resistant Plasmodium falciparum. We were drawn to Malaria Box compound 1 (MMV665831) by virtue of its excellent in vitro potency, and twelve analogs were prepared to probe its structure–activity relationship. Modulation of the diethyl amino group was fruitful, producing compound 25, which was twice as potent as 1 against cultured parasites. Efforts were made to modify the phenolic Mannich base functionality of 1, to prevent formation of a reactive quinone methide. Homologated analog 28 had reduced potency relative to 1, but still inhibited growth with EC50 ≤ 200 nM. Thus, the antimalarial activity of 1 does not derive from quinone methide formation. Chemical stability studies on dimethyl analog 2 showed remarkable hydrolytic stability of both the phenolic Mannich base and ethyl ester moieties, and 1 was evaluated for in vivo efficacy in P. berghei-infected mice (40 mg/kg, oral). Unfortunately, no reduction in parasitemia was seen relative to control. These results are discussed in the context of measured plasma and hepatocyte stabilities, with reference to structurally-related, orally-efficacious antimalarials.
- Carlier, Paul R.,Ding, Sha,Fike, Katherine R.,Klemba, Michael
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- Heterocyclic β-Enamino Esters, 27. Synthesis of Heterocondensed 6H-1,3-Oxazin-6-ones from N-Acylenamino Esters in the System Triphenylphosphane/Hexachloroethane/Triethylamine
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A simple ring closure reaction of N-acylenamino esters (1b, e, 2, 3a - f, 7) in the system triphenylphosphane/hexachloroethane/triethylamine is described proceeding with high yields.Under chlorinating 3-ester cleavage heterocondensed 6H-1,3-oxazin-6-ones
- Achakzi, Darwizah,Ertas, Muemtaz,Appel, Rolf,Wamhoff, Heinrich
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p. 3188 - 3194
(2007/10/02)
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