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At least 613 records · Page 34Linked to original sources
PubMed2004

[Analytical evaluation of 1-(dipropalamino-3-piperidine-propane-1-yl)-3-pentyloxyphenylcarbamate (CK-3635)].

The paper presents the results of analytical and pharmacological evaluation and study of some physicochemical properties of a potential drug marked as CK-3635 with high local anaesthetic activity. The structure of the substance has been confirmed by IR and UV spectroscopy. The melting point, solubility, partition coefficient, capacity factor, surface activity, and dissociation constant were determined. The chromatographic behaviour of the drug on a thin layer was also investigated. For the content determination, spectrophotometry in the ultraviolet region of the spectrum at the wavelenght of the second absorption maximum of the substance, the titration in the two-phases ambient, and high-performance liquid chromatography were used.

Anesthetics, Local↗
PubMed1992

In vitro evidence for direct complexation of ADR-529/ICRF-187 [(+)-1,2-bis-(3,5-dioxo-piperazin-1-yl)propane] onto an existing ferric-anthracycline complex.

ADR-529 protects against anthracycline cardiotoxicity, possibly by preventing free radical induction. We hypothesize that this occurs by ADR-529 forming a ternary anthracycline-iron-ADR-529 complex. This study used 200-MHz Fourier-transformed NMR to demonstrate the ability of ADR-529 to do this. Peak assignments were by proton-correlated spectroscopy and proton-carbon heteronuclear-correlated spectroscopy. Ga3+ served as a probe for Fe3+, and D2O was the system solvent. Doxorubicin and epirubicin were the studied drugs. Proton spectra of multiple combinations (including pure standards as controls) were obtained. Both Ga3+ plus ADR-529 and Ga3+ plus doxorubicin showed evidence of complexation, as seen by appropriate peak shifts and changes in the associated coupling constants. Ga3+ plus ADR-529 plus epirubicin showed complexation different from that of Ga3+ plus ADR-529 or Ga3+ plus doxorubicin and consistent with the proposed structure. We conclude that ADR-529 would be able to form a ternary complex with an existing anthracycline-Fe3+ complex in an isolated aqueous environment.

Antibiotics, Antineoplastic↗
PubMed1990

Ameliorative effects of ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] on the cardiotoxicity induced by doxorubicin or by isoproterenol in the mouse.

CD 1 female mice were treated with Doxorubicin (5 mg/Kg i.v.) once a week for 8 weeks or with Isoproterenol (20 mg/Kg s.c.) once a week for 5 weeks. Other mice were treated with the chelating agent ICRF-187 (100 mg/Kg i.p.) 30 min. before Doxorubicin or Isoproterenol administration. The animals were sacrificed 4 weeks after the last administration and their cardiac morphology was evaluated by means of light microscopy. ICRF-187 significantly lessened the extent and the severity of the cardiac lesions by Doxorubicin (-68%, P less than 0.01 in left atrium; -69%, P less than 0.01 in ventricles) and the extent of those induced by Isoproterenol (-56%, P less than 0.05). These data confirm that ICRF-187 has good activity on Doxorubicin-induced myocardiopathy and provide new information about the "in vivo" effects of the compound on the cardiotoxicity caused by Isoproterenol. Moreover, they seem to confirm that a common event, probably the involvement of metal ions, plays a role in the morphologically different myocardiopathies induced by Doxorubicin or Isoproterenol.

Animals↗
PubMed1990

dl-N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diaminopropane (ICRF-198) and d-1,2-bis(3,5-dioxopiperazine-1-yl)propane (ICRF-187) inhibition of Fe3+ reduction, lipid peroxidation, and CaATPase inactivation in heart microsomes exposed to adriamycin.

Iron-catalyzed free radical reactions, such as the peroxidation of membrane lipids or the inactivation of critical enzymes, have been implicated in the cardiotoxicity of Adriamycin. Fe3+ reduction is an important step in both processes. The reduction of Fe3+, Fe3+ ADP, or Fe3(+)-ferritin by rabbit heart microsomes, Adriamycin, and NADPH was 10% inhibited by ICRF-187 (ADR-529) in N2 and 77% inhibited by ICRF-198, the hydrolysis product of ICRF-159 (the racemic form of ICRF-187). Lipid peroxidation and CaATPase inactivation catalyzed by Fe3+, Fe3+ ADP, or Fe3(+)-ferritin were substantially inhibited by ICRF-198 but only partially inhibited by ICRF-187. The cardioprotective action of ICRF-187 during Adriamycin treatment may be a result of its hydrolysis to the d isomer of ICRF-198 which inhibits reduction of Fe3+, thus limiting the role of iron in tissue damaging free radical reactions.

Animals↗
PubMed1990

[Preparation of derivatives of 3-(3,4-dimethoxyphenyl)propanic acid and a study of its biological activity].

From 3-(3,4-dimethoxyphenyl)propenic acid chloride and substituted amines and hydrazides, the appropriate amides and hydrazides (Table 1) were synthesized at 60-80 degrees C in the medium of benzene or toluene. The reaction of this chloride with benzaldehyde hydrazone at 70-80 degrees C yielded N,N'-bis[3-(3,4-dimethoxyphenyl)propenoyl]hydrazine (VIII). At ambient temperature the benzylidene hydrazide of 3-(3,4-dimethoxyphenyl)propenic acid (VII) and a small amount of compound VIII were isolated. In the reaction of 3-(3,4-dimethoxyphenyl)propenic acid chloride with benzylidene hydrazide (VII) at 70-80 degrees C, compound VIII was obtained (Scheme 1). Compounds I, VII, VIII and IX possessed higher indices of increase in fortnight tests of the first degree in the roosters of meat hybrides compared to the negative control, but the indices of conversion were unfavourable. The compounds did not reach the efficacy of the avoparcin standard. Derivatives II and VI possessed 67.5 and 63.5%, respectively, of anthelmintic activity of levamisol against Nippostrongylus brasiliensis. The prepared compounds were not antibacterially effective and they were not mutagenic in the tests following the method of Ames, either.

Animals↗