Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-05-12
1998-02-10
Henley, III, Raymond
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D20700
Patent
active
057171106
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP96/02587 filed Sep. 11, 1996.
TECHNICAL FIELD
The present invention relates to UCH15 compounds which have antibacterial and antitumor activities and, therefore, are useful as antibacterial and antitumor agents.
BACKGROUND ART
Distamycin A which is represented by the formula (II): ##STR2## Chemother. Rep., 18, 15 (1962); Nature, 203, 1064 (1964); Antimicrob. Ag. Chemother., 5, 593 (1965)!. Also known is netropsin of the formula (III): ##STR3##
DISCLOSURE OF THE INVENTION
According to the present invention, provided are UCH15 compounds which are represented by the following formula (I) and have antibacterial and antitumor activities: ##STR4## wherein R.sup.1 represents a hydrogen atom or a hydroxyl group.
Now, the present invention is described in detail hereinafter.
UCH15 compounds include, for example, a compound of the formula (Ia): ##STR5## which is hereinafter referred to as UCH15A, and a compound of the formula (Ib): ##STR6## which is hereinafter referred to as UCH15B.
In the formula (I), the aldehyde group of UCH15A and UCH15B is believed to exist as such in aprotic solvents, but is mostly converted into a hydrated form in aqueous solutions and is mostly either in an alcohol-added hemiacetal or acetal form in alcoholic solutions, as in the following reaction formulae: ##STR7## wherein R.sup.2 represents an alkyl group.
Since these forms are extremely easily converted into an aldehyde group, the hydrate, hemiacetal and acetal forms are chemically equivalent to the aldehyde group.
In the formula (Ia), the guanidino group of UCH15A can be represented as follows: ##STR8##
These groups represent the limiting structures of a single chemical species, and are in a resonance hybrid. As being chemically equivalent to each other, these groups can not be differentiated from each other.
Also in the formula (Ib), the hydroxyguanidino group of UCH15B can be represented as follows: ##STR9##
Also as being chemically equivalent to each other, these groups can not be differentiated from each other.
In addition, the aldehyde group of UCH15A and UCH15B may be racemated through keto-enol equivalent conversion in solutions, as follows: ##STR10##
In fact, in the .sup.1 H NMR spectra of UCH15 in a solution of heavy water (D.sub.2 O) or CD.sub.3 OD, the hydrogen to which the aldehyde group (in fact, this aldehyde group is observed as the hydrated hemiacetal form thereof as in the above) is bound gave time-dependently attenuating or disappearing signals. This phenomenon results from the substitution of said hydrogen atom with a heavy hydrogen atom, as in the following reaction formulae, and indicates that a minor amount of the aldehyde group exists even in protic solvents and that said aldehyde group is in keto-enol equivalency. ##STR11##
It is expected that UCH15A and UCH15B may naturally be produced in the form of a certain diastereomer by UCH15-producing microbes. In a solvent, however, since said diastereomer is easily converted into another diastereomer, UCH15A and UCH15B are to be collected as a mixture of each two diastereomers that are substantially impossible to separate. In addition, the ratios of the diastereomers of the two compounds are changed depending on the method and conditions for isolating and purifying said compounds.
For convenience' sake, UCH15 compounds of the present invention may be represented by the above-mentioned formula (I), but shall include their additives with, for example, water, and even their tautomers and diastereomers as being chemically equivalent to each other, as so mentioned hereinabove.
Now, the physicochemical characteristics of UCH15A and UCH15B are shown below. As so mentioned hereinabove, these compounds are a non-stoichiometric mixture of two diastereomers. The data mentioned below are of the samples obtained according to the method of Example 1 to be mentioned hereinafter, and each sample is in the form of a mixture (trifluoroacetate) of diastereomers of about 1:1.
Physicochemical Properties of UCH15A trifluoroacetate aldehyde hydrate
REFERENCES:
patent: 4766142 (1988-08-01), Arcamone et al.
patent: 5175182 (1992-12-01), Mongelli et al.
patent: 5472976 (1995-12-01), Animati et al.
JACS, 73, 341 (1951).
Cancer Res. suppl. 3, 18 (1951).
Cancer Chemother. Rep., 18, 15 (1962).
Nature, 203, 1064 (1964).
Antimicrob. Ag. Chemother., 5, 593 (1965).
Asai Akira
Ashizawa Tadashi
Kakita Shingo
Mihara Akira
Mizukami Tamio
Henley III Raymond
Kyowa Hakko Kogyo Co. Ltd.
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