Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1989-08-15
1990-05-22
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514433, 514436, 514439, 514473, 514480, 514485, 514488, 514510, 514513, 514529, 514560, 514680, 514863, 552208, 552271, 552289, 552290, 549 14, 549 20, 549 21, 549 30, 549 35, 549 36, 549 89, C07C14936, A61K 3110
Patent
active
049278452
DESCRIPTION:
BRIEF SUMMARY
This invention relates to new compounds of the anthraquinone series which are useful in the treatment of psoriasis.
It has been well known for many years that the compound known as anthralin (dithranol, or 1,8-dihydroxy-9-anthrone) is useful for the topical treatment of psoriasis. While this compound is effective, however, it has the strong disadvantages of also causing staining and irritation. Staining of the skin normally clears within about four weeks after treatment ceases, but the staining also affects bed linen, clothing, and equipment, and so is a major drawback in practical use in many senses, especially to out-patients.
Irritation is a major drawback which can be sufficiently severe as to require treatment to be discontinued for about 10% of patients for whom anthralin therapy would otherwise be appropriate. The staining is not only objectionable to the patients, but also is difficult to remove from fabrics and bathroom fittings.
Accordingly, there is a great need for a treatment agent which does not have these disadvantages.
We have now found that these disadvantages can be reduced by a modification of the structure of the anthralin molecule.
Thus according to our invention we provide new organic compounds, useful for the treatment of psoriasis, which are analogues of anthralin having a thio substituent in the molecule.
Alternatively, these compounds can be described as 1,8-dihydroxy-9-anthrones having a thio substituent in the molecule.
The thio substituent may be present in any position in the anthralin molecule, but it is easier to establish it in some positions than in others. Thus, the positions in which it can be built into the molecule are mainly determined by the ease of providing a reactive centre through which the thio substituent can be attached, and consequently, it is preferred that it be attached in one or more of the positions 2, 7 and 10 in the anthralin ring system, and especially in position 10.
The term "thio substituent" is used herein to mean a substituent containing a sulphide linkage (i.e. a C--S linkage, especially a C--S--C or a C--SH linkage) and does not include substituents in which the sulphur is in an oxidised state, as for example in sulphoxides, sulphones or sulphonic acids.
Such thio substituents may take a wide variety of different forms. Most conveniently, it may be part of a larger group containing the sulphur bound in as indicated above but as a small part of the structure. This allows for adjusting the properties of the molecule as a whole and, in some instances, better stability or ease of manufacture.
In general it is possible to make the products of the invention by various routes, according to the ease of obtaining the desired starting materials.
According to the invention we provide a method for the manufacture of analogues of anthralin having a thio substituent in the molecule, which comprises interaction between a thiol and an anthralin containing a substituent which is reactive towards the thiol to form a sulphur-containing molecular link.
The substituent which is reactive towards the thiol to form a thio (i.e. sulphur-containing) link may be especially in one or more of the positions 2, 7 and 10 in the anthralin ring system, and especially in the 10-position.
There are two main variants of this method. One starts from the thiol and a derivative of anthralin containing a substituent which is reactive towards the thiol, so that the desired product containing a sulphide (C--S--C) bond is obtained directly. The other is to use a derivative of anthralin containing a reactive group and react this with a compound which, though not itself containing a thiol group, contains a group which is convertible to a thio group.
When the reactive group is attached directly to a carbon atom of the anthralin ring system, this method is applicable to making 10-substituted anthralin derivatives, because nucleophilic substitution of the anthralin ring can be made to take place most readily in the 10-position. Thus, the procedure may start from a 10-halogenated anthralin (a
REFERENCES:
Synthesis, Journal of Synthetic Organic Chemistry, No. 5, May 1986, (Stuttgart, DE), M.d'Ishia et al.: "Synthesis of 10-Alkylthio-and Arylthio-1,8-Dihydroxy-9-Anthrones, a New Class of Anthracene Derivatives of Potential Pharmacological Interest", pp. 430-431.
Covington Raymond
Raymond Richard L.
The Victoria University of Manchester
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