Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-06-01
1995-08-01
Richter, Johann
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540 36, 540 37, 552610, 552611, 552618, 552619, 552622, 552630, 552639, C07J 100, C07J 4100
Patent
active
054381347
DESCRIPTION:
BRIEF SUMMARY
The invention concerns unsaturated 17.alpha.-cyanomethyl-17.beta.-hydroxy steroids, pharmaceutical preparations containing the latter, as well a a process for their production.
Unsaturated 17.alpha.-cyanomethyl-17.beta.-hydroxy steroid derivatives are steroid compounds of pharmacological interest or also intermediate products for synthesizing pharmacologically highly-effective steroid products, e.g. 17.alpha.-cyanomethyl-17.beta.-hydroxy-13-alkyl-4,9-gonadiene-3-one such as "Dienogest" or also17.alpha.-cyanomethyl-17.beta.-hydroxy-13-alkyl-4,9,11-gonatriene-3-on e derivatives which can be used in human and veterinary medicine in an advantageous manner for the treatment of endocrine disorders and for reproductive control based on their specific hormonal or anti-hormonal actions. A particular advantage in its application is the good compatibility of the compounds, which also produce hardly any unwanted side effects in increased dosages and also represent a desirable enrichment of the range of steroid ingredients of pharmacological interest in comparison to the known 17.alpha.-ethinyl-17.beta.-hydroxy steroids.
The introduction of an additional double bond in these 17.alpha.-cyanomethyl-17.beta.-hydroxy steroids in the C.sub.15 /C.sub.16 position of the basic structure of the steroid leads to a significant increase in effectiveness. A series of these new derivatives show particularly favorable dissociations of characteristic partial effectiveness.
According to the invention, the new unsaturated 15-dehydro-17.alpha.-cyanomethyl-17.beta.-hydroxy steroids of the invention have a ring structure as shown in formula I below: ##STR2## wherein R.sub.1 is methyl or ethyl; and alkoxy having 1 to 6 carbon atoms, or hydroxy, acetoxy and alkoxy having 1 to 6 carbon atoms, or selected from the group consisting of --O--CH.sub.2 --CH--O--; --O--CH.sub.2 --C(CH.sub.3).sub.2 --CH.sub.2 --O--; and --OCH(CH.sub.3)--CH.sub.2 --CH(CH.sub.3)--O--;
The new steroids of formula (I) also have at least one other double bond in the ring structure between the 1 and 2 positions, the 2 and 3 positions, the 3 and 4 positions, the 4 and 5 positions, the 5 and 6 positions, the 5 and 10 positions, the 9 and 10 positions and the 9 and 11 positions, the 1,2,3,-4,5,6,9,10 and 11 positions being shown in formula I above, with the proviso that R.sub.2 cannot be methyl, when there is a double bond between the 5 and 10 positions or the 9 and 10 positions.
Dosages up to a maximum of 2 mg of active ingredient per day are advantageous in the application of these new compounds for controlling fertility. These new compounds are administered in combination with estrogen-active steroids such as ethinyl estradiol in the known pharmaceutical preparation forms as tablets or capsules.
Another area of use of the new active ingredients is the treatment of special diseases, e.g. the treatment of endometriosis. The dosage is up to 2 mg per day over a period if 4 to 6 months in this case also. These low dosages show the superiority of the new compounds particularly clearly while, according to the conventional treatment of these indications with danazol, the dosage is 400 to 800 mg of danazol daily.
The synthesis of 17.alpha.-cyanomethyl-17.beta.-hydroxy steroids has been described in a series of patents. According to the latter, 17-ketosteroids are converted in a multiple-step synthesis into the steroid-17.beta.-spiro-1',2'-oxirane which is then converted with alkali cyanide into 17.alpha.-cyanomethyl-17.beta.-hydroxy steroid derivatives. According to K. Ponsold, et al., DD-PS 132 497, 3-methoxy-13-alkylgona-2,5(10)-diene-17.beta.-spiro-1',2'-oxiran (produced according to DD-PS 80 023) is converted into 17.alpha.-cyanomethyl-17.beta.-hydroxy-13-alkylgon-5(10)-en-3-one by reacting with alkali cyanide and subsequent enol-ether hydrolysis. An improvement of this synthesis was described by K. Ponsold, et al. in DD-WP 160 418, according to which the unstable starting material of the aforementioned process (DD-WP 132 497) is replaced by 3,3-dimethoxy-13-alkylgon-5(10)-en-3
REFERENCES:
CA119: 250245 (Abstract of Bittler).
"Immobilisation, Entgiftung und Zerstorung von Chemikalen", Dr. Dieter Martinez, Verlag Harri Deutsch, Thun Frankfurt am Main, pp. 210-211.
Steroids, Band 39, Nr. 4, Apr. 1982.
Die Pharmazie, Band 39, No. 7, 1984.
Chemical Abstracts, Band 104, No. 23, 9 Jun. 1986.
Die Pharmazie, Band 39, No. 7, 1984.
Die Pharmazie, Band 41, No. 9, 1986.
Chemical Abstracts, Band 103, No. 15, 14 Oct. 1985.
Chemical Abstracts, Band 89, No. 23, 4 Dec. 1978.
Tetrahedron, Band 28, No. 9, May 1972.
Studies in Organic Chemistry, Poznan, 9-14. Jul. 1984, No. 20, K. Schubert, et al.: "Synthesis, effects and metabolism of the progestagen . . . ".
Derwent Information Research Service abstract of International Patent Appl. WO 93/13122, 1994.
Muller Gerd
Teichmuller Gerhard
Jenapharm GmbH
Richter Johann
Scalzo Catherine S. K.
Striker Michael J.
LandOfFree
Process for the production of unsaturated 17 .alpha.-cyanomethyl does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the production of unsaturated 17 .alpha.-cyanomethyl, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the production of unsaturated 17 .alpha.-cyanomethyl will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-734447