Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-06-09
1995-05-30
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514258, 514267, 544250, 544281, 544220, A61K 3153, A61K 31505, C07D48704, C07D23138
Patent
active
054201284
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel pyrimidine derivatives which inhibit expression of action of androgen, method of manufacturing the same, and androgen inhibitor.
BACKGROUND OF THE INVENTION
Androgen (male hormone) is mainly synthesized in the testes of adult males, and possesses the actions for maintaining the functions of the reproductive organ and accessory reproductive organs (prostate, seminal gland), spermatogenesis, etc. If the balance of androgen and estrogen (female hormone) is broken and the action of androgen is encouraged, it is known to induce prostatic hypertrophy, prostatic carcinoma, female hairiness, male baldness or pimple. Hypertrophy of the prostate is observed in about 30% of male of 60 years or elder, and symptoms of benign prostatic hypertrophy (BPH) such as dysuria are noted in half of them.
Varieties of androgen and known to include testosterone, androstenedione, dehydroepiandrosterone, and others. It is also known that 85% of androgens synthesized in the tests of the adult men is testosterone.
The testosterone is transformed, in the cells of the prostate, into 5.alpha.-dihydrotestosterone (5.alpha.-DHT) by 5.alpha.-reductase, and is bound with a receptor to get into the nucleus, and activates the genes, thereby expressing the actions as mentioned above.
As substances inhibiting expression of such actions of androgens, for example, chlormadinone acetate, flutamide, and hydroxyflutamide are known. However, the androgen activity inhibiting actions by these compounds were not sufficiently satisfactory, the therapeutic effects on benign prostatic hypertrophy, prostatic carcinoma, female hairiness, male baldness or pimple were not sufficient.
It is hence a primary object of the invention to provide novel compounds excellent in inhibitory action of expression of actions of androgens, and excellent in therapeutic effects of benign prostatic hypertrophy, prostatic carcinoma, female hairiness, male baldness or pimple.
DISCLOSURE OF THE INVENTION
The present inventors, as a result of intensive research in order to achieve the above object, obtained a new finding that the pyrimidine derivatives expressed in Formula [I] and their pharmaceutically available salts are excellent in the effect of inhibiting the expression of action of androgens, and completed the invention. ##STR2## [where R.sup.1 denotes a hydrogen atom or a hydroxyl group, R.sup.2 denotes a hydrogen atom, lower alkoxycarbonyl group, lower alkoxy group, halogen atom, lower alkyl group, cyclocalkyl group with 3 to 8 carbon atoms, lower alkoxycarbonyl lower alkyl group, carboxyl group, carboxy lower alkyl group, group: --CONHR.sup.6 (R.sup.6 is hydrogen atom, phenyl group which may possess a halogen atom, or lower alkyl group), cyano group, phenyl group which may possess a group selected from the group consisting of hydroxyl group, halogen atom, lower alkyl group, lower alkoxy group and phenylthio group as substituent, phenyl lower alkyl group which may possess a group selected from the group consisting of hydroxyl group and lower alkoxy group as substituent on phenyl ring, lower alkanoyloxy lower alkyl group, benzoyl group, lower alkanoyl group which may possess a halogen atom, or hydroxy lower alkyl group which may possess a group selected from the group consisting of phenyl group and halogen atom as substituent, R.sup.3 denotes a hydrogen atom, hydroxyl group, lower alkyl group, cycloalkyl group with 3 to 8 carbon atoms, halogen lower alkyl group, or phenyl group, R.sup.4 denotes a hydrogen atom, lower alkyl group, or lower alkoxy group, and R.sup.5 denotes a hydrogen atom, lower alkyl group, lower alkoxy lower alkyl group, or halogen lower alkyl group; provided that, R.sup.2 and R.sup.3 may be bound to each other to form lower alkylene group with 3 to 5 carbon atoms.]
The pyrimidine derivatives [I] of the invention and the pharmaceutically available salts are novel compounds not found in literature, and possess a strong inhibitory action on bonding of receptor in cell and 5.alpha.-DHT, bonding
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Derwent Abstract 89-057722/08 for JP-1-9971 (no date).
Chone Yoshifumi
Hashimoto Kinji
Inai Masatoshi
Inoue Makoto
Kiyokawa Hiroshi
Berch Mark L.
Otsuka Pharmaceutical Co. Ltd.
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