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AssigneeAstellas Pharma Inc.
InventorsMasaaki Hirano, Eiji Kawaminami, Isao Kinoyama, Shunichiro Matsumoto, Kei Ohnuki, Kazuyoshi Obitsu, Toshiyuki Kusayama
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Compounds useful as GnRH receptor antagonists are provided. The present inventors have further examined propane-1,3-dione derivatives and confirmed as a result that a propane-1,3-dione having 2-(1,3-dihydro-2H-benzimidazol-2-ylidene), or a compound which has benzene or thiophene ring substituted with a group derived from 1-hydroxymethyl, shows excellent availability, in addition to its excellent GnRH receptor antagonism, thereby accomplishing the invention. Since the compound of the invention shows excellent availability, in addition to its strong GnRH receptor antagonism, it can be expected that it exerts superior drug effect in the living body, and it is useful for the treatment of sex hormone dependent diseases such as prostate cancer, breast cancer, endometriosis, uterine leiomyoma, benign prostatic hypertrophy and the like. In addition, since the compound of the invention is excellent in metabolic stability in human and also is less in drug interaction, it has more desirable properties as a medicament to be used for the aforementioned diseases.
A propane-1,3-dione derivative represented by formula (I) or a pharmaceutically acceptable salt thereof
A propane-1,3-dione derivative represented by formula (Ib) or a pharmaceutically acceptable salt thereof
Dependencies are inferred from the claim text.
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Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
Of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH: for decreasing, blocking or antagonising the activity of the anterior…
Drugs for disorders of the urinary system: of the prostate
Drugs for genital or sexual disorders
Term ended 4 Aug 2026 (estimated)
The present invention relates to a novel propane-1,3-dione derivative useful as a medicament, particularly a therapeutic agent for sex hormone dependent diseases.
It is known that a hypothalamic hormone or a pituitary hormone is concerned in the secretion controlling mechanism of peripheral hormones. In general, secretion of anterior pituitary hormones is controlled by a secretion accelerating hormone or a secretion inhibiting hormone secreted from its upper central hypothalamus or by a peripheral hormone secreted from a target organ of respective hormone.
Gonadotropin releasing hormone (to be referred to as GnRH hereinafter, and GnRH is also called luteinizing hormone releasing hormone; LHRH) is known as a hormone which controls secretion of sex hormones at the highest position, and controls secretion of anterior pituitary hormones luteinizing hormone (to be referred to as LH hereinafter) and follicle-stimulating hormone (to be referred to as FSH hereinafter) and sex hormones in sex glands, via a receptor which is present in the anterior pituitary (to be referred to as GnRH receptor hereinafter) (Hormone To Rinsho (Hormone and Clinics), a special number for spring, 46, 46-57 (1998)). Since antagonists specific and selective for this GnRH receptor regulate the action of GnRH and control secretion of subordinate LH and FSH and sex hormones, they are expected as preventive or therapeutic agents for sex hormone dependent diseases (aforementioned Hormone and Clinics, a special number for spring (1998)).
Preferred embodiments of the invention are shown below.
(1) A propane-1,3-dione derivative or a pharmaceutically acceptable salt thereof, wherein in the general formula (I), ring A is benzene ring which may be substituted with halogen atom or lower alkyl, ring B is benzene ring, R1 is H, R2 is OH, R3 is H, and X is lower alkylene which may be substituted.
(2) The propane-1,3-dione derivative of the aforementioned (1) or a pharmaceutically acceptable salt thereof, wherein X is methylene which may be substituted.