- Nitrogen-containing heterocyclic group substituted pyrimidinedione compound and application thereof
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The invention belongs to the technical field of medicines, and relates to a nitrogen-containing heterocyclic group substituted pyrimidinedione compound and application thereof, and a pharmaceutical composition containing the compound, which can be used as a gonadotropin releasing hormone receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis,hysteromyoma, precocious puberty and the like.
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Paragraph 0206; 0211; 0212; 0213
(2020/11/23)
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- Nitrogen-containing heteroaryl substituted pyrimidinedione compound and application thereof
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The invention belongs to the technical field of medicines, and relates to a nitrogen-containing heteroaryl substituted pyrimidinedione compound and application thereof, and a pharmaceutical composition containing the compound, and the nitrogen-containing heteroaryl substituted pyrimidinedione compound and the pharmaceutical composition can be used as gonadotropin releasing hormone receptor antagonists. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis, hysteromyoma, precocious puberty and the like.
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Paragraph 0130; 0135; 0150-0152
(2020/11/25)
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- Bicyclic nitrogen-containing heteroaryl substituted pyrimidinedione compounds and application thereof
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The invention belongs to the technical field of medicines, and relates to bicyclic nitrogen-containing heteroaryl substituted pyrimidinedione compounds, application thereof, and a pharmaceutical composition containing the compounds. The compounds can be used as a gonadotropin releasing hormone receptor antagonist. The invention also relates to a method for preparing the compounds and the pharmaceutical composition, and application of the compounds and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis, hysteromyoma, precocious puberty and the like.
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Paragraph 0139; 0141; 0156-0159
(2020/10/30)
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- Five-membered nitrogen-containing heteroaryl substituted pyrimidinedione compound and application thereof
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The invention belongs to the technical field of medicines, and relates to a five-membered nitrogen-containing heteroaryl substituted pyrimidinedione compound and application thereof, and a pharmaceutical composition containing the five-membered nitrogen-containing heteroaryl substituted pyrimidinedione compound, and the five-membered nitrogen-containing heteroaryl substituted pyrimidinedione compound and the pharmaceutical composition can be used as gonadotropin releasing hormone receptor antagonists. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis, hysteromyoma, precocious puberty and the like.
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Paragraph 0131; 0146-0149
(2021/01/15)
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- Substituted pyrimidinedione compound and application thereof
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The invention belongs to the technical field of medicines, and relates to a substituted pyrimidinedione compound and application thereof, and a pharmaceutical composition containing the compound, which can be used as a gonadotropin releasing hormone receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in prevention or treatment of sex hormone dependent diseases including but not limited to prostate cancer, endometriosis, hysteromyoma, precocious puberty and the like.
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Paragraph 0151; 0171; 0183-0185
(2020/12/29)
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- Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6- methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3- d ]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor
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We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carried out. We focused our synthetic efforts on chemical modification at the 5 and 3 positions of the thieno[2,3-d]pyrimidine-2,4-dione ring based on computational modeling, which resulted in the discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3- yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl} -3-methoxyurea (16b) as a highly potent and orally active GnRH antagonist. Compound 16b showed potent in vitro GnRH antagonistic activity in the presence of fetal bovine serum (FBS) without CYP inhibition. Oral administration of 16b maintained the suppressive effect of the plasma luteinizing hormone levels in castrated cynomolgus monkeys at a 3 mg/kg dose for more than 24 h. Compound 16b is currently under clinical development with the code name of TAK-385.
- Miwa, Kazuhiro,Hitaka, Takenori,Imada, Takashi,Sasaki, Satoshi,Yoshimatsu, Mie,Kusaka, Masami,Tanaka, Akira,Nakata, Daisuke,Furuya, Shuichi,Endo, Satoshi,Hamamura, Kazumasa,Kitazaki, Tomoyuki
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experimental part
p. 4998 - 5012
(2011/09/19)
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- Thienopyrimidine compounds, their production and use
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A compound of the formula: wherein R1and R2each is hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxy-carbonyl or C1-4alkyl which may be substituted; R3is hydrogen, halogen, hydroxy or C1-4alkoxy which may be substituted; or adjacent two R3may form C1-4alkylenedioxy; R4is hydrogen or C1-4alkyl; R6is C1-4alkyl which may be substituted or a group of the formula: wherein R5is hydrogen or R4and R5may form heterocycle; and n is 0-5, or a salt thereof, has an excellent GnRH-antagonizing activity, and is useful for preventing or treating sex hormone-dependent diseases.
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Page column 23-24
(2010/01/30)
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- Thienopyrimidine compounds, their production and use
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A compound of formula (I) wherein R1and R2each is hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxy-carbonyl or C1-4alkyl which may be substituted; R3is hydrogen, halogen, hydroxy or C1-4alkoxy which may be substituted; or adjacent two R3may form C1-4alkylenedioxy; R4is hydrogen or C1-4alkyl; R6is C1-4alkyl which may be substituted or a group of the formula (A) wherein R5is hydrogen of R4and R5may form heterocycle; and n is 0-5, or a salt thereof, has an excellent GnRH-antagonizing activity, and is useful for preventing or treating sex hormone-dependent diseases.
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