- PREMATURE OVULATION PREVENTIVE AGENT
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The present invention provides a premature ovulation inhibitor for use in in vitro fertilization or embryo transfer process, which contains a nonpeptidic compound having a gonadotropin releasing hormone antagonistic action. The premature ovulation inhibitor for use in in vitro fertilization or embryo transfer process of the present invention is low toxic, permits oral administration, and has a superior inhibitory effect on premature ovulation in in vitro fertilization or embryo transfer process.
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Page/Page column 31-32
(2008/12/04)
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- PREVENTIVES/REMEDIES FOR HOTFLASH
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It is intended to provide a preventing or treating agent for hot flash which comprises a nonpeptidic compound having gonadotropin releasing hormone antagonistic activity, in particular, a preventing or treating agent for hot flash which comprises a nonpeptidic compound having gonadotropin releasing hormone antagonistic activity, wherein said compound is capable of entering the brain.
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- MEDICINAL SOLUTIONS
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The present invention relates to a pharmaceutical solution containing a physiologically active non-peptide substance, an organic acid and a biocompatible organic solvent, and provides a pharmaceutical solution wherein a physiologically active non-peptide
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- SUSTAINED RELEASE COMPOSITIONS
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A composition prepared by containing or blending a physiologically active non-peptide substance and a biodegradable polymer having two or more carboxylic groups at its end or a salt thereof features: (1) larger content of the physiologically active non-peptide substance can be contained, as well as release of the same can be controlled or accelerated, whereby secure pharmaceutical effect is achieved; (2) when the physiologically active non-peptide substance causes subcutaneous stimulation, an activity of canceling the stimulation by strongly acidic group at its end is expected; and (3) high glass transition point and high stability.
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- SOLID PREPARATIONS
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The present invention aims at providing a granule comprising a slightly soluble in water and highly water-repellent physiologically active substance in a large content, and a solid preparation comprising the granule, which is superior in disintegration property and dissolution of the physiologically active substance from the preparation. The present invention relates to (1) a granule comprising a physiologically active substance and a cellulose-type disintegrant, (2) a granule comprising a physiologically active substance, a cellulose-type disintegrant and a binder, (3) a solid preparation comprising the granule described in (1) or (2), a cellulose-type disintegrant and a stearic acid-type lubricant and (4) the solid preparation described in (3), which is an oval tablet.
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- Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidine-2,4-dione derivatives as potent GnRH receptor antagonists
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The synthesis and SAR studies of thieno[2,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists to treat reproductive diseases are discussed. It was found that the 2-(2-pyridyl)ethyl group on the 5-aminomethyl functionality of the core structure wa
- Guo, Zhiqiang,Chen, Yongsheng,Wu, Dongpei,Zhu, Yun-Fei,Struthers, R. Scott,Saunders, John,Xie, Qiu,Chen, Chen
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p. 3617 - 3622
(2007/10/03)
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- Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: A highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor
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We have previously disclosed the first potent and orally effective non-peptide antagonist for the human luteinizing hormone-releasing hormone (LHRH) receptor, a thieno[2,3-b]pyridin-4-one derivative, T-98475 (1). Extensive research on developing non-peptide LHRH antagonists has been carried out by employing a strategy of replacing the thienopyridin-4-one nucleus with other heterocyclic surrogates. We describe herein the design and synthesis of a series of thieno-[2,3-d]pyrimidine-2,4-dione derivatives containing a biaryl moiety, which led to the discovery of a highly potent and orally active non-peptide LHRH antagonist, 5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-6-[4- (3-methoxyureido)phenyl]-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (9k: TAK-013). Compound 9k showed high binding affinity and potent in vitro antagonistic activity for the human receptor with half-maximal inhibition concentration (IC50) values of 0.1 and 0.06 nM, respectively. Oral administration of 9k caused almost complete suppression of the plasma LH levels in castrated male cynomolgus monkeys at a 30 mg/kg dose with sufficient duration of action (more than 24 h). The results demonstrated that the thienopyrimidine-2,4-dione core is an excellent surrogate for the thienopyridin-4-one and that thienopyrimidine-2,4-diones and thienopyridin-4-ones constitute a new class of potent and orally bioavailable LHRH receptor antagonists. Furthermore, molecular modeling studies indicate that the unique methoxyurea side chain of 9k preferentially forms an intramolecular hydrogen bond between the aniline NH and the methoxy oxygen atom. The hydrogen bond will shield the hydrogen bonding moieties from the solvent and reduce the desolvation energy cost. It is therefore speculated that the intramolecular hydrogen bond resulting from judicious incorporation of an oxygen atom into the terminal alkyl group of the urea may increase the apparent lipophilicity to allow increased membrane permeability and consequently to improve the oral absorption of 9k in monkeys. On the basis of its profile, compound 9k has been selected as a candidate for clinical trials and it is expected that it will provide a new class of potential therapeutic agents for the clinical treatment of a variety of sex-hormone-dependent diseases.
- Sasaki, Satoshi,Cho, Nobuo,Nara, Yoshi,Harada, Masataka,Endo, Satoshi,Suzuki, Nobuhiro,Furuya, Shuichi,Fujino, Masahiko
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p. 113 - 124
(2007/10/03)
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- Preventives/remedies for alzheimer's disease
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The present invention provides an agent for the prophylaxis or treatment of Alzheimer's disease. The agent for the prophylaxis or treatment of Alzheimer's disease of the present invention containing a compound having a GnRH antagonistic action shows low toxicity and has a superior preventive and therapeutic effect on Alzheimer's disease.
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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 19-20
(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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