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1. 发明申请

WO1997044359A1 NOVEL HUMAN G-PROTEIN COUPLED RECEPTOR 审中-公开
标题翻译：新的人类G蛋白偶联受体
公开(公告)号：WO1997044359A1
公开(公告)日：1997-11-27
申请号：PCT/US1996007622
申请日：1996-05-20
申请人： HUMAN GENOME SCIENCES, INC. , TAKEDA CHEMICAL INDUSTRIES, LTD. , SOPPET, Daniel, R. , RUBEN, Steven, M. , LI, Yi , FUJII, Ryo , HINUMA, Shuji
发明人： HUMAN GENOME SCIENCES, INC. , TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07K14/705
CPC分类号： G01N33/5091 , A61K38/00 , C07K14/70571 , C07K14/715 , C07K14/723 , G01N33/5008 , G01N33/567
摘要： Human G-protein coupled receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the G-protein coupled receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the G-protein coupled receptor nucleic acid sequences and an altered level of the soluble form of the receptors.
摘要翻译：公开了人G蛋白偶联受体多肽，编码这些多肽的DNA（RNA）和使用重组技术生产这种多肽的方法。描述了使用这些多肽鉴定这些多肽的拮抗剂和激动剂的方法，以及使用这些激动剂和拮抗剂用于治疗目的的方法，以进一步治疗与低表达相关的病症。或过表达G蛋白偶联受体核酸序列中的突变以及修饰的可溶形式水平的诊断方法。这些接收器。

2. 发明申请

WO1997044360A1 NOVEL HUMAN G-PROTEIN COUPLED RECEPTOR 审中-公开
标题翻译：新型人G蛋白偶联受体
公开(公告)号：WO1997044360A1
公开(公告)日：1997-11-27
申请号：PCT/US1996013239
申请日：1996-08-14
申请人： HUMAN GENOME SCIENCES, INC. , TAKEDA CHEMICAL INDUSTRIES, LTD. , SOPPET, Daniel, R. , RUBEN, Steven, M. , LI, Yi , FUJII, Ryo , HINUMA, Shuji
发明人： HUMAN GENOME SCIENCES, INC. , TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07K14/705
CPC分类号： G01N33/5091 , A61K38/00 , C07K14/70571 , C07K14/715 , C07K14/723 , G01N33/5008 , G01N33/567
摘要： Human G-protein coupled receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the G-protein coupled receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the G-protein coupled receptor nucleic acid sequences and an altered level of the soluble form of the receptors.
摘要翻译：公开了人G-蛋白偶联受体多肽和编码此类多肽的DNA（RNA）以及通过重组技术产生此类多肽的方法。还公开了利用这种多肽来鉴定这种多肽的拮抗剂和激动剂的方法，以及分别在治疗上使用激动剂和拮抗剂治疗与G蛋白偶联受体多肽的低表达和过表达相关的病症的方法。还公开了用于检测G蛋白偶联受体核酸序列中的突变和受体的可溶形式的改变水平的诊断方法。

3. 发明申请

WO1997024436A2 LIGAND POLYPEPTIDES FOR THE G-PROTEIN-COUPLED RECEPTOR PROTEIN, THEIR PRODUCTION AND USE 审中-公开
标题翻译： G蛋白偶联受体蛋白质的配体多肽，其生产和使用
公开(公告)号：WO1997024436A2
公开(公告)日：1997-07-10
申请号：PCT/JP1996003821
申请日：1996-12-26
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , HINUMA, Shuji , HABATA, Yugo , KAWAMATA, Yuji , HOSOYA, Masaki , FUJII, Ryo , FUKUSUMI, Shoji , KITADA, Chieko
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C12N15/12
CPC分类号： C07H21/04 , A61K38/00 , C07K14/575 , C07K14/705 , C07K14/72 , C07K16/28
摘要： The present invention relates to the ligand polypeptide for the human pituitary- and mouse pancreas-derived G protein-coupled receptor proteins. The ligand polypeptide or the DNA which codes for the ligand polypeptide can be used for (1) development of medicines such as pituitary function modulators, central nervous system function modulators, and pancreatic function modulators, and (2) development of receptor binding assay systems using the expression of recombinant receptor proteins and screening of pharmaceutical candidate compounds. In particular, by the receptor binding assay systems utilizing the expression of recombinant G protein-coupled receptor proteins in accordance with the invention, agonists and antagonists of G protein-coupled receptors which are specific to human and other warm-blooded animals can be screened and the agonists or antagonists obtained can be used as therapeutic and prophylactic agents for various diseases.
摘要翻译：本发明涉及用于人垂体和小鼠胰腺衍生的G蛋白偶联受体蛋白质的配体多肽。编码配体多肽的配体多肽或DNA可用于（1）开发药物如垂体功能调节剂，中枢神经系统功能调节剂和胰功能调节剂，以及（2）开发受体结合测定系统，其使用重组受体蛋白的表达和药物候选化合物的筛选。特别地，通过利用根据本发明的重组G蛋白偶联受体蛋白表达的受体结合测定系统，可以筛选对人类和其他温血动物特异性的G蛋白偶联受体的激动剂和拮抗剂，获得的激动剂或拮抗剂可用作各种疾病的治疗和预防剂。

4. 发明申请

WO1996005302A1 G PROTEIN COUPLED RECEPTOR PROTEIN, PRODUCTION, AND USE THEREOF 审中-公开
标题翻译： G蛋白偶联受体蛋白，生产和使用
公开(公告)号：WO1996005302A1
公开(公告)日：1996-02-22
申请号：PCT/JP1995001599
申请日：1995-08-10
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , HINUMA, Shuji , HOSOYA, Masaki , FUJII, Ryo , OHTAKI, Tetsuya , FUKUSUMI, Shoji , OHGI, Kazuhiro
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C12N15/12
CPC分类号： C12Q1/6876 , C07K14/705 , C07K14/70571 , C07K14/723 , C12Q2600/158
摘要： DNA primers effective in screening G protein coupled receptor protein-encoding DNA fragments are provided. The primers which are complementary to nucleotide sequences that are in community with (homologous to) the nucleotide sequences encoding amino acid sequences corresponding to or near the first membrane-spanning domain or the sixth membrane-spanning domain each of known various G protein coupled receptor proteins were designed and synthesized. Methods of amplifying G protein coupled receptor protein-encoding DNAs using the above DNA primers, and novel target G protein coupled receptor protein-encoding DNAs are also provided. Screening of DNA libraries can be efficiently carried out. Human pituitary gland or amygdala-derived and mouse pancreas-derived G protein coupled receptor proteins, etc., or salts thereof, partial peptides thereof, DNAs coding for the above G protein coupled receptor proteins, processes for producing the above G protein coupled receptor proteins, methods of determining ligands for the above G protein coupled receptor proteins, methods of screening compounds that inhibit the binding between the ligand and the G protein coupled receptor proteins or screening kits therefor, compounds or salts thereof obtained by the above screening method or the screening kit, pharmaceutical compositions containing the above compounds or salts thereof, and antibodies against the above protein coupled receptor proteins or partial peptides thereof are provided.
摘要翻译：提供了有效筛选编码G蛋白偶联受体蛋白的DNA片段的DNA引物。与与编码对应于或接近第一跨膜结构域或第六跨膜结构域的氨基酸序列的核苷酸序列（同源的）的核苷酸序列互补的引物，每个已知的各种G蛋白偶联受体蛋白被设计和合成。还提供了使用上述DNA引物扩增G蛋白偶联受体蛋白质编码DNA的方法，以及新的靶向G蛋白偶联受体蛋白质编码DNA。可以有效地进行DNA文库的筛选。人垂体腺或来自扁桃体的小鼠胰腺衍生的G蛋白偶联受体蛋白等，或其盐，其部分肽，编码上述G蛋白偶联受体蛋白的DNA，用于产生上述G蛋白偶联受体蛋白的方法测定上述G蛋白偶联受体蛋白质配体的方法，筛选抑制配体与G蛋白偶联受体蛋白质结合的化合物或其筛选试剂盒的方法，通过上述筛选方法获得的化合物或其盐提供了包含上述化合物或其盐的药物组合物和针对上述蛋白质偶联受体蛋白质或其部分肽的抗体。

5. 发明申请

WO1995028405A1 BICYCLIC THIOPHENE DERIVATIVES AND USE AS GONADOTROPIN RELEASING HORMONE ANTAGONISTS 审中-公开
标题翻译：双羟基噻吩衍生物和用作GONADOTROPIN释放HORMONE ANTAGONISTS
公开(公告)号：WO1995028405A1
公开(公告)日：1995-10-26
申请号：PCT/JP1995000728
申请日：1995-04-14
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , FURUYA, Shuichi , CHOH, Nobuo , KATO, Koichi , HINUMA, Shuji
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07D495/04
CPC分类号： C07D495/04
摘要： A gonadotropin-releasing hormone antagonistic composition, which comprises an optionally substituted condensed-bicyclic compound consisting of a homo or hetero 5 to 7 membered ring and a homo or hetero 5 to 7 membered ring such as compounds of formulae (I) or (II) is effective as a propylactic or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of the uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myoma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); can be used as a contraceptive of male or female, as an ovulation-inducing agent of female; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent for improving the quality of edible meat or promoting the growth of animals; is useful as an agent of spawning promotion in fish.
摘要翻译：一种促性腺激素释放激素拮抗剂组合物，其包含任选取代的稠合双环化合物，其由同质或杂的5至7元环和均一或杂的5至7元环组成，例如式（I）或（II）的化合物，作为预防或治疗几种激素依赖性疾病（例如性激素依赖性癌症（例如前列腺癌，子宫颈癌，乳腺癌，垂体腺瘤）），良性前列腺肥大，肌瘤的丙氨酸或治疗剂是有效的子宫内膜异位症，早熟性青春期，闭经，经前期综合征，多囊卵巢综合征和寻常型痤疮; 作为两性生育调节剂（例如妊娠控制剂和月经周期控制剂）是有效的; 可作为男性或女性的避孕方法，作为女性的排卵诱导剂; 可以通过使用由于其施用停止而产生的反弹效应而用作不育处理剂; 可用作调整动物饲养领域的发情周期，作为提高食用肉质量或促进动物生长的药剂; 作为鱼类产卵促销的代理人是有用的。

6. 发明申请

WO1997046668A1 NOVEL PEPTIDE, PROCESS FOR THE PRODUCTION OF THE SAME, AND USE OF THE SAME 审中-公开
标题翻译：新肽，其生产方法及其用途
公开(公告)号：WO1997046668A1
公开(公告)日：1997-12-11
申请号：PCT/JP1997001911
申请日：1997-06-05
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , HINUMA, Shuji , FUKUSUMI, Shoji , KITADA, Chieko
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C12N15/00
CPC分类号： C07K14/575 , A61K38/00 , C07K14/655 , Y10S514/806 , Y10S930/16
摘要： A peptide, its precursor or salts thereof useful as a drug such as a preventive and/or remedy for hormone-producing tumor, acromegaly, giantism, dementia, gastric ulcer, etc., a hormone secretion inhibitor, a tumor multiplication inhibitor, a neural inhibitor or a sleep regulator. A DNA encoding this peptide or its precursor is useful as a drug such as a gene preventive and/or remedy for hormone-producing tumor, acromegaly, giantism, dementia, gastric ulcer, etc., a hormone secretion inhibitor, a tumor multiplication inhibitor, a neural inhibitor or a sleep regulator. Such a DNA is also useful as a gene diagnostic drug for various diseases such as hormone-producing tumor, acromegaly, giantism, dementia and gastric ulcer. An antibody against the peptide, its precursor or salts thereof is usable in, for example, assaying the peptide, its precursor or salts thereof in test solutions. The peptide, its precursor or salts thereof are usable as a reagent for screening a compound capable of altering the binding property of the peptide, its precursor or salts thereof to a receptor.
摘要翻译：可用作药物的肽，其前体或盐，例如用于激素产生的肿瘤，肢端肥大症，巨细胞病，痴呆，胃溃疡等的预防和/或补救，激素分泌抑制剂，肿瘤增殖抑制剂，神经元抑制剂或睡眠调节剂。编码该肽或其前体的DNA可用作药物，例如用于激素产生的肿瘤，肢端肥大症，巨细胞病，痴呆，胃溃疡等的基因预防和/或补救，激素分泌抑制剂，肿瘤增殖抑制剂，神经抑制剂或睡眠调节剂。这样的DNA也可用作各种疾病如激素产生肿瘤，肢端肥大症，巨细胞病，痴呆和胃溃疡的基因诊断药物。针对肽，其前体或其盐的抗体可用于例如在测试溶液中测定肽，其前体或盐。肽，其前体或其盐可用作筛选能够改变肽，其前体或其盐与受体的结合性的化合物的试剂。

7. 发明申请

WO1996024597A1 THIENOPYRIMIDINE DERIVATIVES, THEIR PRODUCTION AND USE 审中-公开
标题翻译：三烯酰基衍生物，其生产和使用
公开(公告)号：WO1996024597A1
公开(公告)日：1996-08-15
申请号：PCT/JP1996000263
申请日：1996-02-07
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , FURUYA, Shuichi , CHOH, Nobuo , KATO, Koichi , HINUMA, Shuji
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07D495/04
CPC分类号： C07D495/04
摘要： A thienopyrimidine derivative of formula (I) is effective as a prophylactic or therapeutic agent for the prevention or treatment of several hormone dependent diseases, for example, a sex hormone dependent cancer (e.g. prostatic cancer, cancer of uterine cervix, breast cancer, pituitary adenoma), benign prostatic hypertrophy, myeloma of the uterus, endometriosis, precocious puberty, amenorrhea, premenstrual syndrome, polycystic ovary syndrome and acne vulgaris; is effective as a fertility controlling agent in both sexes (e.g. a pregnancy controlling agent and a menstrual cycle controlling agent); can be used as a contraceptive of male or female, as an ovulation-inducing agent of female; can be used as an infertility treating agent by using a rebound effect owing to a stoppage of administration thereof; is useful as modulating estrous cycles in animals in the field of animal husbandry, as an agent for improving the quality of edible meat or promoting the growth of animals; and is useful as an agent of spawning promotion in fish.
摘要翻译：式（I）的噻吩并嘧啶衍生物作为预防或治疗几种激素依赖性疾病的预防或治疗剂是有效的，例如性激素依赖性癌症（例如前列腺癌，子宫颈癌，乳腺癌，垂体腺瘤），良性前列腺肥大，子宫骨髓瘤，子宫内膜异位症，早熟性青春期，闭经，经前期综合征，多囊卵巢综合征和寻常型痤疮; 作为两性生育调节剂（例如妊娠控制剂和月经周期控制剂）是有效的; 可作为男性或女性的避孕方法，作为女性的排卵诱导剂; 可以通过使用由于其施用停止而产生的反弹效应而用作不育处理剂; 可用作调整动物饲养领域的发情周期，作为提高食用肉质量或促进动物生长的药剂; 作为鱼类产卵促销的代理人是有用的。

8. 发明申请

WO1998029136A1 STABILIZED TRICYCLIC COMPOUND 审中-公开
标题翻译：稳定的三聚体化合物
公开(公告)号：WO1998029136A1
公开(公告)日：1998-07-09
申请号：PCT/JP1997004819
申请日：1997-12-25
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , IMOTO, Soichiro , YOSHIOKA, Minoru , KASHIHARA, Toshio
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： A61K47/14
CPC分类号： A61K31/437 , A61K9/4858 , A61K31/4985 , A61K47/14
摘要： The present invention provides a pharmaceutical composition which contains an oleginous base and a tricyclic compound or a pharmaceutically acceptable salt.
摘要翻译：本发明提供了一种药物组合物，其含有一种含水基和三环化合物或其药学上可接受的盐。

9. 发明申请

WO1998015263A2 A METHOD FOR PRODUCING A MICROPARTICLE 审中-公开
标题翻译：一种生产微生物的方法
公开(公告)号：WO1998015263A2
公开(公告)日：1998-04-16
申请号：PCT/JP1997003608
申请日：1997-10-08
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , TAKECHI, Nobuyuki , NONOMURA, Muneo , HIGUCHI, Shigehiro , BEPPU, Toshiharu
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： A61K09/16
CPC分类号： A61K31/683 , A61K9/1647 , A61K31/38 , A61K31/382 , A61K31/67 , B02C23/06
摘要： This invention provides a method for producing a microparticle which comprises pulverizing a solid preparation comprising a compound represented by formula (I), wherein ring A is an optionally substituted benzene ring; R is a hydrogen atom or an optionally substituted hydrocarbon group; B is an optionally esterified or amidated carboxyl group; X is -CH(OH)- or -CO-; k is 0 or 1; and n is 0, 1 or 2 or a pharmaceutically acceptable salt thereof and a biodegradable polymer of alpha -hydroxycarboxylic acid in the presence of a pulverizing auxiliary, which can provide microparticles which are less adhesive and involve less aggregation and are thus excellent in drug entrapment ratio and control of drug release in a desired particle size.
摘要翻译：本发明提供一种微粒的制造方法，其特征在于，包括粉碎由式（I）表示的化合物的固体制剂，其中环A为任选取代的苯环; R是氢原子或任选取代的烃基; B是任选酯化或酰胺化的羧基; X是-CH（OH） - 或-CO-; k为0或1; 和n为0,1或2或其药学上可接受的盐和α-羟基羧酸的可生物降解的聚合物，其在粉碎助剂的存在下，可提供粘合性较小并且聚集较少并因此优异的药物捕获的微粒比例和控制所需粒度的药物释放。

10. 发明申请

WO1998009958A1 CONDENSED 4,5,6,7-TETRAHYDROBENZO[C]THIOPHENES AS ENHANCER FOR CELL DIFFERENTIATION INDUCTION FACTOR ACTION 审中-公开
标题翻译：浓缩的4,5,6,7-四氢苯并[C]噻吩作为细胞分化诱导因子作用的增强剂
公开(公告)号：WO1998009958A1
公开(公告)日：1998-03-12
申请号：PCT/JP1997003122
申请日：1997-09-05
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , YASUMA, Tsuneo , ODA, Tsuneo , HAZAMA, Masatoshi , TAKETOMI, Shigehisa
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07D333/72
CPC分类号： C07D495/04 , C07D513/04 , C07F9/6561
摘要： A compound represented by formula (I') wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R represents an optionally substituted hydrocarbon group; R represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.
摘要翻译：由式（I'）表示的化合物，其中X表示硫原子或氧原子; Y表示任选氧化的硫原子或氧原子; Z表示键或二价烃基; R 1表示任选取代的烃基; R 2表示任选的酰胺化或酯化的羧基; 环A表示任选取代的芳族5元杂环; 或其盐。上述化合物具有细胞分化诱导因子作用增强活性和抗基质金属蛋白酶活性，可用于预防和治疗骨质疏松症，骨折，骨关节炎和类风湿性关节炎，动脉硬化，癌症转移等骨疾病，和基于神经变性的疾病。

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