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1. 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。

2. 发明申请

WO1996001267A1 PHOSPHONIC ACID COMPOUNDS, THEIR PRODUCTION AND USE 审中-公开
标题翻译：磷酸化合物，其生产和使用
公开(公告)号：WO1996001267A1
公开(公告)日：1996-01-18
申请号：PCT/JP1995001328
申请日：1995-07-03
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , SOHDA, Takashi , TAKETOMI, Shigehisa , ODA, Tsuneo
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07F09/40
CPC分类号： C07F9/657181 , C07F9/3882 , C07F9/4056 , C07F9/60 , C07F9/65517 , C07F9/65522 , C07F9/655345 , C07F9/65539 , C07F9/6561
摘要： The present invention relates to a compound of general formula (I), wherein ring A is a benzene ring that may be substituted; Y is a divalent group as a constituent member of ring B forming a 5- to 8-membered ring; Q1 is a group of the formula -X-P(O)(OR )(OR ) wherein X is a bond or a divalent group; R and R ; identical or different, are hydrogen or a lower alkyl, or may be combined together to form a ring; Q2 is hydrogen, a hydrocarbon group that may be substituted or a heterocyclic group that may be substituted; and the group of the formula -CON(Q1)(Q2) is connected to the a- or b-position carbon atom, or a salt thereof, which is useful as prophylactic and therapeutic agents of various metabolic bone diseases such as osteoporosis.
摘要翻译：本发明涉及通式（I）的化合物，其中环A是可被取代的苯环; Y是作为形成5-至8-元环的环B的构成成员的二价基团; Q1是式-X-P（O）（OR 1）（OR 2））的基团，其中X是键或二价基团; R 1和R 2; 相同或不同的是氢或低级烷基，或可以组合在一起形成环; Q2是氢，可以被取代的烃基或可以被取代的杂环基; 并且式-CON（Q1）（Q2）的基团与a-或b-位碳原子或其盐连接，其可用作各种代谢骨疾病如骨质疏松症的预防和治疗剂。

3. 发明申请

WO1996039134A1 OSTEOGENETIC PROMOTING PHARMACEUTICAL COMPOSITION 审中-公开
标题翻译：营养促进药物组合物
公开(公告)号：WO1996039134A1
公开(公告)日：1996-12-12
申请号：PCT/JP1996001506
申请日：1996-06-04
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , HOSHINO, Tetsuo , MURANISHI, Hiroya , TAKETOMI, Shigehisa , IWASA, Susumu
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： A61K31/38
CPC分类号： A61K31/67 , A61K9/0019 , A61K9/1647 , A61K9/2031 , A61K47/26 , A61K47/36
摘要： This invention provides a pharmaceutical composition comprising a non-peptide osteogenetic promoting substance and a biodegradable polymer, which can be safely used as a prophylactic/therapeutic agent for various bone diseases (e.g., bone fractures).
摘要翻译：本发明提供了包含非肽成骨促进物质和生物可降解聚合物的药物组合物，其可以安全地用作各种骨疾病（例如骨折）的预防/治疗剂。

4. 发明申请

WO1996010014A1 ALDEHYDE DERIVATIVES AS UPSTEINE PROTEASE INHIBITORS 审中-公开
标题翻译： ALDEHYDE衍生物作为UPSTEINE PROTEASE抑制剂
公开(公告)号：WO1996010014A1
公开(公告)日：1996-04-04
申请号：PCT/JP1995001933
申请日：1995-09-25
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , SOHDA, Takashi , FUJISAWA, Yukio , YASUMA, Tsuneo , MIZOGUCHI, Junji
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07D209/16
CPC分类号： C07D401/12 , A61K38/00 , C07C311/19 , C07D209/16 , C07K5/06043
摘要： The present invention relates to a compound of formula (Ia'), wherein Q' stands for one or two amino acid residual groups which may be substituted; R stands for a hydrogen atom or an optinally substituted hydrocarbon or heterocyclic group; R stands for an optionally esterified carboxy group or an acyl group; and X stands for an optionally substituted straight-chain or branched divalent hydrocarbon group having a chain length of 1 to 4 atoms as the linear moiety, or a salt thereof, which has strong cysteine protease inhibitory activities and is a useful prophylactic and therapeutic agent of various diseases, including bone diseases, caused by abnormal exasperation of cysteine protease.
摘要翻译：本发明涉及式（Ia'）化合物，其中Q'代表一个或两个可被取代的氨基酸残基; R 1表示氢原子或光取代的烃或杂环基; R 4代表任选酯化的羧基或酰基; X表示具有1〜4个链长的任选取代的直链或支链二价烃基作为直链部分，或其盐具有强半胱氨酸蛋白酶抑制活性，并且是有用的预防和治疗剂各种疾病，包括由于半胱氨酸蛋白酶异常激怒引起的骨骼疾病。

5. 发明申请

WO1996025929A1 USE OF HELIOXANTHIN AS AN ENHANCER OF CELL DIFFERENTIATION INDUCING FACTORS 审中-公开
标题翻译：作为细胞分化增强因子诱导因子的增强剂的使用
公开(公告)号：WO1996025929A1
公开(公告)日：1996-08-29
申请号：PCT/JP1996000375
申请日：1996-02-20
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , FUJISAWA, Yukio , HAZAMA, Masatoshi , IWAKAMI, Norihisa
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： A61K31/365
CPC分类号： A61K31/36 , A61K31/365
摘要： An enhancer for a cell differentiation inducing factor, a composition for preventing or treating a bone disease or a nerve degenerative disease, and an osteogenesis promoter, each of which comprises helioxanthin, or its lactone-open form compound or its salt.
摘要翻译：细胞分化诱导因子的增强剂，预防或治疗骨病或神经退行性疾病的组合物和成骨促进剂，其各自包含甲基黄嘌呤或其内酯开放型化合物或其盐。

6. 发明申请

WO1998007705A1 NAPHTHOLACTAMS AND LACTONES AS BONE MORPHOGENETIC PROTEIN ACTIVE AGENTS 审中-公开
标题翻译：作为骨形态蛋白活性剂的石蜡和乳糖
公开(公告)号：WO1998007705A1
公开(公告)日：1998-02-26
申请号：PCT/JP1997002858
申请日：1997-08-19
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , MARUI, Shogo , HAZAMA, Masatoshi , NOTOYA, Kohei , OGINO, Masaki
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07D217/24
CPC分类号： C07D401/04 , A61K31/4035 , A61K31/4741 , A61K31/4745 , C07D209/64 , C07D209/66 , C07D317/70 , C07D405/04 , C07D471/04 , C07D491/04
摘要： A compound of formula (I) wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; Z is a C1-3 alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; Z is an optionally substituted C1-3 alkylene group; Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; one of R and R is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or R and R taken together with adjacent -c=c- form a ring; and ring A is a benzene ring which may be substituted in addition to R and R ; or a salt thereof.
摘要翻译：式（I）的化合物，其中Q是任选取代的碳原子或N（O）p，其中p是0或1; Y是任选取代的亚甲基，S（O）q，其中q是0-2的整数，或任选取代的亚氨基; Z 1是可以具有氧代基或硫代基的C 1-3亚烷基，并且可以在碳链内含有醚化的氧或硫; Z 2是任选取代的C 1-3亚烷基; Ar是任选取代的碳环基团或任选取代的杂环基团; R 1和R 2之一是氢原子，卤素原子，羟基，任选取代的低级烷基或任选取代的低级烷氧基; 另一个是卤素原子，羟基，任意取代的低级烷基或任意取代的低级烷氧基; 或R 1和R 2与相邻的-c = c-一起形成环; 并且环A是除R 1和R 2之外可以被取代的苯环; 或其盐。

7. 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。

8. 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。

9. 发明申请

WO1998009624A1 WATER-SOLUBLE VITAMIN COMPOSITION THAT PROVIDES EXCELLENT TABLETS AND PROCESS FOR PRODUCING THE SAME 审中-公开
标题翻译：提供优异的片剂的水溶性维生素组合物及其生产方法
公开(公告)号：WO1998009624A1
公开(公告)日：1998-03-12
申请号：PCT/JP1996003079
申请日：1996-10-23
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , ASHIDA, Hiroshi , IZUTSU, Daisuke , YAMASHITA, Akio
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： A61K31/375
CPC分类号： A61K9/1623 , A61K9/1652 , A61K9/1688 , A61K9/2018 , A61K9/2095 , A61K31/375
摘要： A water-soluble vitamin composition which contains from 90 to 99.8 % by weight of water-soluble vitamins together with at least one additive selected from among polymeric binders, monosaccharides, disaccharides, sugar alcohols, dextrin and organic acids. The composition can provide tablets having a high mechanical strength (hardness) and being easily disintegrable without causing so much tableting disorder.
摘要翻译：一种水溶性维生素组合物，其含有90至99.8重量％的水溶性维生素以及至少一种选自聚合物粘合剂，单糖，二糖，糖醇，糊精和有机酸的添加剂。组合物可以提供具有高机械强度（硬度）并容易崩解的片剂，而不会引起如此多的压片障碍。

10. 发明申请

WO1997048726A1 METHOD FOR PRODUCING PEPTIDES 审中-公开
标题翻译：生产肽的方法
公开(公告)号：WO1997048726A1
公开(公告)日：1997-12-24
申请号：PCT/JP1997002097
申请日：1997-06-19
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , HATANAKA, Chitoshi , ABE, Yasuaki , YAMANO, Mitsuhisa
发明人： TAKEDA CHEMICAL INDUSTRIES, LTD.
IPC分类号： C07K07/23
CPC分类号： C07K7/23 , Y02P20/55
摘要： A peptide of the formula (I): 5-oxo-Pro-R -Trp-Ser-R -R -R -Arg-Pro-R , wherein R represents His, Tyr, Trp or p-NH2-Phe, R represents Tyr or Phe, R represents an optionally substituted Gly or an optionally substituted alpha -D-amino acid residue, R represents Leu, Ile or Nle, R represents (1) Gly-NH-R , wherein R represents a hydrogen atom or an alkyl group which may optionally be substituted with a hydroxyl group, or (2) NH-R , wherein R represents a hydrogen atom, an alkyl group which may optionally be substituted with a hydroxyl group or an ureido group (-NH-CO-NH2), is produced advantageously in an industrial scale by reacting a peptide of the the formula (II): 5-oxo-Pro-R -Trp-Ser-R -R -OH, wherein R , R and R have the same meanings as defined above or its salts, with a peptide of the formula (III): H-R -R -Pro-R , wherein R and R have the same meaning as defined above and R represents Arg which has been protected or its salts, to produce a peptide of the formula (I'): 5-oxo-Pro-R -Trp-Ser-R -R -R -R -Pro-R , wherein R , R , R , R , R and R have the same meanings as defined above or its salt, and then subjecting thus obtained peptide (I') to a de-protecting group reaction.
摘要翻译：式（I）的肽：5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -R 4 -Arg-Pro-R 6，其中R R 1表示Tyr或Phe，R 3表示任选取代的Gly或任选取代的α-D-氨基酸残基，R 4表示His，Tyr，Trp或p-NH 2-Phe，表示Leu，Ile或Nle，R 6表示（1）Gly-NH-R 7，其中R 7表示氢原子或可任选被羟基取代的烷基，或（2 ）NH-R 8，其中R 8表示氢原子，可任选被羟基或脲基（-NH-CO-NH 2）取代的烷基，有利地以工业规模生产通过使式（II）的肽：5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -OH反应，其中R 1，R 2和 R 3具有与上述相同的含义或其盐，与式（III）的肽：HR 4 -R 5 -Pro-R 6，其中R 4和R“ 6>具有与上述相同的含义，R 5表示被保护的Arg或其盐，以产生式（I'）的肽：5-氧代-Pro-R 1 -Trp-Ser-R 2 -R 3 -R 4 -R 5 - Pro-R 6，其中R 1，R 2，R 3，R 4，R 5和R 6具有与上述相同的含义或其盐，然后将如此得到的肽（I'）进行脱保护基反应。

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