公开(公告)号：US20070037834A1

公开(公告)日：2007-02-15

申请号：US10516750

申请日：2003-06-06

申请人： Hitoshi Arai ,  Tsutomu Matsumura ,  Hiroshi Ishida ,  Yosuke Yamaura ,  Seiji Aratake ,  Etsuo Ohshima ,  Koji Yanagawa ,  Motoki Miyama ,  Koji Suzuki ,  Ari Kawabe ,  Satoshi Nakanishi ,  Katsuya Kobayashi ,  Takashi Sato ,  Ichiro Miki ,  Kimihisa Ueno ,  Shinya Fujii ,  Miho Iwase

发明人： Hitoshi Arai ,  Tsutomu Matsumura ,  Hiroshi Ishida ,  Yosuke Yamaura ,  Seiji Aratake ,  Etsuo Ohshima ,  Koji Yanagawa ,  Motoki Miyama ,  Koji Suzuki ,  Ari Kawabe ,  Satoshi Nakanishi ,  Katsuya Kobayashi ,  Takashi Sato ,  Ichiro Miki ,  Kimihisa Ueno ,  Shinya Fujii ,  Miho Iwase

IPC分类号： A61K31/519 ,  C07D487/02

CPC分类号： C07D263/58 ,  C07D471/04 ,  C07D487/04

摘要： [wherein m and n may be the same or different and each represents an integer of 1 to 3 wherein m+n is 4 or less; R1 represents —NR4R5 (wherein R4 and R5 may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl or the like); R2 represents the above Formula (II), Formula (IV) or the like; A represents a single bond, —C(═O)—, —SO2—, —OC(═O)— or the like; and R3 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aralkyl or the like]Bicyclic pyrimidine derivatives represented by the above Formula (I), or quaternary ammonium salts thereof, or pharmaceutically acceptable salts thereof, or the like, are provided. These have anti-inflammatory activities or modulation activities on the functions of TARC and/or MDC and are useful for treating and/or preventing a disease which is related to T cells, such as an allergic disease, an autoimmune disease or transplant rejection.

摘要翻译： [其中m和n可以相同或不同，并且各自表示1〜3的整数，其中m + n为4以下; R 1表示-NR 4 R 5（其中R 4，R 5和R 5） 可以相同或不同，各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳烷基等）; R 2表示上述式（II），式（IV）等; A表示单键，-C（-O） - ， - SO 2 - ， - OC（-O） - 等; 和R 3表示取代或未取代的低级烷基，取代或未取代的环烷基，取代或未取代的芳烷基等〕由上式（I）表示的双环嘧啶衍生物或其季铵盐或药学上可接受的盐 可接受的盐等。 它们具有对TARC和/或MDC的功能的抗炎活性或调节活性，并且可用于治疗和/或预防与T细胞相关的疾病，例如过敏性疾病，自身免疫疾病或移植排斥反应。

公开(公告)号：US07524852B2

公开(公告)日：2009-04-28

申请号：US10516750

申请日：2003-06-06

申请人： Hitoshi Arai ,  Tsutomu Matsumura ,  Hiroshi Ishida ,  Yosuke Yamaura ,  Seiji Aratake ,  Etsuo Ohshima ,  Koji Yanagawa ,  Motoki Miyama ,  Koji Suzuki ,  Ari Kawabe ,  Satoshi Nakanishi ,  Katsuya Kobayashi ,  Takashi Sato ,  Ichiro Miki ,  Kimihisa Ueno ,  Shinya Fujii ,  Miho Iwase

发明人： Hitoshi Arai ,  Tsutomu Matsumura ,  Hiroshi Ishida ,  Yosuke Yamaura ,  Seiji Aratake ,  Etsuo Ohshima ,  Koji Yanagawa ,  Motoki Miyama ,  Koji Suzuki ,  Ari Kawabe ,  Satoshi Nakanishi ,  Katsuya Kobayashi ,  Takashi Sato ,  Ichiro Miki ,  Kimihisa Ueno ,  Shinya Fujii ,  Miho Iwase

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P29/00

CPC分类号： C07D263/58 ,  C07D471/04 ,  C07D487/04

摘要： [wherein m and n may be the same or different and each represents an integer of 1 to 3 wherein m+n is 4 or less; R1 represents —NR4R5 (wherein R4 and R5 may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl or the like); R2 represents the above Formula (II), Formula (IV) or the like; A represents a single bond, —C(═O)—, —SO2—, —OC(═O)— or the like; and R3 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aralkyl or the like] Bicyclic pyrimidine derivatives represented by the above Formula (I), or quaternary ammonium salts thereof, or pharmaceutically acceptable salts thereof, or the like, are provided. These have anti-inflammatory activities or modulation activities on the functions of TARC and/or MDC and are useful for treating and/or preventing a disease which is related to T cells, such as an allergic disease, an autoimmune disease or transplant rejection.

摘要翻译： [其中m和n可以相同或不同，并且各自表示1〜3的整数，其中m + n为4以下; R1表示-NR4R5（其中R4和R5可以相同或不同，各自表示氢原子，取代或未取代的低级烷基，取代或未取代的芳烷基等）; R2表示上述式（II），式（IV）等; A表示单键，-C（-O） - ， - SO 2 - ， - OC（-O） - 等; 并且R 3表示取代或未取代的低级烷基，取代或未取代的环烷基，取代或未取代的芳烷基等〕上式（I）表示的双环嘧啶衍生物或其季铵盐，或其药学上可接受的盐等， 被提供。 它们具有对TARC和/或MDC的功能的抗炎活性或调节活性，并且可用于治疗和/或预防与T细胞相关的疾病，例如过敏性疾病，自身免疫疾病或移植排斥反应。

公开(公告)号：US20060046992A1

公开(公告)日：2006-03-02

申请号：US10519630

申请日：2003-06-25

申请人： Daisuke Machii ,  Koji Suzuki ,  Tsutomu Matsumura ,  Hitoshi Arai ,  Miho Iwase ,  Hiroshi Yano ,  Satoshi Nakanishi ,  Fumiko Ogino ,  Kotaro Takasaki ,  Hideaki Kusaka

发明人： Daisuke Machii ,  Koji Suzuki ,  Tsutomu Matsumura ,  Hitoshi Arai ,  Miho Iwase ,  Hiroshi Yano ,  Satoshi Nakanishi ,  Fumiko Ogino ,  Kotaro Takasaki ,  Hideaki Kusaka

IPC分类号： A61K31/519 ,  C07D487/04

CPC分类号： C07D471/04 ,  A61K31/437 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/55 ,  C07D487/04

摘要： The present invention provides a compound represented by formula (I): [wherein X—Y-Z represents R5N—C═O (wherein R5 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted lower alkenyl, or substituted or unsubstituted lower alkynyl), etc; R1 and R2 may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, etc; and R3 and R4 may be the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, etc], or a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明提供由式（I）表示的化合物：[其中XYZ表示R 5 NCO（其中R 5表示氢原子，取代或未取代的低级烷基，取代的 或未取代的芳烷基，取代或未取代的低级烯基，或取代或未取代的低级炔基）等; R 1和R 2可以相同或不同，各自表示氢原子，取代或未取代的低级烷基等; R 3和R 4可以相同或不同，各自表示氢原子，取代或未取代的低级烷基等]或其药学上可接受的盐。

公开(公告)号：US06692758B1

公开(公告)日：2004-02-17

申请号：US09806151

申请日：2001-03-28

申请人： Masatoshi Ito ,  Yuriko Kawai ,  Seiji Okazaki ,  Masahiko Tanahashi ,  Kang Jung Kim ,  Miho Iwase

发明人： Masatoshi Ito ,  Yuriko Kawai ,  Seiji Okazaki ,  Masahiko Tanahashi ,  Kang Jung Kim ,  Miho Iwase

IPC分类号： A61K31663

CPC分类号： A61K31/663 ,  A61L27/54 ,  A61L2300/216 ,  A61L2300/432 ,  C07F9/3839

摘要： The present invention relates to an implant attachment stabilizer having, as an effective component, a methanebisphosphonic acid derivative represented by general formula (I) [where, in the formula, X, Y, m, n, , A, B, R1, R2, R3 and R4 are as defined in the Specification], or hydrate thereof. The methanebisphosphonic acid derivatives represented by general formula (I) or the hydrates thereof, to which the present invention relates, have an interstitial tissue proliferation inhibiting action and an osteolytic factor production inhibiting action and, in particular, since they inhibit osteolysis through the inhibition of the interstitial tissue proliferation which accompanies implant attachment and the inhibition of osteolysis factor production at the implant periphery, they are effective in the prevention of implant loosening and detachment, and it is possible to extend the implant attachment period in the case of implants such as artificial joints, and implants in the oro-dental field.

摘要翻译： 本发明涉及具有通式（I）表示的甲烷二膦酸衍生物作为有效成分的植入物附着稳定剂[式中，X，Y，m，n，，A，B，R 1，R 2，R 本发明涉及的通式（I）表示的甲烷二膦酸衍生物或其水合物具有间质组织增殖抑制作用 并且特别是由于它们通过抑制伴随植入物附着的间质组织增殖和抑制植入物周围的骨质疏松因子产生而抑制骨质溶解，因此它们有效地防止植入物松动和 脱离，它是可能的 e以在诸如人造关节的植入物和牙科领域中的植入物的情况下延长植入物固定周期。