公开(公告)号：WO1997019078A1

公开(公告)日：1997-05-29

申请号：PCT/JP1996003389

申请日：1996-11-20

Applicant: YAMANOUCHI PHARMACEUTICAL CO., LTD. ,  TAKAYAMA, Kazuhisa ,  HISAMICHI, Hiroyuki ,  IWATA, Masahiro ,  KUBOTA, Hideki ,  AOKI, Motonori

Inventor： YAMANOUCHI PHARMACEUTICAL CO., LTD.

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: Compounds represented by general formula (I) or pharmaceutically acceptable salts thereof which have the effect of inhibiting the activity of type IV phosphodiesterases and are usable as drugs, in particular, type IV phosphodiesterase inhibitors or preventives and remedies for diseases in association with the sthenic type IV phosphodiesterase activity, in particular, respiratory diseases such as bronchial asthma. In said formula (I), X represents oxygen or sulfur; R represents lower alkyl, cycloalkyl(lower alkyl) or cycloalkyl; R represents hydrogen, halogeno, lower alkyl, halo(lower alkyl), hydroxy(lower alkyl), mercapto(lower alkyl), (lower alkoxy)(lower alkyl), (lower alkylthio)(lower alkyl), (lower alkanoyloxy)(lower alkyl), (lower alkanoylthio)(lower alkyl), (lower alkanoyl)(lower alkyl), hydroxyimino(lower alkyl), (lower alkoxyimino)(lower alkyl), cycloalkyl, aryl or lower alkanoyl; R represents hydrogen, halogeno or lower alkyl; R represents hydrogen, or lower alkyl; R represents cycloalkyl optionally substituted by the same group as R ; naphthyl optionally substituted by the same group as R ; a 5- or 6-membered monocyclic heterocycle optionally substituted by the same group as R , optionally fused with a benzene ring and having one to four heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur atoms; or a group of formula (a); and R represents halogeno, lower alkyl, halo(lower alkyl), hydroxy, lower alkoxy, cyano or nitro.

Abstract translation: 具有抑制IV型磷酸二酯酶活性的通式（I）表示的化合物或其药学上可接受的盐，可用作药物，特别是IV型磷酸二酯酶抑制剂或预防药物以及与该类型相关的疾病的治疗方法 IV磷酸二酯酶活性，特别是呼吸道疾病如支气管哮喘。 在所述式（I）中，X表示氧或硫; R 1表示低级烷基，环烷基（低级烷基）或环烷基; R 2表示氢，卤代低级烷基，卤代（低级烷基），羟基（低级烷基），巯基（低级烷基），（低级烷氧基）（低级烷基），（低级烷硫基） （低级烷基），（低级烷酰基）（低级烷基），（低级烷酰基）（低级烷基），羟基亚氨基（低级烷基），（低级烷氧基亚氨基）（低级烷基），环烷基，芳基或低级烷酰基。 R 3表示氢，卤代或低级烷基; R 4表示氢或低级烷基; R 5表示任选被与R 6相同的基团取代的环烷基; 任选被与R 6相同基团取代的萘基; 任选地被与R 6相同的基团取代的5-或6-元单环杂环，任选地与苯环稠合并具有一至四个选自氮，氧和硫原子的杂原子; 或一组式（a）; 和R 6表示卤代，低级烷基，卤代（低级烷基），羟基，低级烷氧基，氰基或硝基。

公开(公告)号：WO0075113A8

公开(公告)日：2001-03-15

申请号：PCT/JP0003767

申请日：2000-06-09

Applicant: YAMANOUCHI PHARMA CO LTD ,  HISAMICHI HIROYUKI ,  KAWAZOE SOUICHIROU ,  TANABE KAZUHITO ,  ICHIKAWA ATSUSHI ,  ORITA AKIKO ,  SUZUKI TAKAYUKI ,  ONDA KENICHI ,  TAKEUCHI MAKOTO

Inventor： HISAMICHI HIROYUKI ,  KAWAZOE SOUICHIROU ,  TANABE KAZUHITO ,  ICHIKAWA ATSUSHI ,  ORITA AKIKO ,  SUZUKI TAKAYUKI ,  ONDA KENICHI ,  TAKEUCHI MAKOTO

IPC: A61P29/00 ,  A61P37/08 ,  A61P43/00 ,  C07D213/82 ,  C07D239/48 ,  C07D241/26 ,  C07D253/07 ,  A61K31/455 ,  A61K31/4965 ,  A61K31/505

CPC classification number: C07D213/82 ,  C07D239/48 ,  C07D241/26 ,  C07D253/07

Abstract: Nitrogenous six-membered heterocycle compounds bearing as the substituents -X-A-R , -N-(R )-(R -substituted Ph) and -CONH2; salts or prodrugs thereof; and Syk inhibitors containing the compounds, the salts or the prodrugs as the active ingredient, wherein A is (substituted) lower alkylene, (substituted) arylene, or the like; X is NR , CONR , NR CO, O, or S; R and R are each H, lower alkyl, -CO-lower alkyl, or -SO2-lower alkyl; R is H, (substituted) lower alkyl, -O-lower alkyl, -S-lower alkyl, -O-aryl, nitro, cyano, or the like; and R is -CO2H, -CO2-lower alkyl, -lower alkylene-CO2H, -NH2, -alkylene-NH2, or the like.

Abstract translation: 带有取代基-X-A-R 3，-N-（R 1） - （R 2取代的Ph）和-CONH 2的含氮六元杂环化合物; 其盐或前药; 和含有所述化合物，所述盐或前药作为活性成分的Syk抑制剂，其中A为（取代的）低级亚烷基，（取代的）亚芳基等; X是NR 4，CONR 4，NR 4 CO，O或S; R 1和R 4各自为H，低级烷基，-CO-低级烷基或-SO 2 - 低级烷基; R 2是H，（取代的）低级烷基，-O-低级烷基，-S-低级烷基，-O-芳基，硝基，氰基等; R 3为-CO 2 H，-CO 2 - 低级烷基， - 低级亚烷基-CO 2 H，-NH 2， - 亚烷基-NH 2等。

公开(公告)号：WO1994022874A1

公开(公告)日：1994-10-13

申请号：PCT/JP1994000472

申请日：1994-03-24

Applicant: YAMANOUCHI PHARMACEUTICAL CO., LTD. ,  HARA, Ryuichiro ,  ITAHANA, Hirotsune ,  SAKAMOTO, Kenichiro ,  HISAMICHI, Hiroyuki ,  NAGANO, Noriaki

Inventor： YAMANOUCHI PHARMACEUTICAL CO., LTD.

IPC: C07D501/20

CPC classification number: C07D501/00 ,  Y02P20/55

Abstract: A cephalosporin derivative represented by general formula (I) or a salt thereof, wherein R represents hydrogen, lower alkenyl, lower alkynyl, cycloalkyl, hydroxyl-protecting group, or (un)substituted lower alkyl; R represents hydrogen, ester residue, or negative charge; R represents either (1) a group represented by general formula (a), wherein R and R represent each independently lower alkoxy or (un)substituted amino, or R and R may be combined together with the neighboring tetrahydropyridazine ring to form an (un)substituted fused 5- or 6-membered ring, or (2) a group represented by general formula (b) or (c), wherein R and R represent each independently hydrogen, halogen, amino, azido, carbamoyl, lower alkyl which may be substituted by amino, azido, carbamoyl or halogen, carbamoyl, or (un)substituted 5- or 6-membered heterocyclic group (provided the nitrogen atom of the heterocycle may be substituted to form a quaternary amine); X represents methine (-CH=) or nitrogen; and ring A represents a 4- to 5-membered nitrogenous heterocycle which may contain oxygen.

Abstract translation: 由通式（I）表示的头孢菌素衍生物或其盐，其中R 1表示氢，低级烯基，低级炔基，环烷基，羟基保护基或（取代的）取代的低级烷基; R 2表示氢，酯残基或负电荷; R 3表示（1）由通式（a）表示的基团，其中R 4和R 5各自独立地代表低级烷氧基或（未）取代的氨基，或R 4和R 5 可以与相邻的四氢哒嗪环一起形成（未）取代的稠合的5元或6元环，或（2）由通式（b）或（c）表示的基团，其中R 6和 R 7各自独立地表示氢，卤素，氨基，叠氮基，氨基甲酰基，可以被氨基，叠氮基，氨基甲酰基或卤素取代的低级烷基，氨基甲酰基或（取代的）取代的5-或6-元杂环基团 杂环的氮原子可以被取代以形成季胺）; X表示次甲基（-CH =）或氮; 环A表示可含有氧的4-至5-元含氮杂环。