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    Pyridine compounds for treating amnesia
    2.
    发明公开
    Pyridine compounds for treating amnesia 失效
    吡啶化合物用于遗忘症的治疗。

    公开(公告)号：EP0558094A1

    公开(公告)日：1993-09-01

    申请号：EP93103799.8

    申请日：1989-09-13

    申请人： YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

    发明人： Oe, Takanori ,  Ono, Yuji ,  Kawasaki, Kazuyuki ,  Nakajima, Tohru

    IPC分类号： C07D213/64 ,  A61K31/44 ,  C07D213/643 ,  C07D213/74 ,  C07D409/06 ,  C07D409/14 ,  C07D413/14 ,  C07D401/04 ,  C07D405/06 ,  C07D401/14 ,  C07D401/06

    CPC分类号： C07D213/64 ,  C07D213/643 ,  C07D213/70 ,  C07D213/74 ,  C07D213/75 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14

    摘要： A novel compound of the formula

    wherein R¹ means hydrogen and R² means hydrogen or a straight-chain or branched chain alkyl having 1 to 8 carbon atoms; Ar means phenyl, a phenyl substituted by 1 to 3 substituent(s) selected from among halogens, straight-chain or branched chain alkyls having 1 to 8 carbon atoms, straight-chain or branched chain alkoxys having 1 to 8 carbon atoms, trifluoromethyl, amino, nitro and cyano, furyl, a furyl substituted by 1 to 3 substituent(s) selected from among halogens, straight-chain or branched chain alkyls having 1 to 8 carbon atoms, straight-chain or branched chain alkoxys having 1 to 8 carbon atoms, trifluoromethyl, straight-chain or branched chain alkylthiols having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfinyls having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfonyls having 1 to 8 carbon atoms, amino, nitro and cyano, thienyl, a thienyl substituted by 1 to 3 substituent(s) selected from among halogens, straight-chain or branched chain alkyls having 1 to 8 carbon atoms, straight-chain or branched chain alkoxys having 1 to 8 carbon atoms, trifluoromethyl, straight-chain or branched chain alkylthiols having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfinyls having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfonyls having 1 to 8 carbon atoms, amino, nitro and cyano, pyrrolyl, a pyrrolyl substituted by 1 to 3 substituent(s) selected from among halogens, straight-chain or branched chain alkyls having 1 to 8 carbon atoms, straight-chain or branched chain alkoxys having 1 to 8 carbon atoms, trifluoromethyl, straight-chain or branched chain alkylthiols having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfinyls having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfonyls having 1 to 8 carbon atoms, amino, nitro and cyano, pyridyl, or a pyridyl substituted by 1 to 3 substituent(s) selected from among halogens, straight-chain or branched chain alkyls having 1 to 8 carbon atoms, straight-chain or branched chain alkoxys having 1 to 8 carbon atoms, trifluoromethyl, straight-chain or branched chain alkylthiols having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfinyls having 1 to 8 carbon atoms, straight-chain or branched chain alkylsulfonyls having 1 to 8 carbon atoms, amino, nitro and cyano: Y means a single bond or a straight-chain or branched chain alkylene having 1 to 8 carbon atoms which may have double bond(s) in the chain; W means a group of the formula (i)

    (wherein R³ and R⁴ are the same or different and respectively mean hydrogen or a halogen, X means -O- or -S-, Z means a single bond or -O-, A is a straight-chain or branched chain alkylene having 1 to 8 carbon atoms, B means -N(R⁸)(R⁹) (wherein R⁸ and R⁹ are the same or different and respectively mean hydrogen or a straight-chain or branched chain alkyl having 1 to 8 carbon atoms, or combinedly means a group forming, taken together with the adjacent nitrogen, 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, piperidino, 1-piperazinyl, a 1-piperazinyl substituted by a straight-chain or branched chain alkyl having 1 to 8 carbon atoms at the 4-position, 1-homopiperazinyl, morpholino and thiomorpholino) or a group of the formula (ii)

    (wherein R¹² and R¹³ are the same or different and respectively mean hydrogen or a straight-chain or branched chain alkyl having 1 to 8 carbon atoms, P is -S- and Q is hexamethylene, heptamethylene, octamethylene, 1-methylpentamethylene, 1-methylhexamethylene, 1-methylheptamethylene, -(CH₂)₂S(CH₂)₃-, -(CH₂)₂S(CH₂)₆-.

    or

    a pharmaceutically acceptable salt thereof or a hydrate thereof.
    The compounds exhibit inhibitory activity on prolylendopeptidase. Also disclosed are pharmaceutical compositions containing the novel pyridine compounds.

    Pyridine compounds and pharmaceutical use thereof
    3.
    发明公开
    Pyridine compounds and pharmaceutical use thereof 失效
    Pyridin-Verbindungen und ihre pharmazeutische Verwendung。

    公开(公告)号：EP0359547A1

    公开(公告)日：1990-03-21

    申请号：EP89309297.3

    申请日：1989-09-13

    申请人： YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

    发明人： Oe, Takanori ,  Ono, Yuji ,  Kawasaki, Kazuyuki ,  Nakajima, Tohru

    IPC分类号： C07D213/64 ,  A61K31/44 ,  C07D213/643 ,  C07D213/74 ,  C07D409/06 ,  C07D409/14 ,  C07D413/14 ,  C07D401/04 ,  C07D405/06 ,  C07D401/14 ,  C07D401/06

    CPC分类号： C07D213/64 ,  C07D213/643 ,  C07D213/70 ,  C07D213/74 ,  C07D213/75 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/14 ,  C07D417/06 ,  C07D417/14

    摘要： A novel pyridine compound of the formula
    wherein R¹ and R² are the same or different and respectively mean hydrogen, a halogen, an alkyl, an alkoxy or an optionally substituted phenyl; Ar means an optionally substituted aryl or heteroaryl; Y means a single bond or an alkylene which may have double bond(s) in the chain; W means a group of the formula
    (wherein R³ and R⁴ are the same or different and respectively mean hydrogen, a halogen, an alkyl, an alkoxy or an optionally substituted phenyl, X means -O-, -S- or -N(R⁵)- (wherein R⁵ means hydrogen, an alkyl or an acyl), Z means a single bond, -O-, -S-, -N(R⁶)- (wherein R⁶ means hydrogen, an alkyl or an acyl) or -CON(R⁷)- (wherein R⁷ means hydrogen, an alkyl or an acyl), A means an alkylene, B means an alkoxycarbonyl, carboxyl, hydroxyl group, -N(R⁸)(R⁹) (wherein R⁸ and R⁹ are the same or different and respectively mean hydrogen, an alkyl, a hydroxyalkyl, an acyl or an optionally substituted aralkyl or heteroaralkyl or conbinedly means a group forming, taken together with the adjacent nitrogen, a heterocyclic group) or -CON(R¹⁰)(R¹¹) (wherein R¹⁰ and R¹¹ are the same or different and respectively mean hydrogen, an alkyl, a hydroxyalkyl, an acyl or an optionally substituted aralkyl or heteroaralkyl, or combinedly mean a group forming, taken together with the adjacent nitrogen, a heterocyclic group), a group of the formula
    (wherein R¹² and R¹³ are the same or different and respectively mean hydrogen, an alkyl, a hydroxyalkyl, an acyl, an optionally substituted phenyl or an optionally substituted aralkyl or heteroaralkyl, or combinedly mean a group forming, taken together with the adjacent nitrogen atom, a heterocyclic group, P means -O-, -S(O) p - (wherein p means an integer of 0 to 2), -N(R¹⁴)- (wherein R¹⁴ means hydrogen, an alkyl or an acyl) or -N(R¹⁵)CO- (wherein R¹⁵ means hydrogen, an alkyl or an acyl), Q means an alkylene having not less than 5 carbon atoms, a cyclic alkylene, an alkylene having not less than 4 carbon atoms which has an interposing oxygen or a sulfur therein or an alkylene having not less than 5 carbon atoms which has carbonyl group at the terminus, with the proviso that Q means an alkylene having not less than 3 carbon atoms, when P is -N(R¹⁵)CO-) or a group of the formula
    (wherein n means an integer of 3 to 5), or a salt thereof.
    The compounds exhibit inhibitory activity on prolylendopeptidase. Also disclosed are pharmaceutical compositions containing the novel pyridine compounds.

    摘要翻译： 式的新颖的吡啶化合物，其中R 1和R 2分别相同或不同，分别表示氢，卤素，烷基，烷氧基或任选取代的苯基; Ar表示任选取代的芳基或杂芳基; Y表示单键或在链中可具有双键的亚烷基; W表示式的基团（其中R 3和R 4分别相同或不同，分别表示氢，卤素，烷基，烷氧基或任选取代的苯基，X表示-O- ，-S-或-N（R 5） - （其中R 5表示氢，烷基或酰基），Z表示单键，-O - ， - S - ， - N（R 6） （其中R 6表示氢，烷基或酰基）或-CON（R 7） - （其中R 7表示氢，烷基或酰基），A表示亚烷基，B 是指烷氧基羰基，羧基，羟基，-N（R 8）（R 9）（其中R 8和R 9分别相同或不同，分别表示氢，烷基，羟基烷基， 酰基或任选取代的芳烷基或杂芳烷基或共轭意指与相邻氮原子一起形成杂环基团）或-CON（R 1）（R 1）（其中 R 1和R 1分别相同或不同，分别表示氢，烷基，羟基烷基，酰基或任选取代的芳烷基或杂芳烷基，或组合 意指与相邻氮原子一起形成杂环基的基团），式CHEM（其中R 1，2和R 3）分别相同或不同， 平均氢，烷基，羟基烷基，酰基，任选取代的苯基或任选取代的芳烷基或杂芳烷基，或组合表示与相邻氮原子一起形成杂环基的基团，P表示-O-， - S（O）p - （其中p表示0至2的整数），-N（R 1）4 - （其中R 1表示氢，烷基或酰基）或 - N（R 15）CO-（其中R 1 5表示氢，烷基或酰基），Q表示不少于5个碳原子的亚烷基，环状亚烷基，具有 不少于4个具有插入氧或硫的碳原子或具有不少于5个碳原子的亚烷基，其末端具有羰基，条件是Q表示不少于3个碳原子的亚烷基，当时 P是 - N（R 1）5）CO-）或式CHEM（其中n表示3〜5的整数）的基团或其盐。 该化合物对脯氨酰前肽酶表现出抑制活性。 还公开了含有新的吡啶化合物的药物组合物。