公开(公告)号：US20090048223A1

公开(公告)日：2009-02-19

申请号：US12071921

申请日：2008-02-27

申请人： Koki Matsubara ,  Atsushi Iesato ,  Akifumi Oomura ,  Koh Kawasaki ,  Rintaro Yamada ,  Minoru Seto

发明人： Koki Matsubara ,  Atsushi Iesato ,  Akifumi Oomura ,  Koh Kawasaki ,  Rintaro Yamada ,  Minoru Seto

IPC分类号： A61K31/397 ,  C07D401/14 ,  A61K31/4725 ,  C07D401/02 ,  A61K31/496 ,  A61K31/5377 ,  C07D413/14 ,  C07D487/02 ,  A61K31/5025

CPC分类号： A61K31/55 ,  A61K31/47 ,  C07D401/12

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an acyl group, an acyloxy group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; Y represents a single bond, or —C(R3)(R4)— (R3 and R4 represent hydrogen atom, or an alkyl group, or alkylene groups which combine together to form a saturated hydrocarbon ring group); G4 represents hydroxyl group (Y is a single group), or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a saturated heterocyclic group, an alkylsulfonyl group, an acyl group, or an amidino group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基，炔基，烷氧基，烷硫基，氨基，烷基亚磺酰基，烷基磺酰基或芳基 组; G3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基，炔基，烷氧基，烷硫基，氨基，烷氧基羰基，酰基， 酰氧基，烷基亚磺酰基，烷基磺酰基或芳基; Y表示单键，或-C（R3）（R4） - （R3和R4表示氢原子，或烷基或结合在一起形成饱和烃环基的亚烷基）; G4表示羟基（Y为单一基团）或-N（R1）（R2）（R1和R2表示氢原子，烷基，芳烷基，烯基，炔基，饱和杂环基， 烷基磺酰基，酰基或脒基）; G5是A的环构成碳原子上的取代基，代表氢原子，氟原子或烷基，或其盐，或其作为前体药物的衍生物，其有效抑制Rho激酶。

公开(公告)号：US07964613B2

公开(公告)日：2011-06-21

申请号：US12071921

申请日：2008-02-27

申请人： Koki Matsubara ,  Atsushi Iesato ,  Akifumi Oomura ,  Koh Kawasaki ,  Rintaro Yamada ,  Minoru Seto

发明人： Koki Matsubara ,  Atsushi Iesato ,  Akifumi Oomura ,  Koh Kawasaki ,  Rintaro Yamada ,  Minoru Seto

IPC分类号： A01N43/42 ,  A01N43/00 ,  A61K31/47 ,  A61K31/00 ,  C07D217/00 ,  C07D217/22

CPC分类号： A61K31/55 ,  A61K31/47 ,  C07D401/12

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an acyl group, an acyloxy group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; Y represents a single bond, or —C(R3)(R4)— (R3 and R4 represent hydrogen atom, or an alkyl group, or alkylene groups which combine together to form a saturated hydrocarbon ring group); G4 represents hydroxyl group (Y is a single group), or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a saturated heterocyclic group, an alkylsulfonyl group, an acyl group, or an amidino group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基，炔基，烷氧基，烷硫基，氨基，烷基亚磺酰基，烷基磺酰基或芳基 组; G3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基，炔基，烷氧基，烷硫基，氨基，烷氧基羰基，酰基， 酰氧基，烷基亚磺酰基，烷基磺酰基或芳基; Y表示单键，或-C（R3）（R4） - （R3和R4表示氢原子，或烷基或结合在一起形成饱和烃环基的亚烷基）; G4表示羟基（Y为单一基团）或-N（R1）（R2）（R1和R2表示氢原子，烷基，芳烷基，烯基，炔基，饱和杂环基， 烷基磺酰基，酰基或脒基）; G5是A的环构成碳原子上的取代基，代表氢原子，氟原子或烷基，或其盐，或其作为前体药物的衍生物，其有效抑制Rho激酶。

公开(公告)号：US20060247266A1

公开(公告)日：2006-11-02

申请号：US11286399

申请日：2005-11-25

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： A61K31/4745 ,  C07D471/06

CPC分类号： C07D471/06

摘要： A novel compound represented by the following formula (1) or a salt thereof [wherein R1, R5, R6, R7, and R8 represent hydrogen atom, a halogen atom, hydroxyl group, an alkyl group, an alkenyl group and the like; X1 . . . X2 represents —CH(R2)—CH(R3)—, —CH(R2)—CH(R3)—CH(R4)—, —C(R2)═C(R3)—, or —C(R2)═C(R3)—CH(R4)—(R2, R3, and R4 represent hydrogen atom, or an alkyl group); A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents —CH(A3)-, —CH(A3)-C(A4)(A41)-, —CH(A3)-C(A4)(A41)-C(A5)(A51)-, or a single bond (A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group), and Z represents hydroxyl group, or —N(A6)(A61)(A6 represents hydrogen atom, or an alkyl group, and A61 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like)], having an action of potently inhibiting phosphorylation of myosin regulatory light chain.

摘要翻译： 由下式（1）表示的新化合物或其盐[其中R 1，R 5，R 6，R 6， > 7，R 8表示氢原子，卤素原子，羟基，烷基，烯基等; X 1> 。 。 。 X 2表示-CH（R 2）CH（R 3） - ， - CH（R 2） ）-CH（R 3）CH（R 4） - ， - C（R 2） - C（R 3） - （R 4） - （R 4） - 或（R 3） - （R 3） R 2，R 3，R 4和R 4代表氢原子或烷基; A 1，A 2，A 2和A 21代表氢原子或烷基; Y表示-CH（低级） - ， - CH（低级） - （A 4 - ）（A 4） CH 3） - ， - （CH 3）C（A 4） （A 5+） - 或单键（A 3，S 4，A 4，A 41， A，S 5和A 51代表氢原子或烷基，Z表示羟基，或-N（A 6） （A 61）（A 6）代表氢原子或烷基，A 61代表氢原子，烷基 基团，取代的烷基等）]，具有有力抑制肌球蛋白调节轻链的磷酸化的作用。

公开(公告)号：US07618984B2

公开(公告)日：2009-11-17

申请号：US11511395

申请日：2006-08-29

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： C07D401/00 ,  A61K31/47

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G4 represents hydroxyl group, or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits phosphorylation of the myosin regulatory light chain.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基等; G3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基等; G4表示羟基或-N（R1）（R2）（R1和R2表示氢原子，烷基，芳烷基，烯基，炔基或饱和杂环基）。 G5是A的环构成碳原子上的取代基，表示作为前药的氢原子，氟原子或烷基或其盐或其衍生物，其有效抑制肌球蛋白调节光的磷酸化 链。

公开(公告)号：US07094789B2

公开(公告)日：2006-08-22

申请号：US10623751

申请日：2003-07-22

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： C07D217/02 ,  A61K31/44

CPC分类号： C07D217/04

摘要： A compound represented by the following formula (1) or a salt thereof: wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents —O—X—C(A1)(A11)-C(A2)(A21)-N(A31)(A3) (X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.

摘要翻译： 由下式（1）表示的化合物或其盐：其中R 1表示氢原子，卤素原子等; R 2表示氢原子，卤素原子，C 1-6烷基等; 和R 3表示-OXC（A 1）（A 11）-C（A 2）（A 2）（A 2） N（A 30）（A 3 S）（X表示亚丙基等，A 11， 而A 21代表氢原子或C 1-6烷基，A 31是C 1-6烷基， 被羟基或氢原子取代的亚烷基，A 1，A 2和A 3代表氢原子，C 1-6烷基等）等，其对肌球蛋白调节轻链的磷酸化具有抑制活性，并且可用于治疗与各种细胞等的收缩有关的疾病 。

公开(公告)号：US20100093789A1

公开(公告)日：2010-04-15

申请号：US12526000

申请日：2007-02-27

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： A61K31/4725 ,  A61P27/06 ,  C07D401/02

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G4 represents hydroxyl group, or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基等; G3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基等; G4表示羟基或-N（R1）（R2）（R1和R2表示氢原子，烷基，芳烷基，烯基，炔基或饱和杂环基）。 G5是A的环构成碳原子上的取代基，代表氢原子，氟原子或烷基，或其盐，或其作为前体药物的衍生物，其有效抑制Rho激酶。

公开(公告)号：US20070179127A1

公开(公告)日：2007-08-02

申请号：US11511395

申请日：2006-08-29

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： A61K31/4709 ,  C07D401/02

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G4 represents hydroxyl group, or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits phosphorylation of the myosin regulatory light chain.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G 1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基等; G 3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基等; G 4表示羟基，或-N（R 1）2（R 2）（R 1）和R 2 代表氢原子，烷基，芳烷基，烯基，炔基或饱和杂环基）; G 5是A的构成环的碳原子上的取代基，代表氢原子，氟原子或烷基，或其盐或作为其前体药物的衍生物，其中 有效抑制肌球蛋白调节轻链的磷酸化。

公开(公告)号：US20050096310A1

公开(公告)日：2005-05-05

申请号：US10859098

申请日：2004-06-03

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： A61K31/4745 ,  A61K31/55 ,  A61P11/06 ,  A61P25/00 ,  A61P27/06 ,  A61P43/00 ,  C07D471/02 ,  C07D471/06

CPC分类号： C07D471/06

摘要： A novel compound represented by the formula (1): [R1 represents hydrogen atom, chlorine atom, or hydroxyl group; X1 . . . X2 represents —CH(R2)—CH(R3)—, —CH(R2)—CH(R3)—CH(R4)—, etc.; R2to R4represent hydrogen atom, or an alkyl group; A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents —CH(A3)-, —CH(A3)-C(A4)(A41)-, —CH(A3)-C(A4)(A41)-C(A5)(A51)-, or a single bond; A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group; Z represents hydroxyl group, or —N(A6)(A61); A6 represents hydrogen atom, or an alkyl group, A61 represents hydrogen atom, an alkyl group, an aralkyl group, etc.; and groups in each of one or more combinations selected from the group consisting of combinations of A6 and A3, A6 and A4, A6 and A1, A6 and A2, A2 and A3, A2 and A4, A6 and A5, A3 and A1, and A5 and A1 may bind to each other to form a 5- or 6-membered ring], or a salt thereof, which potently inhibits the phosphorylation of myosin regulatory light chain.

公开(公告)号：US08415372B2

公开(公告)日：2013-04-09

申请号：US12526000

申请日：2007-02-27

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： C07D401/02 ,  A61K31/47

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G4 represents hydroxyl group, or —N(R1)(R2) (R1 and R2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

摘要翻译： 由式（1）表示的化合物[A表示含氮饱和环; m表示0〜2的整数。 n表示1〜4的整数， G1表示氢原子，氯原子，羟基，烷氧基或氨基; G 2表示卤素原子，羟基，氰基，羧基，烷基，烯基等; G3表示氢原子，卤素原子，羟基，氰基，羧基，烷基，烯基等; G4表示羟基或-N（R1）（R2）（R1和R2表示氢原子，烷基，芳烷基，烯基，炔基或饱和杂环基）。 G5是A的环构成碳原子上的取代基，代表氢原子，氟原子或烷基，或其盐，或其作为前体药物的衍生物，其有效抑制Rho激酶。

公开(公告)号：US07160894B2

公开(公告)日：2007-01-09

申请号：US10859098

申请日：2004-06-03

申请人： Rintaro Yamada ,  Minoru Seto

发明人： Rintaro Yamada ,  Minoru Seto

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D455/04 ,  C07D471/00 ,  C07D491/00

CPC分类号： C07D471/06

摘要： A novel compound represented by the formula (1): [R1 represents hydrogen atom, chlorine atom, or hydroxyl group; X1 . . . X2 represents—CH(R2)—CH(R3)—, —CH(R2)—CH(R3)—CH(R4)—, etc.; R2 to R4represent hydrogen atom, or an alkyl group; A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents —CH(A3)—, —CH(A3)—C(A4)(A41)—, —CH(A3)—C(A4)(A41)—C(A5)(A51)—, or a single bond; A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group; Z represents hydroxyl group, or —N(A6)(A61); A6 represents hydrogen atom, or an alkyl group, A61 represents hydrogen atom, an alkyl group, an aralkyl group, etc.; and groups in each of one or more combinations selected from the group consisting of combinations of A6 and A3, A6 and A4, A6 and A1, A6 and A2, A2 and A3, A2 and A4, A6 and A5, A3 and A1, and A5 and A1 may bind to each other to form a 5- or 6-membered ring], or a salt thereof, which potently inhibits the phosphorylation of myosin regulatory light chain.