Remedy for angiospasm accompanying subarachnoid hemorrhage containing thrombin receptor antagonist as the active ingredient
AssigneesEisai R&D Mangement Co., Ltd., Kyushu University, National University Corporation
InventorsKatsuya Hirano, Yoshihisa Maeda, Tomio Sasaki, Hideo Kanaide, Yasutoshi Kai
Life of this patent
Estimating the term…
Abstract
A therapeutic agent for subarachnoid hemorrhage or a drug for improving prognosis of subarachnoid hemorrhage, comprising a compound having a PAR1 inhibitory effect, its pharmaceutically acceptable salt or a hydrate thereof
Claims19
A method of treating or improving the prognosis of subarachnoid hemorrhage, comprising administering to a patient a therapeutic agent comprising a compound, its pharmaceutically acceptable salt or a hydrate thereof, having an effect of inhibiting the function of protease-activated receptor-1.
A method of treating or improving the prognosis of subarachnoid hemorrhage, comprising administering to a patient a therapeutic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (I)
- [wherein, ring A indicates a pyrrolidine ring;
- ring B indicates a benzene ring or a pyridine ring;
- R101, R102 and R103 independently indicate, identically or differently, a hydrogen atom, a halogen atom, C1-C6 alkyl group or C1-C6 alkoxy group;
- R5 indicates a hydrogen atom, C1-C6 alkyl group or C1-C6 alkoxy C1-C6 alkyl group;
- R6 indicates a hydrogen atom, C1-C6 alkyl group or C1-C6 alkyloxy carbonyl group;
- Y1 indicates a single bond or —CH2—;
- Y2 indicates a single bond or —CO—;
- Ar1 indicates a hydrogen atom or a group represented by Formula (II)
- (wherein, R10, R11, R12, R13 and R14 independently indicate, identically or differently, a hydrogen atom, C1-C6 alkyl group, hydroxyl group, C1-C6 alkoxy group, morpholinyl group, piperazinyl group which may or may not have a substituent, piperidinyl group which may or may not have a substituent or pyrrolidinyl group which may or may not have a substituent, and R11 and R12 or R12 and R13 may bind to each other to form a 5-8-membered heterocycle)],
- its pharmaceutically acceptable salt, or a hydrate thereof.
A method of treating or improving the prognosis of subarachnoid hemorrhage, comprising administering to a patient a therapeutic agent for comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (III)
- [wherein, R1 and R2 independently indicate, identically or differently, a hydrogen atom, methoxy group or ethoxy group;
- X1 indicates a hydrogen atom or a halogen atom;
- Ar2 indicates methyl group, ethyl group, methoxy group, ethoxy group, t-butyl group, morpholinyl group or phenyl group which may be substituted with one or more substituents selected from substituents represented by the following Formula (IV),
- wherein, W indicates —CH— or a nitrogen atom;
- A1 indicates —CH2— or a single bond;
- R3 indicates a hydrogen atom or —OR5a;
- X2 indicates —CH2—, an oxygen atom, a single bond or carbonyl group;
- Y indicates a single bond or C1-C4 alkylene group;
- R4 indicates a hydrogen atom, —OR6a, cyano group or —COOR7;
- R5a, R6a and R7 independently indicate, identically or differently, a hydrogen atom or C1-C4 alkyl group],
- its pharmaceutically acceptable salt or a hydrate thereof.
A method of treating or improving the prognosis of subarachnoid hemorrhage, comprising administering to a patient a therapeutic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is one selected from the group consisting of compounds represented by Formulae (V)-(XI), its pharmaceutically acceptable salt or a hydrate thereof.
A method of treating or improving the prognosis of subarachnoid hemorrhage, comprising administering to a patient a therapeutic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (V), its pharmaceutically acceptable salt or a hydrate thereof.
A method of inhibiting the function of protease-activated receptor-1, comprising administering to a patient an antivasospastic agent comprising a compound, its pharmaceutically acceptable salt or a hydrate thereof, having an effect of inhibiting the function of protease-activated receptor-1.
A method for inhibiting the function of protease-activated receptor-1, comprising administering to a patient an antivasospastic agent comprising-a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (I)
- [wherein, ring A indicates a pyrrolidine ring;
- ring B indicates a benzene ring or a pyridine ring;
- R101, R102 and R103 independently indicate, identically or differently, a hydrogen atom, a halogen atom, C1-C6 alkyl group or C1-C6 alkoxy group;
- R5 indicates a hydrogen atom, C1-C6 alkyl group or C1-C6 alkoxy C1-C6 alkyl group;
- R6 indicates a hydrogen atom, C1-C6 alkyl group or C1-C6 alkyloxy carbonyl group;
- Y1 indicates a single bond or —CH2—;
- Y2 indicates a single bond or —CO—;
- Ar1 indicates a hydrogen atom or a group represented by Formula (II)
- (wherein, R10, R11, R12, R13 and R14 independently indicate, identically or differently, a hydrogen atom, C1-C6 alkyl group, hydroxyl group, C1-C6 alkoxy group, morpholinyl group, piperazinyl group which may or may not have a substituent, piperidinyl group which may or may not have a substituent or pyrrolidinyl group which may or may not have a substituent, and R11 and R12 or R12 and R13 may bind to each other to form a 5-8-membered heterocycle)],
- its pharmaceutically acceptable salt or a hydrate thereof.
A method of inhibiting the function of protease-activated receptor-1, comprising administering to a patient an antivasospastic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (III)
- [wherein, R1 and R2 independently indicate, identically or differently, a hydrogen atom, methoxy group or ethoxy group;
- X1 indicates a hydrogen atom or a halogen atom;
- Ar2 indicates methyl group, ethyl group, methoxy group, ethoxy group, t-butyl group, morpholinyl group or phenyl group which may be substituted with one or more substituents selected from substituents represented by the following Formula (IV),
- (wherein, W indicates —CH— or a nitrogen atom;
- A1 indicates —CH2— or a single bond;
- R3 indicates a hydrogen atom or —OR5a;
- X2 indicates —CH2—, an oxygen atom, a single bond or carbonyl group;
- Y indicates a single bond or C1-C4 alkylene group;
- R4 indicates a hydrogen atom, —OR6a, cyano group or —COOR7;
- R5a, R6a and R7 independently indicate, identically or differently, a hydrogen atom or C1-C4 alkyl group)],
- its pharmaceutically acceptable salt or a hydrate thereof.
A method of inhibiting the function of protease-activated receptor-1, comprising administering to a patient an antivasospastic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is any one selected from the group consisting of compounds represented by Formulae (V)-(XI), its pharmaceutically acceptable salt or a hydrate thereof.
A method of inhibiting the function of protease-activated receptor-1, comprising administering to a patient an antivasospastic agent comprising a 2-iminopyrrolidine derivative, wherein the 2-iminopyrrolidine derivative is a compound represented by Formula (V), its pharmaceutically acceptable salt or a hydrate thereof.
A method for treating subarachnoid hemorrhage or a method for improving prognosis of subarachnoid hemorrhage, comprising administering an effective amount of a compound having an effect of inhibiting the function of protease-activated receptor-1, its pharmaceutically acceptable salt or a hydrate thereof to a patient.
19-22. (canceled)
Dependencies are inferred from the claim text.