Method for treating thrombosis or embolism and related diseases

Abstract

A method for treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing is provided. The method includes administration of an effective amount of a compound represented by formula (1):

1 - 52 . (canceled) 
   
   
       53 . A method for treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing, comprising administering to a patient in need thereof an effective amount of a compound a compound represented by formula (1): 
     
       
         
         
             
             
         
       
     
     wherein
 R 1 , R 2  and R 3  represent a hydrogen atom; 
 R 4  represents a 5 or 6 membered heterocyclic group; 
 Q 1  represents a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, a saturated or unsaturated, 5- to 7-membered heterocyclic group which may be substituted, a saturated or unsaturated, bicyclic or tricyclic condensed hydrocarbon group which may be substituted, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group which may be substituted; 
 Q 2  represents a single bond, a linear or branched alkylene group having 1 to 6 carbon atoms, a linear or branched alkenylene group having 2 to 6 carbon atoms, a linear or branched alkynylene group having 2 to 6 carbon atoms, a saturated or unsaturated, 5- or 6-membered divalent cyclic hydrocarbon group which may be substituted, a saturated or unsaturated, 5- to 7-membered divalent heterocyclic group which may be substituted, a saturated or unsaturated, divalent bicyclic or tricyclic condensed hydrocarbon group which may be substituted, or a saturated or unsaturated, divalent bicyclic or tricyclic condensed heterocyclic group which may be substituted; 
 Q 4  represents an aryl group which may be substituted, an arylalkenyl group which may be substituted, an arylalkynyl group which may be substituted, a heteroaryl group which may be substituted, a heteroarylalkenyl group which may be substituted, a saturated or unsaturated, bicyclic or tricyclic condensed hydrocarbon group which may be substituted, or a saturated or unsaturated, bicyclic or tricyclic condensed heterocyclic group which may be substituted; 
 T 0  represents a carbonyl or thiocarbonyl group; and 
 T 1  represents a carbonyl group, sulfonyl group, group —C(═O)—C(═O)—N(R′)—, group —C(═S)—C(═O)—N(R′)—, group —C(═O)—C(═S)—N(R′)—, group —C(═S)—C(═S)—N(R′)— (wherein R′ represents a hydrogen atom, hydroxyl group, alkyl group or alkoxy group), group —C(═O)-A 1 -N(R″)— (wherein A 1  represents an alkylene group which has 1 to 5 carbon atoms and may be substituted, and R″ represents a hydrogen atom, hydroxyl group, alkyl group or alkoxy group, group), —C(═O)—NH—, group —C(═S)—NH—, group —C(═O)—NH—NH—, group —C(═O)-A 2 -C(═O)— (wherein A 2  represents a single bond or alkylene group having 1 to 5 carbon atoms), group —C(═O)-A 3 -C(═O)—NH— (wherein A 3  represents an alkylene group having 1 to 5 carbon atoms), group —C(═O)—C(═NOR a   13  N(R b ), group —C(═S)-C(═NOR a )—N(R b )— (wherein R a  represents a hydrogen atom, alkyl group or alkanoyl group, and R b  represents a hydrogen atom, hydroxyl group, alkyl group or alkoxy group), group —C(═O)—N═N—, group —C(═S)—N═N—, group —C(═NOR c )—C(═O)—N(R d )— (wherein R c  represents a hydrogen atom, alkyl group, alkanoyl group, aryl group or aralkyl group, and R d  represents a hydrogen atom, hydroxyl group, alkyl group or alkoxy group), group —C(═N—N(R e )(R f ))—C(═O)—N(R g )— (wherein R e  and R f  each independently represent a hydrogen atom, alkyl group, alkanoyl group or alkyl(thiocarbonyl) group, and R g  represents a hydrogen atom, hydroxyl group, alkyl group or alkoxy group), group —C(═O)—NH—C(═O)—, group —C(═S)—NH—C(═O)—, group —C(═O)—NH—C(═S)—, group — C(═S)—NHC(═S)—, group —C(═O)—NH—SO 2 —, group —SO 2 —NH—, group —C(═NCN)—NH—C(═O)—, group —C(═S)—C(═O)— or thiocarbonyl group; or 
 a salt thereof. 
 
   
   
       54 - 62 . (canceled) 
   
   
       63 . The method for treatment of cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing, according to  claim 53 , wherein the effective amount of the compound represented by formula (1) is from about 1 mg to about 1 g. 
   
   
       64 - 65 . (canceled) 
   
   
       66 . A method for treatment of cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing, comprising orally administering to a patient in need thereof, an effective amount of the a solid drug composition comprising:
 at least one pharmaceutically acceptable additive selected from the group consisting of additives consisting of a filler, an extender, a binder, a disintegrator, a dissolution accelerator, a humectant and a lubricant; and   the compound of formula (1) according to  claim 53 .   
   
   
       67 . A method for treatment of cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing, comprising administering by injection to a patient in need thereof, an effective amount of a liquid drug composition comprising:
 water, a pharmaceutically acceptable solvent or a mixture of water and a pharmaceutically acceptable solvent;   at least one additive selected from the group of additives consisting of a stabilizer, a preservative, a dissolution aid, a suspending agent and an emulsifier; and   the compound of formula (1) according to  claim 53 .