Method of treatment using inhibitors of mitosis

Abstract

Methods of treating diseases caused by cell division or that are treated by inhibiting mitosis by administering two doses of an inhibitor of mitosis between the biologically effective dose and the maximum tolerated dose in a dosing cycle that allows for the recovery or subsiding of side effects, wherein the second dose is administered 24 to 48 hours after the first dose.

1 - 137 . (canceled) 
     
     
         138 . A method for treating cancer by administering to a patient in need thereof two doses of an inhibitor of mitosis selected from the group consisting of the '161 KSP Inhibitors between the biologically effective dose and the maximum tolerated dose in a 21 day dosing cycle, wherein the first dose is administered on day one of the dosing cycle and the second dose is administered 12 to 60 hours after the first dose, and the '161 KSP Inhibitors are selected from the group consisting of 2-(3-aminopropyl)-5-(3-fluorophenyl)-N-(2-methoxyethyl)-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide, 2-(3-aminopropyl)-5-(3-fluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide, 2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide, (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide, (R)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide, and 2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-hydroxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide. 
     
     
         139 . A method of  claim 138 , wherein the second dose is administered 24 hours after the first dose. 
     
     
         140 . A method of  claim 138 , wherein the second dose is administered 48 hours after the first dose. 
     
     
         141 . A method of  claim 139 , wherein the two doses are at the maximum tolerated dose. 
     
     
         142 . A method of  claim 140 , wherein the two doses are at the maximum tolerated dose. 
     
     
         143 . A method of  claim 138 , wherein the cancer is a hematological tumor selected from lymphoma, leukemia and multiple myeloma. 
     
     
         144 . A method of  claim 143 , wherein the hematological tumor is selected from advanced myeloid leukemia, relapsed multiple myeloma and refractory multiple myeloma. 
     
     
         145 . A method of  claim 138 , wherein the '161 KSP Inhibitor is (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide. 
     
     
         146 . A method of  claim 138 , wherein the '161 KSP Inhibitor is (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3 (2H)-carboxamide. 
     
     
         147 . A method of  claim 138 , wherein the '161 KSP Inhibitor is (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3 (2H)-carboxamide. 
     
     
         148 . A method of  claim 138 , wherein the '161 KSP Inhibitor is (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide.