Substituted 4h-chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof

Abstract

The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the general Formula I: wherein R 1 -R 5 , A, Y and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

1 . A method of treating a disorder responsive to the induction of apoptosis in an animal suffering therefrom, comprising administering to an animal in need of such treatment an effective amount of a compound selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-bromophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methoxy-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3trifluoromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl)-4 methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-5-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene;    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       2 . The method of  claim 1 , wherein said compound is selected from the group consisting of: 
 2-Amino-3-cyano-7-ethylamino-4-(3-bromophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methoxy-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       3 . The method of  claim 1 , wherein said compound is selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2 Amino 3 cyano 7 amino 4 (3 fluorophenyl)-4H chromene;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-trifluromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl-4-methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-5-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene;    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran; 
 or a pharmaceutically acceptable salt thereof.  
   
   
   
       4 . The method of  claim 1 , wherein said animal is a mammal.  
   
   
       5 . The method of  claim 1 , wherein said disorder is cancer.  
   
   
       6 . The method of  claim 5 , wherein said cancer is selected from the group consisting of Hodgkin's disease, non-Hodgkin's lymphoma, acute lymphatic leukemia, chronic lymphocytic leukemia, multiple myeloma, neuroblastoma, breast carcinoma, ovarian carcinoma, lung carcinoma, Wilms' tumor, cervical carcinoma, testicular carcinoma, soft-tissue sarcoma, chronic lymphocytic leukemia, primary macroglobulinemia, bladder carcinoma, chronic granulocytic leukemia, primary brain carcinoma, malignant melanoma, small-cell lung carcinoma, stomach carcinoma, colon carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, head or neck carcinoma, osteogenic sarcoma, pancreatic carcinoma, acute granulocytic leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, malignant hypercalcemia, cervical hyperplasia, renal cell carcinoma, endometrial carcinoma, polycythemia vera, essential thrombocytosis, adrenal cortex carcinoma, skin cancer and prostatic carcinoma.  
   
   
       7 . The method of  claim 5 , wherein said disorder is a drug resistant cancer.  
   
   
       8 . The method of  claim 5 , additionally comprising administering at least one known cancer chemotherapeutic agent, or a pharmaceutically acceptable salt of said agent.  
   
   
       9 . The method of  claim 8 , wherein said known cancer therapeutic agent is selected from the group consisting of busulfan, cis-platin, mitomycin C, carboplatin, colchicine, vinblastine, paclitaxel, docetaxel, camptothecin, topotecan, doxorubicin, etoposide, 5-azacytidine, 5-fluorouracil, methotrexate, 5-fluoro-2′-deoxy-uridine, ara-C, hydroxyurea, thioguanine, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, octreotide, retinoic acid, tamoxifen, Herceptin®, Rituxan® and alanosine.  
   
   
       10 . The method of  claim 5 , additionally comprising treating said animal with radiation-therapy.  
   
   
       11 . The method of  claim 5 , wherein said compound is administered after surgical treatment of said animal for said cancer.  
   
   
       12 . The method of  claim 1 , wherein said disorder is an autoimmune disease.  
   
   
       13 . The method of  claim 1 , wherein said disorder is rheumatoid arthritis.  
   
   
       14 . The method of  claim 1 , wherein said disorder is inflammation or inflammatory bowel disease.  
   
   
       15 . The method of  claim 1 , wherein said disorder is a skin disease.  
   
   
       16 . (canceled)  
   
   
       17 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-bromophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methoxy-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3trifluoromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5 dimethoxyphenyl dimethoxyphenyl)-4-methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-5-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene;    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2,7 Diamino 3 cyano 4 phenyl 4H-chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran, 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       18 . The pharmaceutical composition of  claim 17 , wherein said compound is selected from the group consisting of: 
 2-Amino-3-cyano-7-ethylamino-4-(3-bromophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2,7 Diamino 3 cyano 4 (3 nitrophenyl)-4H chromene;    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methoxy-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazo[   2,3-h]chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       19 . The pharmaceutically composition of  claim 17 , wherein said compound is selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2 Amino 3 cyano 7 amino 4 (3 fluorophenyl)-4H chromene;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-trifluromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl-4-methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-S-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene;    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[   3,2-h]chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[   2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       20 . The pharmaceutical composition of  claim 17 , further comprising at least one known cancer chemotherapeutic agent, or a pharmaceutically acceptable salt of said agent.  
   
   
       21 . The pharmaceutical composition of  claim 20 , wherein said known cancer chemotherapeutic agent is selected from the group consisting of busulfan, cis-platin, mitomycin C, carboplatin, colchicine, vinblastine, paclitaxel, docetaxel, camptothecin, topotecan, doxorubicin, etoposide, 5-azacytidine, 5-fluorouracil, methotrexate, 5-fluoro-2′-deoxy-uridine, ara-C, hydroxyurea, thioguanine, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, octreotide, retinoic acid, tamoxifen, Herceptin®, Rituxan® and alanosine.  
   
   
       22 . The pharmaceutical composition of  claim 17 , wherein said excipient or carrier is selected from the group consisting of saccharides, starch pastes, gelatin, tragacanth, cellulose preparations, calcium phosphates and polyvinyl pyrrolidone.  
   
   
       23 - 28 . (canceled)  
   
   
       29 . A compound selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-bromophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-methoxy-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-trifluoromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl)-4-methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-5-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene;    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene;    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       30 . The compound of  claim 29 , selected from the group consisting of: 
 2-amino-3-cyano-7-methoxy-4-(1,2,3,6-tetrahydrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethyl amino-4-(3-bromophenyl)-4H-chromene,    2-Amino-3-cyano-7-ethylamino-4-(3-chlorophenyl)-4H-chromene,    2-Amino-3-cyano-7-ethylamino-4-(3-nitrophenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3,5-dimethoxyphenyl)-4H-chromene,    2-Amino-3-cyano-7-ethylamino-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-ethylamino-4-(3-cyanophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-bromophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-cyanophenyl)-4H-chromene,    2,7-Diamino-3-cyano-4-(3-methoxyphenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-chlorophenyl)-4H-chromene,    2,7-Diamino-3-cyano-4-(3-methylphenyl)-4H-chromene,    2-Amino-3-cyano-7-methoxy-4-phenyl-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7,8-methylenedioxy-4-(3-methoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-phenylbutanoyloxy)phenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-(2-methylbutanoyloxy)phenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-iodophenyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3,45-trimethoxyphenyl)-4H-chromene,    2-Amino-3-cyano-7-hydroxy-4-(3,4,5-trimethoxyphenyl)-4H-chromene,    2-Amino-3-cyano-7-(2-methylbutanoylamino)-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene,    2-Amino-3-cyano-7-methoxy-4-(3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-7-ethylamino-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methyl-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-bromo-3-pyridyl)-4H-chromene;    2,7-Diamino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-methyl-3-pyridyl)-4H-indolo[4,5-b]pyran    2-Amino-3-cyano-4-(5-methoxy-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-bromo-3-pyridyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[[7,6-b]pyran;    2-Amino-3-cyano-4-(3,4,5-trimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-nitrophenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-imidazo[4,5-h]chromene,    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrazo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-furo[2,3-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-furo[2,3-h]chromene; and    2-amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-thieno[2,3-h]chromene; 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       31 . (canceled)  
   
   
       32 . The compound of  claim 29 , selected from the group consisting of: 
 2-Amino-3-cyano-7-hydroxy-4-(3-cyanophenyl)-4H-chromene;    2-Amino-3-cyano-7,8-dihydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-dichlorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-8-methyl-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-hydroxy-8-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(3-fluorophenyl)-4H-chromene;    2-Amino-3-cyano-7-amino-4-(3,5-difluorophenyl)-4H-chromene;    2-Amino-6-chloro-3-cyano-7-methyl-4-phenyl-4H-chromene;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-7-dimethylamino-4H-chromene;    3-Cyano-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-2,7-diamino-4H-chromene;    2-Amino-3-cyano-7-pyrrolidine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-piperazine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-N-morpholine-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-pyrrole-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-dimethylamino-4-(3-bromo-4,5-dimethoxyphenyl-4-methylchromene;    2-Amino-3-cyano-4-phenyl-4-methylchromene;    2-Amino-3-cyano-7-amino-8-hydroxy-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene;    2-Amino-3-cyano-7-methoxy-4-(2,4-dimethoxypyrimidinyl)-4H-chromene;    2-Amino-3-cyano-4-(3,5-dichlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-chlorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3,5-difluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-fluorophenyl)-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4-phosphoric acid-di piperidine salt-5-methoxyphenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-ethoxycarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl]-4H-indolo[4,5-b]pyran;    2-Amino-3-methylcarboxyl-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[4,5-b]pyran;    2-Amino-4-(3-bromo-4-hydroxy-5-methoxyphenyl)-3-cyano-4H-indolo[7,6-b]pyran,    2-Amino-3-cyano-4-(3-cyano-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-trifluoromethyl-phenyl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-methyl-4H-imidazo[4,5-h]chromene,    2-Amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-9-methyl-4H-imidazo[4,5-h]chromene,    2-Amino-3-cyano-4-(5-methyl-pyridin-3-yl)-4H-indolo[7,6-b]pyran,    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(5-cyano-pyridin-3-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-4-(quinoxalin-2-yl)-4H-indolo[4,5-b]pyran;    2-Amino-3-cyano-4-(6-methyl-pyrazin-2-yl)-4H-indolo[7,6-b]pyran;    2-Amino-3-cyano-7-methoxy-4-(3-methoxyphenyl)-4H-thiochromene;    2-Amino-3-cyano-4-phenyl-1,4-dihydroquinoline,    3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene,    2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-9-methyl-4H-pyrrolo[3,2-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-pyrazino[2,3-h]chromene;    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-8-oxo-4,7,8,9-tetrahydroimidazo[4,5-h]chromene,    2-Amino-3-cyano-4-(3-methoxyphenyl)-8-oxo-4,7,8,9-tetrahydro-imidazo[4,5-h]chromene;    2-Amino-3-cyano-4-(3-methoxyphenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene; and    2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxy-phenyl)-4,7,8,9,10-pentahydro-8,9-dioxypyrazine[2,3-h]chromene, 
 or a pharmaceutically acceptable salt or prodrug thereof.  
   
   
   
       33 - 46 . (canceled)  
   
   
       47 . A method of treating a disorder responsive to the induction of apoptosis in an animal suffering therefrom, comprising administering to an animal in need of such treatment an effective amount of a compound having Formula I:  
     
       
         
         
             
             
         
       
       wherein:  
       Y is CN, COR 7 , CO 2 R 7  or CONR x R y , wherein R 7 , R x  and R y  are independently hydrogen, C 1-10  alkyl, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl or aminoalkyl; or  
       R x  and R y  are taken together with the nitrogen to form a heterocycle;  
       Z is NR 8 R 9 , NHCOR 8 , N(COR 8 ) 2 , N(COR 8 )(COR 9 ), N═CHOR 8  or N═CHR 8 , wherein R 8  and R 9  are independently H, C 1-4  alkyl or aryl, or R 8  and R 9  are combined together with the group attached to them to form a heterocycle;  
       R 1 -R 2  are independently amino;  
       R 3 -R 4  are independently hydrogen, halo, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, C 1-10  alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitro, amino, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, methylenedioxy, carbonylamido or alkylthiol;  
       R 5  is hydrogen or C 1-10  alkyl; and  
       A is optionally substituted and is aryl, heteroaryl, saturated carbocyclic, partially saturated carbocyclic, saturated heterocyclic, partially saturated heterocyclic or arylalkyl; or  
       a pharmaceutically acceptable salt or prodrug thereof.  
     
   
   
       48 . The method of  claim 47 , wherein said animal is a mammal.  
   
   
       49 . The method of  claim 47 , wherein said disorder is cancer.  
   
   
       50 . The method of  claim 49 , wherein said cancer is selected from the group consisting of Hodgkin's disease, non-Hodgkin's lymphoma, acute lymphatic leukemia, chronic lymphocytic leukemia, multiple myeloma, neuroblastoma, breast carcinoma, ovarian carcinoma, lung carcinoma, Wilms' tumor, cervical carcinoma, testicular carcinoma, soft-tissue sarcoma, chronic lymphocytic leukemia, primary macroglobulinemia, bladder carcinoma, chronic granulocytic leukemia, primary brain carcinoma, malignant melanoma, small-cell lung carcinoma, stomach carcinoma, colon carcinoma, malignant pancreatic insulinoma, malignant carcinoid carcinoma, choriocarcinoma, mycosis fungoides, head or neck carcinoma, osteogenic sarcoma, pancreatic carcinoma, acute granulocytic leukemia, hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma, genitourinary carcinoma, thyroid carcinoma, esophageal carcinoma, malignant hypercalcemia, cervical hyperplasia, renal cell carcinoma, endometrial carcinoma, polycythemia vera, essential thrombocytosis, adrenal cortex carcinoma, skin cancer and prostatic carcinoma.  
   
   
       51 . The method of  claim 47 , wherein said disorder is a drug resistant cancer.  
   
   
       52 . The method of  claim 47 , wherein said disorder is an autoimmune disease.  
   
   
       53 . The method of  claim 47 , wherein said disorder is rheumatoid arthritis.  
   
   
       54 . The method of  claim 47 , wherein said disorder is inflammation or inflammatory bowel disease.  
   
   
       55 . The method of  claim 47 , wherein said disorder is a skin disease.  
   
   
       56 . (canceled)  
   
   
       57 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound having Formula I:  
     
       
         
         
             
             
         
       
       wherein:  
       Y is CN, COR 7 , CO 2 R 7  or CONR x R y , wherein R 7 , R x  and R y  are independently hydrogen, C 1-10  alkyl, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl or aminoalkyl; or  
       R x  and R y  are taken together with the nitrogen to form a heterocycle;  
       Z is NR 8 R 9 , NHCOR 8 , N(COR 8 ) 2 , N(COR 8 )(COR 9 ), N═CHOR 8  or N═CHR 8 , wherein R 8  and R 9  are independently H, C 1-4  alkyl or aryl, or R 8  and R 9  are combined together with the group attached to them to form a heterocycle;  
       R 1 -R 2  are independently amino;  
       R 3 -R 4  are independently hydrogen, halo, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, C 1-10  alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitro, amino, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, methylenedioxy carbonylamido or alkylthiol;  
       R 5  is hydrogen or C 10  alkyl; and  
       A is optionally substituted and is aryl, heteroaryl, saturated carbocyclic, partially saturated carbocyclic, saturated heterocyclic, partially saturated heterocyclic or arylalkyl; or  
       a pharmaceutically acceptable salt or prodrug thereof.  
     
   
   
       58 . The pharmaceutical composition of  claim 57 , further comprising at least one known cancer chemotherapeutic agent, or a pharmaceutically acceptable salt of said agent.  
   
   
       59 . The pharmaceutical composition of  claim 58 , wherein said known cancer chemotherapeutic agent is selected from the group consisting of busulfan, cis-platin, mitomycin C, carboplatin, colchicine, vinblastine, paclitaxel, docetaxel, camptothecin, topotecan, doxorubicin, etoposide, 5-azacytidine, 5-fluorouracil, methotrexate, 5-fluoro-2′-deoxy-uridine, ara-C, hydroxyurea, thioguanine, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, octreotide, retinoic acid, tamoxifen, Herceptin®, Rituxan® and alanosine.  
   
   
       60 . The pharmaceutical composition of  claim 57 , wherein said excipient or carrier is selected from the group consisting of saccharides, starch pastes, gelatin, tragacanth, cellulose preparations, calcium phosphates and polyvinyl pyrrolidone.  
   
   
       61 . A compound having Formula I:  
     
       
         
         
             
             
         
       
       wherein:  
       Y is CN, COR 7 , CO 2 R 7  or CONR x R y , wherein R 7 , R x  and R y  are independently hydrogen, C 1-10  alkyl, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl or aminoalkyl; or  
       R x  and R y  are taken together with the nitrogen to form a heterocycle;  
       Z is NR 9 R 9 , NHCOR 8 , N(COR 8 ) 2 , N(COR 8 )(COR 9 ), N═CHOR 8  or N═CHR 8 , wherein R 8  and R 9  are independently H, C 1-4  alkyl or aryl, or R 8  and R 9  are combined together with the group attached to them to form a heterocycle;  
       R 1 -R 2  are independently amino;  
       R 3 -R 4  are independently hydrogen, halo, haloalkyl, aryl, fused aryl, carbocyclic, a heterocyclic group, a heteroaryl group, C 1-10  alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitro, amino, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, methylenedioxy carbonylamido or alkylthiol;  
       R 5  is hydrogen or C 1-10  alkyl; and  
       A is optionally substituted and is aryl, heteroaryl, saturated carbocyclic, partially saturated carbocyclic, saturated heterocyclic, partially saturated heterocyclic or arylalkyl; or  
       a pharmaceutically acceptable salt or prodrug thereof.