Vinca derivatives
AssigneeAlbany Molecular Research, Inc.
InventorsIan L. Scott, Jeffrey M. Ralph, Matthew E. Voss
Life of this patent
Estimating the term…
Abstract
The present invention relates to derivatives of vinca alkaloids. Pharmaceutical compositions containing these compounds as well as processes of preparation and treatment of various conditions are also disclosed.
Claims50
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of the compound of Formula (I) as follows:
- where:
- R1 is:
- alkyl;
- alkenyl;
- alkynyl;
- aryl;
- 3-methylpyrazol-1-yl;
- pyridyl;
- thienyl;
- thiazolyl;
- piperidinyl;
- morpholinyl;
- pyrrolidinyl;
- azetidinyl;
- Cl;
- Br;
- F;
- CN;
- C(O)NR5R6;
- C(O)NHR5;
- C(O)NH2;
- C(O)NHNH2;
- C(O)NR5NH2;
- C(O)NR5NHR6;
- C(O)NR5NR6R7;
- C(O)NHNHR5;
- C(O)NHNR5R6;
- C(O)NHOH;
- SO2NHNH2;
- SO2NR5NH2;
- SO2NR5NHR6;
- SO2NR5NR6R7;
- SO2NHNHR5;
- SO2NHNR5R6;
- CO2R5;
- SR5;
- SSR5;
- SO2NHR5;
- SO2NR5R6;
- B(OR5)2;
- CF3;
- SH;
- SO2NH2;
- NH2;
- NHR5;
- NHSO2R5;
- NR5R6;
- NHCOR5;
- NR5COR6;
- or
- NR5SO2R6;
- R2=alkyl or CH(O);
- R3=hydrogen, alkyl, or C(O)R5;
- R4=hydrogen or C(O)R5;
- R5, R6 and R7 each are independently alkyl, alkenyl, alkynyl, or aryl;
- R8=hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, acyl, or thioalkyl;
- R9═OH and R10═H or R9 and R10 together form a bridging double bond;
- R5 and R6 can form a ring or R6 and R7 can form a ring;
- X═OR5, NR5R6, NHNH2, NHNHC(O)R5, OH, NHR5, NH2, or NHNHC(O)H;
- R4 and X can be linked together with intervening atoms to form a ring;
- R1 and R8 can be linked together;
- or a pharmaceutically acceptable salt thereof, wherein the alkyl and alkenyl groups can be branched or straight, with the proviso, that when R8═H, R9═OH, and R10═H, then R1≠Br and the proviso that if R1 is an unsubstituted aryl, then R2≠CH3.
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of leukemia, carcinoma of the breast, lymphosarcoma, ovarian cancer, squamous cell cancer of the lung, and Hodgkin's disease in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of the compound of Formula (I) as follows:
- where:
- R1 is:
- alkyl;
- alkenyl;
- alkynyl;
- aryl;
- 3-methylpyrazol-1-yl;
- pyridyl;
- thienyl;
- thiazolyl;
- piperidinyl;
- morpholinyl;
- pyrrolidinyl;
- azetidinyl;
- Cl;
- Br;
- F;
- CN;
- C(O)NR5R6;
- C(O)NHR5;
- C(O)NH2;
- C(O)NHNH2;
- C(O)NR5NH2;
- C(O)NR5NHR6;
- C(O)NR5NR6R7;
- C(O)NHNHR5;
- C(O)NHNR5R6;
- C(O)NHOH;
- SO2NHNH2;
- SO2NR5NH2;
- SO2NR5NHR6;
- SO2NR5NR6R7;
- SO2NHNHR5;
- SO2NHNR5R6;
- CO2R5;
- SR5;
- SSR5;
- SO2NHR5;
- SO2NR5R6;
- B(OR5)2;
- CF3;
- SH;
- SO2NH2;
- NH2;
- NHR5;
- NHSO2R5;
- NR5R6;
- NHCOR5;
- NR5COR6;
- or
- NR5SO2R6;
- R2=alkyl or CH(O);
- R3=hydrogen, alkyl, or C(O)R5;
- R4=hydrogen or C(O)R5;
- R5, R6 and R7 each are independently alkyl, alkenyl, alkynyl, or aryl;
- R8=hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, acyl, or thioalkyl;
- R9═OH and R10═H or R9 and R10 together form a bridging double bond;
- R5 and R6 can form a ring or R6 and R7 can form a ring;
- X═OR5, NR5R6, NHNH2, NHNHC(O)R5, OH, NHR5, NH2, or NHNHC(O)H;
- R4 and X can be linked together with intervening atoms to form a ring;
- R1 and R8 can be linked together;
- or a pharmaceutically acceptable salt thereof, wherein the alkyl and alkenyl groups can be branched or straight, with the proviso, that when R8═H, R9═OH, and R10═H, then R1≠Br and the proviso that if R1 is an unsubstituted aryl, then R2≠CH3.
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
A method for treating a condition selected from the group consisting of choricarcinoma, neuroblastoma, acute lung organs leukemia, chronic lung organs leukemia, testicular cancers, non-Hodgkin's lymphoma, acute childhood leukemia, lymphatic leukemia, Wilm's tumor, rhabdosarcoma, reticulum cell sarcoma, melanoma, and squamous cell cancer of the cervix in mammals comprising:
- administering to a mammal a therapeutically effective amount of a compound having the following chemical formula:
Dependencies are inferred from the claim text.