Nitro and amino substituted heterocycles as topoisomerase I targeting agents
AssigneeRutgers, The State University of New Jersey
InventorsEdmond J. LaVoie, Sudhir K. Singh, Leroy F. Liu
Life of this patent
Estimating the term…
Abstract
The invention provides compounds of formula I: 1 wherein: R1-R5, “a” and X have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I, and therapeutic methods for treating cancer using compounds of formula I.
Claims63
A compound of formula I:
- 4
- wherein:
- one of R1 and R2 is nitro or NRaRb;
- the other of R1 and R2 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, NRaRb, COORc, or ORd;
- and R3 and R4 are each independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, NRaRb, COORc, or ORd, or R3 and R4 taken together are methylenedioxy, 1,2-ethylenedioxy, or 1,3-propylenedioxy;
- or
- R1 and R2 are each independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, NRaRb, COORc, or ORd, or R1 and R2 taken together are methylenedioxy, 1,2-ethylenedioxy, or 1,3-propylenedioxy;
- one of R3 and R4 is nitro or NRaRb;
- and the other of R3 and R4 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, NRaRb, COORc, or ORd;
- R5 is (C1-C6)alkyl substituted with one or more solubilizing groups;
- X is two hydrogens, ═O, ═S, or ═NRe;
- the bond marked “a” is a single bond or a double bond:
- Ra and Rb are each independently hydrogen or (C1-C6)alkyl, or Ra and Rb together with the nitrogen to which they are attached form a pyrrolidino, piperidino or morpholino ring;
- each Rc is hydrohgen, (C1-C6)alkyl, aryl, or aryl(C1-C6)alkyl;
- each Rd is hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, aryl, or aryl(C1-C6)alkyl;
- and
- Re is hydrogen, (C1-C6)alkyl, aryl, or aryl(C1-C6)alkyl;
- or a pharmaceutically acceptable salt thereof.
Any one of compounds 4a, 4b, 8a, and 8b wherein R5 is 2-(N,N-dimethylamino)ethyl, 2-(N,N-dimethylamino)propyl, 2-( N,N-diethylamino)ethyl, or 2-(N,N-diethylamino)propyl or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.