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US 10,604,480 B2Granted
(Thio, oxo, and seleno) semicarbazone derivatives and their use for treating cancer
AssigneesRutgers, The State University of New Jersey, The Research Foundation for The State University of New York
InventorsDavid J. Augeri, Anthony F. Bencivenga, Adam Blanden, Darren R. Carpizo, John A. Gilleran, Spencer David Kimball, Stewart N. Loh, Xin Yu
Life of this patent
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Abstract
The invention provides compounds of formula I and II and salts thereof, wherein R1, R2, Y, R3, and R4 have any of the meanings described in the specification, as well as compositions comprising such compounds and salts, and methods for treating cancer using such compounds and salts.
Claims28
A compound selected from compounds of formulas (I) and (II):
- or a salt thereof, wherein:
- R1 is selected from the group consisting of:
- wherein R1 is optionally substituted with one or more groups independently selected from halo, cyano, —N(Ra)2, carboxy, phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino wherein any phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, and (C3-C6)cycloalkyl, is optionally substituted with one or more groups independently selected from halo, cyano, hydroxy, nitro, —N(Ra)2, carboxy, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino;
- R2 is selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl is optionally substituted with one or more groups independently selected from halo, —N(Rb)2, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkanoyloxy, (C2-C6)alkoxycarbonyl, (C2-C6) alkylaminocarbonyl, and (C2-C6) alkanoylamino;
- provided that if R1 is 2-pyridinyl, then R2 is not H or (C1-C6)alkyl;
- Y is S, O, Se;
- R3 is selected from H, (C1-C6)alkyl, piperidinyl, and piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl;
- R4 is selected from (C1-C6)alkyl, piperidinyl, and piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl;
- or R3 and each R4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, or 8 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;
- each Ra is independently selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Ra taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- each Rb is independently selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Rb taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- and
- each Rc is independently selected from the group consisting of H and (C1-C6)alkyl that is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy.
12 more elements
A compound selected from the group consisting of:
- or a salt thereof.
A compound selected from compounds of formulas (I) and (II):
- or a salt thereof, wherein:
- R1 is selected from the group consisting of:
- wherein R1 is optionally substituted with one or more groups independently selected from halo, cyano, —N(Ra)2, carboxy, phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino wherein any phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, and (C3-C6)cycloalkyl, is optionally substituted with one or more groups independently selected from halo, cyano, hydroxy, nitro, —N(Ra)2, carboxy, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino;
- R2 is selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl is optionally substituted with one or more groups independently selected from halo, —N(Rb)2, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkanoyloxy, (C2-C6)alkoxycarbonyl, (C2-C6) alkylaminocarbonyl, and (C2-C6) alkanoylamino;
- provided that if R1 is 2-pyridinyl, then R2 is not H or (C1-C6)alkyl;
- Y is S, O, Se;
- R3 and R4 are each independently selected from H, (C1-C6)alkyl, piperidinyl, or piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl;
- or R3 and each R4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, or 8 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;
- each Ra is independently selected from the group consisting of (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Ra taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- each Rb is independently selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Rb taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- and
- each RC is independently selected from the group consisting of H and (C1-C6)alkyl that is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy.
11 more elements
A compound selected from compounds of formulas (I) and (II):
- or a salt thereof, wherein:
- R1 is selected from the group consisting of:
- wherein R1 is optionally substituted with one or more groups independently selected from halo, cyano, hydroxy, nitro, —N(Ra)2, carboxy, phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino wherein any phenyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, and (C3-C6)cycloalkyl, is optionally substituted with one or more groups independently selected from halo, cyano, hydroxy, nitro, —N(Ra)2, carboxy, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C2-C6)alkanoyloxy, (C4-C6)heterocycloalkyl, (C2-C6)alkylaminocarbonyl and (C2-C6)alkanoylamino;
- R2 is selected from the group consisting of H, phenyl, heteroaryl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl, wherein any phenyl, heteroaryl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, and (C3-C6)cycloalkyl is optionally substituted with one or more groups independently selected from halo, —N(Rb)2, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkanoyloxy, (C2-C6)alkoxycarbonyl, (C2-C6) alkylaminocarbonyl, and (C2-C6) alkanoylamino;
- Y is S, O, Se;
- R3 and R4 are each independently is selected from H, (C1-C6)alkyl, piperidinyl, and piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl;
- or R3 and each R4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, 8, or 9 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;
- each Ra is independently selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Rb taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- each Rb is independently selected from the group consisting of H, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl, (C1-C6)alkanoyl, and (C1-C6)alkoxycarbonyl, is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
- or two Rb taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring;
- and
- each Rc is independently selected from the group consisting of H and (C1-C6)alkyl that is optionally substituted with one or more groups independently selected from halo, (C3-C6)cycloalkyl, and (C1-C6)alkoxy.
10 more elements
Dependencies are inferred from the claim text.