US 7,842,805 B2Granted

Pharmaceutical compounds as activators of caspases and inducers of apoptosis and the use thereof

AssigneesMyrexis, Inc., EpiCept Corporation

InventorsSui Xiong Cai, Mark B. Anderson, Adam Willardsen, Songchun Jiang, Robert J. Halter, Rachel Slade, Yevgeniya Klimova

Life of this patent

Estimating the term…

Abstract

Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

Claims14

Dependent claims

A pharmaceutical composition comprising an effective amount of a compound having a structure according to Formula II:

or a pharmaceutically acceptable salt thereof, wherein:
Ar is aryl or heteroaryl;
each of which is optionally substituted by one or more substituents;
L is —(CRaRb)n- or —N(Ra)C(═O)— wherein n is 0, 1 or 2, and Ra and Rb independently are H, optionally substituted alkyl, methyl, ethyl, propyl, isopropyl, or C1-4 haloalkyl;
R1 is C1-6 alkyl;
B is nitrogen;
D is nitrogen;
R3-R6 are independently selected from:
(a) H, halo, N3, nitro, hydroxy, thiol, and CN,
(b) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, carbocycle, heterocycle, aryl, heteroaryl, —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
(c) carbocycle, heterocycle, aryl, and heteroaryl, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —N(R52)(R53), —N(R52)C(═O)R42, —N(R52)C(═O)N(R52)(R53), —C(═O)N(R52)(R53), —OC(═O)N(R52)(R53), R42C(═O)—, R42C(═O)O—, R42C(=G1)-, R42C(=G1)G2-, R42C(=G1)G2(R52)—, —C(=G1)G2R43, or —G4C(=G1)G2R43,
(d) —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
G1 is S or N;
G2 and G3 are independently S or N(R50);
G4 is N(R52);
R40 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy and C1-6 alkylthiol, wherein R40 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R41 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R41 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R42 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, and C1-6 alkylthiol, wherein R42 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R43 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R43 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R50 and R51 are independently H, OH (R50 and R51 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, carbocycle, heterocycle, aryl, heteroaryl, or R50 and R51 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R50 and R51 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
R52 and R53 are independently H, OH (R52 and R53 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, or R52 and R53 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R52 and R53 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
and
Q, T, U, and V are carbon;
and
another anticancer agent selected from the group consisting of alkylating agents, antimitotic agents, topo I inhibitors, topo II inhibitors, RNA/DNA antimetabolites, EGFR inhibitors, angiogenesis inhibitors, tubulin inhibitors, proteosome inhibitors, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, octreotide, retinoic acid, tamoxifen, Gleevec® and alanosine.

24 more elements

A compound having a structure according to Formula III:

or a pharmaceutically acceptable salt thereof, wherein:
R1 is C1-6 alkyl;
B is nitrogen;
D is nitrogen;
R3-R11 are independently selected from:
(a) H, halo, N3, nitro, hydroxy, thiol, and CN,
(b) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, carbocycle, heterocycle, aryl, heteroaryl, —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
(c) carbocycle, heterocycle, aryl, and heteroaryl, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —N(R52)(R53), —N(R52)C(═O)R42, —N(R52)C(═O)N(R52)(R53), —C(═O)N(R52)(R53), —OC(═O)N(R52)(R53), R42C(═O)—, R42C(═O)O—, R42C(=G1)-, R42C(=G1)G2-, R42C(=G1)G2(R52)—, —C(Gl)G2R43, -G4C(=G1)G2R43,
(d) —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
G1 is S or N;
G2 and G3 are independently S or N(R50);
G4 is N(R52);
R40 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy and C1-6 alkylthiol, wherein R40 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R41 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R41 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R42 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, and C1-6 alkylthiol, wherein R42 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R43 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R43 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R50 and R51 are independently H, OH (R50 and R51 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, carbocycle, heterocycle, aryl, heteroaryl, or R50 and R51 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R50 and R51 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
and
R52 and R53 are independently H, OH (R52 and R53 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, or R52 and R53 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R52 and R53 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
and
Q, T, U, and V are carbon, W, X, Y, and Z are independently nitrogen or carbon, two of W, X, Y, and Z are nitrogen, provided that when W, X, Y, or Z are nitrogen then there is no substituent at the nitrogen.

20 more elements

A compound having a structure according to Formula IV:

or a pharmaceutically acceptable salt thereof, wherein
R1 is C1-6 alkyl;
B is nitrogen;
D is nitrogen;
R3-R11 are independently selected from:
(a) H, halo, N3, nitro, hydroxy, thiol, and CN,
(b) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, carbocycle, heterocycle, aryl, heteroaryl, —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C)(=G1)G2R41 or -G3C(=G1)G2R41,
(c) carbocycle, heterocycle, aryl, and heteroaryl, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —N(R52)(R53), —N(R52)C(═O)R42, —N(R52)C(═O)N(R52)(R53), —C(═O)N(R52)(R53), —OC(═O)N(R52)(R53), R42C(═O)—, R42C(═O)O—, R42C(=G1)-, R42C(=G1)G2-, R42C(=G1)G2(R52)-, —C(=G1)G2R43, or -G4C(=G1)G2R43,
(d) —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)-, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)-, —C(=G1)G2R41 or -G3C(=G1)G2R41,
G1 is S or N;
G2 and G3 are independently S or N(R50);
G4 is N(R52);
R40 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy and C1-6 alkylthiol, wherein R40 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R41 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R41 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R42 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, and C1-6 alkylthiol, wherein R42 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R43 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R43 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R50 and R51 are independently H, OH (R50 and R51 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O-C1-6 alkyl-, carbocycle, heterocycle, aryl, heteroaryl, or R50 and R51 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R50 and R51 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
and
R52 and R53 are independently H, OH (R52 and R53 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, or R52 and R53 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R52 and R53 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
with the proviso that R9 is not halo, and if R9 is H, then R8 and R10 are not H or halo.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/773,293Filed 3 Jul 2007 · continuation
Priority: 3 Jan 2005
Published: US 2008/0020985 A124 Jan 2008
Granted: 30 Nov 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 237/34
Phthalazines: with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 31/12
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antivirals
A61P 35/00
Antineoplastic agents

Family

Application60/641,356Us provisional application · filed 3 Jan 2005
PCT/US2006/000176Parent of this continuation · filed 3 Jan 2006
US 2008/0020985 A1Pre-grant publication · published 24 Jan 2008
US 7,842,805 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A pharmaceutical composition comprising an effective amount of a compound having a structure according to Formula II:

or a pharmaceutically acceptable salt thereof, wherein:
Ar is aryl or heteroaryl;
each of which is optionally substituted by one or more substituents;
L is —(CRaRb)n- or —N(Ra)C(═O)— wherein n is 0, 1 or 2, and Ra and Rb independently are H, optionally substituted alkyl, methyl, ethyl, propyl, isopropyl, or C1-4 haloalkyl;
R1 is C1-6 alkyl;
B is nitrogen;
D is nitrogen;
R3-R6 are independently selected from:
(a) H, halo, N3, nitro, hydroxy, thiol, and CN,
(b) C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, carbocycle, heterocycle, aryl, heteroaryl, —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
(c) carbocycle, heterocycle, aryl, and heteroaryl, each of which being optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —N(R52)(R53), —N(R52)C(═O)R42, —N(R52)C(═O)N(R52)(R53), —C(═O)N(R52)(R53), —OC(═O)N(R52)(R53), R42C(═O)—, R42C(═O)O—, R42C(=G1)-, R42C(=G1)G2-, R42C(=G1)G2(R52)—, —C(=G1)G2R43, or —G4C(=G1)G2R43,
(d) —N(R50)(R51), —N(R50)C(═O)R40, —N(R50)C(═O)N(R50)(R51), —C(═O)N(R50)(R51), —OC(═O)N(R50)(R51), R40C(═O)—, R40C(═O)O—, R40C(=G1)-, R40C(=G1)G2-, R40C(=G1)G2(R50)—, —C(=G1)G2R41 or -G3C(=G1)G2R41,
G1 is S or N;
G2 and G3 are independently S or N(R50);
G4 is N(R52);
R40 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy and C1-6 alkylthiol, wherein R40 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R41 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R41 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, carbocycle, heterocycle, aryl and heteroaryl;
R42 is selected from:
H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, and C1-6 alkylthiol, wherein R42 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R43 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, wherein R43 is optionally substituted with from one to three substituents independently selected from halo, N3, nitro, hydroxy, thiol, CN and C1-6 alkyl;
R50 and R51 are independently H, OH (R50 and R51 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, carbocycle, heterocycle, aryl, heteroaryl, or R50 and R51 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R50 and R51 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
R52 and R53 are independently H, OH (R52 and R53 are not both OH), C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 alkoxy, C1-10 alkylthiol, C2-10 alkenyloxy, C2-10 alkynyloxy, C1-10 haloalkyl, C2-6 hydroxyalkyl, C1-6 alkyl-O—C1-6 alkyl-, or R52 and R53 together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein R52 and R53 each is optionally substituted with one to three substituents wherein each substituent is independently halo, N3, nitro, hydroxy, thiol, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(═O)N(R54)(R55), R44C(═O)— or —N(R54)(R55), wherein R54 and R55 are independently H, OH or C1-4 alkyl, and wherein R44 is H or C1-4 alkyl;
and
Q, T, U, and V are carbon;
and
another anticancer agent selected from the group consisting of alkylating agents, antimitotic agents, topo I inhibitors, topo II inhibitors, RNA/DNA antimetabolites, EGFR inhibitors, angiogenesis inhibitors, tubulin inhibitors, proteosome inhibitors, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, octreotide, retinoic acid, tamoxifen, Gleevec® and alanosine.

24 more elements

Facts

Application

11/773,293Filed 3 Jul 2007 · continuation

Priority

3 Jan 2005

Published

US 2008/0020985 A124 Jan 2008

Granted

30 Nov 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07D 237/34
Phthalazines: with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 31/12
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antivirals
A61P 35/00
Antineoplastic agents