US 2013/0274239 A1Published application

Poly (adp-ribose) polymerase (parp) inhibitors

AssigneeTakeda Pharmaceutical Company Limited

InventorsAnthony R. Gangloff, Andrew John Jennings, Benjamin Jones, Andre A. A. Kiryanov

Life of this patent

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Abstract

Disclosed are compounds of the following formula: in which R1, R2, R3, R4, R5, R6, R7, X, and t are defined in the specification. Also disclosed are pharmaceutical compositions, kits, and articles of manufacture, which contain the compounds, methods and intermediates useful for making the compounds, and methods of using the compounds to treat diseases, disorders, and conditions related to PARP activity.

Claims36

Dependent claims

A compound of the formula:

or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein
X is selected from the group consisting of O, S and NR8;
R1 is -L1-R13;
L1 is —(CR14R15)r—;
R2 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R3 is selected from the group consisting of hydrogen, (C1-10)alkoxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R4 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R5 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
or R3 and one of R4 and R5, together with the atoms to which they are attached, form a ring selected from (C3-5)heterocycloalkyl and (C3-4)heteroaryl, the heterocycloalkyl moiety having 1 or 2 heteroatoms selected from N, O, and S, provided that at least one of the heteroatoms is a nitrogen atom, and the heteroaryl moiety having 1 or 2 nitrogen heteroatoms, and the ring is optionally substituted with halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloalkyl, (C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R6 is selected from the group consisting of hydrogen, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R7 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R8 is selected from the group consisting of hydrogen, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicyclo aryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R13 is selected from the group consisting of
each R14 and R15 is independently selected from the group consisting of hydrogen, halo, and (C1-3)alkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen and (C1-3)alkyl optionally substituted with one or more substituents independently selected from halo, nitro, cyanohydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10), hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl;
R21 and R22 are each independently selected from the group consisting of (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloalkyl, and hetero(C4-12)bicycloaryl, wherein the (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, carbonyl, sulfonyl, halo(C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C4-12)aryl, and hetero(C1-10)aryl;
the optional carbonyl substituent is substituted with hydrogen, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C1-10)alkylamino or amino optionally substituted with (C3-12)cycloalkyl;
the optional sulfonyl substituent is substituted with (C1-10)alkyl or (C1-10)alkylamino;
the optional (C3-12)cycloalkyl and hetero(C3-12)cycloakyl substituents are each optionally substituted with one or more substituents independently selected from cyano, oxo, hydroxy, (C1-10)alkoxy, amino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C3-12)cycloalkyl, and hetero(C3-12)cycloalkyl;
and the optional (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, and (C1-10)azaalkyl;
each R28 is independently selected from the group consisting of hydrogen, halo, (C1-3)alkyl, (C1-3)alkoxy, amino, and thio;
r is selected from the group consisting of 1, 2 and 3;
s is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7 and 8;
and
Y is selected from the group consisting of O and S;
with the provisos that (a) if R1 is hydrogen, chloro, methyl, 3,4-difluorophenyl, or 1-chloro-3-methyl-1-oxopentan-3-yl-aminocarbonyl, then R6 is hydrogen, and (b) if the R3 substituent and the R4 and R5 substituents are attached to adjacent nitrogen and carbon atoms, respectively, then at least one of R3, R4, and R5 is not hydrogen.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/889,585Filed 8 May 2013
Priority: 23 Jan 2009
Published: 17 Oct 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 513/14
In which the condensed system contains three hetero rings: ortho-condensed systems
A61K 31/4985
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrazines or piperazines…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…

Family

Application61/146,740Us provisional application · filed 23 Jan 2009
Application61/228,879Us provisional application · filed 27 Jul 2009
Application12/691,668Division · filed 21 Jan 2010
Application13/041,200Division · filed 4 Mar 2011
Application13/352,902Division · filed 18 Jan 2012
Application13/889,585Division
US 2010/0190763 A1Published application
US 2011/0158989 A1Published application
US 2012/0122835 A1Published application
US 7,928,105 B2Related patent
US 8,124,606 B2Related patent
US 8,450,323 B2Related patent
US 8,822,470 B2Related patent
US 2013/0274239 A1This patent

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

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Abstract

A compound of the formula:

or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein
X is selected from the group consisting of O, S and NR8;
R1 is -L1-R13;
L1 is —(CR14R15)r—;
R2 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R3 is selected from the group consisting of hydrogen, (C1-10)alkoxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R4 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R5 is independently selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
or R3 and one of R4 and R5, together with the atoms to which they are attached, form a ring selected from (C3-5)heterocycloalkyl and (C3-4)heteroaryl, the heterocycloalkyl moiety having 1 or 2 heteroatoms selected from N, O, and S, provided that at least one of the heteroatoms is a nitrogen atom, and the heteroaryl moiety having 1 or 2 nitrogen heteroatoms, and the ring is optionally substituted with halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloalkyl, (C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R6 is selected from the group consisting of hydrogen, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R7 is selected from the group consisting of hydrogen, halo, nitro, cyano, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C1-10)oxaalkyl, (C1-10)oxoalkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicycloaryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C4-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R8 is selected from the group consisting of hydrogen, hydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, aza(C1-10)alkyl, (C3-12)cycloalkyl(C1-5)alkyl, hetero(C3-12)cycloalkyl(C1-10)alkyl, aryl(C1-10)alkyl, hetero(C1-10)aryl(C1-5)alkyl, (C9-12)bicycloaryl(C1-5)alkyl, hetero(C8-12)bicyclo aryl(C1-5)alkyl, hetero(C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl and hetero(C4-12)bicycloaryl;
R13 is selected from the group consisting of
each R14 and R15 is independently selected from the group consisting of hydrogen, halo, and (C1-3)alkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen and (C1-3)alkyl optionally substituted with one or more substituents independently selected from halo, nitro, cyanohydroxy, (C1-10)alkoxy, (C4-12)aryloxy, hetero(C1-10)aryloxy, amino, (C1-10)alkylamino, (C1-10)alkyl, halo(C1-10), hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloaryl, and hetero(C4-12)bicycloaryl;
R21 and R22 are each independently selected from the group consisting of (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C9-12)bicycloalkyl, hetero(C3-12)bicycloalkyl, (C4-12)aryl, hetero(C1-10)aryl, (C9-12)bicycloalkyl, and hetero(C4-12)bicycloaryl, wherein the (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, carbonyl, sulfonyl, halo(C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C1-10)azaalkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C4-12)aryl, and hetero(C1-10)aryl;
the optional carbonyl substituent is substituted with hydrogen, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, (C1-10)alkylamino or amino optionally substituted with (C3-12)cycloalkyl;
the optional sulfonyl substituent is substituted with (C1-10)alkyl or (C1-10)alkylamino;
the optional (C3-12)cycloalkyl and hetero(C3-12)cycloakyl substituents are each optionally substituted with one or more substituents independently selected from cyano, oxo, hydroxy, (C1-10)alkoxy, amino, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, (C3-12)cycloalkyl, and hetero(C3-12)cycloalkyl;
and the optional (C4-12)aryl and hetero(C1-10)aryl substituents are each optionally substituted with one or more substituents independently selected from halo, nitro, cyano, amino, hydroxy, (C1-10)alkoxy, (C1-10)alkyl, halo(C1-10)alkyl, hydroxy(C1-10)alkyl, and (C1-10)azaalkyl;
each R28 is independently selected from the group consisting of hydrogen, halo, (C1-3)alkyl, (C1-3)alkoxy, amino, and thio;
r is selected from the group consisting of 1, 2 and 3;
s is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7 and 8;
and
Y is selected from the group consisting of O and S;
with the provisos that (a) if R1 is hydrogen, chloro, methyl, 3,4-difluorophenyl, or 1-chloro-3-methyl-1-oxopentan-3-yl-aminocarbonyl, then R6 is hydrogen, and (b) if the R3 substituent and the R4 and R5 substituents are attached to adjacent nitrogen and carbon atoms, respectively, then at least one of R3, R4, and R5 is not hydrogen.

23 more elements

Facts

Application

13/889,585Filed 8 May 2013

Priority

23 Jan 2009

Published

17 Oct 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 513/14
In which the condensed system contains three hetero rings: ortho-condensed systems
A61K 31/4985
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrazines or piperazines…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…

Family

Application61/146,740Us provisional application · filed 23 Jan 2009

Application61/228,879Us provisional application · filed 27 Jul 2009

Application12/691,668Division · filed 21 Jan 2010

Application13/041,200Division · filed 4 Mar 2011

Application13/352,902Division · filed 18 Jan 2012

Application13/889,585Division

US 2010/0190763 A1Published application

US 2011/0158989 A1Published application

US 2012/0122835 A1Published application

US 7,928,105 B2Related patent

US 8,124,606 B2Related patent

US 8,450,323 B2Related patent

US 8,822,470 B2Related patent

US 2013/0274239 A1This patent

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