US 2010/0305138 A1Published application

Pyridyl derivatives and their use as therapeutic agents

AssigneeXenon Pharmaceuticals Inc.

InventorsMelwyn Abreo, Daniel F. Harvey, Mikhail A. Kondratenko, Wenbao Li, Rajender Kamboj, Vishnumurthy Kodumuru, Michael D. Winther, Heinz W. Gschwend, Nagasree Chakka, Shifeng Liu, Serguei Sviridov, Shaoyi Sun

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Abstract

Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): wherein W, V, x, y, R1, R2, R3, R4, R5, R6, R7, R7a, R8, R8a, R9, R9a, R10 and R10a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

Claims71

Dependent claims

A method of inhibiting human stearoyl-CoA desaturase (hSCD) activity comprising contacting a source of hSCD with a compound of formula (I):

wherein:
x and y are each independently 1, 2 or 3;
W is —O—, —N(R1)—, —C(O)—, —S(O)t—;
(where t is 0, 1 or 2), —N(R1)S(O)2—, —S(O)2N(R1)—, —OS(O)2N(R1)—, —C(O)N(R1)—, —OC(O)N(R1)—, —C(S)N(R1)—, —OC(S)N(R1)—, —N(R1)C(O)— or —N(R1)C(O)N(R1)—;
V is —C(O)—, —C(S)—, —C(O)N(R1)—, —C(O)O—, —S(O)2—, —S(O)2N(R1)— or —C(R11)H—, provided that when x and y are both 1, and W is —C(O)N(R1)— or —N(R1)C(O)—, then V is not —C(O)—;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl, and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10 and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R7 and R7a together, or R8 and R8a together, or R9 and R9a together, or R10 and R10a together are an oxo group, provided that when V is —C(O)—, R7 and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
R11 is hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

15 more elements

A method of treating a disease or condition mediated by stearoyl-CoA desaturase (SCD) in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of formula (I):

wherein:
x and y are each independently 1, 2 or 3;
W is —O—, —N(R1)—, —C(O)—, —S(O)t—;
(where t is 0, 1 or 2), —N(R1)S(O)2—, —S(O)2N(R1)—, —C(O)N(R1)—, —OC(O)N(R1)—, —C(S)N(R1)—, —OC(S)N(R1)—, —N(R1)C(O)— or —N(R1)C(O)N(R1)—;
V is —C(O)—, —C(S)—, —C(O)N(R1)—, —C(O)O—, —S(O)2—, —S(O)2N(R1)— or —C(R11)H—, provided that when x and y are both 1, and W is —C(O)N(R1)— or —N(R1)C(O)—, then V is not —C(O)—;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl, and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10 and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R7 and R7a together, or R8 and R8a together, or R9 and R9a together, or R10 and R10a together are an oxo group, provided that when V is —C(O)—, R7 and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
R11 is hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

15 more elements

A compound of formula (IIa):

wherein:
x and y are each independently 1, 2 or 3, provided that x and y are not each 1;
R1 is selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C7-C12alkyl, C3-C12alkenyl, C7-C12hydroxyalkyl, C1-C12alkoxy, C2-C12alkoxyalkyl, C3-C12hydroxyalkenyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, C13-C19aralkyl, C1-C12heteroaryl, C3-C12heterocyclylalkyl and C3-C12heteroarylalkyl, provided that R2 is not pyrazinyl, pyridinonyl, pyrrolidinonyl, or imidazolyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C3-C12alkyl, C3-C12alkenyl, C3-C12hydroxyalkyl, C3-C12hydroxyalkenyl, C3-C12alkoxy, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12 heteroaryl and C3-C12heteroarylalkyl;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R9 and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R7, R7a, R10 and R10a, together with one of R8, R8a, R9 and R9a, form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

10 more elements

A compound of formula (IIb):

wherein:
x and y are each independently 1, 2 or 3, provided that x and y are not each 1;
R1 is selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C1-C6alkoxy, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, C7-C19aralkyl, C3-C12 heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R2 is phenyl optionally substituted with one or more substituents selected from halo and C1-C6trihaloalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is phenyl optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6trihaloalkyl, C1-C6trihaloalkoxy, C1-C6alkylsulfonyl, —N(R12)2, —OC(O)R12, —C(O)OR12, —S(O)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl, provided that R3 is not phenyl substituted with optionally substituted thienyl;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R9 and R9a together, or R10 and R10a together form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R7, R7a, R10 and R10a, together with one of R8, R8a, R9 and R9a, form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R12 is independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkyl, aryl or aralkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

13 more elements

A compound of formula (III):

wherein:
x and y are each independently 1, 2 or 3;
Va is —C(O)—, —C(S)—, —C(O)N(R1)—, —C(O)O—, —S(O)2— or —S(O)2N(R1)—;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C1-C6alkoxy, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R7 and R7a together, or R8 and R8a together, or R9 and R9a together, or R10 and R10a together are an oxo group, provided that when Va is —C(O)—, R7 and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or O1—C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

12 more elements

A compound of formula (IV):

wherein:
x and y are each independently 1, 2 or 3;
Va is —C(O)—, —C(S)—, —C(O)N(R1)—, —C(O)O—, —S(O)2— or —S(O)2N(R1)—;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R7 and R7a together, or R8 and R8a together, or R9 and R9a together, or R10 and R10a together are an oxo group, provided that when Va is —C(O)—, R7 and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

12 more elements

A compound of formula (V):

wherein:
x and y are each independently 1, 2 or 3;
Wa is —O—, —N(R1)— or —S(O)t— (where t is 0, 1 or 2);
Va is —C(O)—, —C(S)—, —C(O)N(R1)—, —C(O)O—, —S(O)2— or —S(O)2N(R1)—;
x and y are each independently 1, 2 or 3;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C2-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R7 and R7a together, or R8 and R8a together, or R9 and R9a together, or R10 and R10a together are an oxo group, provided that when Va is —C(O)—, R7 and R7a together or R8 and R8a together do not form an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

14 more elements

A compound of formula (VIa):

wherein:
x and y are each independently 1, 2 or 3, provided that x and y are not each 1;
R1 is selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C7-C12alkyl, C3-C12alkenyl, C7-C12hydroxyalkyl, C2-C12alkoxyalkyl, C3-C12hydroxyalkenyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, C13-C19aralkyl, C3-C12heterocyclylalkyl, and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is selected from the group consisting of C3-C12alkyl, C3-C12alkenyl, C3-C12hydroxyalkyl, C3-C12hydroxyalkenyl, C3-C12alkoxy, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12heterocyclyl, C3-C12heterocyclylalkyl, C5-C12 heteroaryl and C3-C12heteroarylalkyl;
or R3 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl and where some or all of the rings may be fused to each other;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R9 and R9a together, or R10 and R10a together are an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
including a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

11 more elements

A compound of formula (VIb):

wherein:
x and y are each independently 1, 2 or 3, provided that x and y are not each 1;
each R1 is independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12hydroxyalkyl, C4-C12cycloalkylalkyl and C7-C19aralkyl;
R2 is selected from the group consisting of C1-C12alkyl, C2-C12alkenyl, C2-C12hydroxyalkyl, C2-C12hydroxyalkenyl, C3-C12alkoxyalkyl, C3-C12cycloalkyl, C4-C12cycloalkylalkyl, aryl, C7-C19aralkyl, C3-C12 heterocyclyl, C3-C12heterocyclylalkyl, C1-C12heteroaryl and C3-C12heteroarylalkyl;
or R2 is a multi-ring structure having 2 to 4 rings wherein the rings are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, where some or all of the rings may be fused to each other;
R3 is naphthyl or phenyl, each optionally substituted by one or more substituents selected from the group consisting of halo, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6trihaloalkyl, C1-C6trihaloalkoxy, C1-C6alkylsulfonyl, —N(R12)2, —OC(O)R12, —C(O)OR12, —S(O)2N(R12)2, cycloalkyl, heterocyclyl, heteroaryl and heteroarylcycloalkyl, provided that R3 is not phenyl substituted with optionally substituted thienyl, and provided that when R3 is naphthyl, R2 can not be C1-C6alkyl, C2-C6hydroxyalkyl or phenyl substituted by amino;
R4, R5 and R6 are each independently selected from hydrogen, fluoro, chloro, methyl, methoxy, trifluoromethyl, cyano, nitro or —N(R13)2;
R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or R9 and R9a together, or R10 and R10a together are an oxo group, while the remaining R7, R7a, R8, R8a, R9, R9a, R10, and R10a are each independently selected from hydrogen or C1-C3alkyl;
or one of R10, R10a, R7, and R7a together with one of R8, R8a, R9 and R9a form an alkylene bridge, while the remaining R10, R10a, R7, R7a, R8, R8a, R9, and R9a are each independently selected from hydrogen or C1-C3alkyl;
each R12 is independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkyl, aryl or aralkyl;
and
each R13 is independently selected from hydrogen or C1-C6alkyl;
a stereoisomer, enantiomer or tautomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof or a prodrug thereof.

11 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/816,076Filed 15 Jun 2010
Priority: 29 Jul 2003
Published: 2 Dec 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/501
Pyridazines; Hydrogenated pyridazines: not condensed and containing further heterocyclic rings

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Application60/491,140Us provisional application · filed 29 Jul 2003
Application60/491,116Us provisional application · filed 30 Jul 2003
Application60/491,080Us provisional application · filed 30 Jul 2003
Application60/491,141Us provisional application · filed 30 Jul 2003
Application60/491,322Us provisional application · filed 30 Jul 2003
Application10/566,857Division · filed 30 Jan 2006
Application12/816,076Division
US 2006/0293308 A1Published application
US 7,763,618 B2Related patent
US 8,383,628 B2Related patent
US 2010/0305138 A1This patent

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