| US 7,468,378 B2 | ||
| Substituted quinoline compounds | ||
| Peter Bertinato, Old Lyme, Conn. (US); Michel A. Couturier, Pawcatuck, Conn. (US); Ernest S. Hamanaka, Gales Ferry, Conn. (US); Marcus D. Ewing, Colchester, Conn. (US); Ralph P. Robinson, Gales Ferry, Conn. (US); and Derek L. Tickner, Waterford, Conn. (US) | ||
| Assigned to Pfizer Inc., New York, N.Y. (US) | ||
| Filed on Feb. 03, 2005, as Appl. No. 11/49,852. | ||
| Claims priority of provisional application 60/541678, filed on Feb. 04, 2004. | ||
| Claims priority of provisional application 60/633763, filed on Dec. 06, 2004. | ||
| Prior Publication US 2005/0234099 A1, Oct. 20, 2005 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. A61K 31/44 (2006.01); C07D 275/04 (2006.01) | ||
| U.S. Cl. 514—312 [546/156] | 34 Claims |
1. A compound of Formula (I)
 R1 is a group of the formula R1a or R1b
 m is an integer from 0 to 2;
n is an integer from 0 to 4;
p is an integer from 0 to 5;
q is an integer from 0 to 3;
r is a bond or an integer from 1 to 3;
X is —N— or C(Ra)— where Ra is H or R9;
X1 is —N— or —C(Rb)— where Rb is H or R7;
R2, R7, R8 and R9 are each independently selected from the group consisting of halo, —OH, —CN, (C1-C4)alkyl, (C1-C4)alkoxy-, alkoxyalkyl- having 2 to 4 carbon atoms, halo-substituted(C1-C4)alkyl-, halo-substituted(C1-C4)alkoxy-, (C1-C4)alkylthio-, hydroxy(C1-C4)alkyl-, benzyloxy-, (C2-C4)alkenyl, (C2-C4)alkynyl, —C(O)N(Rc)(R11), —N(R11)C(O)R12, —N(R11)CO2R12, —N(R11)S(O)sR12, —C(O)R12, —CO2R12, —OC(O)R12, —SO2N(Rc)(R11) and —S(O)vR12;
each Rc is independently H or (C1-C4)alkyl;
s is the integer 1 or 2;
v is an integer from 0 to 2;
R3 and R4 are each H or are taken together with the carbon atom to which they are attached to form a carbonyl group;
R5 and R10 are each independently selected from the group consisting of H, (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, (C3-C7)cycloalkyl, —C(O)R12, alkoxyalkyl- having 2 to 4 carbon atoms, alkylthioalkyl- having 2 to 4 carbon atoms and —SO2R12;
R6 is (C1-C10)alkyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, —OH and —CN,
or
R6 is pyridyl, phenyl or phenyl(C1-C6)alkyl- in which the pyridyl and phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with
1 to 3 substituents independently selected from the group consisting of (C1-C4)alkyl, halo-substituted (C1-C4)alkyl, (C1-C4)alkoxy-, halo-substituted (C1-C4)alkoxy-, halo, —OH and —CN, or
R6 is (C2-C10)alkenyl, (C2-C10)alkynyl, —CH2N(Rc)(R13), —C(O)N(R4)(R15), —CO2R20 or —CH2—W—Y where W is —O— or —S—; and
Y is selected from the group consisting of H, (C1-C8)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, phenyl and phenyl(C1-C6)alkyl-, where the (C1-C8)alkyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo,
oxo, —OH, —CN, —CF3, —OCF3, —OR12, —C(O)R12, —C(O)OR12, —OC(O)R12, —N(R11)C(O)R12 and —C(O)N(Rc)(R11); the (C3-C7)cycloalkyl group and the cycloalkyl moiety of the cycloalkylalkyl group are optionally substituted with 1 to 3 substituents
independently selected from the group consisting of halo, oxo, (C1-C6)alkyl, —OH, —CN, —CF3, —OCF3, —C(O)OR12 and —OR12; and the phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with 1 to 3 substituents
independently selected from the group consisting of halo, (C1-C6)alkyl, —OH, —CN, —CF3, —OCF3, —C(O)OR12 and —OR12;
each R11 is independently selected from the group consisting of H, (C1-C4)alkyl, halo-substituted(C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C3)alkoxy(C2-C4)alkyl- having 3 to 5 carbon atoms and (C1-C3)alkylthio(C2-C4)alkyl- having 3 to 5 carbon atoms;
each R12 is independently (C1-C4)alkyl or (C3-C7)cycloalkyl, where the (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of (C1-C4)alkoxy-, halo, —OH, —CN, —CF3 and —OCF3;
R13 is selected from the group consisting of (C3-C6)alkyl, phenylmethyl-, —C(O)R16 and —S(O)2R16;
R14 is selected from the group consisting of H, (C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, phenyl and phenyl(C1-C6)alkyl-,
where the (C1-C6)alkyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo,
oxo, —OH, —CN, —CF3, —OCF3, —OR12—C(O)R12, —CO2R12, —OC(O)R12, —N(R11)C(O)R12 and —C(O)N(Rc)(R11);
the (C3-C7)cycloalkyl group and the cycloalkyl moiety of the cycloalkylalkyl group are optionally substituted with 1 to 3 substituents
independently selected from the group consisting of halo, oxo, (C1-C6)alkyl, —OH, —CN, —CF3, —OCF3 and —OR12; and
the phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with 1 to 3 substituents independently
selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy-, —OH, —CN, —CF3, —OCF3 and —OR12;
R15 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, phenyl, phenyl(C1-C6)alkyl-, pyridyl, pyridyl(C1-C6)alkyl-, —C(O)R12 and —SO2R12;
where the (C1-C8)alkyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo,
oxo, —OH, —CN, —CF3, —OCF3, —OR12, —C(O)R12, —C(O)OH, —C(O)OCH2C6H5, —C(O)OCH2C(O)N(Rc)(R11), —C(O)OR12, —OC(O)R12, —N(R11)C(O)R12 and —C(O)N(Rc)(R11); and
the phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with 1 to 3 substituents independently
selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy-, —OH, —CN, —CF3, —OCF3, —OR1, —C(O)OH, —C(O)OCH2C6H5 and —C(O)OR12; or
R15 is —(CH2)tN(R17)(R18) where t is an integer from 2 to 4 and R17 and R18 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring containing 3 to 6 ring-atoms
in which rings containing 5 or 6 ring-atoms are optionally substituted with oxo and optionally include an additional heteroatom
moiety selected from the group consisting of —O—, —S— and —N(R19)—; or
R14 and R15 are taken together with the nitrogen atom to which they are attached to form a heterocyclic ring containing 3 to 6 ring-atoms
in which rings containing 5 or 6 ring-atoms are optionally substituted with oxo and optionally include an additional heteroatom
moiety selected from the group consisting of —O—, —S— and —N(R19)—;
R19 is H, (C1-C6)alkyl or halo-substituted(C1-C6)alkyl;
R16 is (C1-C6)alkyl, phenyl or phenyl(C1-C4)alkyl-,
where the (C1-C6)alkyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo,
—CN, (C1-C4)alkoxy- and (C1-C4)alkylthio; and
the phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with 1 to 3 substituents independently
selected from the group consisting of halo, (C1-C4)alkyl and (C1-C4)alkoxy-; and
R20 is selected from the group consisting of (C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl-, phenyl and phenyl(C1-C6)alkyl-;
where the (C1-C6)alkyl group is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo,
oxo, —OH, —CN, —CF3, —OCF3, —OR12—C(O)R12, —CO2R12, —OC(O)R12, —N(R11)C(O)R12 and —C(O)N(Rc)(R11);
the (C3-C7)cycloalkyl group and the cycloalkyl moiety of the cycloalkylalkyl group are optionally substituted with 1 to 3 substituents
independently selected from the group consisting of halo, oxo, (C1-C6)alkyl, —OH, —CN, —CF3, —OCF3 and —OR12; and
the phenyl group and the phenyl moiety of the phenylalkyl group are optionally substituted with 1 to 3 substituents independently
selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy-, —OH, —CN, —CF3, —OCF3 and —OR12; or a pharmaceutically acceptable salt thereof.
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