| US 7,550,465 B2 | ||
| Pyrido[3,2-e]pyrazines, their use as inhibitors of phosphodiesterase 10, and processes for preparing them | ||
| Norbert Höfgen, Ottendorf-Okrills (Germany); Hans Stange, Riesa (Germany); Barbara Langen, Radebaul (Germany); Ute Egerland, Radebeul (Germany); Rudolf Schindler, Dresden (Germany); Thomas Pfeifer, Radebeul (Germany); and Chris Rundfeldt, Coswig (Germany) | ||
| Assigned to Elbion GmbH, Radebeul (Germany) | ||
| Filed on May 24, 2007, as Appl. No. 11/753,207. | ||
| Claims priority of provisional application 60/809242, filed on May 30, 2006. | ||
| Prior Publication US 2008/0027064 A1, Jan. 31, 2008 | ||
| Int. Cl. A61K 31/4985 (2006.01) | ||
| U.S. Cl. 514—250 [544/346] | 11 Claims |
1. A compound of formula (II)
 A is C when the bond is a double bond and CH when the bond is a single bond;
m is 0 or 1;
n is 0 or 1;
R1 and R2 are independently selected from
H,
a cyclic radical;
C1-8 alkyl, optionally mono- or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical;
C2-8 alkenyl, optionally mono- or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical;
C2-8 alkynyl, optionally mono- or polysubstituted with at least one of halo, OH, O—C1-3-alkyl or a cyclic radical;
a saturated, monounsaturated or polyunsaturated carbocycle ring system with 3 to 8 atoms or a heterocyclic ring with 5 to
15 ring atoms, each optionally mono- or polysubstituted with at least one of halo, amino, C1-3 alkylamino, di-C1-3 alkylamino, nitro, C1-3 alkyl, O—C1-3 alkyl or a cyclic radical; and
R3 is selected from
H,
a cyclic radical,
N3,
CN,
R6, OR6, SR6, SOR6,SO2R6,
NH(CO)OR6, N((CO)OR6)2, NR6((CO)OR6),
NH—(C═O)—NH2, NR6—(C═O)—NH2,
NH—(C═O)—NHR6, NR6—(C═O)—NHR6,
NH—SO2R6, N(SO2R6)2 and NR6(SO2R6),
wherein R6 is independently,
a cyclic radical,
C1-8 alkyl, C3-8 cyclo(hetero)alkyl,
C2-8 alkenyl, C3-8 cyclo(hetero)alkenyl,
or C2-8 alkynyl each optionally mono or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical,
R7, OR7, SR7, NHSO2R7, N(SO2R7), or N(R8)SO2R7,
wherein R7 is aryl, heteroaryl, aryl-C1-5 alkyl, heteroaryl-C1-5 alkyl,
wherein aryl is phenyl or naphthyl, heteroaryl is an aromatic heterocyclic ring system of 5 to 15 ring atoms containing at
least one atom selected from N including N-oxide, S, and O and wherein aryl and heteroaryl are optionally mono- or polysubstituted
with at least one of halo, amino, C1-3 alkylamino, di-C1-3 alkylamino, nitro, C1-3 alkyl, O—C1-3 alkyl or a cyclic radical and
R8 is C1-5 alkyl, optionally mono or polysubstituted with at last one of halo, OH, O—C1-3 alkyl or a cyclic radical,
R4 is selected from
H,
halo,
a cyclic radical,
R9,
OH or OR9,
NH(C═O)—C1-3 alkyl, optionally mono- or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical,
NH2, NHR9 or NR9R10,
wherein R9 and R10 are independently selected from a cyclic radical,
C1-6 alkyl or C3-6 cyclo(hetero)alkyl, optionally mono- or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical,
aryl-C1-5-alkyl wherein aryl is phenyl, optionally mono- or polysubstituted with at least one of halo, amino, C1-3 alkylamino, di-C1-3 alkylamino, nitro, C1-3 alkyl, O—C1-3 alkyl or a cyclic radical or
NR9R10 together form a saturated or unsaturated five-, six- or seven-membered ring which can contain up to 3 heteroatoms, preferably
N including N-oxide, S or O, optionally mono- or polysubstituted with at least one of halo, amino, C1-3 alkylamino, di-C1-3 alkylamino, nitro, C1-3 alkyl, O—C1-3 alkyl or aryl-C1-5-alkyl, wherein aryl is phenyl, optionally mono- or polysubstituted with at least one of halo, amino, C1-3 alkylamino, di-C1-3 alkylamino, nitro, C1-3 alkyl, O—C1-3 alkyl or a cyclic radical,
and R5 is selected from
H,
C1-5 alkyl, C3-6 cycloalkyl or (CO)—C1-5 alkyl, optionally mono or polysubstituted with at least one of halo, OH, O—C1-3 alkyl or a cyclic radical,
or a pharmaceutically acceptable salt or prodrug thereof, wherein if m and n are 1,
A and N are not a double bond;
wherein if m is 1 and n is O, A and N are not a double bond;
wherein if n is 1 and m is O, A and N are not a single bond; and
wherein if m and n are O, A and N are not a single bond.
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