| US 7,544,688 B2 | ||
| Hetereoaryl nitrile derivatives | ||
| Eva Altmann, Reinach (Switzerland); Claudia Betschart, Basel (Switzerland); Kenji Hayakawa, Hyogo Pref. (Japan); Osamu Irie, Ibaraki Pref. (Japan); Junichi Sakaki, Ibaraki Pref. (Japan); Genji Iwasaki, Ibaraki Pref. (Japan); Rene Lattmann, Oberwil (Switzerland); Martin Missbach, Gipf-Oberfrick (Switzerland); and Naoki Teno, Ibaraki Pref. (Japan) | ||
| Assigned to Novartis AG, Basel (Switzerland) | ||
| Appl. No. 10/525,658 PCT Filed Aug. 29, 2003, PCT No. PCT/EP03/09621 § 371(c)(1), (2), (4) Date Aug. 23, 2005, PCT Pub. No. WO2004/020441, PCT Pub. Date Mar. 11, 2004. |
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| Claims priority of application No. 0220187.9 (GB), filed on Aug. 30, 2002. | ||
| Prior Publication US 2006/0142575 A1, Jun. 29, 2006 | ||
| Int. Cl. C07D 239/47 (2006.01); C07D 239/48 (2006.01); A61K 31/505 (2006.01); A61K 31/506 (2006.01); A61P 19/02 (2006.01) | ||
| U.S. Cl. 514—256 [514/269; 544/319; 544/326; 544/320] | 11 Claims |
1. A compound of formula IV, or a pharmaceutically acceptable salt thereof
 in which
R is H, —R2, —OR2 or NR1R2,
wherein R1 is H, lower alkyl or C3 to C10 cycloalkyl, and
R2 is lower alkyl or C3 to C10 cycloalkyl, and
wherein R1 and R2 are independently, optionally substituted by halo, hydroxy, lower alkoxy, CN, NO2, or optionally mono- or di-lower alkyl substituted amino;
R8′ is optionally substituted aryl-lower alkyl
wherein R8′ is optionally substituted by R10 which represents from 1 to 4 substitutents selected from halo, hydroxy, CN, NO2, —O—C(O)—, optionally substituted (lower-alkyl, C3-C10cycloalkyl, lower-alkoxy, lower-alkenyl, lower-alkynyl, optionally mono- or di-lower alkyl-substituted amino or N-heterocyclyl),
where N-heterocyclyl denotes a saturated, partially unsaturated or aromatic nitrogen containing heterocyclic moiety attached
via a nitrogen atom thereof having from 3 to 8 ring atoms optionally containing a further 1, 2 or 3 heteroatoms selected from
N, NR6, O , S, S(O) or S(O)2 wherein R6 is H or optionally substituted (lower alkyl, carboxy, formyl, acetyl, propionyl, benzoyl, amido, aryl, S(O) or
S(O)2), and wherein the N-heterocyclyl is optionally fused in a bicyclic structure with a benzene or pyridine ring, and wherein
the N-heterocyclyl is optionally linked in a spiro structure with a 3 to 8 membered cycloalkyl or heterocyclic ring wherein
the heterocyclic ring has from 3 to 10 ring members and contains from 1 to 3 heteroatoms selected from N, NR6, O, S, S(O)
or S(O)2 wherein R6 is as defined above;
wherein R10 is optionally substituted by R11 which represents from 1 to 4 substituents selected from halo, hydroxy, CN, NO2, oxo, optionally substituted (optionally mono- or di-lower alkyl-substituted amino, lower alkyl, optionally-lower alkyl substituted
COOH, sulphinyl, sulphonyl, or N-heterocyclyl which is as defined above;
wherein R11 is optionally substituted by R12 which represents from 1 to 4 substituents selected from halo, hydroxy, CN, NO2, oxo, hydroxy lower alkyl, C3-C10cycloalkyl, optionally lower alkyl-substituted carboxy, hydroximine, or N-heterocyclyl as defined above,
and wherein
R9 is H or optionally substituted lower alkyl, and
wherein R9 is optionally substituted by halo, hydroxy, oxo, lower alkoxy, CN, NO2, or optionally mono- or di-lower alkyl substituted amino.
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