| US 7,592,356 B2 | ||
| Triazoles as farnesyl transferase inhibitors | ||
| Ashis Kumar Saha, Harleysville, Pa. (US); David William End, Ambler, Pa. (US); Bart Lieven Daniel De Corte, Southampton, Pa. (US); Henry Joseph Breslin, Lansdale, Pa. (US); and Li Liu, Doylestown, Pa. (US) | ||
| Assigned to Janssen Pharmaceutica N.V., Beerse (Belgium) | ||
| Filed on Oct. 29, 2007, as Appl. No. 11/926,858. | ||
| Application 11/143814 is a division of application No. 10/130322, granted, now 7,049,324, previously published as PCT/EP00/11393, filed on Nov. 15, 2000. | ||
| Application 11/926858 is a continuation of application No. 11/143814, filed on Jun. 02, 2005. | ||
| Claims priority of provisional application 60/165434, filed on Nov. 15, 1999. | ||
| Prior Publication US 2008/0103150 A1, May 01, 2008 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. A61K 31/47 (2006.01); C07D 249/08 (2006.01) | ||
| U.S. Cl. 514—311 [548/262.2; 548/267.2; 546/152; 546/174; 514/383] | 10 Claims |
1. A compound of formula
 a prodrug, N-oxide, addition salt, quaternary amine or stereochemically isomeric form thereof, wherein
L1 and L2 are R1—Y— wherein each (R1—Y)— substituent is defined independently of the other;
Y is C1-4alkanediyl, C2-4alkenediyl, C2-4alkynediyl, C(═O), or a direct bond;
R1 is hydrogen, cyano, aryl or a substituted or unsubstituted C1-14heterocycle;
═Z1—Z2═Z3— represents a radical of formula
═N—N═CH— (a-1)
═N—CH═N— (a-2)
═CH—N═N— (a-3)
X is SO2, (CH2)n wherein n is 1 to 4, C(═O), C(═S), or a direct bond R2 is aryl, C3-7cycloalkyl, C3-7cycloalkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or
unsubstituted C1-14heterocycle, C3-7cycloalkyl, hydroxycarbonyl, C1-6alkyloxycarbonyl, hydroxyC1-6alkyl, hydroxyC1-6alkyloxy, hydroxyC1-6alkylthio and arylC1-6alkylthio, C1-12alkyl or C1-12alkyl substituted with one or more substituents independently selected from hydroxy, aryl, aryloxy, a substituted or unsubstituted
C1-14heterocycle, C3-7cycloalkyl, hydroxycarbonyl, C1-6alkyloxycarbonyl, hydroxyC1-6alkyl, hydroxyC1-6alkyloxy, hydroxyC1-6alkylthio and arylC1-6alkylthio;
R3 is aryl, —NR5R6, a substituted or unsubstituted C1-14heterocycle, or C2-4alkenediyl substituted with a substituted or unsubstituted C1-14heterocycle or aryl;
R4 is hydrogen, aryl, C3-7cycloalkyl, C1-6alkyl or C1-6alkyl substituted with C3-7cycloalkyl, hydroxycarbonyl, C1-4alkyloxycarbonyl or aryl;
R5 and R6 are each independently selected from hydrogen, a substituted or unsubstituted C1-14heterocycle, aryl, C1-12alkyl and C1-12alkyl substituted with one or more substituents selected from hydroxy, aryl, aryloxy or a substituted or unsubstituted C1-14heterocycle;
R7 is substituted or unsubstituted phenyl, —NR8R9 or a substituted or unsubstituted C1-14heterocycle;
R8 and R9 are independently selected from hydrogen, substituted or unsubstituted phenyl, C3-6cycloalkyl, a substituted or unsubstituted C1-14heterocycle, C1-6alkyl and C1-6alkyl substituted with one or more substituents independently selected from C1-4alkyloxycarbonyl,hydroxycarbonyl, substituted or unsubstituted phenyl and a substituted or unsubstituted C1-14heterocycle;
aryl, as a group or part of a group, is naphthyl or phenyl each of which may optionally be substituted with one or more substituents
selected from trifluoromethyl, trifluoromethyloxy, halo, cyano, nitro, C1-12alkyl, C1-12alkyloxy, phenylC1-6alkyl, phenylC1-6alkyloxy, phenyloxy, phenylcarbonyl, hydroxycarbonyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, amino, mono- or di(C1-4alkyl)amino, mono- or di(C1-4alkyl)amino wherein said C1-4alkyl is substituted with one or more substituted or unsubstituted phenyl, S(O)2—R7, C1-6alkylcarbonylamino, substituted or unsubstituted phenyl, and a substituted or unsubstituted C1-14heterocycle.
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