US 7,504,511 B2
2-acylamino-4-phenylthiazole derivatives, preparation thereof and therapeutic application thereof
Pierre Carayon, Montpellier (France); Pierre Casellas, Montpellier (France); Daniel Floutard, Combaillaux (France); Pierre Fraisse, Juvignac (France); Samir Jegham, Montferrier-sur-Lez (France); and Bernard Labeeuw, Montpellier (France)
Assigned to Sanofi-Aventis, Paris (France)
Filed on Oct. 19, 2005, as Appl. No. 11/253,998.
Application 11/253998 is a continuation of application No. PCT/FR04/00981, filed on Apr. 22, 2004.
Claims priority of application No. 03 05213 (FR), filed on Apr. 25, 2003.
Prior Publication US 2006/0135575 A1, Jun. 22, 2006
Int. Cl. C07D 211/68 (2006.01); C07D 277/00 (2006.01); A61K 31/425 (2006.01)
U.S. Cl. 546—194  [548/198; 514/371] 16 Claims
 
1. A compound of the formula (I):

OG Complex Work Unit Drawing
wherein:
R1 represents a hydrogen or halogen atom or a (C1-C4) alkyl, trifluoroethyl, hydroxyl, (C1-C4)alkoxy, trifluoromethoxy, trifluoroethoxy, (C3-C8)cycloalkyloxy, allyloxy, cyclopropylmethoxy or (C1-C4)alkylthio group;
R2 represents a hydrogen or halogen atom or a (C1-C8)alkyl, trifluoroethyl, perfluoro(C1-C4)alkyl, (C3-C10)cycloalkyl, phenyl, (C1-C8)alkoxy, trifluoromethoxy, trifluoroethoxy, allyloxy, (C3-C8)cycloalkylmethoxy, (C3-C8)cycloalkyloxy or (C3-C8) cycloalkylmethyl group;
R3 represents
—O—(C2-C4)alk-A, —O—(C1-C4)alk-B, —O-E, —(C1-C4) alk-A, -B, —(C1-C4)alk-NR4—(C2-C3)alk-A, —(C1-C4) alk-NR4—(C1-C3) alk-B, —CONR4—(C2-C4)alk-A, —CONR4—(C1-C4)alk-B, —CONR4-E, —CO-D-(C1-C2)alk-A, —CO-G-A,

OG Complex Work Unit Drawing
R4 represents a hydrogen atom or a (C1-C4)alkyl group;

OG Complex Work Unit Drawing
R5 and R6 each represent, independently of each other, a hydrogen atom or a (C1-C6)alkyl, allyl, (C2-C4)alk-O—(C1-C4)alkyl, (C2-C4)alk-OH, (C1-C3)alk-CON(R4)2, (C2-C3)alk-NHCO—(C1-C4)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkylmethyl, —CO—(C1-C4)alkyl, benzyl, pyrrolidinyl optionally substituted with a —CO—(C1-C4)alkyl group, tetrahydropyranyl, tetrahydropyranylmethyl, dimethyltetrahydropyranyl, tetrahydrofuryl or tetrahydrofurylmethyl group;
or R5 and R6, together with the nitrogen atom to which they are attached, constitute a heterocyclic radical selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, perhydroazepinyl, morpholinyl, piperazinyl, tropanyl, quinuclidinyl, 2-azabicyclo[2,2,1]heptanyl, and 2-azabicyclo[2,2,2]octanyl, the said heterocyclic radicals being unsubstituted or substituted with a phenyl, halophenyl, trifluoromethylphenyl, trifluoromethyl, hydroxyl, methoxy, hydroxymethyl, methoxymethyl, formamido or trifluoroacetylamino group, a group —NR4R7, tetrahydropyran-4-ylamino, —CON(R4)2, —CONR4R′4, —CH2CON(R4)2, (C1-C4)alkyl-CONR4—, (C3-C8)cycloalkyl-CONR4—, (C1-C4)alkyl-OCONR4—, (C3-C8)cycloalkyl-OCONR4—, (C1-C4)alkyl-OCO)2N— or (C1-C4)alkyl-COO—, or substituted with one or more methyl groups;
R′4 represents a group (CH2)s linked to the carbon atom bearing —CONR4R′4;
R7 represents a hydrogen atom, a (C1-C4)alkyl or an —SO2CH3 group or R4 and R7, together with the nitrogen atom to which they are attached, constitute a pyrrolidinyl or piperidinyl radical;
p represents 1, 2, 3, 4 or 5;
q represents 0, 1 or 2;
r represents 1 or 2;
s represents 2 or 3;
p+q being less than or equal to 5;
p+r being less than or equal to 5; and
alk represents an alkylene;
provided that R1 and R2 are not simultaneously a hydrogen atom; ora pharmaceutically acceptable salt thereof.