US 7,320,978 B2
Oxazole derivatives, preparation and therapeutic use thereof
Francis Barth, Saint Georges d'Orques (France); Joelle Arnaud-Taillades, Montpellier (France); Christian Congy, Saint Gely du Fesc (France); and Murielle Rinaldi-Carmona, Saint Georges d'Orques (France)
Assigned to Sanofi-Aventis, Paris (France)
Filed on Aug. 01, 2006, as Appl. No. 11/461,629.
Application 11/461629 is a continuation of application No. PCT/FR2005/000321, filed on Feb. 11, 2005.
Claims priority of application No. 04 01507 (FR), filed on Feb. 13, 2004.
Prior Publication US 2007/0043060 A1, Feb. 22, 2007
Int. Cl. A61K 31/422 (2006.01); A61K 31/445 (2006.01); A61K 31/496 (2006.01); C07D 413/02 (2006.01); C07D 263/30 (2006.01)
U.S. Cl. 514—252.13  [544/224; 544/358; 544/366; 544/369; 546/184; 546/192; 546/207; 546/209; 548/215; 548/235; 548/236; 514/252.12; 514/315; 514/326; 514/374] 11 Claims
 
1. A compound of the formula (I):

OG Complex Work Unit Drawing
wherein:
R1 represents hydrogen or (C1-C4)alkyl;
R2 represents:
(C4-C10)alkyl;
a nonaromatic C3-C12 carbocyclic radical that is unsubstituted or substituted one or more times with (C1-C4)alkyl;
a 1,2,3,4-tetrahydronaphth-1yl or -2-yl;
a saturated, monooxygen or monosulfur-containing heterocyclic radical having from 5 to 7 atoms, that is unsubstituted or substituted one or more times with (C1-C4)alkyl;
a saturated, mononitrogen heterocyclic radical having from 5 to 7 atoms, the nitrogen atom being substituted with (C1-C4)alkyl, phenyl, benzyl, (C1-C4)alkoxycarbonyl or (C1-C4)alkanoyl group;
(C1-C3)alkylene group carrying a nonaromatic C3-C12 carbocyclic radial that is unsubstituted or substituted one or more times with (C1-C4) alkyl;
(C1-C3)alkylene, that is unsubstituted or substituted on the alkylene with one or more methyl or (C1-C4)alkoxycarbonyl groups, and unsubstituted or substituted on the phenyl with one or more substituents, that may be identical or different, chosen from halogen, (C1-C4)alkyl, trifluoromethyl, (C1-C4)alkoxy or trifluoromethoxy;
a group NR9R10;
or R1 and R2, together with the nitrogen atom to which they are attached, constitute:
either a piperazin-1-yl or 1,4-diazepan-1-yl radical substituted in the 4-position with a phenyl or benzyl group;
or a piperidin-1-yl or pyrrolidin-1-yl radical mono- or disubstituted with groups, that are identical or different, chosen from phenyl, benzyl, (C1-C4)alkyl, hydroxyl, cyano, (C1-C3)alkanoyl, (C1-C4)alkoxycarbonyl or (C1-C4)alkoxycarbonylamino group, or with a group CONR11R12 or NR11R12; and wherein said phenyl or benzyl is unsubstituted or substituted with one or more substituents chosen from halogen, methyl, hydroxyl, methoxy, cyano, acetyl or methoxycarbonyl;
or a spiro[1H-inden-1,4′-piperidine] radical or a 3H-spiro[2-benzofuran-1,4′-piperidine] radical, said radical being unsubstituted or substituted with an oxo group;
R3, R4, R5, R6, R7 and R8 each represent, independently of one another, a hydrogen or halogen atom, a (C1-C6)alkyl, (C1-C6)alkoxy or trifluoromethyl group or a group S(O)nAlk; with the proviso that R3, R4, R5, R6, R7 and R8 are not simultaneously hydrogen;
R9 represents hydrogen or methyl;
R10 represents (C3-C6)alkyl, phenyl or (C3-C10)cycloalkyl, said phenyl and cycloalkyl being unsubstituted or substituted with one or more substituents chosen from halogen or (C1-C4)alkyl;
or R9 and R10, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical having from 5 to 11 atoms, which is optionally bridged, optionally comprising a spiro carbon and optionally containing a second hetero atom chosen from O or N, said radical being unsubstituted or substituted one or more times with a substituent group chosen from hydroxyl, (C1-C4)alkyl or (C1-C4)alkoxycarbonyl or phenyl that is unsubstituted or substituted with one or more substituents chosen from halogen or (C1-C4)alkyl;
R11 and R12 each represent, independently of one another, hydrogen or (C1-C4)alkyl;
or R11 and R12, together with the nitrogen atom to which they are attached, constitute a saturated heterocyclic radical having from 3 to 7 atoms, optionally containing a second hetero atom chosen from O or N, said heterocyclic radical being unsubstituted or substituted one or more times with methyl;
n represents 0, 1 or 2; and
Alk represents a (C1-C4)alkyl group; or
a salt thereof, or a hydrate or a solvate of said compound or said salt.