PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR CCR5

• Main Authors: TAKER KHAUARD, FAULL ALAN
• Format: Patent
• Language: English; Russian
• Published: 27.09.2009
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

FIELD: chemistry. ^ SUBSTANCE: in new compounds with formula (I): (I) A is absent or represents (CH2)2; L is CH or N; M is NR1, O, S, S(O) or S(O)2; R1 is C1-6alkyl, substituted with phenyl {which itself is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, CF3}; phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, CF3, C1-4alkylthio}, S(O)2R, S(O)2NR6R7, C(O)R8; R2 is phenyl (which is possibly substituted with halogen, CN or C1-4halogenalkyl), thienyl or halogenthienyl; R3 is hydrogen or methyl; Rb is hydrogen or C1-3alkyl; R4 is a five- or six-member heterocycle, containing at least one carbon atom, one to four nitrogen atoms and, possibly, one oxygen or sulphur atom, where the carbon atom in the said heterocycle R4 is possibly substituted with oxo, C1-6alkyl [which is possibly substituted with halogen, OH, C1-4alkoxy, S(C1-4alkyl) group or piperidinyl {which it self is possibly substituted with benzene [which is possibly substituted with a S(O)2(C1-4alkyl) group], C(O)(C1-4alkoxy) group, C(O)NH2, C(O)NH(C1-4alkyl), C(O)N(C1-4alkyl)2 or S(O)2(C1-4alkyl) [where alkyl is possibly substituted with fluoro]}], C3-6cycloalkyl, CN, C(O)NH2, C(O)NH(phenylC1-2alkyl) group, phenyl [which is possibly substituted with a S(O)2(C1-4alkyl) group] or benzyl [which is possibly substituted with a S(O)2(C1-4alkyl) group]; if possible, the nitrogen atom in the said heterocycle R4 is substituted with C1-6alkyl [which is possibly substituted with C1-4alkoxy, S(O)(C1-4alkyl) group, S(O)2(C1-4alkyl), C(O)(C1-4alkoxy), CONH2, CONH(C1-4alkyl), CON(C1-4alkyl)2, phenyl{which is possibly substituted with C1-4alkyl, C1-4alkoxy, S(O)(C1-4alkyl) group or S(O)2(C1-4alkyl)}, piperidinyl {which is possibly substituted with a S(O)(C1-4alkyl) group or S(O)2(C1-4alkyl)}], C3-6cycloalkyl, CO(C1-4alkyl) group [which is possibly substituted with a halogen], S(O)2(C1-4alkyl) group [which is possibly substituted with fluorine], COO(C1-6alkyl) group, phenyl [which is possibly substituted with a S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) group]; - under the condition that the nitrogen atom in the said heterocycle R4 is substituted with an alky group, the said alkyl does not have C1-4alkoxy, S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) substitute on the carbon atom, bonded to the nitrogen atom in the said heterocycle R4; - five- or six-member heterocyle R4 is possibly condensed with cyclohexane, piperadine, benzole, pyridine, pyridazine, pyrimidine or pyrazine ring; ring carbon atoms in the said condensed cyclohexane, piperadine, benzole, pyridine, pyridazine, pyrimidine or pyrazine ring are possibly substituted with a halogen, C1-4alkyl, C1-4alkoxy, CF3, S(C1-4alkyl), S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) group; and the nitrogen atom of the condensed piperidine ring is possibly substituted with C1-4alkyl [which is possibly substituted with oxo, halogen, OH, C1-4alkoxy, C(O)(C1-4alkoxy), C(O)NH2, C(O)NH(C1-4alkyl) group, C(O)N(C1-4alkyl)2 group, C(O)(C1-4alkyl)group [where alkyl is possibly substituted with C1-4alkoxy or halogen], benzene [which is possibly substituted with S(O)(C1-4alkyl) or S(O)2(C1-4alkyl)], C(O)(C1-4alkoxy), C(O)NH2, C(O)NH(C1-4alkyl), C(O)N(C1-4alkyl)2 or S(O)2(C1-4alkyl) group [where alkyl is possibly substituted with fluoro]; R5 is C1-6alkyl [which is possibly substituted with a halogen (for example fluoro), C1-4alkoxy, phenyl {which itself is possibly substituted with a halogen, C1-4alkyl, C1-4alkoxy}], C3-7cycloalkyl (which is possibly substituted with a halogen or C1-6alkyl), piranyl, phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}, or a 5- or 6-member saturated nitrogen-containing heterocyclic ring {which is possibly substituted with a S(O)2(C1-4alkyl) or C(O)(C1-4alkyl) group}; R8 is hydrogen, C1-4alkyl [which is possibly substituted with halogen (for example fluro), C1-4alkoxy, phenyl{which itself is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}], C3-7cycloalkyl (which is possibly substituted with halogen or C1-4alkyl), piranyl, phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}, or a 5- or 6-member saturated nitrogen-containing heterocyclic ring {which is possibly substituted with S(O)2(C1-4alkyl) or C(O)(C1-4alkyl) group}; R6 and R7 are bonded, forming a 5- or 6-member ring which is possibly substituted with C1-4alkyl; R9 and R10 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts. The invention also relates to a method of obtaining compounds in paragraph 1, to a method of modulating activity of CCR5 receptor, as well as to a pharmaceutical composition. ^ EFFECT: obtaining new biologically active compounds with modulating effect towards CCR5 receptor. ^ 15 cl, 29 ex, 12 tbl Изобретение относится к новым соединениям формулы (I): ! ! где: А отсутствует или представляет собой (CH2)2; L представляет собой CH или N; М представляет собой NR1, О, S, S(O) или S(O)2; R1 представляет собой C1-6алкил, замещенный фенилом {который сам возможно замещен галогено, С1-4алкилом, C1-4алкокси, CF3}; фенил {который возможно замещен галогено, С1-4алкилом, С1-4алкокси, CF3, С1-4алкилтио}, S(O)2R5, S(O)2NR6R7, C(O)R8; R2 представляет собой фенил (который возможно замещен галогено, CN или С1-4галогеноалкилом), тиенил или галогенотиенил; R3 представляет собой водород или метил; Rb представляет собой водород или C1-3алкил; R4 представляет собой пяти- или шестичленный гетероцикл, содержащий по меньшей мере один атом углерода, от одного до четырех атомов азота и, возможно, один атом кислорода или серы, причем кольцевой атом углерода указанного гетероцикла R4 возможно замещен оксо, С1-6алкилом [который возможно замещен галогеном, ОН, C1-4алкокси, группой S(С1-4алкил) или пиперидинилом {который сам возможно замещен бензилом [который возможно замещен группой S(O)2(С1-4алкил)], группой C(O)(C1-4алкокси), C(O)NH2, C(O)NH(C1-4алкил), С(O)N(С1-4алкил)2 или S(O)2(С1-4алкил) [где алкил возможно замещен фторо]}], С3-6циклоалкилом, CN, C(O)NH2, группой С(O)NH(фенилС1-2алкил), фенилом [который возможно замещен группой S(O)2(C1-4алкил)] или бензилом [который возможно замещен группой S(O)2(С1-4алкил)]; - если это возможно, кольцевой атом азота указанного гетероцикла R4 возможно замещен C1-6алкилом [который возможно замещен С1-6алкокси, группой S(O)(С1-4алкил), S(O)2(C1-4алкил), С(O)(С1-4алкокси), CONH2, СОNH(С1-4алкил), СОN(С1-4алкил)2, фенилом {который возможно замещен С1-4алкилом, С1-4алкокси, группой S(O)(С1-4алкил) или S(O)2(С1-4алкил)}, пиперидинилом {который возможн