Patent TW-I259180-B (TW)
Title: 4-Phenyl-pyridine derivatives
Inventor: GODEL THIERRY
IPC: C07D409/04
Filed: 2001-07-26
Granted: 2006-08-01
Abstract: The present invention relates to compounds of the general formula, wherein R is hydrogen or halogen; R1 is -(C=C)mR1' or -(CR'=CR"")mR1' wherein R1' is (a) halogen, (b) cyano, or the following groups, (c) formula, (d) -C(O)NR'R"", (e) -C(O)O(CH2)mR5, (f) -C(O)R5, (g) -N(OH)-(CH2)mR5, (h) -NR'C(O)-(CH2)mR5', (i) -N[C(O)-R']2, (j) -OR6, (k) -(CH2)m-SR6, -(CH2)m-S(O)R6, -(CH2)m-S(O)2R6, (l) aryl, optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)OR', -C(O)NR'R"" or -C(O)R', (n) is a five or six membered saturated cyclic tertiary amine of the group, which may contain one additional heteroatom, selected from N, O or S, R'/R"" are independently from each other hydrogen, hydroxy, lower alkyl, cycloalkyl or aryl, wherein the lower alkyl, cycloalkyl or aryl group may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'""R"""", nitro, -(CH2)nOR'"", -C(O)NR'""R"""", -C(O)OR'"" or -C(O)R""', R'""/R"""" are independently from each other hydrogen, lower alkyl, cycloalkyl or aryl, R5 is hydrogen, cyano, hydroxy, halogen, trifluoromethyl, -C(O)OR', -OC(O)R' or aryl, wherein the aryl may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)NR'R"", -C(O)OR' or -C(O)R', or is a five or six membered heteroaryl group, containing one to four heteroatoms, selected from N, O or S and may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)NR'R"", -C(O)OR' or -C(O)R', R5' is cyano, hydroxy, halogen, trifluoromethyl, -C(O)OR', -OC(O)R' or aryl, wherein the aryl may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)NR'R"", -C(O)OR' or -C(O)R', or is a five or six membered heteroaryl group, containing one to four heteroatoms, selected from N, O or S and may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)NR'R"", -C(O)OR' or -C(O)R', R6 is hydrogen, lower alkyl, trifluoromethyl, or aryl, wherein the lower alkyl or aryl group may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -C(O)NR'R"", -(CH2)nOR', -C(O)OR' or -C(O)R', or is a five or six membered heteroaryl group, containing one to four heteroatoms, selected from N, O or S and may be optionally substituted by one or more substituents, selected from halogen, trifluoromethyl, lower alkyl, lower alkoxy, cyano, hydroxy, -NR'R"", nitro, -(CH2)nOR', -C(O)NR'R"", -C(O)OR' or -C(O)R', R7 is -C(O)-(CH2)mOH or an oxo group; R2 hydrogen, lower alkyl, lower alkoxy, halogen or CF3; R3/R3' are independently from each other hydrogen, lower alkyl or form together with the carbon atom to which they are attached a cycloalkyl group; R4/R4' are independently from each other hydrogen, halogen, CF3, lower alkyl or lower alkoxy; R and R2 or R4 and R4' may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl, halogen or lower alkoxy; X is -C(O)N(R8)-, (CH2)pO-, -(CH2)pN(R8)-, -N(R8)C(O)- or -N(R8)-(CH2)p-; wherein R8 is hydrogen or lower alkyl; n is 1 or 2; m is 0, 1, 2, 3 or 4; o is 1 or 2; and p is 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. It has been found that the compounds of the present invention are antagonists of the Neurokinin 1 (NK-1, substance P) receptor, and they are therefore useful in the treatment of diseases, related to this receptor.