Imidazoline derivatives, their preparation and their use as tachykinin receptor antagonists

摘要

A compound of the formula wherein: m is 0 or 1; n is 0 or 1; X is -(CHR<4>)p-(CHR<6>)q-, where, p is 0 or 1; q is 0 or 1; and R<4> and R<6> are independently selected from the group consisting of hydrogen and C1-C3 alkyl; R<2> is phenyl, 2- or 3-indolyl, 2- or 3-indolinyl, benzothienyl, benzofuranyl, or naphthyl; any one of which groups may be substituted with one or two moieties independently selected from the group consisting of halo, C1-C3 alkoxy, trifluoromethyl, C1-C4 alkyl, phenyl-C1-C3 alkoxy, and C1-C4 alkanoyl groups; R<1> is hydrogen, trityl, phenyl, diphenylmethyl, phenoxy, phenylthio, hexamethyleneiminyl, piperazinyl, piperidinyl, pyrrolidinyl, morpholinyl, indolinyl, indolyl, benzothienyl, benzofuranyl, quinolinyl, isoquinolinyl, tetrahydropyridinyl, reduced quinolinyl, reduced isoquinolinyl, phenyl-(C1-C6 alkylidenyl)-, phenyl-(C1-C4 alkoxy)-, quinolinyl-(C1-C6 alkylidenyl)-, isoquinolinyl-(C1-C6 alkylidenyl)-, reduced quinolinyl-(C1-C6 alkylidenyl)-, reduced isoquinolinyl-(C1-C6 alkylidenyl)-, benzoyl-(C1-C6 alkylidenyl)-, C1-C4 alkyl, or -NH-CH2-R<5>; any one of which R<1> groups may be substituted with halo, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, amino, C1-C4 alkylamino, or di(C1-C4 alkyl)amino; or any one of which R<1> groups may be substituted with phenyl, piperazinyl, C3-C8 cycloalkyl, benzyl, C1-C4 alkyl, piperidinyl, pyridinyl, pyrimidinyl, C2-C6 alkanoylamino, pyrrolidinyl, C2-C6 alkanoyl, or C1-C4 alkoxycarbonyl; any one of which groups may be substituted with halo, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, amino, C1-C4 alkylamino, di(C1-C4 alkyl)amino, or C2-C4 alkanoylamino; or R<1> is amino, a leaving group, hydrogen, C1-C4 alkylamino, or di(C1-C4 alkyl)amino; R<5> is pyridyl, anilino-(C1-C6 alkylidenyl)-, or anilinocarbonyl; R<8> is hydrogen or C1-C6 alkyl; and R<3> is phenyl, phenyl-(C1-C6 alkylidenyl)-, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C1-C8 alkyl, naphthyl, C2-C8 alkenyl, or hydrogen; any one of which groups except hydrogen may be substituted with one or two halo, C1-C3 alkoxy, C1-C3 alkylthio, nitro, trifluoromethyl, or C1-C3 alkyl groups; or a salt or solvate thereof. This invention provides a novel series substituted 2-imidazolines which are useful in the treatment or prevention of a physiological disorder associated with an excess of tachykinins. This invention also provides methods for the treatment of such physiological disorders as well as pharmaceutical formulations which employ these novel compounds.