A method for treating or preventing a condition selected from the group consisting of a vasomotor symptom, sexual dysfunction, gastrointestinal disorder, genitourinary disorder, chronic fatigue syndrome, fibromyalgia syndrome, depression disorder, diabetic neuropathy, endogenous behavioral disorder, cognitive disorder, pain, and combinations thereof in a subject in need thereof, comprising the step of:
- administering to said subject an effective amount of a compound of formula I:
- or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof;
- wherein:
- n is an integer from 0 to 4;
- m is an integer from 0 to 6;
- X is, independently at each occurrence, C(R7)2, N(R3), O, S, S(═O), or S(═O)2;
- Y is C;
- or
- Y and an adjacent X together form —CR7═CR7—, —C≡C—, or arylenyl substituted with 0-3 R10;
- R1 is, independently at each occurrence, H, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R11, heteroaryl substituted with 0-3 R11, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide substituted with 0-3 R5, alkylamido, or arylamido substituted with 0-3 R5;
- R2 is aryl substituted with 0-3 R9 or heteroaryl substituted with 0-3 R9;
- R3 is, independently at each occurrence, H, halo, hydroxy, alkyl substituted with 0-3 R13, a heterocyclic ring, aryl substituted with 0-3 R12, or heteroaryl substituted with 0-3 R12;
- R4 is, independently at each occurrence, H, alkyl substituted with 0-3 R13, arylalkyl substituted with 0-3 R13 or heteroarylmethyl substituted with 0-3 R13;
- R5 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkylsulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido;
- R6 is, independently at each occurrence, H, hydroxy, C1-C4 alkyl, C1-C6 alkoxy, halo, aryl substituted with 0-3 R1, heteroaryl substituted with 0-3 R1, —N(R3)2, —S(R3), or —R8—O—R3;
- or both R6 groups form a cycloalkyl, a heterocyclic ring, ═O or ═N—OH;
- provided that if each R3 is H, each X is CH2, and either each R6 is H or one R6 is hydroxy;
- then, both of said R4, together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO2, and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, minoalkyl, or a heterocyclic ring, F, or CF3;
- and where any additional N atom may be optionally substituted with C1-C4 alkyl;
- R7 is, independently at each occurrence, H, hydroxy, alkoxy, or C1-C4 alkyl;
- R8 is, independently at each occurrence, straight or branched alkylenyl;
- or
- one of said R3 and one of said R4, together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO2, and where any carbon ring atom may be optionally substituted with one or two alkyl, F, or CF3;
- and where any additional N atom may be optionally substituted with alkyl;
- or
- both of said R4, together with the nitrogen through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO2, and where any carbon ring atom may be optionally substituted with one or two alkyl, hydroxyalkyl, aminoalkyl, a heterocyclic ring, F, or CF3;
- and where any additional N atom may be optionally substituted with alkyl;
- or
- one of said R6 or one of said R7 and one of said R4, together with the nitrogen and carbon atoms through which they are attached, form a monocyclic or bicyclic heterocyclic ring of 3 to 12 ring atoms, where one carbon may be optionally replaced with N, O, S, or SO2, and where any carbon ring atom may be optionally substituted with one or two C1-C4 alkyl, F, or CF3;
- and where any additional N atom may be optionally substituted with C1-C4 alkyl;
- provided that R4 and R7, taken together, do not form a piperidinyl ring;
- R9 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, aryl substituted with 0-3 R11, heteroaryl substituted with 0-3 R11, alkylsulfoxide, alkylsulfone, alkylsulfonamide, arylsulfonamide, alkylamido, or arylamido;
- R10 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;
- R11 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;
- R12 and R13 are each, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, hydroxy, hydroxyalkyl, aminoalkyl, a heterocyclic ring, alkanoyloxy, nitro, nitrile, alkenyl, or alkynyl;
- and
- wherein 1-3 carbon atoms in ring A may optionally be replaced with N.