1-(1h-indol-1-yl)-3-(4-methylpiperazin-1-yl)-1-phenyl propan-2-ol derivatives and related compounds as modulators of the norepinephrine (ne) and the serotonine (5-ht) activity and the monoamine reuptake for the treatment of vasomotor symptoms (vms)

Compound of formula I: or a pharmaceutically acceptable salt thereof; wherein: the dotted line between Y and Z represents an optional double bond; the dotted line between the two R4 groups represents an optional heterocyclic ring of 4 to 6 ring atoms that may be formed between the two R4 groups, together with the nitrogen through which they are attached; Y is N, CR6 or C = O; Z is N, NR7, CR5 or C (R5) 2; R1 is, independently at each occurrence, alkyl, alkoxy, halo, CF3, OCF3, arylalkyloxy substituted with 0 to 3 R11, aryloxy substituted with 0 to 3 R11, aryl substituted with 0 to 3 R11, heteroaryl substituted with 0 to 3 R11, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkyl sulfoxide, dimethyl phenyl substituted with 0 to 3 R11, alkylsulfone, phenylsulfone substituted with 0 to 3 R11, alkylsulfonamide, phenylsulfonamide substituted with 0 to 3 R11, heteroaryloxy substituted with 0 to 3 R11, I heteroarilmetiloxi substituted with 0 to 3 R11, alkylamido, or arylamido substituted con0 I to 3 R11; or two adjacent R1 also represent methylenedioxy; R2 is aryl substituted with 0 to 3 R1, or heteroaryl substituted with 0 to 3 R1; R3 is H or C1-C4 alkyl; R4 is, independently each occurrence, H, C1-C4 alkyl, arylalkyl, heteroarylmethyl, cycloheptylmethyl, cyclohexylmethyl, cyclopentylmethyl or cyclobutylmethyl, or both R4 groups together with the nitrogen through which they are attached form a heterocyclic ring of 4 to 6 atoms ring, wherein one carbon may be optionally substituted with N, O, S or SO2, and wherein any ring carbon atom or N atom a further optionally substituted with alkyl may C1-C4 alkyl, F or CF3; R5 is, independently each occurrence, H, C1-C4 alkyl, aryl substituted with 0 to 3 R1, or cyano; or two R5 when present, form a carbocyclic ring of 3 to 7 carbons; R6 is H, C1-C4 alkyl or cyano; R7 is H, C1-C6 alkyl, C3-C6 cycloalkyl or aryl substituted with 0 to 3 R1; R8 is H or C1-C4 alkyl; R9 is H or C1-C4 alkyl; R10 is, independently at each occurrence, H or C1-C4 alkyl; or R10 and R4 together with the nitrogen to which R4 is attached form a nitrogen containing ring of 3 to 6 carbon atoms; n is an integer from 0 to 4; x is an integer from 1 to 2; and R11 is alkyl, alkoxy, halo, CF3, OCF3, hydroxy, alkanoyloxy, nitro, nitrile, alkenyl, alkynyl, alkyl sulfoxide, alkylsulfone, alkylsulfonamide, or alkylamido; or two adjacent R11 also represent methylenedioxy; wherein 1 to 3 carbon atoms in ring A may optionally be substituted with N.