Small molecule modulators of non-endogenous, constitutively activated human serotonin receptors

A compound structurally represented as follows:

• wherein:
• X is O or S;
• Z is H or CH.sub.3 ;
• R.sup.3 and R.sup.10 are each independently selected from H, C.sub.1-8 straight chain or branched alkyl, C.sub.3-8 cycloalkyl, C.sub.4-9 alkylcycloalkyl, and C.sub.2-8 alkenyl;
• R.sup.11 is H, F, Cl, Br, I, R.sup.7, CF.sub.3, CCl.sub.3, NR.sup.8 R.sup.9, NR.sup.10 COR.sup.7, NR.sup.10 SO.sub.2 R.sup.7, OR.sup.7, OCF.sub.3, OCOR.sup.7, OSO.sub.2 R.sup.7, SR.sup.7, SCF.sub.3, SCOR.sup.7, SO.sub.3 R.sup.7, SO.sub.2 NR.sup.8 R.sup.9, NO.sub.2, CN, COOR.sup.7, COSR.sup.7, or CONR.sup.8 R.sup.9,
• with the proviso that when a position adjacent to R.sup.11 is substituted, then R.sup.11 and said adjacent position can together be selected from SCH.sub.2 S, SCH.sub.2 CH.sub.2 S, OCH.sub.2 O, and OCH.sub.2 CH.sub.2 O to form a bi-cyclic structure;
• R.sup.7 is H, C.sub.1-8 straight chain or branched alkyl, C.sub.3-8 cycloalkyl, C.sub.4-9 alkylcycloalkyl, C.sub.2-8 alkenyl, aryl or alkylaryl;
• R.sup.8 and R.sup.9 are independently selected from H, C.sub.1-8 straight chain or branched alkyl, and C.sub.2-8 alkenyl or cycloalkyl, or alkylcycloalkyl, or aryl or CH.sub.2 aryl wherein each moiety within said C.sub.1-8 straight chain or branched alkyl, C.sub.2-8 alkenyl or cycloalkyl, or alkylcycloalkyl, or aryl or CH.sub.2 aryl may be optionally substituted by up to four substituents in any position, whereby each substituent is independently selected from:
• F, Cl, Br, I, CF.sub.3, CCl.sub.3, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, NHC.sub.2 H.sub.5, N(C.sub.2 H.sub.5).sub.2, NHC.sub.3 H.sub.7, N(C.sub.3 H.sub.7).sub.2, NHC.sub.4 H.sub.9, N(C.sub.4 H.sub.9).sub.2, NHCOH, NHCOCH.sub.3, NHCOC.sub.2 H.sub.5, NHCOC.sub.3 H.sub.7, NHCOC.sub.4 H.sub.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 C.sub.2 H.sub.5, NHSO.sub.2 C.sub.3 H.sub.7, NHSO.sub.2 C.sub.4 H.sub.9, OH, OCH.sub.3, OC.sub.2 H.sub.5, OC.sub.3 H.sub.7, OC.sub.4 H.sub.7, OC.sub.4 H.sub.9, OC.sub.5 H.sub.9, OC.sub.5 H.sub.11, OC.sub.6 H.sub.11, OC.sub.6 H.sub.13, OCF.sub.3, OCOCH.sub.3, OCOC.sub.2 H.sub.5, OCOC.sub.3 H.sub.7, OCOC.sub.4 H.sub.9, OSO.sub.2 CH.sub.3, OSO.sub.2 C.sub.2 H.sub.5, OSO.sub.2 C.sub.3 H.sub.7, OSO.sub.2 C.sub.4 H.sub.9, SH, SCH.sub.3, SC.sub.2 H.sub.5, SC.sub.3 H.sub.7, SC.sub.4 H.sub.7, SC.sub.4 H.sub.9, SC.sub.5 H.sub.9, SC.sub.5 H.sub.11, SC.sub.6 H.sub.11, SC.sub.6 H.sub.13,, SCF.sub.3, SCOCH.sub.3, SCOC.sub.2 H.sub.5, SCOC.sub.3 H.sub.7, SCOC.sub.4 H.sub.9, SO.sub.3 CH.sub.3, SO.sub.3 C.sub.2 H.sub.5, SO.sub.3 C.sub.3 H.sub.7, SO.sub.3 C.sub.4 H.sub.9, SO.sub.2 NH, SO.sub.2 NH.sub.2, SO.sub.2 NHCH.sub.3, SO.sub.2 N(CH.sub.3).sub.2, SO.sub.2 NHC.sub.2 H.sub.5, SO.sub.2 N(C.sub.2 H.sub.5).sub.2, SO.sub.2 NHC.sub.3 H.sub.7, SO.sub.2 N(C.sub.3 H.sub.7).sub.2, SO.sub.2 NHC.sub.4 H.sub.9, SO.sub.2 N(C.sub.4 H.sub.9).sub.2, NO.sub.2, CN, COOCH.sub.3, COOC.sub.2 H.sub.5, COOC.sub.3 H.sub.7, COOC.sub.4 H.sub.9, COSCH.sub.3, COSC.sub.2 H.sub.5, COSC.sub.3 H.sub.7, COSC.sub.4 H.sub.9, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, CONHC.sub.2 H.sub.5, CON(C.sub.2 H.sub.5).sub.2, CONHC.sub.3 H.sub.7, CON(C.sub.3 H.sub.7).sub.2, CONHC.sub.4 H.sub.9, and CON(C.sub.4 H.sub.9).sub.2, and
• with the proviso that when either of R.sup.8 or R.sup.9 contain an aryl ring substituted at at least two adjacent positions on said aryl ring, then said two adjacent positions can together be selected from SCH.sub.2 S, SCH.sub.2 CH.sub.2 S, OCH.sub.2 O, or OCH.sub.2 CH.sub.2 O to form a bi-cyclic structure;
• R.sup.12, R.sup.13, R.sup.14, and R.sup.15 are each independently selected from:
• F, Cl, Br, I, CF.sub.3, CCl.sub.3, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, NHC.sub.2 H.sub.5, N(C.sub.2 H.sub.5).sub.2, NHC.sub.3 H.sub.7, N(C.sub.3 H.sub.7).sub.2, NHC.sub.4 H.sub.9, N(C.sub.4 H.sub.9).sub.2, NHCOH, NHCOCH.sub.3, NHCOC.sub.2 H.sub.5, NHCOC.sub.3 H.sub.7, NHCOC.sub.4 H.sub.9, NHSO.sub.2 CH.sub.3, NHSO.sub.2 C.sub.2 H.sub.5, NHSO.sub.2 C.sub.3 H.sub.7, NHSO.sub.2 C.sub.4 H.sub.9, OH, OCH.sub.3, OC.sub.2 H.sub.5, OC.sub.3 H.sub.7, OC.sub.4 H.sub.7, OC.sub.4 H.sub.9, OC.sub.5 H.sub.9, OC.sub.5 H.sub.11, OC.sub.6 H.sub.11, OC.sub.6 H.sub.13, OCF.sub.3, OCOCH.sub.3, OCOC.sub.2 H.sub.5, OCOC.sub.3 H.sub.7, OCOC.sub.4 H.sub.9, OSO.sub.2 CH.sub.3, OSO.sub.2 C.sub.2 H.sub.5, OSO.sub.2 C.sub.3 H.sub.7, OSO.sub.2 C.sub.4 H.sub.9, SH, SCH.sub.3, SC.sub.2 H.sub.5, SC.sub.3 H.sub.7, SC.sub.4 H.sub.7, SC.sub.4 H.sub.9, SC.sub.5 H.sub.9, SC.sub.5 H.sub.11, SC.sub.6 H.sub.11, SC.sub.6 H.sub.13,, SCF.sub.3, SCOCH.sub.3, SCOC.sub.2 H.sub.5, SCOC.sub.3 H.sub.7, SCOC.sub.4 H.sub.9, SO.sub.3 CH.sub.3, SO.sub.3 C.sub.2 H.sub.5, SO.sub.3 C.sub.3 H.sub.7, SO.sub.3 C.sub.4 H.sub.9, SO.sub.2 NH, SO.sub.2 NH.sub.2, SO.sub.2 NHCH.sub.3, SO.sub.2 N(CH.sub.3).sub.2, SO.sub.2 NHC.sub.2 H.sub.5, SO.sub.2 N(C.sub.2 H.sub.5).sub.2, SO.sub.2 NHC.sub.3 H.sub.7, SO.sub.2 N(C.sub.3 H.sub.7).sub.2, SO.sub.2 NHC.sub.4 H.sub.9, SO.sub.2 N(C.sub.4 H.sub.9).sub.2, NO.sub.2, CN, COOCH.sub.3, COOC.sub.2 H.sub.5, COOC.sub.3 H.sub.7, COOC.sub.4 H.sub.9, COSCH.sub.3, COSC.sub.2 H.sub.5, COSC.sub.3 H.sub.7, COSC.sub.4 H.sub.9, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, CONHC.sub.2 H.sub.5, CON(C.sub.2 H.sub.5).sub.2, CONHC.sub.3 H.sub.7, CON(C.sub.3 H.sub.7).sub.2, CONHC.sub.4 H.sub.9, and CON(C.sub.4 H.sub.9).sub.2, and
• with the proviso that when any two adjacent positions of R.sup.12, R.sup.13, R.sup.14, and R.sup.15 are substituted, said two adjacent positions can together be further selected from SCH.sub.2 S, SCH.sub.2 CH.sub.2 S, OCH.sub.2 O, and OCH.sub.2 CH.sub.2 O to form a bi-cyclic structure;
• and
• with the proviso that at least two of R.sup.12, R.sup.13, R.sup.14, and R.sup.15 must be H.