Trisubstituted heteroaromatic compounds as calcium sensing receptor modulators

A compound having the structure

• wherein
• X is C;
• A and B are each N;
• R1 is Ar-L-;
• R2 is hydrogen or alkyl;
• Ar is aryl or heteroaryl;
• L is a linking group containing 1 to 6 atoms in a linear chain, which may be all carbons or may have one or two hetero atoms in the chain selected from N, O, and S, and may be substituted with one, two, three or four substituents;
• R3 and R5 are each independently alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, hydroxy, haloalkyl, haloalkoxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, amino, alkylamino, thiol, alkylthio, alkylsulfinyl, or alkylsulfonyl;
• R4 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, hydroxy, haloalkyl, haloalkoxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, amino, alkylamino, thiol, alkylthio, alkylsulfinyl, or alkylsulfonyl;
• R6 is selected from hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, hydroxy, halo, haloalkyl, haloalkoxy, nitro, cyano, trifluoromethyl, trifluoromethoxy, amino, alkylamino, thiol, alkylthio, alkylsulfinyl, or alkylsulfonyl;
• R7 is alkyl, cycloalkyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, arylalkyl, heteroarylalkyl, arylaminoalkyl, or arylthioalkyl;
• R8 is hydrogen or alkyl;
• provided that R1 and R2 cannot be phenylmethylene or phenylethylene;
• or a pharmaceutically acceptable salt thereof, or all stereoisomers thereof;
• wherein the term “alkyl” alone or as part of another group may be optionally substituted with one, two, three or four substituents (which may be the same or different) commonly attached to such chains, selected from the group consisting of halo, CF3, alkyl, alkoxy, aryl, aryloxy, aryl(aryl) or diaryl, arylalkyl, arylalkyloxy, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkyloxy, optionally substituted amino, hydroxy, hydroxyalkyl, acyl, oxo, alkanoyl, heteroaryl, heteroaryloxy, cycloheteroalkyl, arylheteroaryl, arylalkoxycarbonyl, heteroarylalkyl, heteroarylalkoxy, aryloxyalkyl, aryloxyaryl, alkylamido, alkanoylamino, arylcarbonylamino, alkoxycarbonyl, alkylaminocarbonyl, nitro, cyano, thiol, haloalkyl, trihaloalkyl, alkylthio, and carboxyl;
• the term “Ar” or “aryl” alone or as part of another group
• a) may be optionally fused to an aryl, cycloalkyl, heteroaryl or cycloheteroalkyl ring;
• and
• b) may be optionally substituted through available carbon atoms with one to four substituents, selected from the group consisting of hydrogen, halo, haloalkyl, alkyl, alkoxy, haloalkoxy, alkenyl, trifluoromethyl, trifluoromethoxy, alkynyl, cycloalkylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, aryloxy, aryloxyalkyl, alkoxyalkyl, arylalkoxy, alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, arylalkenyl, heteroarylalkenyl, heteroarylheteroaryl, heteroaryloxy, heteroarylalkoxy, heteroaryloxyalkyl, aminocarbonylalkyl, aminocarbonylaryl, arylthio, arylalkylthio, heteroarylalkylthio, arylazo, hydroxy, nitro, cyano, carboxyl, carboxylalkoxy, alkoxycarbonylalkoxy, amino, and substituted amino, wherein the amino includes 1 or 2 substituents which are selected from the group consisting of alkyl, aryl, thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkoxyarylthio, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloheteroalkylsulfonyl, alkylsulfinyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonylamino, arylsulfonaminocarbonyl and/or any of the alkyl substituents set out above;
• the term “heteroaryl” alone or as part of another group
• a) may be optionally fused to an aryl, cycloalkyl, heteroaryl or cycloheteroalkyl ring;
• and
• b) may be optionally substituted by one to four substituents which can be any of the “alkyl” substituents or “aryl” substituents as defined above;
• the term “cycloheteroalkyl” alone or as part of another group
• a) may be optionally fused to a cycloalkyl, aryl, heteroaryl or cycloheteroalkyl ring;
• and
• b) may be optionally substituted with 1 to 4 substituents selected from the group consisting of alkyl, halo, oxo and any of the substituents for “alkyl” or “aryl” as defined above;
• the term “cycloalkyl” alone or as part of another group
• a) may be optionally fused to an aryl, cycloalkyl, heteroaryl or cycloheteroalkyl ring;
• and
• b) may be optionally substituted with one to four substituents selected from the group consisting of halogen, alkyl, alkoxy, hydroxyl, aryl, aryloxy, arylalkyl, cycloalkyl, alkylamido, alkanoylamino, oxo, acyl, arylcarbonylamino, amino, nitro, cyano, thiol and/or alkylthio and/or any of the substituents for “alkyl” as defined above;
• the term “alkenyl” alone or as part of another group may be optionally substituted with 1 to 4 substituents selected from the group consisting of halogen, haloalkyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, amino, hydroxyl, heteroaryl, cycloheteroalkyl, alkanoylamino, alkylamido, arylcarbonylamino, nitro, cyano, thiol, alkylthio and/or any of the substituents for alkyl as defined above;
• and
• the term “alkynyl” alone or as part of another group may be optionally substituted with 1 to 4 substituents selected from the group consisting of halogen, haloalkyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, amino, heteroaryl, cycloheteroalkyl, hydroxyl, alkanoylamino, alkylamido, arylcarbonylamino, nitro, cyano, thiol, and/or alkylthio, and/or any of the substituents for “alkyl” as defined above.