Aminocyclohexane derivatives as 5-HT receptor agonists
AssigneeMerck Sharp & Dohme Corp.
InventorsAngus Murray MacLeod, Graham Andrew Showell, Leslie Joseph Street
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Abstract
A class of substituted aminocyclohexane derivatives are selective agonists of 5-HT1-like receptors, being potent agonists of the human 5-HT1Dα receptor subtype while possessing at least a 10-fold selective affinity for the 5-HT1Dα receptor subtype relative to the 5-HT1Dβ subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, while eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.
Claims10
A compound of formula I, or a pharmaceutically acceptable salt thereof:
- wherein
- Z represents an optionally substituted triazole wherein the substituent is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, aryl aryl(C1-6) alkyl, C1-6 alkoxy, C1-6 alkylthio, amino, C1-6 alkylamino, di(C1-6)alkyamino halogen, cyano and trifluoromethyl
- E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms;
- Q represents a straight or branched alkylene chain containing from 1 to 6 carbon atoms, optionally substituted in any position by one or more substituents selected from fluoro and hydroxy;
- T represents CH;
- U represents C—R2;
- V represents N—R3;
- R1 represents aryl(C1-6)alkyl or tetrahydronaphthyl, any of which groups may be optionally substituted wherein the substituent is selected from halogen, cyano, trifluoromethyl, hydroxy, keto,C1-6 alkoxy, C1-6 alkylthio, C2-6 alkoxycarbonyl, C2-6 alkylcarbonyl, C1-6 alkylsulphonyl, arylsulphonyl, amino, C1-6 alkylamino, di(C1-6)alkylamino, di(C1-6)alkylaminomethyl, C2-6 alkylcarbonylamino, arylcarbonylamino, C2-6 alkoxycarbonylamino, N—(C1-6)alkyl-N—(C2-6) alkoxycarbonylamino, C1-6 alkylsulphonylamino, arylsulphonylamino, C1-6 alkylsulphonylaminomethyl, aminocarbonylamino, C1-6 alkylaminocarbonylamino, di(C1-6)alkylaminocarbonylamino, mono or diarylaminocarbonylamino, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6)alkylaminocarbonyl, aminosulphonyl, C1-6 alkylaminosulphonyl, di(C1-6)alkylaminosulphonyl, aminosulphonylmethyl, C1-6 alkylaminosulphonylmethyl and di(C1-6)alkylaminosulphonylmethyl;
- and
- R2, R3 and R7 independently represent hydrogen or C1-6 alkyl.
Dependencies are inferred from the claim text.