US 2011/0212946 A1 · Quinolone Neuropeptide S Receptor Antagonists

Abstract

The present invention is directed to quinolone compounds which are antagonists of neuropeptide S receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which the neuropeptide S receptor is involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the neuropeptide S receptor is involved.

A compound of the formula I:

wherein:
R1 is hydrogen or C1-6alkyl, which is unsubstituted or substituted with —O—C1-6alkyl;
R2 is —C0-6alkyl, which is substituted with one or more substituents selected from R4, wherein R4 is selected from the group consisting of:
(1) —C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(2) —C3-8cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13, or where the cycloalkyl may be fused to a phenyl, where the phenyl is unsubstituted or substituted with one or more substituents selected from R13,
(3) —C3-8cycloalkoxyl, where the cycloalkoxyl is unsubstituted or substituted with one or more substituents selected from R13, or where the cycloalkyl may be fused to a phenyl, where the phenyl is unsubstituted or substituted with one or more substituents selected from R13,
(4) -phenyl or -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R13,
(5)-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(6) —NR10R11, wherein R10 and R11 are independently selected from the group consisting of:
(a) hydrogen,
(b) C1-6alkyl, which is unsubstituted or substituted with R13,
(c) C3-6alkenyl, which is unsubstituted or substituted with R13,
(d) C3-6alkynyl, which is unsubstituted or substituted with R13,
(e) C3-6cycloalkyl which is unsubstituted or substituted with R13,
(f) phenyl, which is unsubstituted or substituted with R13, and
(g) heterocycle, which is unsubstituted or substituted with R13;
R3 is selected from the group consisting of:
(1) —C1-6alkyl, where the alkyl is unsubstituted or substituted with one or more substituents selected from R13,
(2) —C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R13,
(3) -phenyl or -napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R13,
(4) -heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R13,
(5) —NR10R11, wherein R10 and R11 are independently selected from the group consisting of:
(a) hydrogen,
(b) C1-6alkyl, which is unsubstituted or substituted with R13,
(c) C3-6alkenyl, which is unsubstituted or substituted with R13,
(d) C3-6alkynyl, which is unsubstituted or substituted with R13,
(e) C3-6cycloalkyl which is unsubstituted or substituted with R13,
(f) phenyl, which is unsubstituted or substituted with R13, and
(g) heterocycle, which is unsubstituted or substituted with R13;
R13 is selected from the group consisting of:
(1) halogen,
(2) hydroxyl,
(3) —(C═O)m—On—C1-6alkyl, where m is 0 or 1, n is 0 or 1 (wherein if m is 0 or n is 0, a bond is present) and where the alkyl is unsubstituted or substituted with one or more substituents selected from R14,
(4) —On—(C1-3)perfluoroalkyl,
(5) —(C═O)m—On—C3-6cycloalkyl, where the cycloalkyl is unsubstituted or substituted with one or more substituents selected from R14,
(6) —(C═O)m—C2-4alkenyl, where the alkenyl is unsubstituted or substituted with one or more substituents selected from R14,
(7) —(C═O)m—C2-4alkynyl, where the alkynyl is unsubstituted or substituted with one or more substituents selected from R14,
(8) —(C═O)m—On-phenyl or —(C═O)m—On-napthyl, where the phenyl or naphthyl is unsubstituted or substituted with one or more substituents selected from R14,
(9) —(C═O)m—On-heterocycle, where the heterocycle is unsubstituted or substituted with one or more substituents selected from R14,
(10) —(C═O)m—NR15R16, where R15 and R16 are independently selected from hydrogen and —C1-6alkyl, which is unsubstituted or substituted with phenyl,
(11) —S(O)2—NR15R16,
(12) —S(O)q—R12, where q is 0, 1 or 2 and where R12 is —C1-6alkyl, which is unsubstituted or substituted with phenyl;
(13) —CO2H,
(14) —CN, and
(15) —NO2;
R14 is selected from the group consisting of:
(1) hydroxyl,
(2) halogen,
(3) C1-6alkyl,
(4) —C3-6cycloalkyl,
(5) —O—C1-6alkyl,
(6) —O(C═O)—C1-6alkyl,
(7) —NH—C1-6alkyl,
(8) phenyl,
(9) heterocycle,
(10) —CO2H, and
(11) —CN;
or a pharmaceutically acceptable salt thereof.

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Quinolone Neuropeptide S Receptor Antagonists

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Quinolone Neuropeptide S Receptor Antagonists

Life of this patent

Abstract

Claims17