Fused heterocyclic compounds
Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.
1 . A compound having the formula (I):
or a pharmaceutically acceptable salt or prodrug thereof, wherein
A and B are independently selected from the group consisting of CR′ and N, wherein R′ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, arylalkyl, —C(O)R 7 , —CO 2 R 8 and —C(O)NR 5 R 6 ;
V is selected from the group consisting of a bond, —O—, —S—, —C(O)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
W is selected from the group consisting of —O—, —S—, —C(O)—, —C(S)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2;
the subscript n is an integer from 0 to 8; and
represents a single or fused aryl or heteroaryl ring, wherein said heteroaryl ring contains from 1 to 4 heteroatoms selected from the group consisting of N, O and S;
with the proviso that R 2 is not hydrogen when
is benzene, A and B are both CH, V is a bond, W is —N(R″)— and Z is —NR—CH 2 —.
2 . The compound of claim 1 , wherein
is selected from the group consisting of benzene, naphthalene, pyrrole, pyrazole, imidazole, pyrazine, oxazole, isoxazole, thiazole, furan, thiophene, pyridine, pyrimidine, benzothiazole, purine, benzimidazole, indole, isoquinoline, quinoxaline and quinoline.
3 . The compound of claim 1 , wherein
is benzene and the subscript n is an integer from 0 to 4.
4 . The compound of claim 1 , wherein
is substituted benzene.
5 . The compound of claim 1 , wherein A and B are both C(R′).
6 . The compound of claim 1 , wherein A is C(R′) and B is N.
7 . The compound of claim 1 , wherein V is selected from the group consisting of a bond, —C(O)— and —N(R″)—.
8 . The compound of claim 1 , wherein W is selected from the group consisting of a bond, —C(O)— and —N(R″)—.
9 . The compound of claim 1 , wherein W is —NH—.
10 . The compound of claim 1 , wherein V is a bond and W is —N(R″)—.
11 . The compound of claim 1 , wherein A and B are both C(R′), V is a bond and W is —N(R″)—.
12 . The compound of claim 1 , wherein V is —C(O)— and W is —N(R″)—.
13 . The compound of claim 1 , wherein V is —N(R″)— and W is —C(O)—.
14 . The compound of claim 1 , wherein Z is —N(R)—(C 1 -C 3 )alkylene-.
15 . The compound of claim 14 , wherein Z is —N(R)—CH 2 —.
16 . The compound of claim 14 , wherein R is (C 1 -C 7 )alkyl or heterocycloalkyl(C 1 -C 7 )alkyl.
17 . The compound of claim 1 , wherein R 2 is (C 1 -C 5 )alkyl or aryl.
18 . The compound of claim 1 , having the formula (II):
wherein
A and B are independently selected from the group consisting of CR′ and N, wherein R′ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, arylalkyl, —C(O)R 7 , —CO 2 R 8 and —C(O)NR 5 R 6 ;
V is selected from the group consisting of a bond, —O—, —S—, —C(O)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
W is selected from the group consisting of —O—, —S—, —C(O)—, —C(S)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
Z is selected from the group consisting of —N(R)—, —N(R)-(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8;
with the proviso that R 2 is not hydrogen when A and B are both CH, V is a bond, W is —N(R″)— and Z is —NR—CH 2 —.
19 . The compound of claim 18 , wherein A and B are both C(R′).
20 . The compound of claim 19 , having the formula (III):
wherein
V is selected from the group consisting of a bond, —O—, —S—, —C(O)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
W is selected from the group consisting of —O—, —S—, —C(O)—, —C(S)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8;
with the proviso that R 2 is not hydrogen when V is a bond, W is —N(R″)— and Z is —NR—CH 2 —.
21 . The compound of claim 1 , having the formula (IV):
wherein
V is selected from the group consisting of a bond, —O—, —S—, —C(O)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
W is selected from the group consisting of —O—, —S—, —C(O)—, —C(S)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8.
22 . The compound of claim 1 , having the formula (V):
wherein
A and B are independently selected from the group consisting of CR′ and N, wherein R′ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, arylalkyl, —C(O)R 7 , —CO 2 R 8 and —C(O)NR 5 R 6 ;
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R′)CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8;
with the proviso that R 2 is not hydrogen when A and B are both CH and Z is —NR-CH 2 —.
23 . The compound of claim 22 , wherein A and B are both C(R′).
24 . The compound of claim 22 , having the formula (VI):
wherein
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C i-C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8;
with the proviso that R 2 is not hydrogen when Z is —NR-CH 2 —.
25 . The compound of claim 22 , wherein A and B are both C(R′) and Z is —N(R)—(C 1 -C 3 )alkylene-.
26 . The compound of claim 25 , wherein R is heterocycloalkyl(C 1 -C 7 )alkyl.
27 . The compound of claim 22 , wherein A and B are both C(R′), Z is —N(R)—(C 1 -C 3 )alkylene- and R 2 is (C 1 -C 5 )alkyl or aryl.
28 . The compound of claim 22 , having the formula (VII):
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C i-C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 , —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8.
29 . The compound of claim 28 , wherein Z is —N(R)—(C 1 -C 3 )alkylene-.
30 . The compound of claim 18 , having the formula:
wherein
V is selected from the group consisting of a bond, —O—, —S—, —C(O)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
W is selected from the group consisting of —O—, —S—, —C(O)—, —C(S)—, —N(R″)— and —N═, wherein R″ is hydrogen or (C 1 -C 5 )alkyl;
Z is selected from the group consisting of —N(R)—, —N(R)—(C 1 -C 3 )alkylene- and —(C 1 -C 3 )alkylene —N(R)—(C 1 -C 3 )alkylene-, wherein R is selected from the group consisting of hydrogen, (C 1 -C 7 )alkyl, heterocycloalkyl(C 1 -C 7 )alkyl, aryl, arylalkyl, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —S(O) m NR 5 R 6 and —S(O) m R 7 ;
each R 1 is independently selected from the group consisting of hydrogen, halogen, (C 1 -C 5 )alkyl, perfluoro(C 1 -C 5 )alkyl, —OR′″, —SR′″, aryl, arylalkyl, —NO 2 , —NR 5 R 6 , —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —N(R 5 )C(O)R 7 , —N(R 5 )CO 2 R 9 , —N(R 7 )C(O)NR 5 R 6 , —S(O) m NR 5 R 6 —S(O) m R 7 , —CN and —N(R 5 )S(O) m R 9 , wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 2 and R 3 are independently selected from the group consisting of hydrogen, —OR′″, ═O, —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 4 is selected from the group consisting of hydrogen —OR′″, —C(O)R 7 , —CO 2 R 8 , —C(O)NR 5 R 6 , —CN, (C 1 -C 5 )alkyl and aryl, wherein R′″ is selected from the group consisting of hydrogen, (C 1 -C 5 )alkyl, aryl and aryl(C 1 -C 5 )alkyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl or combined to form a 4-, 5-, 6-, 7- or 8-membered ring containing from one to three heteroatoms;
R 7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, aryl and arylalkyl;
R 9 is selected from the group consisting of alkyl, aryl and arylalkyl;
the subscript m is an integer from 1 to 2; and
the subscript n is an integer from 0 to 8;
with the proviso that R 2 is not hydrogen when V is a bond and W is —N(R″)—.
31 . The compound of claim 30 , wherein V is a bond and W is —N(R″)—.
32 . The compound of claim 30 , wherein V is —C(O)— and W is —N(R″)—.
33 . The compound of claim 30 , wherein V is —N(R″)— and W is —C(O)—.
34 . The compound of claim 31 , wherein said compound is selected from the group consisting of the group consisting of:
35 . A composition comprising a pharmaceutically acceptable carrier or excipient and a compound of claim 1 .
36 . A method for treating a condition or disorder selected from the group consisting of obesity, an eating disorder, an anxiety disorder and a mood disorder, comprising
administering to a subject in need therof a therapeutically effective amount of a compound of claim 1 .
37 . The method of claim 36 , wherein said compound modulates MCHR.
38 . The method of claim 36 , wherein said compound is administered in combination with an anti-obesity agent, an antidepressant or an anxiolytic agent.
39 . The method of claim 36 , wherein said compound is administered orally.
40 . The method of claim 36 , wherein said compound is administered parenterally.
41 . A method for modifying eating behavior, comprising
administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
42 . The method of claim 41 , wherein food intake is decreased.
43 . The method of claim 41 , wherein food intake is increased.
44 . A method for treating a condition or disorder mediated by MCHR, comprising
administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
45 . The method of claim 44 , wherein said condition or disorder is selected from the group consisting of obesity, an eating disorder, an anxiety disorder and a mood disorder.
46 . The method of claim 45 , wherein said eating disorder is anorexia nervosa.
47 . The method of claim 45 , wherein said anxiety disorder is selected from the group consisting of anxiety, panic disorder and obsessive-compulsive disorder.
48 . The method of claim 45 , wherein said mood disorder is depression.
49 . A method for modulating MCHR, comprising
contacting a cell with a compound of claim 1 .
50 . The method of claim 49 , wherein said compound is an MCHR antagonist.
51 . The method of claim 49 , wherein said compound is an MCHR agonist.