Melanin-concentrating hormone antagonist
View Patent ↗A melanin-concentrating hormone antagonist comprising a compound of the formula (I): wherein Ar 1 is a cyclic group which may be substituted; X and Y are the same or different and are a spacer having a main chain of 1 to 6 atoms; Ar is a condensed polycyclic aromatic ring which may be substituted; R 1 and R 2 are the same or different and are hydrogen atom or a hydrocarbon group which may be substituted; or R 1 and R 2 , together with the adjacent nitrogen atom, may form a nitrogen-containing heterocyclic ring which may be substituted; or R 2 , together with the adjacent nitrogen atom and Y, may form a nitrogen-containing heterocyclic ring which may be substituted; or R 2 , together with the adjacent nitrogen atom, Y and Ar, may form a condensed ring; or a salt thereof is useful as an agent for preventing or treating obesity, etc.
1. A compound of the formula:
wherein Ar 1 is a cyclic group which may be substituted;
X 1 is CONR 8, NR 8 CO (wherein R 8 is hydrogen atom, optionally halogenated C 1-6 alkyl, optionally halogenated C 1-6 alkyl-carbonyl or optionally halogenated C 1-6 alkylsulfonyl), OCO or COO;
Y is —CH 2 —;
Ar is a quinoline ring which may be substituted;
R 1 and R 2 are the same or different and are hydrogen atom or a hydrocarbon group which may be substituted; or R 1 and R 2, together with the adjacent nitrogen atom, may form a pyrrolidine ring which may be substituted;
provided that, when X 1 is CONH, Ar is not 4-methyl-2-quinolone which may have a substituent selected from the group consisting of alkyl, alkoxy and halogen; and,
when X 1 is COO, Ar 1 is not an aromatic group which may be substituted; or a salt thereof.
2. The compound according to claim 1 , wherein X 1 is CONR 8 or NR 8 CO (wherein R 8 is hydrogen atom, optionally halogenated C 1-6 alkyl, optionally halogenated C 1-6 alkyl-carbonyl or optionally halogenated C 1-6 alkylsulfonyl).
3. The compound according to claim 1 , wherein the cyclic group represented by Ar 1 is an aromatic group.
4. The compound according to claim 3 , wherein the aromatic group is formed by removing an optional one hydrogen atom from an aromatic ring assembly formed by 2 or 3 members selected from C 6-14 monocyclic or condensed polycyclic aromatic hydrocarbon and 5- to 10-membered aromatic heterocyclic ring.
5. The compound according to claim 1 , wherein Ar 1 is phenyl, biphenylyl or phenyl-pyridyl, each of which may be substituted with 1 to 3 substituents selected from halogen, optionally halogenated C 1-6 alkyl and optionally halogenated C 1-6 alkoxy.
6. The compound according to claim 1 , wherein Ar 1 is piperidinyl which may be substituted with C 6-14 aryl which may be substituted.
7. The compound according to claim 1 , wherein X 1 is CONH or COO.
8. The compound according to claim 1 , wherein R 1 and R 2 together with the adjacent nitrogen atom, form a pyrrolidine ring which may be substituted.
9. A pharmaceutical composition comprising the compound according to claim 1 , or a salt thereof.
10. The compound according to claim 1 which is:
4′-fluoro-N-[2-(1-pyrrolidinylmethyl)-6-quinolinyl][1,1′-biphenyl]-4-carboxamide;
4(4chlorophenyl)-N-[2-(1-pyrrolidinylmethyl)-6-quinolinyl]-1-piperidinecarboxamide;
N-[2-(1-pyrrolidinylmethyl)-6quinolinyl][1,1′-biphenyl]-4-carboxamide;
6-(4-methylphenyl)-N-[2-(1-pyrrolidinymethyl)-6-quinolinyl]nicotinamide;
or a salt thereof.
11. A process for producing a compound of the formula:
wherein each symbol is as defined in claim 1 , a salt thereof, which comprises reacting a compound of the formula:
Ar 1 —H (XII)
wherein Ar 1 is as defined in claim 1 , or a salt thereof with a compound of the formula:
wherein L is a leaving group and the other symbols are as defined above, or a salt thereof.
12. A method for preventing or treating obesity in a mammal in need thereof, which comprises administering to said mammal an effective amount of the compound according to claim 1 .
13. A method for making a pharmaceutical for preventing or treating obesity comprising combining the compound according to claim 1 with a pharmaceutically acceptable carrier, diluent or excipient.