| 摘要 |
Substituted benzene compounds (I) and their salts, are new. Substituted benzene compounds of formula (I) and their salts, are new. Either R 1>, R 2>H, (1-8C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, (3-8C)-alkenyl, (3-8C)-alkynyl, CO(R 9>), (C(R 1> 0>)(R 1> 1>)) q-R 1> 2>, CO(C(R 1> 3>)(R 1> 4>)) rR 1> 5>, COO(1-8C)-alkyl or CO(C(R 1> 3>)(R 1> 4>)) rN(R 1> 6>)(R 1> 7>); and L 1>C(R 3> 4>)(R 3> 5>), C(R 3> 6>)(R 3> 7>)C(R 3> 8>)(R 3> 9>) or (3-6C)-cycloalkyl; and R 3> 4>-R 3> 9>H or (1-8C)-alkyl; or R 1>R 2>N : 4-10-membered mono-, bi- or spiro-cyclic ring (which additionally contains 0-3 heteroatoms except N, preferably O, N or S), where the heterocyclic ring system is additionally substituted by F, Cl, Br, CF 3, CN, (1-6C)-alkyl, (3-8C)-cycloalkyl, O-(1-8C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, hydroxy-(1-6C)-alkyl, oxo, CO(R 1> 8>), CON(R 1> 9>)(R 2> 0>), OH, COO(R 2> 1>), N(R 2> 2>)CO(1-6C)-alkyl, N(R 2> 3>)(R 2> 4>) or SO 2(1-6C)-alkyl; or R 1>R 3> 4>, R 1>R 3> 5>, R 1>R 3> 6>, R 1>R 3> 7>, R 1>R 3> 8>, R 1>R 3> 9>5-6-membered ring; R 1> 0>, R 1> 1>H, (1-6C)-alkyl, hydroxy-(1-2C)-alkyl, F or OH; either R 9>, R 1> 3>, R 1> 4>, R 1> 6>, R 1> 7>-R 2> 4>H or (1-6C)-alkyl; or R 1> 6>R 1> 7>N, R 2> 3>R 2> 4>N : 5-6 membered ring, which can include further 0-1 heteroatoms except N, which are NH, N-(1-6C)-alkyl, O or S; q, r : 0-6; R 1> 2>, R 1> 5>H, OH, F, O-(1-6C)-alkyl, S-(1-6C)-alkyl, O-phenyl, CN, COO(R 2> 5>), N(R 2> 6>)CO(1-6C)-alkyl, N(R 2> 7>)(R 2> 8>), CON(R 2> 9>)(R 3> 0>), SO 2(1-6C)-alkyl, 3-12-membered mono-, bi- or spiro-cyclic ring (containing 4 heteroatoms of N, O or S, and further substituted by F, Cl, Br, OH, CF 3, NO 2, CN, OCF 3, oxo, O-(1-6C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, S-(1-6C)-alkyl, (1-6C)-alkyl, (2-6C)-alkenyl, (3-8C)-cycloalkyl, O-(3-8C)-cycloalkyl, (3-8C)-cycloalkenyl, O-(3-8C)-cycloalkenyl, (2-6C)-alkynyl, N(R 3> 1>)(R 3> 2>), COO(R 3> 3>), SO 2(1-6C)-alkyl or COOH); either R 2> 5>-R 3> 3>H or (1-8C)-alkyl; or R 2> 7>R 2> 8>N, R 2> 9>R 3> 0>N, R 3> 1>R 3> 2>N : 5-6-membered ring, which includes 0-1 heteroatoms except N, which are NH, N-(1-6C)-alkyl, O or S; R 3>-R 5>H, F, Cl, Br, I, OH, CF 3, NO 2, CN, OCF 3, O-(1-6C)-alkyl, S-(1-6C)-alkyl, O-(1-4C)-alkoxy-(1-4C)-alkyl, (1-6C)-alkyl, CON(R 4> 0>)(R 4> 1>) or CO(R 4> 2>); either R 4> 0>-R 4> 2>H or (1-8C)-alkyl; or R 4> 0>R 4> 1>N : 5-6-membered ring further including 0-1 heteroatoms except N, which are NH, N-(1-6C)-alkyl, O or S; X : O or C(R 4> 3>)(R43a); either R 6>,R6a, R 7>, R7a, R 4> 3>, R43a : H, F, (1-8C)-alkyl, OH, O-(1-6C)-alkyl; or R 6>R6a, R 4> 3>R43a : oxo; L 2>a bond, C(R 4> 4>)(R 4> 5>) or C(O)NR 8>(which binds with A at ortho position over a bridge containing one or two elements of C or N to form 9-10-membered bicyclic ring); R 8>, R 4> 4>, R 4> 5>H or (1-8C)-alkyl; A : 5-6-membered aromatic ring (which contains up to 2 heteroatoms of N, O or S, and substituted by one or more substituents of H, F, Cl, Br, I, OH, CF 3, NO 2, CN, OCF 3, O-(1-6C)-alkyl, O-(1-4C)-alkoxy-(1-4C)-alkyl, (1-6C)-alkyl, N(R 5> 4>)(R 5> 5>), SO 2-CH 3, CON(R 5> 6>)(R 5> 7>), N(R 5> 8>)CO(R 5> 9>) or CO(R 6> 0>)); either R 5> 4>-R 6> 0>H or (1-8C)-alkyl; or R 5> 4>R 5> 5>N, R 5> 6>R 5> 7>N : 5-6-membered ring, which can include 0-1 heteroatoms except N, which are NH, N-(1-6C)-alkyl, O or S; L 3>bond or linker with 1-4 member (where: the member is O, S, SO 2, N(R 6> 1>), CO, C(R 6> 2>)(R 6> 3>) or C?=C, and the linker exhibits no OCO or COO group), or C(R 6> 2>)(R 6> 3>)O; B 1>(1-6C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, hydroxy-(1-6C)-alkyl, 3-10-membered mono-, bi- or spirocyclic non-aromatic ring (which includes 0-3 heteroatoms of O, N or S, and the ring system is further substituted by one or more F, CF 3, (1-6C)-alkyl, O-(1-8C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, hydroxy-(1-4C)-alkyl, oxo, CO(R 6> 4>) or OH), or 4-10-membered mono-, bi- or spirocyclic non-aromatic ring (which includes 1-3 heteroatoms of O, N or S, and further substituted by one or more substituents of F, CF 3, (1-6C)-alkyl, O-(1-8C)-alkyl, (1-4C)-alkoxy-(1-4C)-alkyl, hydroxy-(1-4C)-alkyl, oxo, CO(R 6> 4>) or OH); and R 6> 1>, R 6> 2>, R 6> 3>, R 6> 4>H or (1-8C)-alkyl (when X is C(R 4> 3>)(R43a)). An independent claim is included for a medicament comprising one or more (I). [Image] - ACTIVITY : Metabolic; Antidiabetic; Antilipemic; Anorectic; Antiarteriosclerotic; Cardiant; Vasotropic; Cerebroprotective; Hepatotropic; Thrombolytic; Hypotensive; Cardiovascular-Gen; Neuroleptic; Antidepressant; Tranquilizer; Hypnotic; CNS-Gen; Antiinflammatory; Gastrointestinal-Gen. - MECHANISM OF ACTION : Melamine-concentrating hormone receptor-1 modulator. The ability of (I) to modulate melamine-concentrating hormone receptor-1 was tested using an in-vitro method. The results showed that (I) exhibited an IC 5 0value of less than 1 mu m, preferably 1 nm. |
