RU2000119110A - CHROMAN DERIVATIVES SUBSTITUTED BY CARBOXYL GROUP APPLICABLE AS BETA-3-ADRENERECEPTOR AGONISTS - Google Patents

Claims (14)

1. The compound of the formula

where R means hydrogen, hydroxyl, oxo-, halide, halide alkyl with 1-10 carbon atoms, alkyl with 1-10 carbon atoms, nitrile, nitro, NR ¹ R ¹ , SR ¹ , OR ¹ , SO ₂ R ² , OCOR ² , NR ¹ COR ² , COR ² , NR ¹ SO ₂ R ² , NR ¹ CO ₂ R ¹ , alkoxy with 1-10 carbon atoms, a phenyl, pyrrole group or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from the group comprising O, S, and N atoms, and each fragment may contain hydroxyl, halide, nitrile, NR ¹ R ¹ , SR ¹ , trifluoromethyl, OR ¹ , cycloalkyl with 3 as substituents -8 carbon atoms, phenyl, NR ¹ COR ² , COR ² , SO ₂ R ² , OCOR ² , NR ¹ SO ₂ R ² , NR ¹ CO ₂ R ¹ , alkyl with 1-10 carbon atoms, alkoxy with 1-10 carbon atoms and the OR group and each cyclic moiety may be condensed with a 5-membered heterocyclic ring containing 1 to 4 heteroatoms selected from the group comprising O, S, and N atoms, and the fused heterocyclic ring may also be condensed with a phenyl ring or contain an oxo group as a substituent;
R ¹ means hydrogen, an alkyl group with 1-10 carbon atoms, optionally substituted with 1 to 4 substituents selected from the group consisting of hydroxyl, halide, CO ₂ H, CO ₂ alkyl with 1-10 carbon atoms, SO ₂ alkyl with 1-10 carbon atoms, alkoxy with 1-10 carbon atoms group; or cycloalkyl with 3-8 carbon atoms, a phenyl or naphthyl group, each of which may contain 1 to 4 substituents selected from the group including halide, nitro, oxo, alkyl with 1-10 carbon atoms, alkoxy with 1-10 thioalkyl carbon atoms with 1-10 carbon atoms;
R ² is R ¹ or NR ¹ R ¹ ;
R ³ means hydrogen, an alkyl group with 1-10 carbon atoms, CO ₂ R ¹ or

Ar ¹ means a phenyl group or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from the group comprising O, S and N atoms, and each fragment can be condensed with a 5-membered heterocyclic ring containing from 1 up to 4 heteroatoms selected from the group consisting of O, S and N atoms, and a fused heterocyclic ring may also be condensed with a phenyl ring or may contain an oxo group as a substituent;
m is 1.2 or 3;
n in each case is independently 0.1 or 2;
X means an alkyl group with 1-4 carbon atoms, optionally substituted
halogen;
R ⁴ means a hydroxyl, alkoxy group with 1-10 carbon atoms, OR ¹ or NR ¹ R ¹ ,
and pharmaceutically acceptable salts or esters thereof. 2. The compound according to claim 1, wherein Ar ¹ may contain as substituents a phenyl, pyridyl, pyrimidyl or pyrrolyl group. 3. The compound according to claim 2, wherein R ³ means hydrogen and m = 1. 4. The compound according to claim 3, characterized in that (X) _n - (CO) _n R ^{4 is} attached to the chroman fragment in position 6 and n = 0 for (X) _n , a (CO) _n R ⁴ is CO ₂ R ¹ .  5. The compound according to claim 1, characterized in that in the compound of formula I, the OH group is in the configuration R. 6. Used to obtain the compounds of formula I, the compound of the formula

where R ³ means hydrogen, an alkyl group with 1-10 carbon atoms, CO ₂ R ¹ or

m is 1, 2 or 3;
n in each case is independently 0.1 or 2;
R ⁴ means hydroxyl, OR ¹ , CNS group with 1-10 carbon atoms or NR ¹ R ¹ . 7. The compound according to claim 6, characterized in that (X) _n - (CO) _n R ^{4 is} attached to the chroman fragment in position 6 and n = 0 for (X) _n , a (CO) _n R ⁴ means CO ₂ R ¹ .  8. A method of exerting an agonistic effect on the beta-3 adrenergic receptor of a patient in need of such exposure by administering an effective pharmaceutical amount of the compound according to claim 1.  9. A pharmaceutical composition containing an effective amount of a compound according to claim 1 in combination with a carrier acceptable from a pharmaceutical point of view.  10. A composition containing an effective amount of a compound according to claim 1 in combination with an inert carrier.  11. A method of treating obesity in a mammal, which consists in administering to a patient in need of such treatment a pharmaceutically effective amount of a compound according to claim 1.  12. A method of treating obesity in a mammal, which consists in administering to a patient in need of such treatment a pharmaceutically effective amount of the compound according to claim 9 or a salt or ester thereof.  13. A method of treating diabetes in mammals, which consists in administering to a patient in need of such treatment a pharmaceutically effective amount of a compound according to claim 1.  14. A method of treating diabetes in a mammal, comprising administering to a patient in need of such treatment a pharmaceutically effective amount of a compound according to claim 9 or a salt or ester thereof.