Patent EA-003453-B1 (EA)
Title: beta2-ADRENERGIC RECEPTOR AGONISTS
Inventor: MORAN EDMUND J
IPC: C40B20/00
Filed: 1999-06-07
Abstract: 1. A compound of formula (I): wherein: Ar<1> and Ar<2> are selected from the group consisting of aryl, heteroaryl and heterocyclyl; Ar<2> is selected from the group consisting of phenylene, where groups W and X are attached at the 1, 2-, 1, 3 and 1, 4 positions of the phenyl ring; cyclohexyl optionally substituted with methyl, where groups W and X attached at the 1, 3 and 1, 4 positions of cyclohexyl ring; and piperazinylene, where groups W and X are attached at the 1, 4 position of cyclohexylene; Q is group NHCH2CH(OH)-, W is alkylene group or substituted alkylene group; X is covalent bond; and pharmaceutically acceptable salts thereof. 2. A compound of claim 1, wherein Ar<1>is phenyl ring of formula (c) wherein R<4> is selected from the group consisting of hydrogen, alkyl, halogen and alkoxy; R<5> is selected from the group consisting of hydrogen, hydroxy, halogen, amino, and -NHSO2R<a>, wherein R<a> is alkyl; and R<6> is selected from the group consisting of hydrogen, hydroxy, halogen, substituted alkyl, sulfonylamino, aminoacyl, acylamino. 3. A compound of claim 2, wherein R<4> is selected from the group consisting of hydrogen, methyl, fluoro, chloro, methoxy; R<5> is selected from the group consisting of hydroxy, fluoro, chloro, amino, and -NHSO2CH3 R<6> is selected from the group consisting of hydrogen, fluoro, chloro, methoxy, hydroxymethyl, CH2SO2CH3, NHSO2CH3, NHCHO, CONH2, NHCONH2; 4. A compound of claim 1, wherein Ar<1> is group of formula: 5. A compound of any of claims 2, 3, or 4, wherein Ar<3> is selected from comprising (i) a phenyl ring of formula (c): wherein R<4> is selected from the group consisting of hydrogen, alkyl, halogen and alkoxy; R<5> is selected from the group consisting of hydrogen, hydroxy, halogen, amino, and -NHSO2R<a>, wherein R<a> is alkyl; and R<6> is selected from the group consisting of hydrogen, hydroxy, halogen, substituted alkyl, sulfonylamino, aminoacyl, acylamino; (ii) a phenyl ring of formula (d): wherein R<7> is selected from the group consisting of hydrogen, alkyl, alkenyl, substituted alkyl, halogen, alkoxy, substituted alkoxy, hydroxy, aminoacyl, and heteroaryl; and R<8> is selected from the group, comprising hydrogen, halogen, alkoxy, substituted alkoxy, acylamino; (iii) naphthyl (iv) pyridyl (v) benzimidazole-1-yl; (vi) indolyl; (vii) 2-cyanoindilyl; (viii) carbazolyl; (ix) 4-methylindanyl; (x) 5-(CH3CO2CH2O-)-1,2,3,4-tetrahydronaphthyl; (xi) 1H-2-oxoindol; (xii) 2,3,4-trihydrothianaphthalene; and (xiii) 4-oxo-2,3-dihydrothianaphtalene. 6. A compound of claim 1, wherein Ar<3> is (i) a phenyl ring of formula (c), wherein R<4> is selected from the group consisting of hydrogen, methyl, fluoro, chloro, methoxy; R<5> is selected from the group consisting of hydroxy, fluoro, chloro, amino, and -NHSO2CH3 R<6> is selected from the group consisting of hydrogen, fluoro, chloro, methoxy, hydroxymethyl, CH2SO2CH3, NHSO2CH3, NHCHO, CONH2, NHCONH2; (ii) a phenyl ring of formula (d): wherein R<7> is selected from the group consisting of hydrogen, methyl, propen-2yl, fluoro, chloro, methoxy, CH2CONH2, NHCONH2, imidalol-1-yl, and 1-methyl-4-trifluoromethylimidazol-2-yl; and R<8> is selected from the group consisting of hydrogen, fluoro, chloro, methoxy, -OCH2CO2Me and CONH2. 7. A compound of claim 6, wherein Ar<3> is 1,4-phenylene and, wherein W is methylene, ethylene, or propylene; 8. A compound of claim 1, wherein Ar<2> is 1,4-phenylene; Ar<3> is selected from group comprising W represents methylene, ethylene or propylene; and its pharmaceutically acceptable salts. 9. A compound of claim 8, wherein Ar<1> is selected from group comprising phenyl, 4-hydrophenyl, 3,4-dyhydrophenyl, 3,4-difchlorophenyl, 2-chloroxyphenyl, di-hydroxyphenyl, 3,4-dichlrophenyl, 2-chloro-3, 4-dihydroxyphenyl, 2-fluoro-3, 4-dihydroxuphenyl, 2-chloro-3, 5-dihydroxyphenyl, 2-fluoro-3, 5-dihydroxuphenyl, 4-hydroxy-3-methoxyphenyl, 4-hydroxy-3-hydroxymethylphenyl, 4-hydroxy-3-(HCONH-)phenyl, 4-hydroxy-3-(NH2CO)phenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 4-(CH2SO2NH) phenyl, 4-hydroxy-3-(CH3SO2CH2-)phenyl, 4-hydroxy-3-(CH3SO2NH) phenyl, 4-hydroxy-3-(NH2CONH-)phenyl, and 3,5-dichloro-4-aminophenyl; 10. A compound of claim 9, wherein W is ethylene. 11. A compound of claim 10, wherein Ar<1> is selected from group comprising 4-hydroxy-3-hydroxymethylphenyl, 4-hydroxy-3-(HCONH-) phenyl, 3,5-dichloro-4-aminophenyl, and 12. A compound of claim 11, wherein Ar<3> is phenyl or 4-hydroxy-3-hydroxymethylphenyl. 13. A compound of claim 9 of formula: wherein stereochemistry of *C and **C is (RS) and (RS); (RS) and (R); (RS) and (S); (R) and (S); (R) and (R); and its pharmaceutically acceptable salts. 14. A compound of claim 13, wherein stereochemistry of *C and **C is(R) and (R). 15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of any of claims 1-14. 16. A method for treating diseases mediated by a (2 adrenergic receptor in a mammal, said method comprising administering to said mammal a therapeutically effective amount of a pharmaceutical composition of claim 15. 17. The method of Claim 16 wherein the disease or disease condition is asthma or chronical pulmonary disease. 18. Use of compound of any of claims 1-14 to produce drug for treating of disease or condition, mediated by a (2 adrenergic receptor activity in a mammal. 19. The use by claim 18, wherein a disease or condition is asthma or chronical stagnant pulmonary disease.