Patent ID: 6586441
Filing Date: 2003-07-01
Classification: A61K,A61P,C07D

Abstract:
A method of treatment of a disease state caused by malfunction of the adenosine receptor system comprising administering to a patient in need of such treatment, an effective amount of a composition for treating said disease state, said composition containing a compound that binds to an adenosine receptor and a pharmaceutically acceptable carrier, said compound having the formula: wherein A is selected from the group consisting of a bond, â€”Sâ€”, â€”N(R)â€”, â€”(CH2)2â€”, â€”CH&boxH;CHâ€”, â€”Câ‰¡Câ€” or â€”Oâ€”; X and Y each are independently selected from the group consisting of â€”N&boxH; and &boxH;Nâ€”; R1 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, halogen, cyano, cycloalkyl, â€”(CH2)nâ€”C(O)O-lower alkyl, â€”(CH2)nâ€”C(O)O-lower alkyl-phenyl, â€”(CH2)nâ€”NHâ€”C(O)O-lower alkyl-phenyl, â€”(CH2)nâ€”O-lower alkyl, â€”(CH2)nâ€”O-phenyl, â€”(CH2)nâ€”NH-phenyl, â€”(CH2)n-phenyl, â€”(CH2)n-phenyl substituted by 1 or 2 substituents selected from the group consisting of hydroxy, lower alkoxy, lower alkyl, CF3-lower alkenyl, halogen, CF3, OCF3, amino, â€”(CH2)nâ€”N-di-lower alkyl, â€”C(O)NH-lower alkyl, and â€”S(O)2-lower alkyl, â€”(CH2)n-morpholinyl, â€”(CH2)n-amino, â€”(CH2)n-amino substituted by lower alkyl or benzyl, â€”(CH2)n-piperidin-1-yl or â€”(CH2)n-piperidin-3-yl, â€”(CH2)n-piperidin-1-yl or â€”(CH2)n-piperidin-3-yl, said â€”(CH2)-piperidin 1-yl or -3-yl being substituted by lower alkyl, â€”(CH2)n-pyridin-2-yl, â€”(CH2)n-pyridin-3-yl, â€”(CH2)n-pyridin-4-yl, â€”(CH2)n-pyridin-2-yl, â€”(CH2)n-pyridin-3-yl or â€”(CH2)n-pyridin-4-yl, said â€”(CH2)-pyridin-2-yl, -3-yl or -4-yl, being substituted by 1 or 2 substituents selected from the group consisting of lower alkyl, hydroxy, nitro, cyano, halogen and CF3, â€”OC(O)N(R)2, â€”(CH2)nâ€”NHâ€”pyridin-2-yl, â€”(CH2)nâ€”NHâ€”pyridin-2-yl, substituted by lower alkyl or halogen, â€”(CH2)n-piperazin-4-yl, â€”(CH2)n-piperazin-4-yl, substituted by lower alkyl, phenyl or carbonyl-phenyl, â€”(CH2)n-phenylâ€”OC(O)-phenyl, â€”(CH2)n-phenylâ€”OC(O)-phenyl substituted by halogen or the group â€”(CH2)n-S-phenyl or â€”(CH2)nâ€”S(O)2-phenyl, â€”(CH2)nâ€”S-lower alkyl, (CH2)n(CH&boxH;CH)m-phenyl, (CH2)n(CHâ‰¡CH)m-phenyl, â€”(CH2)nâ€”NH-cycloalkyl, â€”(CH2)nâ€”NH-phenyl, â€”(CH2)nâ€”NH-phenyl, substituted by amino or nitro, â€”(CH2)n-tetrahydro-pyran-4-yl, â€”(CH2)n-quinolin-2-yl, â€”(CH2)n-naphthyl or â€”(CH2)nâ€”NH-naphthyl, â€”(CH2)n-3,4-dihydro-1H-isoquinolin-2-yl, â€”(CH2)n-benzo[1,3]dioxolyl, â€”(CH2)nâ€”NHâ€”S(O)2-phenyl, â€”(CH2)nâ€”NHâ€”S(O)2-phenyl substituted by halogen, â€”(CH2)n-1,2,3,4-tetrahydro-quinolin-2-yl, â€”(CH2)n-1,2,3,4-tetrahydro-quinolin-2-yl, substituted by lower alkyl, and â€”(CH2)n-furanyl; R2 is selected from the group consisting of hydrogen, halogen, cyano, nitro, lower alkyl, lower alkenyl, â€”C(O)â€”lower alkyl, â€”C(O)O-lower alkyl, â€”C(O)O-lower alkyl-phenyl, lower alkynyl-phenyl, lower alkenylâ€”C(O)O-lower alkyl, lower alkenyl-cyano or phenyl, C(O)O-lower alkyl, â€”C(O)O-lower alkyl-phenyl, lower alkynyl-phenyl, lower alkenyl-C(O)O-lower alkyl, lower alkenyl-cyano or phenyl, substituted by halogen; R3 is selected from the group consisting of lower alkyl, phenyl, phenyl substituted by lower alkyl, lower alkoxy, or halogen, thien-2yl or fur-2yl, thien-2yl or fur-2yl, substituted by a substituent selected from the group consisting of lower alkyl, S-lower alkyl, halogen, lower alkoxy, â€”C(O)O-lower alkyl, â€”C(&boxH;CH2)â€”O-lower alkyl, â€”(CH2)n-halogen, â€”(CH2)nâ€”OH, â€”(CH2)n-lower alkoxy, cyano, CHF2 and CH2F, 2,3-dihydro-benzo[1.4]dioxin-6-yl, benzo[1.3]dioxol-5-yl, isoxazol-5-yl, pyridin-2-yl, pyridin-3-yl, â€”C(&boxH;CH2)O-lower alkyl, 4,5-dihydrofuran-2-yl, 5,6-dihydro-4H-pyran-2-yl, oxazol-2-yl, benzofuranyl, pyrazin-2-yl, â€”Oâ€”(CH2)n-phenyl, â€”Oâ€”(CH2)n-pyridyl, â€”Oâ€”(CH2)n-pyridyl substituted by lower alkyl, â€”Sâ€”(CH2)n-pyridyl, pyrazol-1-yl, and pyrazol-1-yl substituted by lower alkyl or halogen; R4 and R5 are independently from each other selected from the group consisting of hydrogen, â€”COâ€”(CH2)n-phenyl, optionally substituted by halogen or â€”CH2N(R)(CH2)n-lower alkyl, phenyl, phenyl substituted by lower alkoxy and â€”C(O)-phenyl; R is selected from the group consisting of hydrogen or lower alkyl; and A and R2 may be together with the two carbon atoms â€ƒand wherein n is 0,1,2,3 or 4; m is 1 or 2; or a pharmaceutically acceptable salt thereof.