Patent ID: 6638914
Filing Date: 2003-10-28
Classification: A61K,A61P

Abstract:
A method for achieving a therapeutic effect comprising administering to a subject in need an effective amount of a therapeutic agent that is an agonist of the adenosine A1 receptor, the therapeutic effect comprises induction of proliferation of bone marrow cells, wherein said agonist of the adenosine A1 receptor is a compound of general formula (I): whereinR1 represents a lower alkyl, substituted or unsubstituted cycloalkyl; a hydroxyl or hydroxyalkyl; a phenyl or lower alkylphenyl, the phenyl or lower alkylphenyl optionally substituted by one or more substituents; â€”SORc, â€”SO2Rc, â€”SO3H, â€”SO2NRaRb, â€”ORa, â€”SRa, â€”NHSO2Rc, â€”NHCORa, â€”NRaRb, or â€”NHRaCO2Rb; wherein Ra and Rb represent independently a hydrogen, lower alkyl, alkanoyl, amino, phenyl or naphthyl, the alkyl group optionally being substituted with a substituted or unsubstituted phenyl or phenoxy group; or when R1 represents â€”NRaRb, said Ra and Rb form together with the nitrogen atom a 5- or 6-membered heterocyclic ring optionally containing a second heteroatom selected from the group consisting of oxygen and nitrogen, which second nitrogen heteroatom may optionally be substituted by hydrogen or lower alkyl; or â€”NRaRb is a group of general formulae (II) or (III): â€ƒwherein n is an integer from 1 to 4; Z is hydrogen, lower alkyl or hydroxyl; Y is hydrogen, lower alkyl, or ORâ€² where Râ€² is hydrogen, lower alkyl or lower alkanoyl; A is a bond or a lower alkylene; X and Xâ€² are each independently hydrogen, lower alkyl, lower alkoxy, hydroxy, lower alkanoyl, nitro, haloalkyl, halogen, amino, mono- or di-lower alkyl amino, or when X and Xâ€² are taken together a methylenedioxy group; Rc represents a lower alkyl; or R1 represents an epoxide substituent of general formulae (IVa) or (IVb): â€ƒwherein M is a lower alkyl group; R2 represents hydrogen; halogen; substituted or unsubstituted lower alkyl or alkenyl group; lower haloalkyl or alkenyl; cyano; acetoamido; lower alkoxy; lower alkylamino; NRdRe where Rd and Re are independently hydrogen, lower alkyl, phenyl or phenyl substituted by lower alkyl, lower alkoxyl, halogen or haloalkyl; â€”SRf where Rf is hydrogen, lower alkyl, lower alkanoyl, benzoyl or phenyl; W represents the group â€”OCH2â€”, â€”NHCH2â€”, â€”SCH2â€” or â€”NH(C&boxH;O)â€”; R3, R4 and R5 represent independently a hydrogen, lower alkyl or lower alkenyl, branched or unbranched C1-C12 alkanoyl, benzoyl or benzoyl substituted by lower alkyl, lower alkoxy or halo group; or R4 and R5 form together a 5-membered ring optionally substituted by a lower alkyl or alkenyl; or R3 further represents independently a phosphate, hydrogen phosphate or dihydrogen phosphate, or an alkali metal or ammonium or dialkali or diammonium salt thereof; R6 represents a hydrogen or halogen atom; or one of the substituents R1 to R6 is a sulfohydrocarbon radical of the formula Rgâ€”SO3â€”Rhâˆ’, wherein Rg represents a group selected from C1-C10 alkylenyl, phenylenyl and substituted lower alkyl phenylenyl group and Rh represents a monovalent cation; wherein when R1 is a substituent of general formula (IVb), the N1-position of the compound of general formula (1) may optionally bear an oxygen atom; and pharmaceutically acceptable salts or solvates of said compound.