2-propynyl adenosine analogues having A2 adenosine recepter agonist activity and compositions thereof to treat inflammatory responses

摘要

Compounds having general formula (I) are described, wherein Z is CR3R4R5 or NR4R5; each R7 is independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, aryl or aryl (C1-C8)alkylene, heteroaryl, heteroaryl (C1-C8)alkylene- ; Xis-CH2ORa, -CO2Ra,- OC(O)Ra, -CH2OC(O)Ra, -C(O)NRaRb, -CH2SRa, -C(S)ORa, -OC(S)Ra, -CH2OC(S)Ra or C(S)NRaRb or -CH2N(Ra)(Rb) R1 and R2 and the atom to which they are attached is C=O, C=S or C=NRc. Rc is hydrogen or (Cl-C8)-alkyl ; m is 0 to about 8 and p is 0 to 2 ; provided that m is at least 1 when Z is NR4R5 ; or a pharmaceutically acceptable salt thereof. Also described are compounds of general formula (I) and methods of their use for the treatment of inflammatory activity in mammalian tissue. The inflammatory tissue activity can be due to pathological agents or can be due to physical, chemical or thermal trauma, or the trauma of medical procedures, such as organ, tissue or cell transplantation, angioplasty (PCTA), inflammation following ischemia/reperfusion, or grafting. The present compounds comprise a class of 2-alkynyladenosine derivatives, substituted at the ethyn-2-yl position by substituted cycloalkyl and heterocycle (heterocyclic) moieties.