Patent ID: 6605621
Filing Date: 2003-08-12
Classification: A61P,C07D

Abstract:
A radiolabeled compound, comprising a radionuclide and a compound represented by formula I:Xâ€”Lâ€”X1â€ƒâ€ƒ(I) wherein X and X1 each independently represent a compound of formula II: whereinY is NR6, â€”C(R4)(R5)â€”, or â€”Oâ€”; R1 is â€”C(&boxH;O)ORa, â€”C(&boxH;O)N(Ra)2, cyano, (C1-C6)alkyl, (C1-C6)alkanoyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or 1,2,4-oxadiazol-5-yl unsubstituted or substituted at the 3-position by W, wherein any (C1-C6)alkyl, (C1-C6)alkanoyl, (C2-C6)alkenyl, or (C2-C6)alkynyl is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, (C1-C6)alkoxy, (C2-C6)acyloxy, trifluoromethyl, C(&boxH;O)ORb, C(&boxH;O)NRcRd, NReRf, and S(&boxH;O)nRg; and R3 is (C6-C10)aryl, 5-10 membered heteroaryl, (C6-C10)aryl(C1-C6)alkyl, 5-10 membered heteroaryl(C1-C6)alkyl, (C6-C10)arylcarbonyl, biphenyl, or 5-10 membered heteroarylcarbonyl, wherein any aryl, biphenyl, or heteroaryl substituent is unsubstituted or substituted on cabon with 1, 2 or 3 substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C2-C6)acyloxy, trifluoromethyl, C(&boxH;O)ORb, C(&boxH;O)NRcRd, NRcRf, and S(&boxH;O)nRg; or R1 is â€”CH2â€”, or â€”CH2CH2â€”, wherein R1 is attached to a carbon at the ortho position of R3; and R3 is (C6-C10)aryl, or 5-10 membered heteroaryl; R2 is hydrogen or (C1-C6)alkyl; R4 and R5 are independently hydrogen or (C1-C6)alkyl; R6 is hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, (C2-C6)alkenyl, (C2-C6)alkynyl, trifluoromethyl, aryl, heteroaryl, aryl(C1-C4)alkyl, heteroaryl(C1-C4)alkyl, aryl(C1-C4)alkanoyl, or heteroaryl(C1-C4)alkanoyl; wherein any (C2-C6)alkyl, (C2-C6)alkanoyl, (C2C6)alkenyl, or (C2-C6)alkynyl is unsubstituted or substituted on a carbon other than the carbon attached to the piperidine nitrogen with 1, 2 or 3 substituents independently selected from the group consisting of nitro, cyano, hydroxy, (C1-C6)alkoxy, (C2-C6)acyloxy, trifluoromethyl, C(&boxH;O)ORb, C(&boxH;O)NRcRd, and S(&boxH;O)nRg; each n is independently 0, 1 or 2; W is (C1-C6)alkyl, or aryl, unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, nitro, cyano, hydroxy, (C1-C6)alkoxy, (C2-C6)acyloxy, trifluoromethyl, C(&boxH;O)ORb, C(&boxH;O)NRcRd, NReRf, and S(&boxH;O)nRg; Ra is L, hydrogen, (C1-C4)alkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, or heteroaryl(C1-C4)alkyl; each Rb is independently hydrogen, (C1-C4)alkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, or heteroaryl(C1-C4)alkyl; each Rc and Rd is independently hydrogen, (C1-C4)alkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, or heteroaryl(C1-C4)alkyl; or, independently, each NRcRd together is piperidino, pyrrolidino, or morpholino; each Re and Rf is independently hydrogen, (C1-C4)alkyl, (C1-C4)alkanoyl, (C1-C4)alkoxycarbonyl, aryl, heteroaryl, aryl(C1-C4)alkyl, heteroaryl(C1-C4)alkyl, aryl(C1-C4)alkanoyl, or heteroaryl(C1-C4)alkanoyl; or, independently, each NReRf together is piperidino, pyrrolidino, or morpholino; each Rg is independently hydrogen, (C1-C4)alkyl, aryl, heteroaryl, aryl(C1-C4)alkyl, or heteroaryl(C1-C4)alkyl; and L is an unbranched (C2-C12)alkylene chain, unsubstituted or substituted with one, two, or three substituents selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkoxy, hydroxy, oxo, and halo; or L is an unbranched (C2-C10)alkylene chain including, within the chain, at least one divalent radical selected from the group consisting of non peroxide oxy (â€”Oâ€”), thio (â€”Sâ€”), sulfinyl, sulfonyl, â€”OC(&boxH;O)â€”, and â€”N(Rm)C(&boxH;O)â€”; or L is Riâ€”(C2-C10alkylene)â€”Rk wherein Ri and Rk are each independently â€”N(Rm)â€”, â€”Oâ€”, or â€”Sâ€”; each Rm is independently hydrogen or (C1-C4)alkyl; or a pharmaceutically acceptable salt thereof.