Patent ID: 7897560

Claim:
A method of increasing intravascular half-life of an agent, said method comprising converting said agent into a compound of general formula (I): by reacting said agent with a compound of general formula wherein R 1 —CO 2 H can bind reversibly to a plasma protein and R 1 is selected from C 1-30 -alkyl, optionally substituted with one or more —CO 2 H, —SO 3 H, —PO 2 OH, —SO 2 NH 2 , —NH 2 , —OH, —SH, halogen, or aryl, said aryl optionally substituted with —CO 2 H, —SO 3 H, —PO 2 OH, —SO 2 NH 2 , —NH 2 , —OH, —SH, or halogen, or C 1-30 -perfluoroalkyl, optionally substituted with one or more —CO 2 H, —SO 3 H, —PO 2 OH, —SO 2 NH 2 , —NH 2 , —OH, —SH, halogen, or aryl, said aryl optionally substituted with —CO 2 H, —SO 3 H, —PO 2 OH, —SO 2 NH 2 , —NH 2 , —OH, —SH, or halogen, G is NH or CHW, wherein W is hydrogen, fluorine, cyano, nitro, C(═O)-E 1 , S(═O) 2 -E 2 , S(═O)-E 3 , aryl, or C 1-6 -alkyl, wherein E 1 , E 2 , and E 3 independently represent C 1-6 -alkyl, aryl, heteroaryl, C 1-6 -alkoxy, amino, C 1-6 -alkyl-amino, or di-C 1-6 -alkyl-amino, Z is S═O, S(═O) 2 , C(═O), C(═O)O, C(═O)NR 2 , or arylene which is optionally substituted with C 1-6 -alkyl, halogen, nitro, cyano, or heteroarylene, said heteroarylene optionally substituted with C 1 -6 -alkyl, halogen, nitro, or cyano, wherein R 2 represents hydrogen, cyano, or C 1-6 -alkyl, X represents a bond or optionally a spacer selected from C 1 -C 20 -alkylene, arylene, heteroarylene, C 1 -C 20 -perfluoroalkylene, or combinations thereof, or -[(CQ 2 ) n A] m (CQ 2 ) p -, or -[(CQ 2 ) n A] m (CQ 2 ) p -[(CQ 2 ) n E] m (CQ 2 ) p -, wherein n and m independently are 1-20 and p independently is 0-10, each A and E independently are —O—, —S—, —NR 3 —, —N(COR 4 )—, —PR 5 (O)—, or P(OR 6 )(O)—, wherein R 3 , R 4 , R 5 , and R 6 independently represent hydrogen or C 1-6 -alkyl, each Q is independently hydrogen or fluorine, Y 1 is a functional group capable of undergoing a bond-forming reaction with a compound to yield a compound of the general formula (I), Y 1 being selected from —C(═O)-L, —C(═S)-L, —NR 2 (C═O)-L, —OC(═O)-L, —NR 2 (C═S)-L, —C(H 2 )-L, —C(C 1-6 alkyl)(═O), —CH(═O), —S(═O) 2 -L, NR 2 —S(C═O) 2 -L, —SH, —S-L, —NCO, —NCS, —NCNR 2 , —NC, —O—NH 2 , wherein L is a leaving group for nucleophilic displacement, L being selected from hydroxy, halide, 2,6-dichlorobenzoyl, pivaloyl, 2- or 4-nitrophenyloxy, 2,4-dinitrophenloxy, benzotriazole-1-yloxy, 4-benzotriazol-3-yloxy, C 1-6 alkoxycarbonyloxy, 4-oxo-3,4-dihydro-1,2,3-benzotriazin-3-yloxy, perfluorophenyloxy, imidazolyl, 2,5-dioxopyrrolidin-1-yloxy, 1,3-dioxo-2,3-dihydro-1-H-isondol-2-yloxy, 2,4,6-trichlorophenyloxy, or azide, and wherein R 2 represents hydrogen, cyano, or C 1-6 -alkyl, and the agent is selected from the group consisting of a GLP-1 peptide or a GLP-2 peptide.