Patent EP-2123621-A1 (EP)
Inventor: FRIEBE DR MATTHIAS
IPC: A61K51/04
Filed: 2008-05-20
Abstract: Amide compounds (I) are new. Amide compounds of formula (I) are new. A : OH, 1-5C-alkoxy, hydroxy 1-5C-alkoxy, O-1-5C-alkyl-(O-1-4C-alkyl) n-O-1-4C-alkyl, N(1-5C-alkyl) 2, NH 2, N(H)-L, O-L or O-Z; G : OH, O-Z, O-1-5C-alkyl, O-2-5C-alkenyl, O-1-5C-alkyl-(O-1-4C-alkyl) nO-1-4C-alkyl, O-2-5C-alkynyl, or triphenylmethoxy; R 1>, R 2> : H, 1> 8>F-2-5C-alkoxy, 1> 8>F-1-5C-alkyl, 1> 8>F-2-5C-alkenyl, 1> 8>F-2-5C-alkynyl, OH, 1-5C-alkyl or 1-5C-alkoxy; L : 1-5C-alkyl, 2-5C-alkenyl, 1-5C-alkyl-(O-1-4C-alkyl) n-O-1-4C-alkyl or 2-5C-alkynyl; Z : a metal cation equivalent; and n : 0-3. Provided that one of the substituents R 1>or R 2>contains 1> 8>F isotope and the other substitution is free of 1> 8>F isotope and R 1>is not H. Independent claims are included for: (1) a carbonyl compound of formula (II); (2) the preparation of (I); (3) the preparation of (II) comprising reacting a carbonyl compound of formula (III) with F-18 fluoride; (4) the carbonyl compound (III); (5) use of a pyrrolidine compound of formula (IV) for the preparation of (I) or (II); (6) a kit comprising (III) or (IV); and (7) a pharmaceutical composition comprising (I)-(IV) and a suitable carrier. A 1> : OH, 1-5C-alkoxy, hydroxy 1-5C-alkoxy, O-1-5C-alkyl-(O-1-4C-alkyl) n-O-1-4C-alkyl, N(1-5C-alkyl) 2, NH 2, N(H)-L 1>, O-L 1>; G 1> : OH, O-Z 1>, O-1-5C-alkyl, O-2-5C-alkenyl, O-1-5C-alkyl-(O-1-4C-alkyl) nO-1-4C-alkyl, O-2-5C-alkynyl, or triphenylmethoxy; Q : N(H)-tert-butoxycarbonyl, N(H)-benzyloxycarbonyl, -N=C(X 1>)(X 2>) (all preferred), N(H)-allyloxycarbonyl, N(H)-ethoxycarbonyl, N(H)-methoxycarbonyl, N(H)-propoxycarbonyl, N(H)-2,2,2-trichloroethoxycarbonyl, N(H)-1,1-dimethylpropinyl, N(H)-1-methyl-1-phenyl-ethoxycarbonyl, N(H)-1-methyl-1-(4-biphenylyl)-ethoxycarbonyl, N(H)-cyclobutylcarbonyl, N(H)-cyclobutylcarbonyl, N(H)-1-methylcyclobutylcarbonyl, N(H)-vinylcarbonyl, N(H)-allylcarbonyl, N(H)-adamantylcarbonyl, N(H)-diphenylmethylcarbonyl, N(H)-cinnamylcarbonyl, N(H)-formyl, N(H)-benzoyl, N(H)-trityl, N(H)-p-methoxyphenyl-diphenylmethyl, N(H)-di-(p-methoxyphenyl)-phenylmethyl, or N-(tert.butyoxycarbonyl) 2; L 1>, L 2> : L; X 1>, X 2> : aryl, aralkyl or heteroaryl (all optionally substituted) or 1-5C-alkyl; Z 1>, Z 2> : a metal cation equivalent; A 2> : 1-5C-alkoxy, hydroxy 1-5C-alkoxy, O-1-5C-alkyl-(O-1-4C-alkyl) n-O-1-4C-alkyl, N(1-5C-alkyl) 2, NH 2, N(H)-U 1>, N(H)-L 2>or O-L 2>; G 2> : O-Z 2>, O-1-5C-alkyl, O-2-5C-alkenyl, O-1-5C-alkyl-(O-1-4C-alkyl) nO-1-4C-alkyl, O-2-5C-alkynyl, or triphenylmethoxy; R 3>, R 4> : H, E-2-5C-alkoxy, E-1-5C-alkyl, E-2-5C-alkenyl, E-2-5C-alkynyl, OH, 1-5C-alkyl, or 1-5C-alkoxy; E : Cl, Br, methanesulfonyloxy, trifluoromethanesulfonyloxy, nonafluorobutyloxy, tosyloxy or I; Q 1>, Q 3> : Q; G 3> : O-1-5C-alkyl, O-2-5C-alkenyl, O-1-5C-alkyl-(O-1-4C-alkyl) nO-1-4C-alkyl, O-2-5C-alkynyl, or triphenylmethoxy; R 5>, R 6> : H, OH, 1-5C-alkyl, 1-5C-alkoxy or R 7>-E 1>; E 1> : E; and R 7> : 2-5C-alkoxy, 1-5C-alkyl, 2-5C-alkenyl or 2-5C-alkynyl. Provided that: one of the substituent R 3>or R 4>contains E and the other substituent is free of E and R 3>is not H; and one of the substituents of R 5>or R 6>contains E 1>, and the other substituent is free of E 1>and R 5>is not H. [Image] [Image].