A method for parallel solid-phase synthesis of iodinated analogues of the CB1 receptor inverse agonist rimonabant.
A method for the parallel solid-phase synthesis (SPS) of iodinated analogues of Sanofi-Aventis' type 1 cannabinoid (CB1) receptor inverse agonist rimonabant (acomplia) has been developed. The method allows the synthesis of a range of C3 amide/hydrazide derivatives from a resin-bound C3 ester precursor. The C-Ge linkage to the Hypogel-200 resin is stable to the diversification conditions but allows ipso-iododegermylative cleavage using NaI/NCS even for the products containing the oxidatively labile hydrazide moiety.
Department of Chemistry, Imperial College, London SW7 2AY, UK. a.c.spivey@imperial.ac.uk
Alan C
AC
Spivey
Chih-Chung
CC
Tseng
Teyrnon C
TC
Jones
Andrew D
AD
Kohler
George J
GJ
Ellames
D054314:Drug Inverse Agonism; D054879:Halogenation; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D000077285:Rimonabant; D013329:Structure-Activity Relationship
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant