Edotreotide yttrium, Yttrium (90Y) edotreotide, Octreother, DOTATOC-[90Y], SMT-487-[90Y], [90Y]-SMT-487

依多曲肽 Chemical Name: [N-[2-[4,7-Bis[(carboxy-kappaO)methyl]-10-(carboxymethyl)-1,4,7,10-tertaazacyclododec-1-yl-kappaN1,kappaN4,kappaN10]acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-threonyl-L-cysteinyl-L-threoninol cyclic (2-7)-disulfidato(3-)]yttrium; [90Y-DOTA0,D-Phe1,Tyr3]-octreotide
CAS No. 189758-25-6, 204318-14-9 (ligand)
项目整合开发状态: Phase II
项目研究机构: Novartis (Originator), National Cancer Institute (Codevelopment)
合成路线:Threoninol cyclic acetal (III),obtained from Fmoc-threoninol (I) and (4-formylphenoxy) acetic acid (II),was linked to a solid-phase resin (IV) to give (V).Then,the Fmoc protecting group of (V) was cleaved by treatment with piperidine in DMF to afford (VI).To this,they were sequentially condensed the following protected amino acids: Fmoc-Cys(S-t-Bu) (VII),Fmoc-Thr (IX),Fmoc-Lys(Boc) (XI) and Fmoc-D-Trp (XIII) to yield the peptide resins (VIII),(X),(XII) and (XIV).The condensation sequence included coupling using dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) and Fmoc-deprotection with piperidine in DMF.

合成路线:The following protected amino acids Fmoc-Tyr (XV),Fmoc-Cys(S-t-Bu) (VII),and Fmoc-D-Phe (XVIII) were sequentially condensed to compound (XIV) to yield the peptide resins (XVI),(XVII),and (XIX),respectively.The condensation sequence included coupling using dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) and Fmoc-deprotection with piperidine in DMF.

合成路线:Treatment of resin (XIX) with tri-n-butyl phosphine and then with H2O2 removed both S-tert-butyl protecting groups and formed the disulfide bridge to give (XX).Peptide (XXI) was then liberated from the resin (XX) by means of 2% trifluoroacetic acid in CH2Cl2.Subsequent condensation with an excess of tetraazacyclododecanetetraacetic acid (DOTA) (XXII) using DCC and N-hydroxysuccinimide (NHS) as the coupling reagents provided the monoacylated peptide,from which the Lys5-N-Boc protecting group was removed by treatment with TFA,to yield (XXIII).

合成路线:Finally,complexation of compound (XXIII) with 90Y+3 provided the target compound.