SU-058(uncomplexed), RP-698

Chemical Name: [N-[2-[4,7,10-Tris(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetyl]-L-glutamyl-N1-[3-[7-[N-(1H-benzimidazol-2-ylmethyl)-N-methylcarbamoyl]-2(S)-(carboxymethyl)-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-4-yl]propyl]-L-alpha-glutaminato(3-)]lutetium-177Lu
CAS No. 277327-56-7 (uncomplexed)
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Condensation of tert-butyl 4-fluoro-3-(bromomethyl)benzoate (I) with N-Boc-1,3-propanediamine (II) afforded the aminomethyl benzoate derivative (III).This was coupled with N-Cbz-L-aspartic acid beta-methyl ester (IV),yielding amide (V).After hydrogenolysis of the carbobenzoxy protecting group of (V),the resultant fluoro amine (VI) was cyclized to the benzodiazepinone (VII) upon treatment with 2,6-di-tert-butylpyridine in hot NMP.Acidic cleavage of both the tert-butyl ester and the N-Boc groups of (VII),followed by reprotection of the amine with Boc2O,furnished the N-Boc acid (VIII).This was then coupled to 2-(methylaminomethyl)benzimidazole (IX) to afford,after acidic Boc group cleavage,the amino amide (X).

合成路线:Coupling between gamma-tert-butoxy glutamic acid (XI) and gamma-tert-butoxy-N-Cbz-glutamic acid succinimidyl ester (XII) produced the protected dipeptide (XIII).This was further coupled to the intermediate amine (X) to furnish the corresponding amide (XIV).After hydrogenolysis of the N-Cbz protecting group of (XIV),the resultant amine (XV) was acylated with tetraazacyclododecanetetraacetic acid tri-tert-butyl ester (XVI),yielding the amide adduct (XVII).

合成路线:Basic hydrolysis of the methyl ester group of (XVII) and subsequent acidic cleavage of the tert-butyl esters gave rise to the hexacarboxylic acid derivative (XVIII).Finally,complexation of (XVIII) with 177LuCl3 furnished the title lutetium complex.