新产品编号:897503
Chemical Name: N-[2-[2-Chloro-6-(beta-D-galactopyranosyloxy)-1,2,3,4-tetrahydrobenzo[f]quinolin-4-ylcarbonyl]-1H-indol-5-yl]-1H-indole-2-carboxamide
CAS No. 371155-19-0
项目整合开发状态: Preclinical
项目研究机构: Georg-August-Universit鋞 G鰐tingen (Originator)
合成路线:The benzoquinolinol derivative (I) is protected as the silyl ether (II) upon treatment with tert-butyldiphenylsilyl chloride and imidazole.Transfer hydrogenolysis of the benzyl ether group of (II) with ammonium formate and Pd/C affords phenol (III).This is then coupled with the trichloroacetimidate of tetraacetylgalactose (IV) in the presence of boron trifluoride etherate to produce the Boc-deprotected galactopyranoside (V).Acylation of (V) with the bis-indolylcarboxylic acid (VI) yields amide (VII).
合成路线:Desilylation of (VII) employing tetrabutylammonium fluoride on silica gel support gives alcohol (VIII),which is converted into chloride (IX) upon treatment with triphenylphosphine in carbon tetrachloride.Finally,solvolysis of the acetate ester groups with methanolic NaOMe affords the title compound.
📌 参考资料/链接：
参考文献标题:Novel prodrugs of 6-hydroxy-2,3-dihydro-1H-indoles,5-hydroxy-1,2-dihydro-3H-pyrrolo[3,2-e]indoles and 5-hydroxy-1,2-dihydro-3H-benzo[e]indoles as well as of 6-hydroxy-1,2,3,4-tetrahydro-benzo[f]quinoline derivs.for use in selective cancer therapy
文献作者:Tietze,L.F.; Fecher,A.; Herzig,T.
参考来源:WO 0183448
📄 详细内容
合成路线:The benzoquinolinol derivative (I) is protected as the silyl ether (II) upon treatment with tert-butyldiphenylsilyl chloride and imidazole.Transfer hydrogenolysis of the benzyl ether group of (II) with ammonium formate and Pd/C affords phenol (III).This is then coupled with the trichloroacetimidate of tetraacetylgalactose (IV) in the presence of boron trifluoride etherate to produce the Boc-deprotected galactopyranoside (V).Acylation of (V) with the bis-indolylcarboxylic acid (VI) yields amide (VII).
合成路线:Desilylation of (VII) employing tetrabutylammonium fluoride on silica gel support gives alcohol (VIII),which is converted into chloride (IX) upon treatment with triphenylphosphine in carbon tetrachloride.Finally,solvolysis of the acetate ester groups with methanolic NaOMe affords the title compound.
参考文献标题:Proof of principle in the selective treatment of cancer by antibody-directed enzyme prodrug therapy: The development of a highly potent prodrug
文献作者:Tietze,L.F.; et al.
参考来源:Angew Chem.Int Ed Engl 2002,41(5),759