【结 构 式】 |
【药物名称】SL-11047 【化学名称】N,N'-Bis[3-(ethylamino)propyl]-2(Z)-butene-1,4-diamine tetrahydrochloride 【CA登记号】206991-64-2, 308145-19-9 (free base) 【 分 子 式 】C14H36Cl4N4 【 分 子 量 】402.28182 |
【开发单位】SLIL Biomedical (Originator) 【药理作用】Lymphoma Therapy, Non-Hodgkin's Lymphoma Therapy, Oncolytic Drugs |
合成路线1
The title tetraamino derivative was prepared by two related methods. Conversion of cis-butenediol (I) into the diamine (II) was effected by Mitsunobu condensation of (I) with HN3 with concomitant reduction of the azido group in the presence of PPh3. Acylation of (II) with mesitylenesulfonyl chloride (III) provided the bis-sulfonamide (IV), which was subsequently alkylated with the bromosulfonamide (V) in the presence of NaH to furnish the protected tetraamine (VI). The sulfonamido groups of (VI) were finally hydrolyzed by an HOAc solution of HBr in the presence of phenol.
【1】 Witiak, D.T.; Frydman, B.J.; Marton, L.J.; Reddy, V.K.; Valasinas, A.L. (Wisconsin Alumni Research Foundation); Conformationally restricted polyamines and their use as antineoplastic agents. JP 2002508739; WO 9817624 . |
【2】 Witiak, D.T.; Frydman, B.J.; Marton, L.J.; Reddy, V.K.; Valasinas, A.L. (Wisconsin Alumni Research Foundation); Conformationally restricted polyamines. US 5889061 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 36965 | (Z)-2-butene-1,4-diol | 6117-80-2 | C4H8O2 | 详情 | 详情 |
(II) | 59440 | (Z)-2-butene-1,4-diamine; (Z)-4-amino-2-butenylamine | C4H10N2 | 详情 | 详情 | |
(III) | 41158 | 2,4,6-trimethylbenzenesulfonyl chloride | 773-64-8 | C9H11ClO2S | 详情 | 详情 |
(IV) | 59441 | N-{(Z)-4-[(mesitylsulfonyl)amino]-2-butenyl}-2,4,6-trimethylbenzenesulfonamide | C22H30N2O4S2 | 详情 | 详情 | |
(V) | 59442 | N-(3-bromopropyl)-N-ethyl-2,4,6-trimethylbenzenesulfonamide | C14H22BrNO2S | 详情 | 详情 | |
(VI) | 59443 | N-{3-[ethyl(mesitylsulfonyl)amino]propyl}-N-{(Z)-4-[{3-[ethyl(mesitylsulfonyl)amino]propyl}(mesitylsulfonyl)amino]-2-butenyl}-2,4,6-trimethylbenzenesulfonamide | C50H72N4O8S4 | 详情 | 详情 |
合成路线2
Alternatively, diol (I) was converted to the bis-sulfonate ester (VII) under phase-transfer conditions. Alkylation of the sodium salt of N-ethyl-1,3-propanediamine disulfonamide (VIII) with the bis-mesytilate (VII) produced (VI), which was then deprotected as above.
【1】 Reddy, V.K.; Valasinas, A.; Sarkar, A.; Basu, H.S.; Marton, L.J.; Frydman, B.; Conformationally restricted analogues of 1N,12N-bisethylspermine: Synthesis and growth inhibitory effects on human tumor cell lines. J Med Chem 1998, 41, 24, 4723. |
【2】 Witiak, D.T.; Frydman, B.J.; Marton, L.J.; Reddy, V.K.; Valasinas, A.L. (Wisconsin Alumni Research Foundation); Conformationally restricted polyamines and their use as antineoplastic agents. JP 2002508739; WO 9817624 . |
【3】 Witiak, D.T.; Frydman, B.J.; Marton, L.J.; Reddy, V.K.; Valasinas, A.L. (Wisconsin Alumni Research Foundation); Conformationally restricted polyamines. US 5889061 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 36965 | (Z)-2-butene-1,4-diol | 6117-80-2 | C4H8O2 | 详情 | 详情 |
(III) | 41158 | 2,4,6-trimethylbenzenesulfonyl chloride | 773-64-8 | C9H11ClO2S | 详情 | 详情 |
(VI) | 59443 | N-{3-[ethyl(mesitylsulfonyl)amino]propyl}-N-{(Z)-4-[{3-[ethyl(mesitylsulfonyl)amino]propyl}(mesitylsulfonyl)amino]-2-butenyl}-2,4,6-trimethylbenzenesulfonamide | C50H72N4O8S4 | 详情 | 详情 | |
(VII) | 59444 | (Z)-4-[(mesitylsulfonyl)oxy]-2-butenyl 2,4,6-trimethylbenzenesulfonate | C22H28O6S2 | 详情 | 详情 | |
(VIII) | 59445 | N-ethyl-N-{3-[(mesitylsulfonyl)amino]propyl}-2,4,6-trimethylbenzenesulfonamide | C23H34N2O4S2 | 详情 | 详情 |