L-NIL-TA, SC-51
Chemical Name: 2(S)-Amino-6-(1-iminoethylamino)-N-(1H-tetrazol-5-yl)hexanamide dihydrochloride; N6-(1-Iminoethyl)-N1-(1H-tetrazol-5-yl)-L-lysinamide dihydrochloride
CAS No. 179337-70-3, 179337-79-2 (free base), 210416-47-0 (monohydrate)
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:The reaction of N6-(benzyloxycarbonyl)-N2--(tert-butoxycarbonyl)-L-lysine (I) with 1H-tetrazol-5-amine (II) by means of BOP and DIEA or NMM in DMF gives the corresponding amide (III),which is hydrogenolyzed with H2 over Pd/C in etyhanol/HOAc to yield N2-(tert-butoxycarbonyl)-N1-(1H-tetrazol-5-yl)-L-lysine (IV).The reaction of (IV) with methyl acetimidate (V) by means of TEA in DMF (or ethyl acetimidate (VI) and NaOH in ethanol) affords the iminomethyl derivative (VII),which is finally deprotected with HCl in dioxane.
合成路线:The N-tetrazolyl lysinamide derivative (III) was obtained by acylation of 5-aminotetrazole (II) with Boc-L-lysine(Cbz) (I) using BOP as the coupling reagent.The N-benzyloxycarbonyl protecting group of (III) was then removed by hydrogenation over Pd/C to afford amine (IV),which was subsequently condensed with methyl acetimidate (V) producing amidine (VI).The target compound was finally obtained by N-Boc group cleavage in (VI) under acidic conditions
📌 参考资料/链接：
参考文献标题:Aminotetrazole derivs.useful as nitric oxide synthase inhibitors
文献作者:Hallinan,E.A.; Hansen,D.W.Jr.; Tsymbalov,S.(Pharmacia Corp.)
参考来源:EP 0790987; EP 1113011; JP 1998508847; US 5684008; WO 9615120
📄 详细内容
合成路线:The reaction of N6-(benzyloxycarbonyl)-N2--(tert-butoxycarbonyl)-L-lysine (I) with 1H-tetrazol-5-amine (II) by means of BOP and DIEA or NMM in DMF gives the corresponding amide (III),which is hydrogenolyzed with H2 over Pd/C in etyhanol/HOAc to yield N2-(tert-butoxycarbonyl)-N1-(1H-tetrazol-5-yl)-L-lysine (IV).The reaction of (IV) with methyl acetimidate (V) by means of TEA in DMF (or ethyl acetimidate (VI) and NaOH in ethanol) affords the iminomethyl derivative (VII),which is finally deprotected with HCl in dioxane.
合成路线:The N-tetrazolyl lysinamide derivative (III) was obtained by acylation of 5-aminotetrazole (II) with Boc-L-lysine(Cbz) (I) using BOP as the coupling reagent.The N-benzyloxycarbonyl protecting group of (III) was then removed by hydrogenation over Pd/C to afford amine (IV),which was subsequently condensed with methyl acetimidate (V) producing amidine (VI).The target compound was finally obtained by N-Boc group cleavage in (VI) under acidic conditions
参考文献标题:Synthesis and biological characterization of L-N6-(1-iminoethyl)lysine 5-tetrazole-amide,a prodrug of a selective iNOS inhibitor
文献作者:Hallinan,E.A.; Tsymbalov,S.; Dorn,C.R.; Pitzele,B.S.; Hansen,D.W.Jr.; Moore,W.M.; Jerome,G.M.; Connor,J.R.; Branson,L.F.; Widomski,D.L.; Zhang,Y.; Currie,M.G.; Manning,P.T.
参考来源:J Med Chem 2002,45(8),1686
产品链接: CAS No.179337-79-2››