【结 构 式】 |
【药物名称】BIIE-0246 【化学名称】N-[1-[2-[4-(6-Oxo-6,11-dihydro-5H-dibenz[b,e]azepin-11-yl)-1-piperazinyl]cyclopentyl]acetyl]-L-arginine N-[2-(3,5-dioxo-1,2-diphenyl-1,2,3,4-tetrahydro-1,2,4-triazol-4-yl]ethylamide 【CA登记号】246146-55-4, 246146-31-6 (diHCl), 246146-32-7 (monoHCl) 【 分 子 式 】C49H57N11O6 【 分 子 量 】896.07074 |
【开发单位】Boehringer Ingelheim (Originator) 【药理作用】PHARMACOLOGICAL TOOLS, Neuropeptide Y2 (NPY Y2) Antagonists |
合成路线1
The condensation of ethyl allophanate (I) with diphenylhydrazine (II) produced 1,2-diphenylurazole (III). Alkylation of (III) with N-(2-bromoethyl)phthalimide (IV) in the presence of potassium tert-butoxide afforded the 4-(2-phthalimidoethyl)urazole (V), and the subsequent hydrazinolysis of the phthalimide group of (V) yielded the amino derivative (VI). Then, coupling of (VI) with N-(benzyloxycarbonyl)arginine (VII) via activation with 1,1'-carbonyldiimidazole (CDI) furnished amide (VIII). Deprotection of the N-benzyloxycarbonyl group of (VIII) to give (IX) was effected by catalytic hydrogenation over Pd/C.
【1】 Gaida, W.; Schnorrenberg, G.; Dollinger, H.; Doods, H.N.; Esser, F.; Rudolf, K.; Mihm, G. (Boehringer Ingelheim Pharma KG); Novel substd. amino acid derivs., process for their preparation and pharmaceutical compsns. containing them. DE 19816929 . |
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) | 37022 | ethyl aminocarbonylcarbamate | 626-36-8 | C4H8N2O3 | 详情 | 详情 |
(II) | 37023 | 1,2-diphenylhydrazine | 122-66-7 | C12H12N2 | 详情 | 详情 |
(III) | 37024 | 1,2-diphenyl-1,2,4-triazolidine-3,5-dione | C14H11N3O2 | 详情 | 详情 | |
(IV) | 37025 | 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione | 574-98-1 | C10H8BrNO2 | 详情 | 详情 |
(V) | 37026 | 2-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-1H-isoindole-1,3(2H)-dione | C24H18N4O4 | 详情 | 详情 | |
(VI) | 37027 | 4-(2-aminoethyl)-1,2-diphenyl-1,2,4-triazolidine-3,5-dione | C16H16N4O2 | 详情 | 详情 | |
(VII) | 37028 | (2S)-5-[[amino(imino)methyl]amino]-2-[[(benzyloxy)carbonyl]amino]pentanoic acid | C14H20N4O4 | 详情 | 详情 | |
(VIII) | 37029 | benzyl (1S)-4-[[amino(imino)methyl]amino]-1-([[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]amino]carbonyl)butylcarbamate | C30H34N8O5 | 详情 | 详情 | |
(IX) | 37030 | (2S)-2-amino-5-[[amino(imino)methyl]amino]-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]pentanamide | C22H28N8O3 | 详情 | 详情 |
合成路线2
Condensation of piperazinyl dibenzoazepinone (X) with 3,3-tetramethyleneglutaric anhydride (XI) produced piperazide (XII). Further condensation of (XII) with arginine derivative (IX) using CDI yielded the title compound.
【1】 Gaida, W.; Schnorrenberg, G.; Dollinger, H.; Doods, H.N.; Esser, F.; Rudolf, K.; Mihm, G. (Boehringer Ingelheim Pharma KG); Novel substd. amino acid derivs., process for their preparation and pharmaceutical compsns. containing them. DE 19816929 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IX) | 37030 | (2S)-2-amino-5-[[amino(imino)methyl]amino]-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]pentanamide | C22H28N8O3 | 详情 | 详情 | |
(X) | 37031 | 11-(1-piperazinyl)-5,11-dihydro-6H-dibenzo[b,e]azepin-6-one | C18H19N3O | 详情 | 详情 | |
(XI) | 34125 | 8-oxaspiro[4.5]decane-7,9-dione | 5662-95-3 | C9H12O3 | 详情 | 详情 |
(XII) | 37032 | 2-(1-[2-oxo-2-[4-(6-oxo-6,11-dihydro-5H-dibenzo[b,e]azepin-11-yl)-1-piperazinyl]ethyl]cyclopentyl)acetic acid | C27H31N3O4 | 详情 | 详情 |