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【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
Extended Information