藥物詳細合成路線
Name | Tirapazamine;SR-259075;NSC-130181;Win-59075;SR-4233;Tirazone | Chemical Name | 3-Amino-1,2,4-benzotriazine 1,4-dioxide | CAS | 27314-97-2 | Related CAS | | Formula | C7H6N4O2 | Structure | | Formula Weight | 178.15147 | Stage | III 期臨床 | Company | Sanofi-synthélabo (Originator), SRI (Originator), National Cancer Institute (Not Determined) | Activity/Mechanism | Antineoplastic Enhancing Agents, Head and Neck Cancer Therapy, Lung Cancer Therapy, Modulators of the Therapeutic Activity of Antineoplastic Agents, Non-Small Cell Lung Cancer Therapy, ONCOLYTIC DRUGS, Radiation Therapy, Radiosensitizers, Solid Tumors Therapy, DNA-Damaging Drugs | Syn. Route | 1 | Route 1 | tirapazamine can be obtained by several related ways:1) by condensation of benzofurazan (i) with cyanamide disodium salt (ii) in hot methanol/water.2) the condensation of 2-nitroaniline (iii) with cyanamide (iv) by heating at 100 c gives 3-amino-1,2,4-bezotriazine 1-oxide (v), which is then oxidized with 30% aqueous h2o2 in hot acetic acid.3) the reaction of 3-hydroxy-1,2,4-benzotriazine 1-oxide (vi) with refluxing pocl3 and dimethylaniline gives 3-chloro-1,2,4-benzotriazine 1-oxide (vii), which by reaction with dry ammonia in ethanol is converted into the corresponding amino derivative (v), already obtained. | | | List of intermediates | No. | tert-butyl (3r,4s,5s)-4-[((2s)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoate | (i) | tert-butyl (3r,4s,5s)-4-[[(2s)-2-amino-3-methylbutanoyl](methyl)amino]-3-methoxy-5-methylheptanoate | (iii) | (2s)-2-(dimethylamino)-3-methylbutyric acid | (v) | tert-butyl (3r,4s,5s)-4-[((2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoate | (vi) | (2r,3r)-3-[(2s)-1-(tert-butoxycarbonyl)pyrrolidinyl]-3-methoxy-2-methylpropionic acid | (vii) | methyl 6-hydroxy-7-[(1r,2s,3r,5s)-5-hydroxy-2-[(e,3r)-4-phenoxy-3-[(tetrahydro-2h-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2h-pyran-2-yloxy)methyl]cyclopentyl]-4-heptynoate | (iv) | | Reference 1: schofield, k.; robbins, r.f.; polyazabicyclic compounds. part ii. further derivatives of benzo-1:2:4-triazine. j chem soc 1957, 3186. Reference 2: tennant, g.; mason, j.c.; heterocyclic n-oxides. part vi. synthesis and nuclear magnetic resonance spectra of 3-aminobenzo-1,2,4-triazines and their mono- and di-n-oxides. j chem soc b 1970, 911. Reference 3: robinson, c.; castaner, j.; tirapazamine. drugs fut 1995, 20, 3, 256. Reference 4: ley, k.; seng, f.; metzer, k.g. (bayer ag); 3-amino-1,2,4-benzotriazine-1,4-di-n-oxides and processes for their preparation. us 3868371; us 3980779; us 4001410 . | |
來源:藥化網
作者:藥化小編
摘要:本文合成路線介紹的是藥物中文名替拉扎明;英文名Tirapazamine;SR-259075;NSC-130181;Win-59075;SR-4233;Tirazone;CAS[27314-97-2]
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