有机化学人才网 | 最新人才 | 最新职位 | 技术交易 | 药物合成 |
   
全站搜索: |
  您当前位置:网站首页 >> 药物合成路线图解
 

药物详细合成路线

Name Candesartan cilexetil;Candesartan hexetil;H212/91;TCV-116;Kenzen;Blopress 16 mg Plus;Parapres;Ratacand;Blopress;Amias;Atacand
Chemical Name (±)-2-Ethoxy-1-[2-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-benzimidazole-7-carboxylic acid 1-(cyclohexyloxycarbonyloxy)ethyl ester
CAS 145040-37-5
Related CAS
Formula C33H34N6O6
Structure
Formula Weight 610.67553
Stage 上市-1997
Company Takeda (Originator), Abbott (Licensee), Almirall Prodesfarma (Licensee), AstraZeneca (Licensee)
Activity/Mechanism CARDIOVASCULAR DRUGS, Diabetic Nephropathy, Agents for, Diabetic Retinopathy, Agents for, ENDOCRINE DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Nephritis, Agents for, RENAL-UROLOGIC DRUGS, Restenosis Treatment of, Treatment of Diabetic Complications, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Treatment of Renal Diseases, Angiotensin AT1 Antagonists
Syn. Route 1
Route 1
this compound can be obtained by two related ways:1) the partial esterification of 3-nitrophthalic acid (i) with ethanol and h2so4 gives 3-nitrophthalic acid 1-monoethyl ester (ii), which is treated with socl2 in refluxing benzene to yield the corresponding acyl chloride (iii). the reaction of (iii) first with sodium azide in dmf and then with refluxing tert-butanol affords 2-(tert-butoxycarbonylamino)-3-nitrobenzoic acid ethyl ester (iv), which is condensed with 4-(2-cyanophenyl)benzyl bromide (v) by means of nah in thf giving 2-(2-cyanobiphenyl-4-ylmethylamino)-3-nitrobenzoic acid ethyl ester (vi). the reduction of (vi) with sncl2.2h2o in ethanol yields the corresponding 3-amino derivative (vii), which is cyclocondensed with ethyl orthocarbonate and acetic acid affording 1-(2-cyanobiphenyl-4-ylmethyl)-2-ethoxybenzimidazole-7-carboxylic acid ethyl ester (viii). the reaction of (viii) with trimethyltin azide in refluxing toluene gives the 2-(1h-tetrazol-5-yl) derivative (ix), which is saponified with naoh in ethanol to the corresponding free acid (x). protection of (x) with trityl chloride and triethylamine in dichloromethane gives the protected compound (xi), which is finally esterified with cyclohexyl 1-iodoethyl carbonate (xii) by means of k2co3 in dmf.2) compound (viii) can also be obtained by reaction of 2-chloro-1-(2-cyanobiphenyl-4-ylmethyl)benzimidazole-7-carboxylic acid ethyl ester (xiii) with sodium ethoxide in refluxing ethanol.
List of intermediates No.
benzyl (2s)-2-([(2s)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)-5-methylhexanoate (i)
benzyl (2s)-2-amino-3-phenylpropanoate (ii)
benzyl (6s,9s,12s)-12-benzyl-9-isopentyl-6-isopropyl-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate (iii)
(2s)-6-amino-2-[(tert-butoxycarbonyl)amino]-6-oxohexanoic acid (iv)
tert-butyl (3s)-2,6-dioxopiperidinylcarbamate (v)
tert-butyl (3s)-2-hydroxy-6-oxopiperidinylcarbamate (vi)
methyl 2-(diethoxyphosphoryl)acetate (vii)
methyl (e,4s)-8-amino-4-[(tert-butoxycarbonyl)amino]-8-oxo-2-octenoate (viii)
methyl (e,4s)-4,8-diamino-8-oxo-2-octenoate (ix)
chloro(methylsulfanyl)methane (x)
methyl 2-bromo-4-nitrobenzoate (xi)
1-naphthylboronic acid (xii)
methyl 2-(1-naphthyl)-4-nitrobenzoate (xiii)
Reference 1:
    naka, t.; nishikawa, k.; kato, t. (takeda chemical industries, ltd.); benzimidazole derivs., their production and use. ep 0459136; ep 0720982; jp 1992364171; jp 1996099960; us 5196444; us 5328919; us 5401764; us 5703110; us 5705517; us 5962491; us 6004989 .
Reference 2:
    prous, j.; mealy, n.; castaner, j.; tcv-116. drugs fut 1993, 18, 7, 609.
Reference 3:
    obara, y.; kubo, k.; imamiya, e.; sugiura, y.; inada, y.; shibaida, y.; ishikawa, k.; yoshimura, y.; naka, t.; synthesis of tcv-116, a new non-peptide angiontensin ii (aii) receptor antagonist and its aii antagonist action. 113th annu meet pharmaceut soc jpn (march 29-31, osaka) 1993, abst 29cc 13-5.

来源:药化网

作者:药化小编

摘要:本文合成路线介绍的是药物中文名坎地沙坦西来替昔酯;英文名Candesartan cilexetil;Candesartan hexetil;H212/91;TCV-116;Kenzen;Blopress 16 mg Plus;Parapres;Ratacand;Blopress;Amias;Atacand;CAS[145040-37-5]

 
推荐VIP企业
无锡景耀生物科技有限公司
杭州卢普生物科技有限公司
宁波赛伦化工有限公司
苏州昊赛生物科技有限公司
北京嘉盛扬医药科技有限公司
上海泽涵生物医药科技有限公司
河北固安三利化工公司
郑州凯普瑞生物技术有限公司
上海药谷药业有限公司
兰州康寓信生物科技有限公司
湖北朗昕生化药业有限公司
武汉福鑫化工有限公司
嘉兴市英南化工有限公司
苏州迪飞医药科技有限公司
北京富安凯科技有限公司
上海盛中医药化工有限公司
连云港天和化学有限公司
南京晨瑞医药科技有限公司
南京苏如化工有限公司
常州瑞盛化工有限公司
热门文章
FDA 批准罗氏肿瘤免疫疗法
带你认识第一款专门治疗产后抑郁
润丰股份致力于打造欧盟农化品活
欧盟批准罗氏血友病药物 Hem
突出重点环节 强化职责落实 努
华东地区BDO市场持续僵持
PTA止跌在眼前
陕西地区醋酸价格
华东地区醋酸价格
河北地区醋酸价格
山东地区醋酸价格
山东地区辛醇市场保持稳定
华北及山东地区环己酮市场稳定
华东地区BDO市场弱势整理
华南地区正丁醇市场行情
华北地区丁二烯市场报盘走高
华东地区邻苯市场行情维稳
山东地区二氯甲烷市场价格上调
河北地区醋酸价格
华北地区醋酸价格
 友情链接
有机化学人才网  
首页 | 广告服务 | 建站服务 | 关于我们 | 联系我们 | 版权声明