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米格列奈钙的合成 被引量：4

Synthesis of Mitiglinide Calcium
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摘要 目的合成米格列奈钙。方法以丁二酸二甲酯和苯甲醛为原料,经Stobble缩合、水解、脱水,与顺-全氢异吲哚缩合后经还原、拆分、成盐等7步反应制得糖尿病治疗药物米格列奈钙。结果目标化合物经核磁共振氢谱、质谱、红外及元素分析等确证其化学结构,总收率为1 0.1%。结论本工艺操作简便,成本较低,适合于工业化生产。 Objective To synthesize mitiglinide calcium. Methods Starting from dimethyl succinate and benzaldehyde, mitiglinide calcium was obtained via 7 chain steps including Stobble condensation, hydrolization, anhydration, condensation with cis-hexahydroisoindoline, reduction, separation, salt formation. Results The structure of mitiglinide calcium was verified by ^1HNMR, MS, IR and element analysis. The total yield of mitiglinide calcium was 10. 1%. Conclusion A simple, easily controlled and cost-saving process for the synthesis of mitiglinide calcium can be attained.
作者 郑德强 刘文涛 毋立华 孙利民 王长斌
机构地区 山东省生物药物研究院
出处 《食品与药品》 CAS 2007年第11A期13-15,共3页 Food and Drug
关键词 米格列奈钙 合成 降血糖药 mitiglinide calcium synthesis hypoglycemic
分类号 R977.15 [医药卫生—药品]
  • 相关文献

参考文献10

  • 1陈小勇,彭润涛,江宇,张展,李述平,陈颖,张润峰.治疗糖尿病新药米格列奈[J].中国医药情报,2004,10(2):28-31. 被引量：21
  • 2Toshiaki Y,Takashi Y,Hiroshi H,et al.Preparation of optical succinic acid derivatives,Ⅱ.Efficient and practical synthesis of KAD-1229[J].Chem Pharm Bull,1998,46(2):337-340.
  • 3Kiyoshi I,Kazuyasu M,Makoto M,et al.Absence of exacerbation of myocardial stunning in anesthetized dogs treated with KAD-1229,a novel hypoglycemic agent[J].Eur J Pharmacol,2001,431 (3):331-338.
  • 4Yasuhiro S,Tohru G,Tadao S,et al.The effects of mitiglinide KAD-1229,a new anti 2 diabetic drug,on ATP2sensitive K+ channels and insulin secretion:comparison with the sulfonylureas and nateglinide[J].Eur J Pharmacol,2001,431(1):119-125.
  • 5Sorbera L A,Leeson P A,Castaner R M,et al.Mitiglinide calcium (KAD-1229)[J].Drugs Future,2000,25(10):1034-1042.
  • 6Lukas H.Process to separate mixtures of enantiomeric arylpropionic acids:US,4983765[P].1991-01-08.
  • 7Sato F.Succinic acid compounds:US,5202335[P].1993-04-13.
  • 8Yamaguchi T,Yanagi T,Hokari H,et al.Preparation of optically active succinic acid derivatives.I.optical resolution of 2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl)-propionic acid[J].Chem Pharm Bull,1997,45(9):1518-1520.
  • 9Kamijo T.Process for producing benzylsuccinic acid derivatives:EP,0967204[P].1999-12-29.
  • 10Cohen S G,Milovanovic A.Absolute steric course of hydrolysis by a chymotrypsin esters of α-benzylsuccinic,α-methyl-β-phenylpropionic and α-methyl-succinic acids[J].J Am Chem Soc,1968,90 (13):3495-3506.

二级参考文献7

  • 1Pratley RE,Foley JE ,Dunning BE. Rapid actingin sulinotropic agents :restoration of early insulin secretion as a physiologic approach to improve glucose control. Curr Pharm Des, 2001 ; 7 (14) :1375-1397.
  • 2Malaisse WJ, Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: The meglitinide family. Horm Metab Res, 1995,27:263-266.
  • 3Yamato T, Ishikawa K, Ojima K, et al. Effects of KAD-1229 on postgrandial hyperglycemia after oral meal load in STZ-induced diabetic rats. Jpn J Pharmacol, 2001 - 85 (suppll) : AbstP-602.
  • 4Misawa K, Ishikawa K, Oiima K, et al. Effects of KAD-1229,a nonsulfonylurea hypoglycemic agent,on plasma glucose and insulin in streptozotocin-induced diabetic dogs. Pharmacology.2001,62 (2) :65.
  • 5Yamada N, Shigeta Y, Kaneko T,et al. Hypoglycemic effects and safety of a novel rapid-acting insulinotropic agent, KAD-1229, for NIDDM. Diabetes, 1996 ; 45 (Suppl 2) : Abst265.
  • 6Ohnota H,Koizumi T,Tsutsumi N,et al. Novel rapld-and short-acting hypoglycemic agent, a calcium (2S)-2-benzyl-3- (cis-hexahydro-2-isoindolinylcarbonyl ) propionate (KAD-1229) that acts on the sulfonylurea receptor:Comparison of effects between KAD-1229 and gliclazide. J Pharmacol Exp Ther, 1994,269 : 489 - 495.
  • 7Ohnota H, Kitamura T, Kinukawa M, et al. A rapid-and short-acting hypoglycemic agent KAD-1229 improves post-prandial hypoglycernic agent KAD-1229 improves post-prandial hyperglycemia and diabetic complications in steptozotocln-induced non-insulin-dependent diabetes mellitus rats. JPN J Pharmacol, 1996,71:315-323.

共引文献20

同被引文献14

  • 1黄伟,岑均达,姚岚.米格列奈的合成[J].中国医药工业杂志,2005,36(5):257-259. 被引量：6
  • 2高丽梅,李迎红,宋丹青.米格列奈钙二水合物的合成[J].中国新药杂志,2005,14(11):1316-1318. 被引量：8
  • 3虞春晓,朱雄,王尔华,汪会海.米格列奈中间体顺式全氢异吲哚的合成工艺改进[J].药学进展,2006,30(4):179-181. 被引量：3
  • 4杨贯羽,宋延林,嵇耀武,黄志新.1，4－二氢吡啶类化合物的合成[J].郑州大学学报（自然科学版）,1996,28(2):86-89. 被引量：9
  • 5林伟,王德才,江建.抗糖尿病新药米格列奈钙的合成[J].化工时刊,2007,21(6):25-26. 被引量：4
  • 6Tadao T,Masaru I,Kouhei Ol,et all Synthesis of Opitically Active 2-(N-Benzyl-N- methylami-no)ethyl Methyl 2,6-Dimethyl-4(m- nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylat e (Nicardipine) [J]. Cheml PharmlBulll,1980,28(9):2809-2812.
  • 7Sorbera L A,Leeson P A,Castaner R M,et al.Mitiglinide calcium hydrate(KAD-1229)[J].Drugs of the Future,2000,25(10):1034-1042.
  • 8Jianchao Liu,Yushe Yang,Ruyun Ji.An effective and convenient method for the preparation of KAD-1229[J].Helv Chim Acta,2004,87:1935-1939.
  • 9Wolfgang Oppolzer,Osamu Tamura,Jorg Deerberg.Asymmetric synthesis of a-amino acids and a-Nhydroxyamino acids from N-acylbornane-10,2-sultams:1-chloro-1-nitrosocyclohexane as a practical[NH2+]equivalen[J].Helv.Chim.Acta,1992,75:1965-1978.
  • 10Wolfgang Oppolzer,Robert Moretti,Silvia Thomi.Asymmetric alkylation of N-acylsultams:a general route to enantiomerically pure crystalline C(α,α)-disubstituted carboxylic acid derivatives[J].Tetrahedron Letters,1989,30(41):5603-5606.

引证文献4

二级引证文献5

食品与药品
2007年 第11A期

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