TAK-024
2-[4-[2-(4-鸟苷苯甲胺)乙酰]-3(S)-[3-(4-胍苯甲酰胺)丙基]-2-氧哌嗪-1-酰基]醋酸Chemical Name: 2-[4-[2-(4-Guanidinobenzamido)acetyl]-3(S)-[3-(4-guanidinobenzamido)propyl]-2-oxopiperazin-1-yl]acetic acid
CAS No. 186971-69-7, 246874-91-9 (diHCl)
项目整合开发状态: Preclinical
项目研究机构: Takeda (Originator)
合成路线:Condensation of the secondary amine (I) with N5-Boc-N2-Z-ornithine (II) using EDC provided the acetal amide (III),and subsequent acid-catalyzed intramolecular cyclization of (III) in hot toluene gave rise to the pyrazinone (IV).Catalytic hydrogenation of the double bond with concomitant hydrogenolysis of the benzyloxycarbonyl group of (IV) provided the 1,3-substituted-2-oxopiperazine (V).This was condensed with Z-glycine (VI) to give amide (VII).Then,acid cleavage of the tert-butyl ester and N-Boc protecting groups of (VII) provided (VIII).The N-benzyloxycarbonyl group of (VIII) was subsequently removed by hydrogenolysis,yielding diamine (IX).Finally,acylation of (IX) with the imido ester of 4-guanidinobenzoic acid (X) furnished the title bis(4-guanidinobenzamide).
📌 参考资料/链接：
参考文献标题:Piperazinones useful as inhibitors of platelet aggregation
文献作者:Fukushi,H.; Naka,T.; Terashita,Z.; Miyawaki,T.(Takeda Chemical Industries,Ltd.)
参考来源:EP 0822931; JP 1997316059; US 5935963; US 6020334; WO 9633982
📄 详细内容
合成路线:Condensation of the secondary amine (I) with N5-Boc-N2-Z-ornithine (II) using EDC provided the acetal amide (III),and subsequent acid-catalyzed intramolecular cyclization of (III) in hot toluene gave rise to the pyrazinone (IV).Catalytic hydrogenation of the double bond with concomitant hydrogenolysis of the benzyloxycarbonyl group of (IV) provided the 1,3-substituted-2-oxopiperazine (V).This was condensed with Z-glycine (VI) to give amide (VII).Then,acid cleavage of the tert-butyl ester and N-Boc protecting groups of (VII) provided (VIII).The N-benzyloxycarbonyl group of (VIII) was subsequently removed by hydrogenolysis,yielding diamine (IX).Finally,acylation of (IX) with the imido ester of 4-guanidinobenzoic acid (X) furnished the title bis(4-guanidinobenzamide).
参考文献标题:Potent dibasic GPIIb/IIIA antagonists with reduces prolongation of bleeding time: Synthesis and pharmacological evaluation of 2-oxopiperazine
文献作者:Kitamura,S.; Fukushi,H.; Miyawaki,T.; Kawamura,M.; Konishi,N.; Terashita,Z.; Naka,T.
参考来源:J Med Chem 2001,44(15),2438
产品链接: CAS No. 186971-69-7››