CL-331928(monohydrochloride), CL-331002, DMG-DMDOT
N-[(5aR,6aS,7S,9Z,10aS)-9-(氨基-羟基甲亚基)-7-二甲基氨基-1,10a,12-三羟基-8,10,11-三氧代-5a,6,6a,7-四氢-5H-并四苯-2-基]-2-二甲基氨基乙酰胺Chemical Name: (4S,4aS,11aR,12aS)-1-(Dimethylamino)-8-[2-(dimethylamino)acetamido]-2,4a,5,7-tetrahydroxy-4,6-dioxo-1,4,4a,6,11,11a,12,12a-octahydronaphthacene-3-carboxamide; 6-Demethyl-6-deoxy-9-(N,N-dimethylglycinamido)tetracycline; [4S-(4alpha,4aalpha,5aalpha,12aalpha)]-4-(Dimethylamino)-9-[(dimethylamino)acetylamino]-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-naphthacenecarboxamide
CAS No. 151922-17-7
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
📌 参考资料/链接：
参考文献标题:9-(Substd.glycyl)amido-6-demethyl-6-deoxytetracyclines as antibiotic agents
文献作者:Sum,P.-E.; Lee,V.J.; Testa,R.T.(American Cyanamid Co.)
参考来源:EP 0582829; JP 1994199758
📄 详细内容
合成路线:By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
合成路线:This compound can be obtained by two related ways:1) The nitration of minocycline (I) by means of NaNO3 and H2SO4 gives the 9-nitro derivative (II),which is hydrogenated with H2 over Pd/C in 2-methoxyethanol to yield the 9-amino derivative (III).Finally,this compound is acylated with sarcosyl chloride (IV) by means of Na2CO3 in acetonitrile/dimethylpropylenurea.2) The acylation of the 9-amino derivative (III) with N-(succinimidyloxycarbonyl)carbamic acid tert-butyl ester (V) by means of sodium acetate in THF gives the 9-(tert-butoxycarbonyl)glycylamino substituted compound (VI),which is deprotected with trifluoroacetic acid to afford the 9-glycylamino compound (VII).Finally,this compound is methylated with formaldehyde and simultaneous hydrogenation with H2 over Pd/C in 2-methoxyethanol.
合成路线:Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II),which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III).Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V).Finally,this compound is treated with tert-butylamine (VI) to yield,after purification,GAR-936.
参考文献标题:Glycylcyclines.1.A new generation of potent antibacterial agents through modification of 9-aminotetracyclines
文献作者:Sum,P.-E.; Lee,V.J.; Testa,R.T.; Hlavka,J.J.; Ellestad,G.A.; Bloom,J.D.; Gluzman,Y.; Tally,F.P.
参考来源:J Med Chem 1994,37(1),184-8
合成路线:By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
参考文献标题:DMG-DMDOT
文献作者:Fromtling,R.A.; Castar,J.
参考来源:Drugs Fut 1995,20(10),1001
合成路线:By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
合成路线:This compound can be obtained by two related ways:1) The nitration of minocycline (I) by means of NaNO3 and H2SO4 gives the 9-nitro derivative (II),which is hydrogenated with H2 over Pd/C in 2-methoxyethanol to yield the 9-amino derivative (III).Finally,this compound is acylated with sarcosyl chloride (IV) by means of Na2CO3 in acetonitrile/dimethylpropylenurea.2) The acylation of the 9-amino derivative (III) with N-(succinimidyloxycarbonyl)carbamic acid tert-butyl ester (V) by means of sodium acetate in THF gives the 9-(tert-butoxycarbonyl)glycylamino substituted compound (VI),which is deprotected with trifluoroacetic acid to afford the 9-glycylamino compound (VII).Finally,this compound is methylated with formaldehyde and simultaneous hydrogenation with H2 over Pd/C in 2-methoxyethanol.
参考文献标题:The discovery of a new generation of tetracycline antibacterial agents,the "glycylcyclines"
文献作者:Hlavka,J.J.; Gluzman,Y.; Tally,F.P.; Bloom,J.D.; Testa,R.T.; Ellestad,G.A.; Lee,V.J.; Sum,P.-E.
参考来源:33rd Intersci Conf Antimicrob Agents Chemother (Oct 17-20,New Orleans) 1993,Abst 431
产品链接: CAS No. 151922-17-7››