CL-344677, DMG-MINO, CL-329998(as dihydrochloride)
2-萘萺羧酰胺,4,7-双(二甲基氨基)-9-[[2-(二甲氨基)乙酰]氨基]-1,4,4a,5,5a,6,11,12a-辛氢-3,10,12,12a-四羟基-1,11-二氧基-,(4S,4aS,5aR,12aS)-Chemical Name: (1S,4aS,11aR,12aS)-1,10-Bis(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-7-(dimethylamino)-9-(N,N-dimethylglycinamido)tetracycline; [4S-(4alpha,4aalpha,5aalpha,12aalpha)]-4,7-Bis(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. 151922-16-6
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
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.
📌 参考资料/链接：
参考文献标题:Novel 7-substd.-9-substd.amino-6-demethyl-6-deoxytetracyclines
文献作者:Hlavka,J.J.; Sum,P.-E.; Gluzman,Y.; Lee,V.J.; Ross,A.A.(American Cyanamid Co.)
参考来源:EP 0536515; JP 1993255219; US 5494903
📄 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: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:DMG-MINO
文献作者:Fromtling,R.A.; Castar,J.
参考来源:Drugs Fut 1995,20(11),1116
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. 151922-16-6››