| 主权项 |
1.一种式I之新颖 R1R2N-CHX-CO-A-B-D-E-(G)s-K I 其中 R1是甲基; R2是甲基; A是缬胺醯基,异亮胺醯基,2-三级丁基甘胺醯基或2- 乙基甘胺醯基; B是N-甲基-缬胺醯基,N-甲基-异亮胺醯基,N-甲基-2- 三级丁基甘胺醯基,N-甲基-2-乙基甘胺醯基或N-甲 基-新亮胺醯基残基; D是脯胺醯基残基; E是脯胺醯基,反式-4-氟-L-脯胺醯基,顺式-4-氟-L-脯 胺醯基,反式-4-氯-L-脯胺醯基,或顺式-4-氯-L-脯胺 醯基残基; X是乙基,异丙基,二级丁基,或三级丁基; G是L-2-三级丁基甘胺醯基,D-2-三级丁基甘胺醯基,D- 缬胺醯基,D-异亮胺醯基,D-亮胺醯基或2,2-二甲基甘 胺醯基残基; s是0或1; K是-NHC(CH3)3,-NHCH(CH2CH2)CH(CH3)2,-NHCH(CH3)C(CH3)3, -N(CH3)OCH2CH3,-N(CH3)OCH2CH3,-N(CH3)OCH(CH3)2, -N(CH3)O(CH2)3CH3,-N(CH3)OCH2C6H5, -NHC(CH3)2C6H5, -NHC(CH3)2CH2CH3,-NHC(CH3)(CH2 CH3)2,-NHCH[CH(CH3)2]2, -NHCH(CH3)CH(OH)C6H5,-NHC(CH3)2C≡CH, -NHC(CH2CH3)2C≡CH,-NHC(CH3)2 CH2CH2OH, -NHC(CH3)2CH(CH3)2,-NHC(CH3)2 CH2CH2CH3, -NHC(CH3)2 CH2C6H5,-N(OCH3)CH(CH3)2,-N(OCH3)CH2CH3, -N(OCH3)CH2CH2CH3,-N(OCH3)CH2 C6H5,-N(OCH3)C6H5, -N(CH3)OC6H5,-N(OCH3)CH2CH2CH2 CH3,或 K是NHCH(C2H5)2,NHCH(C2H5)CH(CH3)2,NHCH(CH3)CH(CH3)2, NHC(CH3)2C2H5,NHC(CH3)2CH(CH3)2,NHCH(C3H7)2,或 NHCH(C2H5)C3H7,NHCH(CH3)2,或 K是2.一种式I之新颖 R1R2N-CHX-CO-A-B-D-E-(G)s-K I 其中 R1是甲基; R2是甲基; A是缬胺醯基,异亮胺醯基,或2-三级丁基甘胺醯基 残基; B是N-甲基-缬胺醯基,N-甲基-异亮胺醯基,或N-甲基-2 -三级丁基甘胺醯基残基; D是脯胺醯基残基; E是脯胺醯基,顺式-4-氟-L-脯胺醯基,或顺式-4-氯-L- 脯胺醯基残基; X是异丙基,二级丁基,或三级丁基; s是0; K是-NHC(CH3)3,-NHCH(CH2CH2)CH(CH3)2,-NHCH(CH3)C(CH3)3, -N(CH3)OCH2CH3,-N(CH3)OCH2CH3,-N(CH3)OCH(CH3)2, -N(CH3)O(CH2)3CH3,-N(CH3)OCH2C6 H5,-NHC(CH3)2C6H5, -NHC(CH3)2CH2CH3,-NHC(CH3)(CH2 CH3)2,-NHCH[CH(CH3)2]2, -NHCH(CH3)CH(OH)C6H5,-NHC(CH3)2C≡CH, -NHC(CH2CH3)2C≡CH,-NHC(CH3)2 CH2CH2OH, -NHC(CH3)2CH(CH3)2,-NHC(CH3)2CH2 CH2CH3, -NHC(CH3)2CH2C6H5,-N(OCH3)CH(CH3)2,-N(OCH3)CH2CH3, -N(OCH3)CH2CH2CH3,-N(OCH3)CH2C6 H5,-N(OCH3)C6H5, -N(CH3)OC6H5,-N(OCH3)CH2CH2CH2 CH3, 或K是 及其与生理学上可容许酸所形成之盐。3.一种式I 之新颖 R1R2N-CHX-CO-A-B-D-E-(G)s-K I 其中 R1是甲基; R2是甲基; A是缬胺醯基残基; B是N-甲基-缬胺醯基残基; D是脯胺醯基残基; E是脯胺醯基残基; X是异丙基; s是0; K是-NHC(CH3)3,-NHCH(CH2CH2)CH(CH3)2,-NHCH(CH3)C(CH3)3, -N(CH3)OCH2CH3,-N(CH3)OCH2CH3,-N(CH3)OCH(CH3)2, -N(CH3)O(CH2)3CH3,-N(CH3)OCH2C6 H5,-NHC(CH3)2C6H5, -NHC(CH3)2CH2CH3,-NHC(CH3)(CH2 CH3)2,-NHCH[CH(CH3)2]2, -NHCH(CH3)CH(OH)C6H5,-NHC(CH3)2C≡CH, -NHC(CH2CH3)2C≡CH,NHC(CH3)2 CH2CH2OH, -NHC(CH3)2CH(CH3)2,-NHC(CH3)2CH2 CH2CH3, -NHC(CH3)2CH2C6H5,-N(OCH3)CH(CH3)2, -N(OCH3)CH2CH3, -N(OCH3)CH2CH2CH3,-N(OCH3)CH2C6H5,-N(OCH3)C6H5,-N(CH3)OC6H5, -N(OCH3)CH2CH2CH2CH3, 或K是 及其与生理学上可容许酸所形成之盐。4.一种式I 之新颖 R1R2N-CHX-CO-A-B-D-E-(G)s-K 其中 R1为甲基; R2是甲基; A为缬胺醯基残基; B为N-甲基-缬胺醯基残基; D为丙基残基; E为丙基残基; X为异丙基; s为0; K为NHC(CH3)3,NHCH(CH3)C2H5,NHCH(C2H5)2, NHCH(C2H5)CH(CH3)2,NHCH(CH3)CH(CH3)2,NHCH(CH3)C(CH3)3, NHC(CH3)2C2H5,NHCH[CH(CH3)2]2,NHC(CH3)2CH(CH3)2,NHCH(C3H7)2, NHCH(C2H5)C3H7,NH环己基,NH环庚基,N(CH3)OC3H7,NHC(CH3)2 苯基,NHC(CH3)(C2H5)2,NHC(CH3)2C≡CH,NHC(CH3)2CH2CH2OH, NHCH(CH3)2或N(OCH3)CH2苯基或K为5.根据申请专利范围 第1项之新颖, 其中 R1为甲基; R2是甲基; A为缬胺醯基残基; B为N-甲基-缬胺醯基残基; D为丙基残基; E为丙基残基; X为异丙基; s为0; K为NHC(CH3)3。6.根据申请专利范围第1,2,3或4项之新 颖,其系用于治疗肿瘤性疾病。7.一种制备根据 申请专利范围第1,2,3或4项之新颖之方法,其特征 在于系使用独单选自二环己基碳化二亚胺(DCC)、 二异丙基碳化二亚胺(DIC)、1-乙氧基羰基-2-乙氧基 -1,2-二氢(EEDQ)、新戊醯氯、1-乙基-3-(3-二甲基 胺基丙基)碳化二至胺盐酸盐(EDCI)、正丙烷膦酸酐 (PPA)、N,N-双(2-氧基-3-唑啶基)-醯基磷醯氯(BOP-C1) 、六氟磷酸溴-参-咯啶并鏻(PyBrop)、二苯基磷醯 叠氮(DPPA)、Castro试剂、O-苯并三唑基-N,N,N',N'-四甲 基金尿盐(HBTU)、O-氮苯并二唑基-N,N,N',N'-四甲基尿 盐(HATU)、二乙基磷醯氰(DEPCN)、2,5-二苯基-2,3-二氢 -3-氧基-4-羟基吩二氧化物(HOTDO)及1,1'-羰基二咪 唑(CDI)之偶合剂,或选由其与N,N-二甲基-4-胺基啶 (DMAP),N-羟基-苯并三唑(HOBt),N-羟基-苯并三(HOOBt), 氮苯井三唑、N-羟基丁二亚醯胺(HOSu)及2-羟基啶 之组合之偶合试剂,形成醯胺键;且使用氧羰基 、第三丁氧羰基或9-芴基甲氧羰基保护技术。 |
