公开(公告)号：US6156758A

公开(公告)日：2000-12-05

申请号：US391843

申请日：1999-09-08

申请人： Pei-Pei Kung ,  Phillip Dan Cook ,  Charles John Guinosso

发明人： Pei-Pei Kung ,  Phillip Dan Cook ,  Charles John Guinosso

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/12 ,  A61K31/517 ,  A61K31/395 ,  C07D239/72

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/12

摘要： Provided are compounds of formula (I) ##STR1## wherein X, Y and Z are independently CH or N; n is 0 or 1; R.sub.1 is selected from OH, alkoxy, aryloxy, aralkyloxy and guanidinyl; R.sub.2 and R.sub.3 are independently selected from H, halogen, amino, hydroxyl, nitro, cyano and carboxyl; R.sub.4 is H, alkyl or acyl; R.sub.5 is selected from H, hydroxyl, halogen, nitro, alkyl, alkoxy, amino, cyclic amino, alkylamino, arylamino and aralkylamino wherein the alkyl, aryl and cyclic moieties are optionally substituted; R.sub.6 and R.sub.7 are independently selected from H, alkyl, alkoxy, halogen and amino; and R.sub.8 and R.sub.9 are independently selected from H, C.sub.1-4 alkyl, alkoxy, acyl, acyloxy, alkoxycarbonyl, hydroxyl, halogen, amino and carboxyl. The compounds have therapeutic or prophylactic use for treating bacterial infection in mammals.

摘要翻译： 提供式（I）的化合物，其中X，Y和Z独立地是CH或N; n为0或1; R1选自OH，烷氧基，芳氧基，芳烷氧基和胍基; R2和R3独立地选自H，卤素，氨基，羟基，硝基，氰基和羧基; R4是H，烷基或酰基; R5选自H，羟基，卤素，硝基，烷基，烷氧基，氨基，环状氨基，烷基氨基，芳基氨基和芳烷基氨基，其中烷基，芳基和环状部分任选被取代; R6和R7独立地选自H，烷基，烷氧基，卤素和氨基; 并且R 8和R 9独立地选自H，C 1-4烷基，烷氧基，酰基，酰氧基，烷氧基羰基，羟基，卤素，氨基和羧基。 该化合物具有用于治疗哺乳动物细菌感染的治疗或预防用途。

公开(公告)号：US07101993B1

公开(公告)日：2006-09-05

申请号：US07967267

申请日：1992-10-27

申请人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

发明人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

IPC分类号： C07H21/00 ,  C07H21/04

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N9/0069 ,  C12N15/1137 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12Q1/68 ,  C12Y113/11012

摘要： Compounds are provided containing purine nucleotides that bear moieties X at the 2′ position thereof wherein X is R1—(R2)n; R1 is C3-C20 alkyl, C4-C20 alkenyl or C2-C20 alkynyl; R2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.

摘要翻译： 提供含有嘌呤核苷酸的化合物，其含有在其2'位置处的部分X，其中X是R 1 - （R 2）N n; R 1是C 3 -C 20烷基，C 4 -C 20烷基，C 1 -C 20烷基， 烯基或C 2 -C 20炔基; R 2是卤素，羟基，硫醇，酮基，羧基，硝基，亚硝基，腈，三氟甲基，三氟甲氧基，O-烷基，S-烷基，NH-烷基，N-二烷基，O-芳基， N-芳基，N-芳基，O-芳烷基，S-芳烷基，NH-芳烷基，氨基，N-苯二甲酰亚氨基，咪唑，叠氮基，肼基，羟基氨基，异氰酸酯基，亚砜，砜，硫醚，二硫化物，甲硅烷基，芳基，杂环， 碳环，嵌入剂，报告分子，缀合物，聚胺，聚酰胺，聚亚烷基二醇，聚醚，增强寡核苷酸的药效学性质的基团或增强寡核苷酸的药代动力学性质的基团; 且n为0至约6的整数。这些化合物可用于调节蛋白质的合成。

公开(公告)号：US06242592B1

公开(公告)日：2001-06-05

申请号：US09457788

申请日：1999-12-09

申请人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

发明人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

IPC分类号： C07H2100

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N9/0069 ,  C12N15/1137 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12Q1/68 ,  C12Y113/11012

摘要： Processes for preparing 2′-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3′-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(&bgr;-D-ribofuranosyl) purine followed by deamination. For uridine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

摘要翻译： 制备2'-O-烷基化鸟苷，尿苷，胞苷和2,6-二氨基嘌呤3'-O-亚磷酰胺的方法包括将核苷前体烷基化，添加合适的封闭基团和磷酸化的步骤。 对于鸟苷2'-O-烷基化的3'-O-亚磷酰胺，对2,6-二氨基-9-（β-D-呋喃核糖基）嘌呤进行烷基化，随后脱氨。 对于尿苷2'-O-烷基化的3'-O-亚磷酰胺，烷基化对尿苷的二烷基亚锡衍生物有影响。 对于胞苷2'-O-烷基化的3'-O-亚磷酰胺，烷基化直接在胞苷上进行。 烷基化直接在2,6-二氨基嘌呤上进行。

公开(公告)号：US06262241B1

公开(公告)日：2001-07-17

申请号：US08383666

申请日：1995-02-03

申请人： Phillip Dan Cook ,  David J. Ecker ,  Charles John Guinosso ,  Oscar Leobardo Acevedo ,  Andrew Kawasaki ,  Kandasamy Ramasamy

发明人： Phillip Dan Cook ,  David J. Ecker ,  Charles John Guinosso ,  Oscar Leobardo Acevedo ,  Andrew Kawasaki ,  Kandasamy Ramasamy

IPC分类号： C12Q168

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K47/51 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N9/0069 ,  C12N15/1131 ,  C12N15/1132 ,  C12N15/1133 ,  C12N15/1135 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12Q1/68 ,  C12Y113/11012

摘要： Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferrably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferrably accomplished. Therapeutics, diagnostics and research methods and also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

摘要翻译： 公开了调节RNA和DNA活性的组合物和方法。 根据优选实施方案，制备包含靶向和反应部分的反义组合物。 优选使用通过骨架糖键切割或通过碱改性而作用或通过磷酸酯键断裂的反应性部分。 根据本发明的某些实施方案，提高寡核苷酸的药效学和药代动力学性质的组也是有用的。 通过组合物与靶RNA的杂交形成的反应性或非反应性官能团的递送也是优选的。 治疗，诊断和研究方法也被披露。 合成核苷和核苷片段也可用于制备用于这些目的的寡核苷酸和寡核苷酸类似物。

公开(公告)号：US06358931B1

公开(公告)日：2002-03-19

申请号：US08295744

申请日：1994-08-30

申请人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

发明人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

IPC分类号： C07H2107

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C07K14/005 ,  C12N9/0069 ,  C12N15/1137 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3511 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12N2740/16322 ,  C12Q1/68 ,  C12Q1/6813 ,  C12Y113/11012

摘要： Compositions and methods for modulating the activity of RNA are disclosed, In accordance with preferred embodiments, antisense compositions are prepared targeting reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.

摘要翻译： 公开了调节RNA活性的组合物和方法。根据优选实施方案，制备靶向反应部分的反义组合物。 反应性部分优选包含通过具有或不具有插入插入部分的接头与靶向寡核苷酸缀合的一个或两个咪唑官能团。 还公开了治疗学，诊断和研究方法，合成核苷和可以被制成寡核苷酸的核苷片段也是公开的。

公开(公告)号：US5856466A

公开(公告)日：1999-01-05

申请号：US888880

申请日：1997-07-07

申请人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

发明人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

IPC分类号： A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/00 ,  C12N9/02 ,  C12N15/113 ,  C12Q1/68

CPC分类号： C12N15/113 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N15/1137 ,  C12N9/0069 ,  C12Q1/68 ,  C12Y113/11012 ,  A61K38/00 ,  A61K48/00 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533

摘要： Processes for preparing 2'-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3'-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(.beta.-D-ribofuranosyl)purine followed by deamination. For uridine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

公开(公告)号：US06610663B2

公开(公告)日：2003-08-26

申请号：US09974326

申请日：2001-10-10

申请人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

发明人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

IPC分类号： A61K4800

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C07K14/005 ,  C12N9/0069 ,  C12N15/1137 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3511 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533 ,  C12N2740/16322 ,  C12Q1/68 ,  C12Q1/6813 ,  C12Y113/11012

摘要： Compositions and methods for modulating the activity of RNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.

公开(公告)号：US6133438A

公开(公告)日：2000-10-17

申请号：US165680

申请日：1998-10-02

申请人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

发明人： Phillip Dan Cook ,  Daniel Peter Claude McGee ,  Charles John Guinosso

IPC分类号： A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/00 ,  C12N9/02 ,  C12N15/113 ,  C12Q1/68

CPC分类号： C12N15/113 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C12N15/1137 ,  C12N9/0069 ,  C12Q1/68 ,  C12Y113/11012 ,  A61K38/00 ,  A61K48/00 ,  C12N2310/3125 ,  C12N2310/315 ,  C12N2310/32 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/333 ,  C12N2310/336 ,  C12N2310/3521 ,  C12N2310/3523 ,  C12N2310/3527 ,  C12N2310/3531 ,  C12N2310/3533

摘要： Processes for preparing 2'-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3'-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(.beta.-D-ribofuranosyl)purine followed by deamination. For uridine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2'-O-alkylated 3'-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

摘要翻译： 制备2'-O-烷基化鸟苷，尿苷，胞苷和2,6-二氨基嘌呤3'-O-亚磷酰胺的方法包括将核苷前体烷基化，添加合适的封闭基团和磷酸化的步骤。 对于鸟苷2'-O-烷基化的3'-O-亚磷酰胺，对2,6-二氨基-9-（β-D-呋喃核糖基）嘌呤进行烷基化，随后脱氨。 对于尿苷2'-O-烷基化的3'-O-亚磷酰胺，烷基化对尿苷的二烷基亚锡衍生物有影响。 对于胞苷2'-O-烷基化的3'-O-亚磷酰胺，烷基化直接在胞苷上进行。 烷基化直接在2,6-二氨基嘌呤上进行。

公开(公告)号：US5914396A

公开(公告)日：1999-06-22

申请号：US373298

申请日：1995-02-22

申请人： Phillip Dan Cook ,  Charles John Guinosso

发明人： Phillip Dan Cook ,  Charles John Guinosso

IPC分类号： C07H19/067 ,  C07H19/10 ,  C07H19/167 ,  C07H21/02

CPC分类号： C07H19/067 ,  C07H19/10 ,  C07H19/167 ,  C07H21/02

摘要： 2'-O-Modified nucleosides, nucleotides, and oligonucleotides. These 2'-O-modified oligonucleotides are resistant to nuclease digestion and can effectively hybridize to a complementary polynucleotide.

摘要翻译： PCT No.PCT / US93 / 06807 Sec。 371日期1995年2月22日 102（e）日期1995年2月22日PCT提交1993年7月20日PCT公布。 公开号WO94 / 02501 日期2月3日，19942'-O-修饰的核苷，核苷酸和寡核苷酸。 这些2'-O-修饰的寡核苷酸对核酸酶消化具有抗性并且可以有效地与互补多核苷酸杂交。