公开(公告)号：US06756496B1

公开(公告)日：2004-06-29

申请号：US08972998

申请日：1997-11-19

申请人： Brian C. Froehler ,  Chris A. Buhr

发明人： Brian C. Froehler ,  Chris A. Buhr

IPC分类号： C07H1904

CPC分类号： C07H19/10 ,  C07H19/04 ,  C07H19/20

摘要： Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides. The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses. A method for making the hydrogen-phosphonodithioates is provided as well as a method for converting same to an activated intermediate for substitution on the phosphorus atom.

摘要翻译： 提供新的氢 - 二硫代磷酸盐组合物，其特别可用于在寡核苷酸或寡核苷酸中形成核苷酸间核苷酸和核苷间键。 通过使用二硫代磷酸氢盐组合物制备的寡核苷酸及其类似物可用作抗病毒和抗癌剂，并且可具有其它治疗或诊断用途。 提供了制备氢二膦酸二氢盐的方法以及将其转化为活性中间体以在磷原子上进行取代的方法。

公开(公告)号：US06555676B2

公开(公告)日：2003-04-29

申请号：US09961154

申请日：2001-09-21

申请人： Gilles Gosselin ,  Jean-Louis Imbach ,  Christian Perigaud

发明人： Gilles Gosselin ,  Jean-Louis Imbach ,  Christian Perigaud

IPC分类号： C07H1904

CPC分类号： C07H19/10 ,  C07F9/65616 ,  C07H19/04 ,  C07H19/20 ,  C07H21/00

摘要： Compounds of formula RS—P(═O)(QR)—Nu where: R is a radical —(CH2)n—W—X; X is a radical —C(═Z)(Y) or —S—U; Z is O or S; W is O or S; Q is O or S; Y and U are an alkyl, aryl or saccharide radical which is optionally substituted with, for example, an OH, SH or NH group; n is equal to 1 to 4, preferably 1 or 2; and Nu is a radical consisting of a residue of a biologically active compound or the dephosphorylated residue of a compound which is biologically active when it bears a phosphate or phosphonate group.

摘要翻译： 式RS-P（= O）（QR）-Nu的化合物，其中：R是基团 - （CH 2）n -W-X; X是基团-C（= Z）（Y）或-S-U; Z是O或S; W为O或S; Q是O或S; Y和U是任选被例如OH，SH或NH基团取代的烷基，芳基或糖基; n等于1至4，优选1或2; 并且Nu是由生物活性化合物的残基组成的基团或当其具有磷酸酯或膦酸酯基团时具有生物活性的化合物的去磷酸化残基。

公开(公告)号：US06469160B1

公开(公告)日：2002-10-22

申请号：US09647962

申请日：2000-10-06

申请人： Bobby Neal Glover ,  Lian-Feng Huang ,  Robert William Lancaster ,  Stacey Todd Long ,  Michele Catherine Rizzolio ,  Eric Allen Schmitt ,  Barry Riddle Sickles

发明人： Bobby Neal Glover ,  Lian-Feng Huang ,  Robert William Lancaster ,  Stacey Todd Long ,  Michele Catherine Rizzolio ,  Eric Allen Schmitt ,  Barry Riddle Sickles

IPC分类号： C07H1904

CPC分类号： C07H19/052 ,  A61K31/4184 ,  A61K31/7056 ,  C07B2200/13 ,  C07D405/04

摘要： The invention relates to Form physical forms of 5,6-dichloro-2-(isopropylamino)-1-&bgr;-L-ribofuranosyl-1H-benzimidazole, pharmaceutical compositions comprising the same, and their use in medical therapy.

摘要翻译： 本发明涉及5,6-二氯-2-（异丙基氨基）-1-β-L-呋喃核糖基-1H-苯并咪唑的形式物理形式，包含它们的药物组合物及其在药物治疗中的用途。

公开(公告)号：US06482938B1

公开(公告)日：2002-11-19

申请号：US09254547

申请日：1999-09-17

申请人： Yoshihide Hayashizaki ,  Takumi Tanaka

发明人： Yoshihide Hayashizaki ,  Takumi Tanaka

IPC分类号： C07H1904

CPC分类号： C07H21/00 ,  C07H19/10 ,  C07H19/20 ,  C12Q1/6869 ,  C12Q2565/1015 ,  C12Q2521/119

摘要： Disclosed are compounds having two kinds of reporters that can be a donor and an acceptor for energy transfer, for example, fluorescent groups, and having a 2′, 3′-dideoxyribonucleotide residue or a 3′-deoxyribonucleotide residue. These compounds can be used as terminators for the chain terminator method. The two kinds of reporters are arranged with a distance sufficient for causing energy transfer from the donor to the acceptor. Also disclosed are methods for determining DNA sequences based on the chain terminator method wherein the chain termination reaction is performed by using the above terminators. Also disclosed are compounds having two kinds of reporters that can be a donor and an acceptor for energy transfer, which can be used as a primer or an initiator in methods for determining DNA sequences utilizing the chain terminator method, and methods for determining DNA sequences utilizing the compounds.

摘要翻译： 公开了具有两种记录者的化合物，其可以是能量转移的供体和受体，例如荧光基团，并具有2'，3'-二脱氧核糖核苷酸残基或3'-脱氧核糖核苷酸残基。 这些化合物可用作链终止剂方法的终止剂。 这两种记者的排列距离足以引起从供体到受体的能量转移。 还公开了基于链终止法测定DNA序列的方法，其中通过使用上述终止子进行链终止反应。 还公开了具有两种记录者的化合物，其可以是供体和用于能量转移的受体，其可以用作引物或引发剂用于使用链终止剂法测定DNA序列的方法，以及利用 化合物。

公开(公告)号：US06458946B1

公开(公告)日：2002-10-01

申请号：US09582642

申请日：2000-07-28

申请人： Hideaki Maeda ,  Toshio Yamada ,  Hiroshi Sato ,  Yutaka Noda

发明人： Hideaki Maeda ,  Toshio Yamada ,  Hiroshi Sato ,  Yutaka Noda

IPC分类号： C07H1904

CPC分类号： C07H19/10 ,  C07H21/02

摘要： The invention provides crystals of p1,P4-di(uridine 5′-) tetraphosphate or a salt thereof; a process for producing the crystals; and a process for producing P1,P4-di(uridine 5′-) tetraphosphate (U2P4) or a salt thereof from UMP serving as a starting material and by use of DPC and PPi, which process comprises at least one of the following treatment steps: (a) adding UMP diphenylphosphate (UMP-DPP) in divided portions during a step of reaction of UMP-DPP with a PPi-organic alkali salt; (b) carrying out reaction of UMP-DPP with a PPi-organic alkali salt in the presence of a base; and (c) further treating the synthesized U2P4 with an alkali. The crystals of U2P4 or a salt thereof obtained through the process according to the invention have high purity and stability and a less hygroscopicity as compared with a lyophilized product, to thereby serve as a useful raw material for preparing a pharmaceutical. The process for producing U2P4 or a salt thereof according to the invention realizes high yield and enables large-scale synthesis.

摘要翻译： 本发明提供了p1，P4-二（尿苷5'-）四磷酸盐或其盐的晶体; 制造晶体的方法; 以及由作为起始原料的UMP生产P1，P4-二（尿苷5'-）四磷酸（U2P4）或其盐的方法，并且使用DPC和PPi，该方法包括以下处理步骤中的至少一个 ：（a）在UMP-DPP与PPi-有机碱盐反应的步骤期间，分份加入UMP二苯基磷酸酯（UMP-DPP）; （b）在碱的存在下进行UMP-DPP与PPi-有机碱盐的反应; 和（c）用碱进一步处理合成的U2P4。 通过本发明的方法获得的U2P4或其盐的结晶与冻干产品相比具有高纯度和稳定性以及较少的吸湿性，从而用作制备药物的有用原料。 根据本发明的制备U2P4或其盐的方法实现高产率并且能够进行大规模合成。

公开(公告)号：US06346615B1

公开(公告)日：2002-02-12

申请号：US09656213

申请日：2000-09-06

申请人： Irena Bronstein ,  Brooks Edwards ,  Alison Sparks

发明人： Irena Bronstein ,  Brooks Edwards ,  Alison Sparks

IPC分类号： C07H1904

CPC分类号： C07D321/00

摘要： Spiroadamantyl dioxetanes bearing an alkoxy substituent, and an aromatic substituent of phenyl or naphthyl on the dioxetane ring can be activated to chemiluminesce if the aromatic substituent bears a moiety designated OX, wherein the X is cleaved by an enzyme with which the dioxetane is permitted to come in contact with. The T½ kinetics of the chemiluminescent reaction, as well as the signal intensity, or quantum yield of the chemiluminescent reaction, can be altered by selection of an electron-withdrawing or an electron-donating group Z, at positions on the aromatic substituent other than those adjacent the point of attachment to the dioxetane. Signal strength can further be enhanced by recognized chemiluminescent enhancers.

摘要翻译： 具有烷氧基取代基的双金刚烷基二氧杂环丁烷和二氧杂环丁烷环上苯基或萘基的芳族取代基可以被活化成化学发光，如果芳族取代基具有指定为OX的部分，其中X被允许二氧杂环丁烷的酶切割 在与接触。 化学发光反应的T 1/2动力学，以及化学发光反应的信号强度或量子产率可以通过选择吸电子基团或给电子基团Z来改变芳香族取代基以外的芳香族取代基的位置 邻近二氧杂环丁烷的连接点。 信号强度可以通过认可的化学发光增强剂进一步增强。

公开(公告)号：US06815542B2

公开(公告)日：2004-11-09

申请号：US10318476

申请日：2002-12-13

申请人： Zhi Hong ,  Jean-Luc Girardet ,  Kanda Ramasamy ,  Johnson Lau

发明人： Zhi Hong ,  Jean-Luc Girardet ,  Kanda Ramasamy ,  Johnson Lau

IPC分类号： C07H1904

CPC分类号： C07H19/056 ,  A61K31/70 ,  C07H19/052

摘要： Nucleosides, novel nucleoside analog compounds and their novel prodrug forms are disclosed. The novel compounds, prodrugs, or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Type 1 and Type 2 activity.

公开(公告)号：US06686461B1

公开(公告)日：2004-02-03

申请号：US09630627

申请日：2000-08-01

申请人： David A. Schwartz ,  Richard I. Hogrefe

发明人： David A. Schwartz ,  Richard I. Hogrefe

IPC分类号： C07H1904

CPC分类号： C07H21/04 ,  C07H19/00 ,  C07H19/04 ,  C07H21/00

摘要： Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.

摘要翻译： 提供了肼基，氧基氨基和羰基单体以及在酶合成期间掺入寡核苷酸的方法。 提供了引入本文提供的单体的修饰的寡核苷酸。 提供含有共价腙或肟键的固定寡核苷酸和寡核苷酸缀合物。 提供了制备表面结合寡核苷酸的方法。 还提供了制备寡核苷酸缀合物的方法。

公开(公告)号：US06642375B2

公开(公告)日：2003-11-04

申请号：US09731279

申请日：2000-12-06

申请人： Hiroko Inomata ,  Hiroshi Shinoki ,  Masayoshi Kojima ,  Yukio Sudo ,  Junji Nishigaki ,  Osamu Seshimoto

发明人： Hiroko Inomata ,  Hiroshi Shinoki ,  Masayoshi Kojima ,  Yukio Sudo ,  Junji Nishigaki ,  Osamu Seshimoto

IPC分类号： C07H1904

CPC分类号： G01N33/582

摘要： The present invention provides a fluorescent substance which is represented by a formula: A-B-C wherein A is a residue of natural or synthetic nucleotide, oligonucleotide, polynucleotide, or derivative thereof, and binds to B at a base moiety in said residue, or A is a residue of avidin or streptavidin; B is a divalent linking group or a single bond; and C is a monovalent group derived from a general formula (I) and binds to B at a reactive group present in R1 or R2: wherein R1 and R2 each independently represent an alkyl group that may be substituted with a reactive group capable of covalently bonding to A-B-; R3, R4, R5, and R6 each independently represent an alkyl group, and R3 and R4, and/or R5 and R6 may bind to each other to form a saturated carbon-ring together with a carbon atom(s) to which they bind; V1, V2, V3, V4, V5, V6, V7, V8, V9 and V10 each independently represent a hydrogen atom or a monovalent substituent, and two adjacent groups thereof may bind to form a ring; L1, L2, and L3 represent a substituted or unsubstituted methine group; each of m, n, s, and t represents 0 or 1, provided that m+n=1 and s+t=1; p represents 1, 2, or 3; M represents a counter ion; and q represents a number required to neutralize the charge of a molecule. The fluorescent substance of the present invention is useful as a labeling substance for nucleic acids, or as a reagent for analyzing biological components such as nucleic acids, proteins or sugars.

摘要翻译： 本发明提供一种荧光物质，其由下式表示：AB-C，其中A是天然或合成的核苷酸，寡核苷酸，多核苷酸或其衍生物的残基，并与所述残基中的碱基部分的B结合，或A是 抗生物素蛋白或链霉亲和素的残基; B是二价连接基团或单键; 和C是衍生自通式（I）的一价基团，并且在R 1或R 2中存在的反应性基团上与B结合：其中R 1和R 2各自独立地表示烷基， 可以被能够与AB-共价结合的反应性基团取代; R 3，R 4，R 5和R 6各自独立地表示烷基，R 3和R 4和/或R 5和R 6独立地表示烷基， 可以彼此结合形成饱和碳环与它们所结合的碳原子一起; V 1，V 2，V 3，V 4，V 5，V 6，V 7，V 8，V 9和V 10 独立地表示氢原子或一价取代基，其两个相邻基团可以结合形成环; L 1，L 2和L 3表示取代或未取代的次甲基; m，n，s和t中的每一个表示0或1，条件是m + n = 1且s + t = 1; p表示1,2或3; M表示抗衡离子; q表示中和分子电荷所需的数。 本发明的荧光物质可用作核酸的标记物质，或用作分析核酸，蛋白质或糖类等生物成分的试剂。

公开(公告)号：US06326490B1

公开(公告)日：2001-12-04

申请号：US08949180

申请日：1997-10-10

申请人： Krzysztof W. Pankiewicz ,  Krystyna Lesiak ,  Kyoichi A. Watanabe

发明人： Krzysztof W. Pankiewicz ,  Krystyna Lesiak ,  Kyoichi A. Watanabe

IPC分类号： C07H1904

CPC分类号： C07H19/10 ,  C07F9/2495 ,  C07F9/3235 ,  C07F9/4025 ,  C07F9/4423 ,  C07F9/657172 ,  C07F9/657181 ,  C07F9/6581 ,  C07H19/20 ,  C07H19/207

摘要： Disclosed are novel bicyclic tris(anhydride)s useful as intermediates in the synthesis of biolologically active compounds, and the compounds which may be synthesized from such intermediates.

摘要翻译： 公开了可用作合成生物活性化合物的中间体的新型双环三（酐），以及可从这些中间体合成的化合物。