公开(公告)号：US06953809B2

公开(公告)日：2005-10-11

申请号：US10194969

申请日：2002-07-15

申请人： Alan Wellington Faull ,  Andrew John Barker ,  Jason Grant Kettle

发明人： Alan Wellington Faull ,  Andrew John Barker ,  Jason Grant Kettle

IPC分类号： C07D401/04 ,  A61K31/00 ,  A61K31/403 ,  A61K31/404 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61P1/00 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00 ,  A61P37/06 ,  A61P43/00 ,  C07D209/04 ,  C07D209/42 ,  C07D405/06 ,  C07D409/04 ,  C07D413/12

CPC分类号： A61K31/00

摘要： The invention concerns the use of a compound of formula (I), in which Z, X, T, A, R1, R2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, in the treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1). Certain of the components of formula (I) are novel and are provided, together with pharmaceutical compositions thereof, as further features of the invention.

摘要翻译： 本发明涉及式（I）化合物的用途，其中Z，X，T，A，R 1，R 2，p和q具有 本文定义的含义及其药学上可接受的盐或体内可水解的酯，用于治疗由单核细胞趋化蛋白-1（MCP-1）介导的疾病或病症。 式（I）的某些组分是新的，并且与其药物组合物一起提供作为本发明的进一步特征。

公开(公告)号：US06897210B2

公开(公告)日：2005-05-24

申请号：US10698388

申请日：2003-11-03

申请人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

发明人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

IPC分类号： A61F13/00 ,  A61F13/02 ,  A61F13/15 ,  A61K20060101 ,  A61K31/505 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P13/12 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P43/00 ,  C07D20060101 ,  C07D207/00 ,  C07D211/00 ,  C07D239/72 ,  C07D239/93 ,  C07D239/94 ,  C07D309/02 ,  C07D317/08 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/02 ,  C07D417/12 ,  A61K31/33

CPC分类号： C07D401/12 ,  A61F13/02 ,  A61F13/023 ,  A61F2013/00221 ,  A61F2013/8408 ,  A61K31/517 ,  A61K31/541 ,  C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR7CO—, —CONR8—, —SO2NR9—, —NR10SO2— or —NR11— (wherein R7, R8, R9, R10 and R11 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); R4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compostions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGP, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

公开(公告)号：US20040009979A1

公开(公告)日：2004-01-15

申请号：US10277957

申请日：2002-10-23

申请人： ZENECA LIMITED

发明人： Roger J. Butlin ,  Thorsten Nowak ,  Jeremy N. Burrows ,  Michael H. Block

IPC分类号： A61K031/53 ,  A61K031/50 ,  A61K031/501 ,  A61K031/497 ,  A61K031/506

CPC分类号： C07D295/192 ,  A61K31/167 ,  C07C235/16 ,  C07C317/40 ,  C07C317/42 ,  C07C317/44 ,  C07C323/65 ,  C07D295/096 ,  C07D295/13 ,  C07D295/15 ,  C07D295/205 ,  C07D295/24 ,  C07D295/26

摘要： The use of compounds of formula (I), and salts thereof; and pharmaceutically acceptable in vivo cleavable prodrugs of said compound of formula (I); and pharmaceutically acceptable salts of said compound or said prodrugs; in formula (I), Ring C is phenyl or a carbon linked heteroaryl ring substituted as defined within; R1 is an ortho substituent as defined within; n is 1 or 2; A-B is a linking group as defined within; R2 and R3 are as defined within; R4 is hydroxy, hydrogen, halo, amino or methyl; in the manufacture of a medicament for use in the elevation of PDH activity in warm-blooded animals such as humans is described. Pharmaceutical compositions, methods and processes for preparation of compounds of formula (I) are also described. 1

摘要翻译： 使用式（I）化合物及其盐; 和所述式（I）化合物的药学上可接受的体内可切割前药; 和所述化合物或所述前药的药学上可接受的盐; 在式（I）中，环C是苯基或被定义为碳原子的杂芳基环; R 1是如上所定义的邻位取代基; n为1或2; A-B是定义的连接基团; R 2和R 3如上所定义; R 4是羟基，氢，卤素，氨基或甲基; 在制备用于升高温血动物（例如人）中PDH活性的药物中的用途。 还描述了制备式（I）化合物的药物组合物，方法和方法。

公开(公告)号：US20030207882A1

公开(公告)日：2003-11-06

申请号：US10427991

申请日：2003-05-02

申请人： ZENECA LIMITED

发明人： Andrew Stocker ,  John Preston ,  Michael James Smithers

IPC分类号： A61K031/5377 ,  A61K031/53 ,  A61K031/506 ,  A61K031/501 ,  A61K031/497 ,  A61K031/496 ,  A61K031/4545 ,  A61K031/4439 ,  C07D43/02 ,  C07D413/02 ,  C07D41/02

CPC分类号： C07D401/14 ,  C07D213/74 ,  C07D237/20 ,  C07D239/42 ,  C07D401/04 ,  C07D401/12

摘要： Compounds of formula (I), wherein G1 is CH or N; G2 is CH or N; R1 is a variety of optional substituents, L1 is (1-4C)alkylene; T1 is CH or N; R2 and R3 are independently hydrogen or (1-4C)alkyl or are joined to form a ring; X1 and X2 represent various linking groups; Ar is phenylene or certain heteroaryl rings and Q represents a variety of aromatic or heterocyclic rings systems, and pharmaceutically acceptable salts thereof are described as useful antithrombotic and anticoagulant agents, and are selective Factor Xa inhibitors. Processes for their preparation and pharmaceutical compositions containing them are also described. 1

摘要翻译： 式（I）的化合物，其中G 1是CH或N; G 2是CH或N; R 1是多种任选的取代基，L 1是（1-4C）亚烷基; T 1是CH或N; R 2和R 3独立地是氢或（1-4C）烷基或连接形成环; X 1和X 2代表各种连接基团; Ar是亚苯基或某些杂芳基环，Q表示各种芳族或杂环体系，其药学上可接受的盐被描述为有用的抗血栓形成和抗凝血剂，并且是选择性因子Xa抑制剂。 还描述了其制备方法和含有它们的药物组合物。

公开(公告)号：US20030144264A1

公开(公告)日：2003-07-31

申请号：US10293561

申请日：2002-11-14

申请人： ZENECA LIMITED

发明人： Michael John Betts ,  Gareth Morse Davies ,  Michael Lingard Swain

IPC分类号： A61K031/407 ,  C07D487/04

CPC分类号： C07D477/20 ,  A61K31/40 ,  A61K31/407 ,  A61K31/41 ,  C07D207/16 ,  C07D403/12 ,  C07F9/568

摘要： The present invention relates to carbapenems and provides a compound of the formula (I): 1 or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C1-4alkyl; R3 is hydrogen or C1-4alkyl; R4 and R5 are the same or different and are selected from hydrogen, halo, cyano, C1-4alkyl, nitro, hydroxy, carboxy, C1-4alkoxy, C1-4alkoxycarbonyl, aminosulphonyl, C1-4alkylaminosulphonyl, di-C1-4-alkylaminosulphonyl, carbamoyl, C1-4alkylcarbamoyl, di-C1-4-alkylcarbamoyl, trifluoromethyl, sulphonic acid, amino, C1-4alkylamino, di-C1-4alkylamino, C1-4alkanoylamino, C1-4alkanoyl(NnullC1-4alkyl)amino, C1-4alkanesulphonamido and C1-4alkylS(O)nnull wherein n is zero, one or two: with the proviso that there is no hydroxy or carboxy substituent in a position ortho to the link to nullNR3null. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.

摘要翻译： 本发明涉及碳青霉烯并提供式（I）化合物或其药学上可接受的盐或体内可水解的酯，其中：R1是1-羟乙基，1-氟乙基或羟甲基; R2是氢或C1-4烷基; R3是氢或C1-4烷基; R4和R5相同或不同，选自氢，卤素，氰基，C1-4烷基，硝基，羟基，羧基，C1-4烷氧基，C1-4烷氧基羰基，氨基磺酰基，C1-4烷基氨基磺酰基，二-C1-4烷基氨基磺酰基， 氨基甲酰基，C 1-4烷基氨基甲酰基，二-C 1-4 - 烷基氨基甲酰基，三氟甲基，磺酸，氨基，C 1-4烷基氨基，二-C 1-4烷基氨基，C 1-4烷酰基氨基，C 1-4烷酰基（N-C 1-4烷基）氨基，C 1-4烷基磺酰氨基 和C 1-4烷基S（O）n - ，其中n为0，一个或两个：条件是在与-NR 3 - 的连接相邻的位置处不存在羟基或羧基取代基。 其制备方法，制备中的中间体，其作为治疗剂的用途和含有它们的药物组合物。

公开(公告)号：US20030113805A1

公开(公告)日：2003-06-19

申请号：US10339552

申请日：2003-01-09

申请人： Zeneca Limited, a London corporation

发明人： Brian Geoffrey Main ,  Richard Eden Shute

IPC分类号： G01N033/53 ,  G01N033/543

CPC分类号： C40B50/16 ,  C07B2200/11 ,  C40B20/04 ,  C40B30/00 ,  C40B40/04 ,  G01N33/58

摘要： A compound library comprises a plurality of different units each comprising a solid support with which is associated a single member of the compound library, each solid support has a defined chemical composition which acts as an intrinsic label capable of identifying the first choice in the synthesis of the associated member of the compound library.

摘要翻译： 化合物文库包括多个不同的单元，每个单元包含固体支持物，与固体支持物相关联，化合物文库的单个成员与每个固体支持物相关联，每个固体支持物具有限定的化学组成，其作为能够鉴定合成中第一选择的内在标记 化合物库的相关成员。

公开(公告)号：US20030077592A1

公开(公告)日：2003-04-24

申请号：US09984842

申请日：2001-10-31

申请人： ZENECA LIMITED

发明人： John Edward Norris Morten

IPC分类号： C12Q001/68 ,  C07H021/04

CPC分类号： C12Q1/6883 ,  C12Q2600/156 ,  Y10S435/81

摘要： This invention relates to single nucleotide polymorphisms in the LTC4 synthase gene, EMBL accession no. U50136, particularly at one or more of positions 375, 815, 1003, 2169 and 2742. The invention also relates to methods and materials for analysing allelic variation in the LTC4 synthase gene, and to the use of LTC4 synthase polymorphism in the diagnosis and treatment of leukotriene mediated diseases such as asthma and allergic rhinitis.

摘要翻译： 本发明涉及LTC4合酶基因中的单核苷酸多态性，EMBL登录号。 U50136，特别是位置375,815,1003,2699和2742中的一个或多个。本发明还涉及用于分析LTC4合酶基因中的等位基因变异的方法和材料，以及在诊断和治疗中使用LTC4合酶多态性 的白三烯介导的疾病如哮喘和过敏性鼻炎。

公开(公告)号：US20020182685A1

公开(公告)日：2002-12-05

申请号：US10193378

申请日：2002-07-11

申请人： Zeneca Limited, a British corporation

发明人： Maurice Ronald Charles Needham ,  Melvin Hollis

IPC分类号： C12P021/04 ,  A01K067/027

CPC分类号： C07K16/00 ,  A61K39/00 ,  A61K48/00 ,  C07K14/52 ,  C07K14/70542

摘要： A method for raising antibodies in a mammalian host using live cells transfected with a biological of interest.

摘要翻译： 使用用感兴趣的生物学转染的活细胞在哺乳动物宿主中培养抗体的方法。

公开(公告)号：US20020119968A1

公开(公告)日：2002-08-29

申请号：US09800745

申请日：2001-03-08

申请人： ZENECA LIMITED

发明人： Alan Wellington Faull ,  Andrew Stocker ,  Colette Marie Mayo ,  John Preston

IPC分类号： A61K031/55 ,  C07D279/04 ,  C07D279/10

CPC分类号： C07D213/74 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14

摘要： The invention concerns compounds of formula (I) 1 wherein each of G1, G2 and G3 is CH or N; m is 1 or 2; R1 includes hydrogen, halogeno and (1-4C)alkyl; M1 is a group of the formula: NR2nullL1nullT1R3 in which R2 and R3 together form a (1-4C)alkylene group, L1 includes (1-4C)alkylene, and T1 is CH or N; A may be a direct link; M2 is a group of the formula: (T2R4)rnullL2nullT3R5 in which r is 0 or 1, each of T2 and T3 is CH or N, each of R4 and R5 is hydrogen or (1-4C)alkyl, or R4 and R5 together form a (1-4C)alkylene group, and L2 includes (1-4C)alkylene; M3 may be a direct link to X; X includes sulphonyl; and Q includes naphthyl and a heterocyclic moiety; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use as antithrombotic or anticoagulant agents.

摘要翻译： 本发明涉及式（I）化合物，其中G1，G2和G3各自为CH或N; m为1或2; R1包括氢，卤代和（1-4C）烷基; M1是下式的基团：其中R2和R3一起形成（1-4C）亚烷基，L 1包括（1-4C）亚烷基，并且T 1是CH或N; A可能是直接链接; M2是下式的基团：（T2R4）r-L2-T3R5，其中r为0或1，每个T2和T3为CH或N，每个R4和R5为氢或（1-4C）烷基，或 R4和R5一起形成（1-4C）亚烷基，L2包括（1-4C）亚烷基; M3可能直接连接到X; X包括磺酰基; 且Q包括萘基和杂环部分; 或其药学上可接受的盐; 其制备方法，含有它们的药物组合物及其作为抗血栓形成或抗凝血剂的用途。

公开(公告)号：US20020077484A1

公开(公告)日：2002-06-20

申请号：US10052550

申请日：2002-01-23

申请人： Zeneca Limited

发明人： Mark Robert James

IPC分类号： C07D275/06

CPC分类号： C07D275/04

摘要： A process for making a 2-alkylbenzisothiazolinone which comprises reacting a bisamide of formula 1 in water or an organic liquid containing water with a bisulphite or bisulphite release agent to form a Bunte salt and converting the Bunte salt under alkaline conditions to 2-alkyl-BIT. R is alkyl. Preferred substituents R are butyl, hexyl, 2-ethylbutyl and 2-ethylhexyl.

摘要翻译： 一种制备2-烷基苯并异噻唑啉酮的方法，其包括将式中的二酰胺在水中或含有水的有机液体与亚硫酸氢盐或亚硫酸氢盐脱模剂反应以形成Bunte盐，并将Bunte盐在碱性条件下转化为2-烷基-BIT。 R是烷基。 优选的取代基R是丁基，己基，2-乙基丁基和2-乙基己基。