公开(公告)号：US06821965B1

公开(公告)日：2004-11-23

申请号：US09762106

申请日：2001-02-02

申请人： Dearg S Brown ,  George R Brown

发明人： Dearg S Brown ,  George R Brown

IPC分类号： C07C23373

CPC分类号： C07D207/08 ,  C07C237/42 ,  C07C255/57 ,  C07C2601/04 ,  C07C2601/14 ,  C07D207/12 ,  C07D211/22 ,  C07D211/46 ,  C07D213/82 ,  C07D215/48 ,  C07D223/08 ,  C07D243/08 ,  C07D261/18 ,  C07D277/24 ,  C07D295/13 ,  C07D295/135 ,  C07D295/155 ,  C07D317/68 ,  C07D401/04

摘要： The invention concerns amide derivatives of the Formula (I) wherein R3 is (1-6C)alkyl or halogeno; Q is aryl or heteroaryl which optionally bears 1, 2, 3 or 4 substituents such as hydroxy, halogeno, trifluoromethyl, cyano, (1-6C)alkyl, (1-6C)alkoxy, halogeno(1-6C)alkyl, hydroxy-(1-6C)alkyl, di-[(1-6C)alklyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, (1-6)alkoxy-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, amino-2(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, aryl-(1-6C)alkoxy, heteroaryl, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyl-(1-6C)alkyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy; p is 0-2 and R2 is a substituent such as hydroxy and halogeno; q is 0-4; and R4 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or in-vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

摘要翻译： 本发明涉及其中R 3为（1-6C）烷基或卤代的式（I）的酰胺衍生物; Q是芳基或杂芳基，其任选地具有1,2,3或4个取代基，例如羟基，卤代，三氟甲基，氰基，（1-6C）烷基，（1-6C）烷氧基，卤代（1-6C）烷基，羟基 - （1-6C）烷基，二 - [（1-6C）烷基]氨基 - （1-6C）烷基，羟基 - （2-6C）烷氧基，（1-6）烷氧基 - （2-6C）烷氧基， - [（1-6C）烷基]氨基 - （2-6C）烷氧基，氨基-2（2-6C）烷基氨基，N-（1-6C）烷基 - （1-6C）烷基氨基 - （2-6C） 芳基，芳基 - （1-6C）烷氧基，杂芳基，杂芳基 - （1-6C）烷氧基，杂环基，杂环基 - （1-6C）烷基，杂环氧基和杂环基 - （1-6C） p为0-2，R 2为取代基，例如羟基和卤素; q为0-4; 且R 4包括任选取代的芳基，环烷基，杂芳基和杂环基; 或其药学上可接受的盐或体内可裂解的酯; 其制备方法，含有它们的药物组合物及其用于治疗由细胞因子介导的疾病或医学病症的用途。

公开(公告)号：US5053415A

公开(公告)日：1991-10-01

申请号：US424611

申请日：1989-10-20

申请人： Andrew G. Brewster ,  George R. Brown ,  Alan W. Faull ,  Reginald Jessup ,  Michael J. Smithers

发明人： Andrew G. Brewster ,  George R. Brown ,  Alan W. Faull ,  Reginald Jessup ,  Michael J. Smithers

IPC分类号： A61K31/357 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/08 ,  A61P29/00 ,  C07D405/00 ,  C07D405/04 ,  C07D405/14 ,  C07D407/14 ,  C07D409/00 ,  C07D409/14

CPC分类号： C07D405/04 ,  C07D407/14 ,  C07D409/14

摘要： The invention concerns novel, pharmaceutically useful 1,3-dioxane alkenoic acid derivatives of the formula I containing a pyridyl moiety at position 4 of the dioxane ring and in which the groups at positions 2, 4 and 5 have cis-relative stereochemistry, X is hydrogen, alkoxy or hydroxy, Y is vinylene, n is 1 or 2, A.sup.1 is alkylene, the substituents R.sup.1 and R.sup.2 at position 2 of the dioxane ring have a variety of values defined hereinafter, and R.sup.4 is hydroxy, a physiologically acceptable alcohol residue or alkanesulphonamido, and the pharmaceutically acceptable salts thereof. The invention also includes processes for the manufacture and use of the acid derivatives as well as pharmaceutical compositions for therapeutic use in one or more of a variety of diseases such as ischaemic heart disease, cerebrovascular disease, asthmatic disease and/or inflammatory disease.

公开(公告)号：US5047412A

公开(公告)日：1991-09-10

申请号：US304718

申请日：1989-02-01

申请人： George R. Brown ,  Michael J. Smithers

发明人： George R. Brown ,  Michael J. Smithers

IPC分类号： C07D319/06

CPC分类号： C07D319/06

摘要： The invention describes novel (2-styryl-, 2-naphthyl- and 2-phenethyl-4-o-hydroxyphenyl-1,3-dioxan-5-yl)alkenoic acids and related tetrazoles and sulphonamides, of the formula I wherein Q completes a benzene or pyridine ring, Y is vinylene, Z is carboxy, 1(H)-tetrazol-5-yl or a group of the formula --CO.NHSO.sub.2 R.sup.6, and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, A.sup.1, A.sup.2, n and m have the meanings defined in the specification, and pharmaceutically acceptable salts thereof, for use in conjunction with their pharmaceutical compositions in treating certain pulmonary and/or vascular disorders. The invention also describes various processes and intermediates for the manufacture of the novel compounds.

公开(公告)号：US4895962A

公开(公告)日：1990-01-23

申请号：US218251

申请日：1988-07-13

申请人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

发明人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

IPC分类号： A61K31/335 ,  A61K31/357 ,  A61P7/02 ,  A61P9/08 ,  A61P9/10 ,  C07D319/06

CPC分类号： C07D319/06

摘要： The invention provides a novel group of 4(Z)-([2,4,5-cis]-2,4-diphenyl-1,3-dioxan-5-yl)hexenoic acids of formula I, wherein X is F, Cl, Br, CF.sub.3, CN, CH.sub.3 O or NO.sub.2 and one of Y and Z is hydrogen or fluoro and the other is hydrogen, and their pharmaceutically acceptable salts; together with their pharmaceutical compositions for use in treating a variety of disease conditions. Also provided are methods for the manufacture of novel compounds. Representative compounds are those in which X is 2-cyano or 2-chloro and Y and Z are both hydrogen.

公开(公告)号：US4803220A

公开(公告)日：1989-02-07

申请号：US750101

申请日：1985-06-28

申请人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

发明人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

IPC分类号： A61K31/335 ,  A61K31/357 ,  A61P7/02 ,  A61P9/08 ,  A61P43/00 ,  C07C51/367 ,  C07C59/64 ,  C07D319/06

CPC分类号： C07D319/06 ,  C07C51/367 ,  C07C59/64

摘要： The invention concerns the novel racemic and laevorotatory optically active forms of the thromboxane A.sub.2 antagonist 5(Z)-7-([ 2,4,5-cis]-4-o-hydroxyphenyl-2-trifluoromethyl-1,3-dioxan-5-yl)heptenoic acid of formula I, their salts, pharmaceutical compositions, and processes for their manufacture and intermediates therefor. The pharmaceutical agents and their compositions are of value in certain pulmonary and/or vascular disorders.

摘要翻译： 本发明涉及血栓素A2拮抗剂5（Z）-7 - （[2,4,5-顺式] -4-邻羟基苯基-2-三氟甲基-1,3-二恶烷-2-酮的新型外消旋和左旋旋光活性形式， 噻唑-5-基）庚烯酸，其盐，药物组合物及其制备方法及其中间体。 药物及其组合物在某些肺和/或血管疾病中是有价值的。

公开(公告)号：US4775685A

公开(公告)日：1988-10-04

申请号：US861329

申请日：1986-05-09

申请人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

发明人： Andrew G. Brewster ,  George R. Brown ,  Michael J. Smithers

IPC分类号： A61K31/335 ,  A61K31/357 ,  A61P7/02 ,  A61P9/08 ,  A61P9/10 ,  C07D319/06

CPC分类号： C07D319/06

摘要： The invention provides a novel group of 4(Z)-([2,4,5-cis]-2,4-diphenyl-1,3-dioxan-5-yl)hexenoic acids of formula I, wherein X is F, Cl, Br, CF.sub.3, CN, CH.sub.3 O or NO.sub.2 and one of Y and Z is hydrogen or fluoro and the other is hydrogen, and their pharmaceutically acceptable salts; together with their pharmaceutical compositions for use in treating a variety of disease conditions. Also provided are methods for the manufacture of novel compounds. Representative compounds are those in which X is 2-cyano or 2-chloro and Y and Z are both hydrogen.

摘要翻译： 本发明提供了式I的4（Z） - （[2,4,5-顺式] -2,4-二苯基-1,3-二恶烷-5-基）己烯酸的新型基团，其中X为F， Cl，Br，CF 3，CN，CH 3 O或NO 2，Y和Z中的一个为氢或氟，另一个为氢，及其药学上可接受的盐; 以及用于治疗各种疾病状况的药物组合物。 还提供了制备新化合物的方法。 代表性的化合物是其中X是2-氰基或2-氯并且Y和Z都是氢的化合物。

公开(公告)号：US2240508A

公开(公告)日：1941-05-06

申请号：US31212840

申请日：1940-01-02

申请人： A L TAPLIN ,  GEORGE R BROWN ,  S C KARDELL

发明人： LEWIS TED I

CPC分类号： F23N1/022

公开(公告)号：US06465455B1

公开(公告)日：2002-10-15

申请号：US09674428

申请日：2000-11-01

申请人： Dearg S Brown ,  George R Brown

发明人： Dearg S Brown ,  George R Brown

IPC分类号： C07C23556

CPC分类号： C07D295/155 ,  C07C235/56 ,  C07C235/84 ,  C07C237/40 ,  C07C255/57

摘要： The invention concerns amide derivatives of Formula (I) wherein: R1 and R2 include hydroxy, C1-6alkoxy, mercapto, C1-6akylthio, amino and heterocyclyl; m and p are independently 0-3; R3 is halo, cyano or C1-6alkoxy; q is 0-4; and R4 is aryl or cycloalkyl wherein R4 is optionally substituted with up to 3 substituents having any value defined for each R1 group; or a pharmaceutically-acceptable salt or in-vivo-cleavable ester thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

摘要翻译： 本发明涉及式（I）的酰胺衍生物，其中：R 1和R 2包括羟基，C 1-6烷氧基，巯基，C 1-6烷硫基，氨基和杂环基; m和p独立为0-3; R3是卤素，氰基或C1-6烷氧基; q为0-4; 并且R 4是芳基或环烷基，其中R 4任选被至多3个具有对每个R 1基定义的任何值的取代基取代; 或其药学上可接受的盐或体内可裂解的酯; 其制备方法，含有它们的药物组合物及其用于治疗由细胞因子介导的疾病或医学病症的用途。

公开(公告)号：US5463011A

公开(公告)日：1995-10-31

申请号：US365761

申请日：1994-12-29

申请人： George R. Brown ,  Richard E. Shute

发明人： George R. Brown ,  Richard E. Shute

IPC分类号： A01N43/40 ,  A61K31/44 ,  C07C275/54 ,  C07D211/26 ,  C08G18/00

CPC分类号： C07C275/54 ,  C07D211/26

摘要： The invention concerns allophanic acid derivatives of formula IR.sup.1 --N(R.sup.2)CO--N(R.sup.3)CO--X.sup.1 --Q--X.sup.2 --GIand pharmaceutically acceptable metabolically labile esters or amides thereof, and pharmaceutically acceptable salts thereof, in which R.sup.1, R.sup.2, R.sup.3, X.sup.1, Q, X.sup.2 and G have the meanings given in the specification. The invention also concerns processes for the preparation of the allophanic acid derivatives of formula I, pharmaceutical compositions containing them and their use as inhibitors of the binding of fibrinogen to glycoprotein IIb/IIIa.

摘要翻译： 本发明涉及式I的吡咯烷酸衍生物R1-N（R2）CO-N（R3）CO-X1-Q-X2-GI及其药学上可接受的代谢不稳定酯或酰胺及其药学上可接受的盐，其中R1， R2，R3，X1，Q，X2和G具有说明书中给出的含义。 本发明还涉及制备式I的脲基甲酸衍生物的方法，含有它们的药物组合物及其作为纤维蛋白原与糖蛋白IIb / IIIa结合的抑制剂的用途。

公开(公告)号：US5366724A

公开(公告)日：1994-11-22

申请号：US652004

申请日：1991-02-07

申请人： Leon E. St. Pierre ,  George R. Brown ,  Gaoming Wu

发明人： Leon E. St. Pierre ,  George R. Brown ,  Gaoming Wu

IPC分类号： A61K31/785 ,  A61K31/74

CPC分类号： A61K31/785

摘要： The invention is concerned with novel ingestible polymeric amines in linear or branched form of the formula: ##STR1## and their pharmaceutically acceptable salts of the formulae: ##STR2## wherein P represents a hydrophilic, cross-linked and digestable polymer backbone; R is a hydrogen atom or a lower alkyl radical; X.sup.- is a pharmaceutically acceptable anion; m is an integer varying from 1 to 10 inclusive; and n, o and p are, independently, integers varying from 2 to 12 inclusive. The polymeric amines of the invention are highly efficient adsorbents for bile acids and salts and can thus be used for reducing hypercholesterolemia in affected humans.

摘要翻译： 本发明涉及以下结构式的直链或支链形式的新颖的可摄取聚合胺：其具有下式的其药学上可接受的盐：其中P代表亲水的，交联和可消化的聚合物主链; R是氢原子或低级烷基; X-是药学上可接受的阴离子; m为1〜10的整数， 并且n，o和p独立地为从2到12的整数。 本发明的聚合胺是胆汁酸和盐的高效吸附剂，因此可用于降低受影响人体的高胆固醇血症。