公开(公告)号：US5427777A

公开(公告)日：1995-06-27

申请号：US856184

申请日：1992-03-23

申请人： Leon E. St. Pierre ,  George R. Brown ,  Zhanjie Tan ,  Sophie-Dorothee Clas

发明人： Leon E. St. Pierre ,  George R. Brown ,  Zhanjie Tan ,  Sophie-Dorothee Clas

IPC分类号： A61K31/80 ,  A61K31/74

CPC分类号： A61K31/80

摘要： Novel ingestible polymeric phosphonium salts have the formula: ##STR1## wherein P' represents a cross-linked and non-digestible polymer backbone; R is a lower alkyl radical; X.sup.- is a pharmaceutically acceptable anion; n, n.sub.1 and n.sub.2 are, independently, integers varying from 0 to 6 inclusive, with the proviso that when m.sub.1 .gtoreq.1, n.sub.2 .gtoreq.1; and o.sub.1, o.sub.2, p.sub.1 p.sub.2, q.sub.1 and q.sub.2 are, independently, integers varying from 1 to 6 inclusive. The polymeric phosphonium salts of the invention are highly efficient sorbents for bile acids and salts and can thus be used for reducing hypercholesterolemia in affected humans.

摘要翻译： 新颖的可摄取聚合鏻盐具有下式：P'[（CH 2）n1P +（R）2] m1 [（CH2）n2P +（R）2] m2R。（m1 + m2）X-（Ia）P' （Ib）或P'（CH 2）n（Ic）其中P'表示交联和不消化的聚合物主链; R是低级烷基; X-是药学上可接受的阴离子; n，n1和n2独立地为0至6的整数，包括1和1，条件是当m1> = 1时，n2> / = 1; 而o1，o2，p1，p2，q1和q2独立地为从1到6的整数。 本发明的聚合鏻盐是胆汁酸和盐的高效吸附剂，因此可用于降低受影响人体中的高胆固醇血症。

公开(公告)号：US5374422A

公开(公告)日：1994-12-20

申请号：US674150

申请日：1991-03-25

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 ,  C08F112/08

CPC分类号： A61K31/785

摘要： The invention is concerned with novel ingestible cross-linked homopolymers having functional groups consisting of linear or branched amines, of the formula: ##STR1## and their pharmaceutically acceptable salts of the formulae: ##STR2## wherein P(or POLYMER .parallel.-) represents a hydrophobic, cross-linked and non-digestible homopolymer 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 6 inclusive; and n, o and p are, independently, integers varying from 2 to 12 inclusive. The amine functionalized and cross-linked homopolymers 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： 本发明涉及具有下列通式的直链或支链胺官能团的新型可摄取的交联均聚物：式中：P [NR（CH 2）n] m N（R）2或（Ia） 式（I）其中P（或聚合物平行 - - ）代表的式（I）的可接受的盐：P [N +（R）2（CH 2）n] m N +（R） 疏水，交联和不消化的均聚物骨架; R是氢原子或低级烷基; X-是药学上可接受的阴离子; m为1〜6的整数， 并且n，o和p独立地为从2到12的整数。 本发明的胺官能化和交联的均聚物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。

公开(公告)号：US5114709A

公开(公告)日：1992-05-19

申请号：US713875

申请日：1991-06-12

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

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

IPC分类号： A61K31/785 ,  A61K31/80

CPC分类号： A61K31/80 ,  A61K31/785 ,  Y10S514/892 ,  Y10S514/911

摘要： The invention is concerned with a metal ion coordinated polyamine resin in which a non-toxic, pharmaceutically acceptable chelating metal ion is coordinated with a cross-linked and non-digestible polymeric amine selected from the group consisting of: (a) polyamine resins with a hydrophilic backbone, of the formula: ##STR1## wherein P represents a hydrophilic, cross-linked and non-digestible homopolymer backbone, m is an integer varying from 1 to 10 inclusive, and n, o and p are, independently, integers varying from 2 to 12 inclusive; (b) polyamine resins with a hydrophobic backbone, of the formula:P'--[NH(CH.sub.2).sub.n ].sub.m NH.sub.2 (II)wherein P' represents a hydrophobic, cross-linked and non-digestible homopolymer backbone, m is an integer varying from 0 to 6 inclusive and n is an integer varying from 2 to 12 inclusive; and (c) cross-linked copolymers of a polyethylenepolyamine containing from 2 to 6 ethylene units and epichlorohydrin. The metal ion coordinated polyamine resins of the invention are highly efficient sorbents for bile acids and salts and can thus be used for reducing hypercholesterolemia in affected humans.

摘要翻译： 本发明涉及金属离子配位聚胺树脂，其中无毒的药学上可接受的螯合金属离子与交联和不可消化的聚合胺配位，所述交联和不可消化的聚合胺选自：（a）多胺树脂与 亲水性骨架，其具有下式：其中P表示亲水性，交联和不消化的均聚物主链，m是从1到10的整数，包括端值在内，n，o和p独立地是从 2到12包含; （b）具有下式的疏水主链的聚胺树脂：P' - [NH（CH 2）n] m NH 2（II）其中P'表示疏水性，交联和不消化的均聚物主链，m是整数 0〜6，n为2〜12的整数， 和（c）含有2-6个乙烯单元的聚亚乙基多胺和表氯醇的交联共聚物。 本发明的金属离子配位聚胺树脂是胆汁酸和盐的高效吸附剂，因此可用于降低受影响人体中的高胆固醇血症。

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。

公开(公告)号：US5236701A

公开(公告)日：1993-08-17

申请号：US381988

申请日：1989-07-19

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

CPC分类号： A61K31/785

摘要： The invention is concerned with novel ingestible cross-linked homopolymers having functional groups consisting of linear or branched amines, of the formula: ##STR1## and their pharmaceutically acceptable salts of the formulae: ##STR2## wherein P represents a hydrophilic, cross-linked and non-digestible homopolymer 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 amine functionalized and cross-linked homopolymers 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： 本发明涉及具有下列通式的直链或支链胺官能团的新颖可摄取的交联均聚物：其[P（（CH 2）n NRR）m R（Ia）或者（Ib））及其药学上可接受的盐 式：P [（CH2）nN +（R）2] mR.mX-（Ic）和（IMA）其中P表示亲水的，交联和不消化的均聚物主链; 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。 本发明的胺官能化和交联的均聚物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。

公开(公告)号：US4908380A

公开(公告)日：1990-03-13

申请号：US118226

申请日：1987-11-03

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 ,  A61K31/415 ,  A61K31/44 ,  A61K45/06 ,  A61P7/02 ,  A61P11/00 ,  A61P29/00 ,  A61P43/00 ,  C07D319/06

CPC分类号： A61K31/335 ,  A61K31/415 ,  A61K31/44

摘要： The invention concerns novel pharmaceutical compositions containing a 4(Z)-6-(2,4-diphenyl-1,3-dioxan-5-yl)-alkenoic acid which antagonizes one or more of the actions of thromboxane A.sub.2, together with a compound which inhibits the synthesis of thromboxane A.sub.2. The compositios are useful as medicines in treating a variety of diseases or medical conditions in which thromboxane A.sub.2 and/or other prostanoid contractile substances are involved.

摘要翻译： 本发明涉及含有4（Z）-6-（2,4-二苯基-1,3-二恶烷-5-基） - 烯酸的新型药物组合物，其拮抗血栓素A2的一种或多种作用，以及 抑制血栓素A2合成的化合物。 组合物可用作治疗涉及血栓素A2和/或其他前列腺素类收缩物质的各种疾病或医学病症的药物。

公开(公告)号：US4831046A

公开(公告)日：1989-05-16

申请号：US861334

申请日：1986-05-09

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

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

IPC分类号： C07D401/06 ,  A61K31/41 ,  A61P7/02 ,  A61P9/08 ,  A61P11/08 ,  A61P43/00 ,  C07D319/00 ,  C07D319/06 ,  C07D405/06 ,  C12N9/99

CPC分类号： C07D405/06 ,  C07D319/06

摘要： The invention describes various novel tetrazole derivatives of the formula I in which R.sup.1 and R.sup.2 are independently hydrogen, trifluoromethyl or (1-6C)alkyl (but R.sup.1 and R.sup.2 is not greater than 6 carbon atoms), or R.sup.1 is optionally substituted phenyl and R.sup.2 is hydrogen, Y is vinylene, n is 1 or 2 and m is 1, 2 or 3, or a pharmaceutically acceptable salt thereof, for use in conjunction with their pharmaceutical compositions in the treatment of various pulmonary and/or vascular disorders. Also described are various processes and intermediates for the manufacture of the novel compounds.

摘要翻译： 本发明描述了式I的各种新型四唑衍生物，其中R 1和R 2独立地为氢，三氟甲基或（1-6C）烷基（但R 1和R 2不大于6个碳原子），或R 1为任选取代的苯基和R 2 是氢，Y是亚乙烯基，n是1或2，m是1,2或3，或其药学上可接受的盐，用于与其药物组合物联合用于治疗各种肺和/或血管疾病。 还描述了用于制备新化合物的各种方法和中间体。

公开(公告)号：US5612352A

公开(公告)日：1997-03-18

申请号：US162093

申请日：1994-07-14

申请人： George R. Brown ,  Peter J. Harrison, deceased ,  Keith B. Mallion

发明人： George R. Brown ,  Peter J. Harrison, deceased ,  Keith B. Mallion

IPC分类号： A61K31/435 ,  A61P9/10 ,  A61P31/04 ,  C07D453/02 ,  A61K31/46 ,  C07D211/22

CPC分类号： C07D453/02

摘要： Biphenylylquinuclidine derivatives of formula I, Q--Ar.sup.1 --Ar.sup.2, in which Q is of formula Ia or Ib, ##STR1## in which R.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, halogeno and hydroxy; or R.sup.1 and R.sup.2 when taken together define an oxo group; Xb is selected from --CH.sub.2 --, .dbd.CH-- and --CH(OH); Xa is selected from --CH.sub.2 --, .dbd.CH--, CO, --O--, and --S(O)n (wherein n=0, 1 or 2); Ar.sup.1 is a phenylene moiety; Ar.sup.2 is phenyl; and wherein one or both of Ar.sup.1 and Ar.sup.2 is optionally unsubstituted or substituted by one or more substituents independently selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, di-alkylamino, N-carbamoyl, N,N-di-alkylcarbamoyl, alkoxycarbonyl, alkylthio, alkylsulphinyl, alkylsulphonyl, halogeno-alkyl, alkanoyl and alkanoylamino; and their pharamaceutically acceptable salts are inhibitors of squalene synthase and hence useful in treating diseases and medical conditions in which a lowering of cholesterol is desirable. The use of these derivatives in medicine is disclosed tohether with novel compounds, processes for their preparation and pharmaceutical composition containing them.

摘要翻译： PCT No.PCT / GB93 / 00754 Sec。 371日期：1994年7月14日 102（e）日期1994年7月14日PCT提交1993年4月8日PCT公布。 公开号WO93 / 21089 日期：1993年10月28日式I的联苯亚基奎宁环衍生物Q-Ar1-Ar2，其中Q为式Ia或Ib，独立地选自氢，烷基，卤代和羟基; 或者R 1和R 2一起定义氧基; Xb选自-CH 2 - ，= CH-和-CH（OH）; Xa选自-CH 2 - ，= CH-，CO，-O-和-S（O）n（其中n = 0,1或2）; Ar1是亚苯基; Ar2是苯基; 并且其中Ar 1和Ar 2之一或两者任选未被取代或被一个或多个独立地选自卤素，羟基，氨基，硝基，氰基，羧基，氨基甲酰基，烷基，烯基，炔基，烷氧基，烷基氨基，二烷基氨基， N-氨基甲酰基，N，N-二 - 烷基氨基甲酰基，烷氧基羰基，烷硫基，烷基亚磺酰基，烷基磺酰基，卤代 - 烷基，烷酰基和烷酰基氨基; 其药物上可接受的盐是角鲨烯合酶的抑制剂，因此可用于治疗胆固醇降低的疾病和医学病症。 这些衍生物在医药中的应用与新化合物，其制备方法和含有它们的药物组合物有关。

公开(公告)号：US5576334A

公开(公告)日：1996-11-19

申请号：US266462

申请日：1994-06-27

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

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

IPC分类号： A61K31/155 ,  A61K31/16 ,  A61K31/17 ,  A61K31/19 ,  A61K31/22 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/445 ,  A61K31/4465 ,  A61P7/02 ,  C07C275/42 ,  C07C275/54 ,  C07C279/18 ,  C07C311/01 ,  C07C311/06 ,  C07D211/22 ,  C07D211/34 ,  C07D211/46 ,  C07D211/62 ,  C07D213/60 ,  C07D295/15 ,  C07D295/215 ,  A61K31/235 ,  C07D211/92 ,  C07D225/00

CPC分类号： C07D295/215 ,  C07C275/54 ,  C07C279/18 ,  C07C311/06 ,  C07D211/22 ,  C07D211/46 ,  C07D295/15

摘要： The invention concerns chemical compounds of formula IR.sup.1 --CON(R.sup.2)--CON(R.sup.3)--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 concerns processes for the preparation of the chemical compounds 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IR1-CON（R2）-CON（R3）-X1-Q-X2-GI和其药学上可接受的代谢不稳定的酯或其酰胺及其药学上可接受的盐的化合物，其中R1，R2，R3，X1 Q，X2和G具有说明书中给出的含义。 本发明涉及制备式I化合物的方法，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：US5494922A

公开(公告)日：1996-02-27

申请号：US462024

申请日：1995-06-05

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

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。