公开(公告)号：US07378424B2

公开(公告)日：2008-05-27

申请号：US10786400

申请日：2004-02-24

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： A61K31/513 ,  A61K31/517 ,  C07D487/14 ,  C07D239/70

CPC分类号： C07D471/04

摘要： The invention provides compounds or salts thereof of the general formula (I): wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2, 3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one).

公开(公告)号：US06794391B2

公开(公告)日：2004-09-21

申请号：US09964260

申请日：2001-09-26

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： A61K31505

CPC分类号： C07D471/04

摘要： The invention provides compounds or salts thereof of the general formula (I): wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2,3,6,7-tetrahydro-4-H-pyrimido[6,1-a]isoquinolin-4-one).

摘要翻译： 本发明提供了通式（I）的化合物或其盐：其中R 1和R 2各自独立地表示C 1-6烷基或C 2-7酰基; X表示OCH 2或基团CR 3 R 4; 其中R 3或R 4各自独立地表示氢原子或C 1-3烷基; R 5表示氢原子或C 1-3烷基，C 2-3烯基或C 2-3炔基; R 6表示氢原子或C 1-6烷基，C 2-6烯基，C 2-6炔基，氨基，C 1-6烷基氨基，二（C 1-6）烷基氨基或C 2-7酰氨基; R 7和R 8中的每一个独立地表示氢或卤素原子或羟基，三氟甲基，C 1-6烷基，C 2-6烯基，C 2-6炔基，C 2-7酰基，C 1-6烷硫基，C 1 -6烷氧基，C3-6环烷基; 并且R 9表示氢或卤素原子或羟基，三氟甲基，C 1-6烷基，C 2-6烯基，C 2-6炔基，C 2-7酰基，C 1-6烷硫基，C 1-6烷氧基或C 3-6 环烷基。 其化合物或其盐可用于治疗呼吸系统疾病如哮喘。 本发明化合物的作用时间长于已知的化合物叶绿素（9,10-二甲氧基-3甲基-2-新三甲基-2,3,6,7-四氢-4H-嘧啶并[6,1-a ]异喹啉-4-酮）。

公开(公告)号：US20120302533A1

公开(公告)日：2012-11-29

申请号：US13568754

申请日：2012-08-07

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： A61K31/519 ,  A61P11/08 ,  A61P29/00 ,  A61K31/56

CPC分类号： C07D471/04

摘要： The present invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their application as inhibitors of phosphodiesterase (PDE) isoenzymes. More particularly the invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their use in medicine for example as bronchodilators with anti-inflammatory properties.

摘要翻译： 本发明涉及嘧啶并[6,1-a]异喹啉-4-酮的衍生物及其作为磷酸二酯酶（PDE）同功酶抑制剂的应用。 更具体地，本发明涉及嘧啶并[6,1-a]异喹啉-4-酮的衍生物及其在医学中的用途，例如具有抗炎性质的支气管扩张剂。

公开(公告)号：US08242127B2

公开(公告)日：2012-08-14

申请号：US12150232

申请日：2008-04-24

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： A01N43/54 ,  A61K31/505

CPC分类号： C07D471/04

摘要： The present invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their application as inhibitors of phosphodiesterase (PDE) isoenzymes. More particularly the invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their use in medicine for example as bronchodilators with anti-inflammatory properties.

摘要翻译： 本发明涉及嘧啶并[6,1-a]异喹啉-4-酮的衍生物及其作为磷酸二酯酶（PDE）同功酶抑制剂的应用。 更具体地，本发明涉及嘧啶并[6,1-a]异喹啉-4-酮的衍生物及其在医学中的用途，例如具有抗炎性质的支气管扩张剂。

公开(公告)号：US20080206163A1

公开(公告)日：2008-08-28

申请号：US12150232

申请日：2008-04-24

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： A61K9/12 ,  C07D471/04 ,  A61K31/519

CPC分类号： C07D471/04

摘要： Compounds of general formula (I) wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy or C3-6 cycloalkyl group; X represents OCH2 or a group CR3R4, wherein each of R3 and R4 independently represents a hydrogen atom or a C1-3 alkyl group; each of R10 and R11 independently represents a hydrogen atom, a C1-3 alkyl, C3-6 cycloalkyl or phenyl group; y represents an oxygen atom or a group CHNO2, NCN, NH or NNO2, n is an integer from 2 to 4; or a salt thereof; are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3-methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one) and do not have trequinsin's very bitter taste.

公开(公告)号：US07105663B2

公开(公告)日：2006-09-12

申请号：US10786650

申请日：2004-02-24

申请人： Alexander William Oxford ,  David Jack

发明人： Alexander William Oxford ,  David Jack

IPC分类号： C07D239/00 ,  C07D487/00 ,  C07D471/00 ,  C07D498/00 ,  C07D453/00 ,  C07D455/00

CPC分类号： C07D471/04

摘要： Compounds of general formula (I) wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6)alkylamino or C2-7 acylamino group, each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy or C3-6 cycloalkyl group; X represents OCH2 or a group CR3R4, wherein each of R3 and R4 independently represents a hydrogen atom or a C1-3 alkyl group; each of R10 and R11 independently represents a hydrogen atom, a C1-3 alkyl, C3-6 cycloalkyl or phenyl group; y represents an oxygen atom or a group CHNO2, NCN, NH or NNO2, n is an integer from 2 to 4; or a salt thereof; are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3-methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]-isoquinolin-4-one) and do not have trequinsin's very bitter taste.

公开(公告)号：US06175014B1

公开(公告)日：2001-01-16

申请号：US08137228

申请日：1993-10-18

申请人： Ian Harold Coates ,  Alexander William Oxford ,  Peter Charles North ,  Thomas Miller ,  Anthony David Baxter ,  Kevin Ian Hammond

发明人： Ian Harold Coates ,  Alexander William Oxford ,  Peter Charles North ,  Thomas Miller ,  Anthony David Baxter ,  Kevin Ian Hammond

IPC分类号： C07D23361

CPC分类号： C07D471/04 ,  C07D487/04 ,  Y02P20/55

摘要： The invention provides a process for the preparation of a compound of general formula (I): wherein Im represents an imidazolyl group of the formula: and R1 represents a hydrogen atom or a group as herein defined including —CO2R5, —COR5, —CONR5R6 or —SO2R5 wherein R5 and R6, which may be the same or different, are as herein defined with the proviso that R5 does not represent a hydrogen atom when R1 represents a group —CO2R5 or —SO2R5; one of the groups represented by R2, R3 and R4 is a hydrogen atom or a C1-6alkyl, C3-7cycloaklyl, C3-6alkenyl, phenyl or phenyl C1-3alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C1-6alkyl group; and n represents 2 or 3; which comprises reacting a compound of formula (II) or a protected derivative thereof, with a compound of formula (III): HOCH2-Im  (III) or a salt thereof in the presence of an acid at an elevated temperature, followed where necessary by removal of any protecting groups.

摘要翻译： 本发明提供了制备通式（I）化合物的方法：其中Im表示下式的咪唑基：R 1表示氢原子或本文定义的基团，包括-CO 2 R 5，-COR 5，-CONR 5 R 6或 -SO 2 R 5，其中R 5和R 6可以相同或不同，如本文所定义，条件是当R 1表示-CO 2 R 5或-SO 2 R 5基团时，R 5不表示氢原子; 由R 2，R 3和R 4表示的基团之一是氢原子或C 1-6烷基，C 3-7环烯基，C 3-6烯基，苯基或苯基C 1-3烷基，其它两个基团可以相同 或不同的，表示氢原子或C 1-6烷基; n表示2或3; 其包括在酸的存在下在升高的温度下使式（II）化合物或其保护的衍生物与式（III）的化合物或其盐反应，然后在需要时通过除去任何保护基团。

公开(公告)号：US3984534A

公开(公告)日：1976-10-05

申请号：US310463

申请日：1972-11-29

申请人： Mervyn Evan Peel ,  Alexander William Oxford

发明人： Mervyn Evan Peel ,  Alexander William Oxford

IPC分类号： C07D257/04 ,  A61K31/41

CPC分类号： C07D257/04

摘要： Compounds of the general formula: ##SPC1##Wherein X represents a 5-[1H]-tetrazolyl group, R.sub.1 represents a hydrogen atom, a halogen atom, a hydroxyl group or a group --OR.sub.2, (in which R.sub.2 may be a lower alkyl or alkenyl group containing from 1 to 6 carbon atoms optionally substituted by one or more hydroxy groups, an aryl group, an aryloxy group, an alkoxy group or a dialkylamino group) or a group --NR.sub.3 R.sub.4, in which R.sub.3 and R.sub.4 which may be the same or different, represent a hydrogen atom, a lower alkyl group containing from 1 to 6 carbon atoms, optionally substituted by a hydroxy group, or R.sub.3 and R.sub.4 together with the nitrogen atom may form a ring which may optionally be substituted with another heteroatom and pharmaceutically acceptable salts thereof.These compounds have useful immunological activity and inhibit the release of spasmogen mediators.

摘要翻译： 通式的化合物：

公开(公告)号：US07417068B2

公开(公告)日：2008-08-26

申请号：US10964831

申请日：2004-10-15

申请人： David Edward Clark ,  Neil Victor Harris ,  Garry Fenton ,  George Hynd ,  Keith Alfred James Stuttle ,  Jonathan Mark Sutton ,  Alexander William Oxford ,  Richard Jon Davis ,  Robert Alexander Coleman ,  Kenneth Lyle Clark

发明人： David Edward Clark ,  Neil Victor Harris ,  Garry Fenton ,  George Hynd ,  Keith Alfred James Stuttle ,  Jonathan Mark Sutton ,  Alexander William Oxford ,  Richard Jon Davis ,  Robert Alexander Coleman ,  Kenneth Lyle Clark

IPC分类号： A61K31/341 ,  C07D307/34

CPC分类号： C07D307/68

摘要： A compound of formula (I): or a salt, solvate and chemically protected form thereof, wherein one of R2 and R5 is: (i) H or an optionally substituted C1-4 alkyl group; or (ii)an optionally substituted C5-7 aryl; and the other of R2 and R5 is the other group; m and n can be 0 or 1, and m+n=1 or 2 RN is H or optionally substituted C1-4 alkyl R3 is either: (i) carboxy; (ii) a group of formula (II): (iii) a group of formula (III): wherein R is optionally substituted C1-7 alkyl, C5-20 aryl, or NRN3RN4, where RN3 and RN4 are independently selected from optionally substituted C1-4 alkyl; or (iv) tetrazol-5-yl.

摘要翻译： 式（I）化合物或其盐，溶剂合物和化学保护形式，其中R 2和R 5中的一个为：（i）H或任选地 取代的C 1-4烷基; 或（ii）任选取代的C 5-7芳基; R 2和R 5中的另一个是另一个基团; m和n可以是0或1，m + n = 1或2 R N是H或任选取代的C 1-4烷基R 3， SUP>是：（i）羧基; （ii）式（II）的基团：（iii）式（III）的基团：其中R是任选取代的C 1-7烷基，C 5〜20 其中R 3，N 3和R 4各自独立地选自任选取代的C 1 -C 6芳基或NR N 3 N， 1-4个C 1-4烷基; 或（iv）四唑-5-基。

公开(公告)号：US07326732B2

公开(公告)日：2008-02-05

申请号：US11055724

申请日：2005-02-11

申请人： Alexander William Oxford ,  Richard Jon Davis ,  Robert Alexander Coleman ,  Kenneth Lyle Clark ,  David Edward Clark ,  Neil Victor Harris ,  Garry Fenton ,  George Hynd ,  Keith Alfred James Stuttle ,  Jonathan Mark Sutton ,  Mark Richard Ashton ,  Edward Andrew Boyd ,  Shirley Ann Brunton

发明人： Alexander William Oxford ,  Richard Jon Davis ,  Robert Alexander Coleman ,  Kenneth Lyle Clark ,  David Edward Clark ,  Neil Victor Harris ,  Garry Fenton ,  George Hynd ,  Keith Alfred James Stuttle ,  Jonathan Mark Sutton ,  Mark Richard Ashton ,  Edward Andrew Boyd ,  Shirley Ann Brunton

IPC分类号： C07C233/65 ,  C07D257/04 ,  A61K31/41 ,  A61K31/164

CPC分类号： C07D213/81 ,  C07C233/75 ,  C07C233/81 ,  C07C235/84 ,  C07D233/90 ,  C07D257/04 ,  C07D277/24 ,  C07D277/26 ,  C07D277/56 ,  C07D307/46 ,  C07D307/68 ,  C07D307/91 ,  C07D333/38 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/12

摘要： A compound of formula (I): or a salt, solvate and chemically protected form thereof, wherein: R5 is an optionally substituted C5-20 aryl or C4-20 alkyl group; A is selected from the group consisting of: wherein X and Y are selected from the group consisting of: O and CR3; S and CR3; NH and CR3; NH and N; O and N; S and N; N and S; and N and O, and where the dotted lines indicate a double bond in the appropriate location, and where Q is either N or CH; R3 is selected from H, F, Cl and optionally substituted C1-4 alkyl, C1-4 alkoxy, C5-7 aryl and C5-7 aryl-C1-4 alkyl groups; R4 is selected from H, F, Cl and optionally substituted C1-4 alkyl, C1-4 alkoxy, C5-7 aryl and C5-7 aryl-C1-4 alkyl groups; R6 is selected from H, F, Cl and optionally substituted C1-4 alkyl, C1-4 alkoxy, C5-7 aryl and C5-7 aryl-C1-4 alkyl groups; D is selected from: B is selected from the group consisting of: where RN′ is selected from H and C1-4 alkyl; where one of RP3 and RP4 is —Cm alkylene-R2 and the other of RP3 and RP4 is H, m and n can be 0 or 1, and m+n=1 or 2; and additionally when RP3 is —Cm alkylene-R2, m can also be 2 or 3, and m+n=1, 2, 3 or 4, and when R2 is tetrazol-5-yl, m+n may be 0; or where one of RP3 and RP4 is —O—CH2—R2, and the other of RP3 and RP4 is H, n is 0; RN is H or optionally substituted C1-4 alkyl; R2 is either: —CO2H (carboxy); —CONH2; —CH2—OH; or tetrazol-5-yl.