公开(公告)号：WO2004024728A3

公开(公告)日：2004-10-21

申请号：PCT/EP0311814

申请日：2003-09-12

Applicant: GLAXO GROUP LTD ,  ALLEN DAVID GEORGE ,  COE DIANE MARY ,  COOK CAROLINE MARY ,  DOWLE MICHAEL DENNIS ,  EDLIN CHRISTOPHER DAVID ,  HAMBLIN JULIE NICOLE ,  JOHNSON MARTIN REDPATH ,  JONES PAUL SPENCER ,  KNOWLES RICHARD GRAHAM ,  LINDVALL MIKA KRISTIAN ,  MITCHELL CHARLOTTE JANE ,  REDGRAVE ALISON JUDITH ,  TRIVEDI NAIMISHA ,  WARD PETER

Inventor： ALLEN DAVID GEORGE ,  COE DIANE MARY ,  COOK CAROLINE MARY ,  DOWLE MICHAEL DENNIS ,  EDLIN CHRISTOPHER DAVID ,  HAMBLIN JULIE NICOLE ,  JOHNSON MARTIN REDPATH ,  JONES PAUL SPENCER ,  KNOWLES RICHARD GRAHAM ,  LINDVALL MIKA KRISTIAN ,  MITCHELL CHARLOTTE JANE ,  REDGRAVE ALISON JUDITH ,  TRIVEDI NAIMISHA ,  WARD PETER

IPC: A61K31/437 ,  A61P11/00 ,  A61P29/00 ,  C07D221/00 ,  C07D231/00 ,  C07D471/04

CPC classification number: C07D471/04

Abstract: The invention relates to a compound of formula (I) or a salt thereof: wherein:R1 is C1-4alkyl, C1-3fluoroalkyl, -CH2CH2OH or -CH2CH2CO2C1-2alkyl;R2 is a hydrogen atom (H), methyl or C1fluoroalkyl;R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee): ; and wherein X is NR4R5 or OR5a. The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.

Abstract translation: 本发明涉及式（I）化合物或其盐：其中：R 1为C 1-4烷基，C 1-3氟烷基，-CH 2 CH 2 OH或-CH 2 CH 2 CO 2 C 1-2烷基; R 2为氢原子（H），甲基或C 1-3氟烷基; （aa），（bb）或（cc）的任选取代的C 3-8环烷基或任选取代的单不饱和-C 5-7环烯基或任选取代的杂环基; 其中n1和n2独立地为1或2; 并且其中Y是O，S，SO 2或NR 10; 或R3是双环基团（dd）或（ee）： 并且其中X是NR 4 R 5或OR 5 a。 这些化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。 还提供了式（I）化合物或其药学上可接受的盐在制备用于治疗和/或预防哺乳动物例如人的炎症和/或过敏性疾病的药物中的用途， 例如慢性阻塞性肺病（COPD），哮喘或过敏性鼻炎。

公开(公告)号：WO0224623A2

公开(公告)日：2002-03-28

申请号：PCT/GB0104226

申请日：2001-09-21

Applicant: GLAXO GROUP LTD ,  LOOKER BRIAN EDGAR ,  REDGRAVE ALISON JUDITH ,  LUNNISS CHRISTOPHER JAMES ,  REYNOLDS DEREK PETER

Inventor： LOOKER BRIAN EDGAR ,  REDGRAVE ALISON JUDITH ,  LUNNISS CHRISTOPHER JAMES ,  REYNOLDS DEREK PETER

IPC: A61K9/12 ,  A61K47/06 ,  A61K47/32 ,  A61P11/00 ,  C07C51/09 ,  C07C51/367 ,  C07C59/125 ,  C07C59/135 ,  C07C69/708 ,  C07C31/18 ,  C07C31/42 ,  C07C67/333 ,  C07C69/34

CPC classification number: C07C69/708 ,  C07C51/09 ,  C07C59/125 ,  C07C59/135 ,  Y10S514/958

Abstract: There are provided according to the invention compounds of the formula (I) or a salt or solvate thereof, wherein: n represents an integer 1 to 6; N represents an integer 1 to 15; R represents (CO)xC1-9alkyl or (CO)xC1-9fluoroalkyl, which fluoroalkyl moiety contains at least 1 fluorine atom and not more than 3 consecutive perfluorocarbon atoms wherein x represents 0 or 1; and R and R independently represent C1-3alkyl or hydrogen. There are also provided pharmaceutical aerosol formulations employing said compounds as suspension stabilising agents.

Abstract translation: 根据本发明提供式（I）化合物或其盐或溶剂化物，其中：n表示1至6的整数; N表示1〜15的整数， R 1表示（CO）x C 1-9烷基或（CO）x C 1-9氟烷基，该氟烷基部分含有至少1个氟原子和不多于3个连续的全氟化碳原子，其中x表示0或1; R 2和R 3独立地表示C 1-3烷基或氢。 还提供了使用所述化合物作为悬浮稳定剂的药物气溶胶制剂。

公开(公告)号：WO1998028319A1

公开(公告)日：1998-07-02

申请号：PCT/EP1997007197

申请日：1997-12-22

Applicant: GLAXO GROUP LIMITED ,  COX, Brian ,  KEELING, Suzanne, Elaine ,  ALLEN, David, George ,  REDGRAVE, Alison, Judith ,  BARKER, Michael, David ,  HOBBS, Heather ,  ROPER, Thomas, Davis, IV ,  GEDEN, Joanna, Victoria

Inventor： GLAXO GROUP LIMITED

IPC: C07H19/167

CPC classification number: C07D473/00 ,  C07H19/16 ,  Y10S514/826 ,  Y10S514/851 ,  Y10S514/885 ,  Y10S514/921 ,  Y10S514/925

Abstract: There are provided according to the invention novel compounds of formula (I) wherein R , R and R are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

Abstract translation: 根据本发明提供了新的式（I）化合物，其中R 1，R 2和R 3如说明书中所述，其制备方法，含有它们的制剂及其在治疗中的用途 治疗炎症性疾病。

公开(公告)号：WO2005090354A1

公开(公告)日：2005-09-29

申请号：PCT/GB2005/000987

申请日：2005-03-15

Applicant: GLAXO GROUP LIMITED ,  COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  TRIVEDI, Naimisha ,  REDGRAVE, Alison, Judith

Inventor： COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  TRIVEDI, Naimisha ,  REDGRAVE, Alison, Judith

IPC: C07D487/04

CPC classification number: C07D471/04

Abstract: The invention provides a compound of formula (I) or a salt thereof: formula (I) wherein: R 1 is C 1-3 alkyl, C 1-3 fluoroalkyl, or -CH 2 CH 2 OH; R 2 is a hydrogen atom (H), methyl or C 1 fluoroalkyl; R 3 is of sub-formula (aa) or (bb): formulae (aa), (bb) wherein Y is NCONH 2 and n 1 is 0 or 1; R 4 is H; and R 5 is a group of the sub-formula (x), (y), (y1) or (z): formulae (x), (y), (y1), (z). The invention also relates to the use of these compounds or salts in therapy as inhibitors of phosphodiesterase type IV (PDE4). For example, it relates to their use in the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis, psoriasis or atopic dermatitis in a mammal such as a human.

Abstract translation: 本发明提供式（I）化合物或其盐：式（I）其中：R 1为C 1-3烷基，C 1-3氟烷基或-CH 2 CH 2 OH; R 2是氢原子（H），甲基或C 1-6烷基; （aa）或（bb）：式（aa），（bb）其中Y为NCONH2且n为0或1; R 4是H; 并且R 5是式（x），（y），（y1）或（z）的子集：式（x），（y），（y1），（z）。 本发明还涉及这些化合物或盐在治疗中作为IV型磷酸二酯酶抑制剂（PDE4）的用途。 例如，它涉及其用于治疗和/或预防哺乳动物例如慢性阻塞性肺疾病（COPD），哮喘，类风湿性关节炎，过敏性鼻炎，牛皮癣或特应性皮炎的炎性和/或过敏性疾病 人类。

公开(公告)号：WO2005058892A1

公开(公告)日：2005-06-30

申请号：PCT/EP2004/014490

申请日：2004-12-17

Applicant: GLAXO GROUP LIMITED ,  ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith ,  ROBINSON, John Edward ,  TRIVEDI, Naimisha

Inventor： ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith ,  ROBINSON, John Edward ,  TRIVEDI, Naimisha

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The invention provides a compound of formula (I) or a salt thereof, wherein Ar has the sub-formula (x) or (z) and wherein R 3 is optionally substituted C 3-8 cycloalkyl, optionally substituted C 5-7 cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc), or a bicyclic group (ee); and wherein R 4 is H, C 1-3 alkyl, C 1-2 fluoroalkyl, cyclopropyl, CH 2 OR 4a , CH(Me)OR 4a , or CH2CH2OR 4a ; and R 5 is inter alia H, C 1-8 alkyl, C 1-8 fluoroalkyl, C 3-8 cycloalkyl, certain substituted alkyl groups, -(CH2) n 13 - Het, or optionally substituted phenyl or CH 2 -Ph; or R 4 and R 5 taken together are -(CH 2 )p 1 - or (CH 2 )p3 X 5 (CH2)p 4 - ; provided that at least one of R 4 and R 5 is not a hydrogen atom (H). The invention also provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis or atopic dermatitis.

Abstract translation: 本发明提供式（I）化合物或其盐，其中Ar具有亚式（x）或（z），其中R 3是任选取代的C 3-8环烷基，任选取代的C 5-7环烯基， 任选取代的杂环基（aa），（bb）或（cc）或双环基（ee）; 并且其中R 4是H，C 1-3烷基，C 1-2 - 氟烷基，环丙基，CH 2 OH 4a，CH（Me）OR 4a或CH 2 CH 2OR 4a。 和R 5尤其是H，C 1-8烷基，C 1-8氟烷基，C 3-8环烷基，某些取代的烷基， - （CH 2）n 13 - 或任选取代的苯基或CH 2 -Ph; 或R 4和R 5一起是 - （CH 2）p - 或（CH 2）p 3 X 5（CH 2）p 4 - ; 条件是R 4和R 5中的至少一个不是氢原子（H）。 本发明还提供了化合物作为IV型磷酸二酯酶抑制剂（PDE4）和/或用于治疗和/或预防炎性和/或过敏性疾病如慢性阻塞性肺疾病（COPD），哮喘，类风湿性关节炎， 过敏性鼻炎或特应性皮炎。

公开(公告)号：WO2005030725A1

公开(公告)日：2005-04-07

申请号：PCT/GB2004/004106

申请日：2004-09-27

Applicant: GLAXO GROUP LIMITED ,  EDLIN, Christopher ,  ELDRED, Colin, David ,  LUNNISS, Christopher, James ,  REDGRAVE, Alison, Judith ,  ROBINSON, John, Edward ,  WOODROW, Michael

Inventor： EDLIN, Christopher ,  ELDRED, Colin, David ,  LUNNISS, Christopher, James ,  REDGRAVE, Alison, Judith ,  ROBINSON, John, Edward ,  WOODROW, Michael

IPC: C07D215/44

CPC classification number: C04B35/632 ,  C07D215/44 ,  C07D401/12 ,  C07D405/12 ,  C07D411/12 ,  C07D417/12

Abstract: Compounds of formula (I) or pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type IV (PDE4) and are of use in the treatment of inflammatory and/or allergic diseases.

Abstract translation: 式（I）化合物或其药学上可接受的盐是IV型磷酸二酯酶（PDE4）的抑制剂，并且可用于治疗炎性和/或过敏性疾病。

公开(公告)号：WO2004056823A1

公开(公告)日：2004-07-08

申请号：PCT/EP2003/014867

申请日：2003-12-19

Applicant: GLAXO GROUP LIMITED ,  ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  COOPER, Anthony, William, James ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith

Inventor： ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  COOPER, Anthony, William, James ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The invention relates to a compound of formula (I) or a salt thereof: Formula (I) wherein: R 1 is C 1-4 alkyl, C 1-3 fluoroalkyl or -(CH 2 ) 2 OH; R 2 is a hydrogen atom (H), methyl or C 1 fluoroalkyl; R 3a is a hydrogen atom (H) or C 1-3 alkyl; R 3 is optionally substituted branched C 3-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted mono-unsaturated-C 5-7 cycloalkenyl, optionally substituted phenyl, or an optionally substituted heterocyclic group of sub-formula (aa), or (bb) or (cc) in which n 1 and n 2 independently are 1 or 2; and Y is O, S, SO 2 , or NR 4 ; and wherein Het is of sub-formula (i), or (ii), or (iii), or (iv) or (v). The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.

Abstract translation: 本发明涉及式（I）化合物或其盐：式（I）其中：R 1为C 1-4烷基，C 1-3氟烷基或 - （CH 2）2 OH; R 2是氢原子（H），甲基或C 1-6烷基; R 3a是氢原子（H）或C 1-3烷基; R 3为任选取代的支链C 3-6烷基，任选取代的C 3-8环烷基，任选取代的单不饱和C 5-7环烯基，任选取代的苯基或任选取代的亚式（aa）杂环基或（bb） 或（cc），其中n 1和n 2独立地为1或2; Y是O，S，SO 2或NR 4; 并且其中Het为子式（i），或（ii），或（iii），或（iv）或（v）。 这些化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。 还提供了式（I）化合物或其药学上可接受的盐在制备用于治疗和/或预防哺乳动物例如人的炎性和/或过敏性疾病的药物中的用途， 例如慢性阻塞性肺疾病（COPD），哮喘或过敏性鼻炎。

公开(公告)号：WO2004024728A2

公开(公告)日：2004-03-25

申请号：PCT/EP2003/011814

申请日：2003-09-12

Applicant: GLAXO GROUP LIMITED ,  ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  KNOWLES, Richard, Graham ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith ,  TRIVEDI, Naimisha ,  WARD, Peter

Inventor： ALLEN, David, George ,  COE, Diane, Mary ,  COOK, Caroline, Mary ,  DOWLE, Michael, Dennis ,  EDLIN, Christopher, David ,  HAMBLIN, Julie, Nicole ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  KNOWLES, Richard, Graham ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  REDGRAVE, Alison, Judith ,  TRIVEDI, Naimisha ,  WARD, Peter

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The invention relates to a compound of formula (I) or a salt thereof: wherein:R1 is C1-4alkyl, C1-3fluoroalkyl, -CH2CH2OH or -CH2CH2CO2C1-2alkyl;R2 is a hydrogen atom (H), methyl or C1fluoroalkyl;R3 is optionally substituted C3-8cycloalkyl or optionally substituted mono-unsaturated-C5-7cycloalkenyl or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc); in which n1 and n2 independently are 1 or 2; and in which Y is O, S, SO2, or NR10; or R3 is a bicyclic group (dd) or (ee): ; and wherein X is NR4R5 or OR5a. The compounds are phosphodiesterase (PDE) inhibitors, in particular PDE4 inhibitors. Also provided is the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment and/or prophylaxis of an inflammatory and/or allergic disease in a mammal such as a human, for example chronic obstructive pulmonary disease (COPD), asthma, or allergic rhinitis.

Abstract translation: 本发明涉及式（I）化合物或其盐：其中：R 1为C 1-4烷基，C 1-3氟烷基，-CH 2 CH 2 OH或-CH 2 CH 2 CO 2 C 1-2烷基; R 2为氢原子（H），甲基或C 1-6烷基; R 3 任选取代的C 3-8环烷基或任选取代的单不饱和C 5-7环烯基或任选取代的亚式（aa），（bb）或（cc）的杂环基; 其中n1和n2独立地为1或2; 并且其中Y是O，S，SO 2或NR 10; 或R 3是双环基（dd）或（ee）：。 并且其中X为NR4R5或OR5a。 这些化合物是磷酸二酯酶（PDE）抑制剂，特别是PDE4抑制剂。 还提供了式（I）化合物或其药学上可接受的盐在制备用于治疗和/或预防哺乳动物例如人的炎性和/或过敏性疾病的药物中的用途， 例如慢性阻塞性肺疾病（COPD），哮喘或过敏性鼻炎。

公开(公告)号：WO2005030212A1

公开(公告)日：2005-04-07

申请号：PCT/EP2004/010844

申请日：2004-09-23

Applicant: GLAXO GROUP LIMITED ,  EDLIN, Christopher, D ,  ELDRED, Colin, David ,  KEELING, Steven, Philip ,  LUNNISS, Christopher, James ,  REDFERN, Tracy, Jane ,  REDGRAVE, Alison, Judith ,  WOODROW, Michael

Inventor： EDLIN, Christopher, D ,  ELDRED, Colin, David ,  KEELING, Steven, Philip ,  LUNNISS, Christopher, James ,  REDFERN, Tracy, Jane ,  REDGRAVE, Alison, Judith ,  WOODROW, Michael

IPC: A61K31/4706

CPC classification number: C07D215/54 ,  C04B35/632 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14

Abstract: Compounds of formula (I) or pharmaceutically acceptable salts thereof: (I) are inhibitors of phosphodiesterase type IV (PDE4) and are of use in the treatment of inflammatory and/or allergic diseases.

Abstract translation: 式（I）化合物或其药学上可接受的盐：（I）是IV型磷酸二酯酶（PDE4）的抑制剂，可用于治疗炎性和/或过敏性疾病。

公开(公告)号：WO2003035237A2

公开(公告)日：2003-05-01

申请号：PCT/EP2002/011635

申请日：2002-10-17

Applicant: GLAXO GROUP LIMITED ,  LOOKER, Brian, Edgar ,  LUNNISS, Christopher, James ,  REDGRAVE, Alison, Judith

Inventor： LOOKER, Brian, Edgar ,  LUNNISS, Christopher, James ,  REDGRAVE, Alison, Judith

IPC: B01F17/00

CPC classification number: A61K9/008 ,  B01F17/0028 ,  B01F17/0035

Abstract: There are provided according to the invention compounds of formula (I) or salts or solvate thereof, wherein:n and N independently represent an integer 2 to 12;m1 and m2 independently represent an integer 1 to 15; and R1 and R2 independently represent -(CO)xC1-9 alkyl or -(CO)xC1-9 fluoroalkyl, which fluoroalkyl moiety contains at least 1 fluorine atom and not more than 3 consecutive perfluorocarbon atoms wherein x represents 0 or 1. The invention includes uses of said compounds and processes for their preparation.

Abstract translation: 根据本发明提供了式（I）的化合物或其盐或溶剂合物，其中：n和N独立地表示2至12的整数; m 1和m 2独立地表示1至15的整数 ; 并且R 1和R 2独立地表示 - （CO）x C 1-9烷基或 - （CO）x C 1-9氟代烷基，其中氟代烷基部分含有至少1个氟原子和不多于3个连续的全氟化碳原子，其中x代表0或1。 包括所述化合物的用途及其制备方法。