公开(公告)号：WO2012032067A1

公开(公告)日：2012-03-15

申请号：PCT/EP2011/065419

申请日：2011-09-06

Applicant: GLAXO GROUP LIMITED ,  HAMBLIN, Julie Nicole ,  JONES, Paul Spencer ,  KEELING, Suzanne Elaine ,  LE, Joelle ,  MITCHELL, Charlotte Jane ,  PARR, Nigel James ,  WILLACY, Robert David

Inventor： HAMBLIN, Julie Nicole ,  JONES, Paul Spencer ,  KEELING, Suzanne Elaine ,  LE, Joelle ,  MITCHELL, Charlotte Jane ,  PARR, Nigel James ,  WILLACY, Robert David

IPC: C07D413/14 ,  A61K31/422 ,  A61P11/00

CPC classification number: A61K31/5377 ,  C07D413/14

Abstract: The present invention is directed to novel polymorphs and salts of a compound which is an inhibitor of kinase activity.

Abstract translation: 本发明涉及作为激酶活性抑制剂的化合物的新型多晶型物和盐。

公开(公告)号：WO2010018134A1

公开(公告)日：2010-02-18

申请号：PCT/EP2009/060267

申请日：2009-08-07

Applicant: SMITHKLINE BEECHAM CORPORATION ,  BAZIN-LEE, Helene ,  COE, Diane, Mary ,  LAZARIDES, Linos ,  MITCHELL, Charlotte, Jane ,  SMITH, Stephen, Allan ,  TRIVEDI, Naimisha

Inventor： BAZIN-LEE, Helene ,  COE, Diane, Mary ,  LAZARIDES, Linos ,  MITCHELL, Charlotte, Jane ,  SMITH, Stephen, Allan ,  TRIVEDI, Naimisha

IPC: A61K31/522 ,  C07D473/16 ,  C07D473/18 ,  A61P29/00

CPC classification number: C07D473/16 ,  A61K31/522 ,  C07D473/18

Abstract: Compounds of formula (I) wherein R 1 is C 1-6 alkylamino, or C 1-6 alkoxy; R 2 is a group having the structure (II): n is an integer having a value of 1 to 6; Het is a 6-membered saturated heterocycle containing one nitrogen atom wherein Het is attached to the -(CH 2 ) n - moiety at any carbon atom of the heterocycle; R 3 is hydrogen, C 1-8 alkyl, or C 3-7 cycloalkylC 0-6 alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

Abstract translation: 其中R 1为C 1-6烷基氨基或C 1-6烷氧基的式（I）化合物; R2是具有结构（II）的基团：n是1至6的整数; Het是含有一个氮原子的6元饱和杂环，其中Het与杂环的任何碳原子连接至 - （CH 2）n - 部分; R3是氢，C1-8烷基或C3-7环烷基C0-6烷基; 其盐是人类干扰素的诱导剂。 诱导人类干扰素的化合物可用于治疗各种疾病，例如治疗过敏性疾病和其它炎性病症，例如过敏性鼻炎和哮喘，治疗感染性疾病和癌症，并且也可用作疫苗佐剂。

公开(公告)号：WO2007036733A1

公开(公告)日：2007-04-05

申请号：PCT/GB2006/003626

申请日：2006-09-29

Applicant: GLAXO GROUP LIMITED ,  EDLIN, Christopher, David ,  HOLMAN, Stuart ,  JONES, Paul, Spencer ,  KEELING, Suzanne, Elaine ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  TRIVEDI, Naimisha

Inventor： EDLIN, Christopher, David ,  HOLMAN, Stuart ,  JONES, Paul, Spencer ,  KEELING, Suzanne, Elaine ,  LINDVALL, Mika, Kristian ,  MITCHELL, Charlotte, Jane ,  TRIVEDI, Naimisha

IPC: C07D471/04 ,  C07D519/00 ,  A61K31/437 ,  A61P29/00

CPC classification number: C07D471/04

Abstract: The invention provides a compound of formula (I) or a salt thereof: wherein R 2 is H, C 1-3 alkyl, n butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl , CN, or CH 2 OH; R 3 is inter alia optionally substituted C 4-7 cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); R a is H, methyl or ethyl; R b is H or methyl; R 4 is H, methyl, ethyl, n propyl, C(O) Me, or C(O) C1fluoroalkyl; and R 5 is: C(O) (CH2) n Ar, C(O) Het, C(O) C 1 6alkyl, C(O) C1fluoroalkyl, C(O) (CH 2 ) 2 C(O) NR 15b NR 15b , C(O) CH 2 C(O) NR 15b NR 15 b, C(O) NR 15b (CH2)m 1 Ar, C(O) NR 15b Het, C(O) NR 15b C 1-6 alkyl, C(O) NR 5a R 5b , S(O) 2 (CH 2 )m 2 - Ar , S(O) 2 Het, S(O) 2 -C 1 - 6 alkyl, or CH 2 Ar; or R 4 and R 5 taken together are -(CH 2 ) p 1 -, (CH 2 ) 2 X 5 (CH 2 ) 2 , C(O) (CH 2 )p 2 ,-C(O)-N(R 15 ) (CH 2 )p 3 ; or NR 4 R 5 is of sub-formula (y), (y1), (y2) or (y3). 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, psoriasis or atopic dermatitis.

Abstract translation: 本发明提供式（I）化合物或其盐：其中R 2为H，C 1-3烷基，正丁基，C 1-2 - 氟烷基，环丙基， 环丙基，（环丙基）甲基，CN或CH 2 OH; 特别是任选取代的C 4-7环烷基或任选取代的杂环基团（aa），（bb）或（cc）; R a是H，甲基或乙基; R b是H或甲基; R 4是H，甲基，乙基，正丙基，C（O）Me或C（O） R 5是C（O）（CH 2）n Ar Ar，C（O）Het，C（O）C 1-6烷基， C（O）C 1-4烷基，C（O）（CH 2）2 C（O）NR 15b R 15 >，C（O）CH 2 C（O）NR 15b -NR 15 B，C（O）NR 15b， （CH2）m 1 Ar，C（O）NR 15b Het，C（O）NR 15b C 1〜 C 1 -C 6烷基，C（O）NR 5a R 5b，S（O）2（CH 2） S（O）2 Het，S（O）2 -C（O）2 -C C 1 -C 6烷基或CH 2 Ar; 或R 4和R 5合在一起是 - （CH 2）2 -

公开(公告)号：WO2005090353A1

公开(公告)日：2005-09-29

申请号：PCT/GB2005/000976

申请日：2005-03-15

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

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

IPC: C07D487/04

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 Et, n-Pr, i-Pr, C 2 fluoroalkyl, or -CH 2 CH 2 OH; R 2 is H, Me, Et, n-Pr, i-Pr, C 1-2 fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-; and NHR 3 has the sub-formula (nhr3): formula (nhr3) wherein R 3a is methyl or ethyl; R 3b is H, methyl or ethyl; R 3c is H, methyl or ethyl, R 3d is H, methyl or ethyl, and R 3e is H or methyl, provided that: (a) R 3b is methyl or ethyl; and/or (b) R 3c and R 3d are independently methyl or ethyl; and provided that: (c) when R 3c is ethyl and/or when R 3d is ethyl and/or when R 3e is methyl, then: R 3a is methyl and/or R 3b is a hydrogen atom (H) or methyl. NHR 3 can for example be [(1S)-1,2-dimethylpropyl]amino or t-butylamino. The invention also relates to the use of these pyrazolo[3,4 b]pyridine compounds in therapy, as inhibitors of phosphodiesterase type IV (PDE4), and 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 or allergic rhinitis.

Abstract translation: 本发明涉及式（I）化合物或其盐：式（I）其中：R 1是Et，n-Pr，i-Pr，C 2 F 2烷基或-CH 2 CH 2 OH; R 2是H，Me，Et，n-Pr，i-Pr，C 1-12氟烷基，环丙基或（环丙基）甲基; 和NHR 3具有其中R 3a是甲基或乙基的子式（nhr3）：式（nhr3） R 3b是H，甲基或乙基; R 3c是H，甲基或乙基，R 3d是H，甲基或乙基，R 3e是H或甲基，条件是：（a）R 3b是甲基或乙基; 和/或（b）R 3c和R 3d独立地是甲基或乙基; 并且条件是：（c）当R 3c为乙基和/或当R 3d为乙基时，和/或当R 3e为甲基时，R 3a为甲基和/或R 3b， 是氢原子（H）或甲基。 NHR 3可以例如是[（1S）-1,2-二甲基丙基]氨基或叔丁基氨基。 本发明还涉及这些吡唑并[3,4b]吡啶化合物在治疗中作为IV型磷酸二酯酶抑制剂（PDE4）的用途，并且涉及它们在治疗和/或预防炎性和/或过敏性疾病中的用途 如慢性阻塞性肺疾病（COPD），哮喘，类风湿关节炎或过敏性鼻炎。

公开(公告)号：WO2005090348A1

公开(公告)日：2005-09-29

申请号：PCT/GB2005/000983

申请日：2005-03-15

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 ,  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 ,  TRIVEDI, Naimisha

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The invention provides a compound of formula (I) or a salt thereof: formula (I) wherein W is Ar, -CR 4 R 5 Ar or a group (y) or (y1), wherein Ar is (x) or (z): formulae (x), (z), (y), (y1) R 1 is C 1-4 alkyl, C 1-3 fluoroalkyl or CH 2 CH 2 OH. R 2 is C 2-6 alkyl, C 3-6 cycloalkyl or -(CH 2 ) n 4 -C 3-6 cycloalkyl; and R 3 is optionally substituted C 3-8 cycloalkyl, optionally substituted mono unsaturated C 5-7 cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc) (in which Y is O, S, SO 2 , or NR 10 ), or a bicyclic group (ee): formulae (aa), (bb), (cc), (ee). The invention also relates to the use of the compounds in therapy 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 or allergic rhinitis.

Abstract translation: 本发明提供式（I）化合物或其盐：其中W是Ar，-CR 4 R 5 Ar或式（y）或（y1）的式（I），其中Ar是（x ）或（z）：式（x），（z），（y），（y1）R 1为C 1-4烷基，C 1-3氟烷基或CH 2 CH 2 OH。 R 2是C 2-6烷基，C 3-6环烷基或 - （CH 2）n 4 -C 3-6环烷基; 任选取代的单不饱和C 5-7环烯基，任选取代的杂环基（aa），（bb）或（cc）（其中Y是O，S，SO2或NR） 10），或双环基（ee）：式（aa），（bb），（cc），（ee）。 本发明还涉及该化合物在治疗中作为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），哮喘的用途 ，类风湿关节炎或过敏性鼻炎。

公开(公告)号：WO2012032065A1

公开(公告)日：2012-03-15

申请号：PCT/EP2011/065417

申请日：2011-09-06

Applicant: GLAXO GROUP LIMITED ,  BALDWIN, Ian Robert ,  DOWN, Kenneth David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie Nicole ,  HARRISON, Zoe Alicia ,  JONES, Katherine Louise ,  JONES, Paul Spencer ,  KEELING, Suzanne Elaine ,  LE, Joelle ,  LUNNISS, Christopher James ,  MITCHELL, Charlotte Jane ,  PARR, Nigel James ,  RITCHIE, Timothy John ,  ROBINSON, John Edward ,  SIMPSON, Juliet Kay ,  SMETHURST, Christian Alan Paul ,  WASHIO, Yoshiaki

Inventor： BALDWIN, Ian Robert ,  DOWN, Kenneth David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie Nicole ,  HARRISON, Zoe Alicia ,  JONES, Katherine Louise ,  JONES, Paul Spencer ,  KEELING, Suzanne Elaine ,  LE, Joelle ,  LUNNISS, Christopher James ,  MITCHELL, Charlotte Jane ,  PARR, Nigel James ,  RITCHIE, Timothy John ,  ROBINSON, John Edward ,  SIMPSON, Juliet Kay ,  SMETHURST, Christian Alan Paul ,  WASHIO, Yoshiaki

IPC: A61K31/416 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5386 ,  A61P31/16

CPC classification number: A61K31/5377 ,  A61K31/416 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5386 ,  C07D413/14

Abstract: The present invention is directed to indazole compounds for use in the treatment or prevention of influenza virus infection.

Abstract translation: 本发明涉及用于治疗或预防流感病毒感染的吲唑化合物。

公开(公告)号：WO2010018133A1

公开(公告)日：2010-02-18

申请号：PCT/EP2009/060265

申请日：2009-08-07

Applicant: SMITHKLINE BEECHAM CORPORATION ,  BIGGADIKE, Keith ,  COE, Diane, Mary ,  LEWELL, Xiao, Qing ,  MITCHELL, Charlotte, Jane ,  SMITH, Stephen, Allan ,  TRIVEDI, Naimisha

Inventor： BIGGADIKE, Keith ,  COE, Diane, Mary ,  LEWELL, Xiao, Qing ,  MITCHELL, Charlotte, Jane ,  SMITH, Stephen, Allan ,  TRIVEDI, Naimisha

IPC: C07D473/18 ,  C07D473/16 ,  A61K31/522 ,  A61P37/00 ,  A61P35/00

CPC classification number: A61K31/522 ,  A61K9/0043 ,  A61K31/55 ,  A61K45/06 ,  A61P29/00 ,  A61P31/00 ,  A61P35/00 ,  A61P37/00 ,  C07D473/16 ,  C07D473/18

Abstract: Compounds of formula (I): wherein R 1 is C 1-6 alkylamino, C 1-6 alkoxy, or C 3-7 cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

Abstract translation: 式（I）化合物：其中R 1是C 1-6烷基氨基，C 1-6烷氧基或C 3-7环烷氧基; m为3〜6的整数， n为0〜4的整数， 其盐是人类干扰素的诱导剂。 诱导人类干扰素的化合物可用于治疗各种疾病，例如治疗过敏性疾病和其它炎性病症，例如过敏性鼻炎和哮喘，治疗感染性疾病和癌症，并且也可用作疫苗佐剂。

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：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。