公开(公告)号：WO2010125082A1

公开(公告)日：2010-11-04

申请号：PCT/EP2010/055666

申请日：2010-04-28

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

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

IPC: C07D413/14 ,  A61K31/422 ,  A61K31/4439 ,  A61P35/00 ,  A61P37/00 ,  A61P11/00 ,  A61P31/12

CPC classification number: A61K31/5377 ,  A61K31/496 ,  A61K31/497 ,  A61K31/535 ,  A61K45/06 ,  C07B2200/13 ,  C07D413/14 ,  Y02A50/409

Abstract: The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.

Abstract translation: 本发明涉及某些新化合物。 具体地，本发明涉及式（I）的化合物及其盐。 本发明的化合物是激酶活性抑制剂，特别是PI3-激酶活性。

公开(公告)号：WO2009147189A1

公开(公告)日：2009-12-10

申请号：PCT/EP2009/056840

申请日：2009-06-03

Applicant: GLAXO GROUP LIMITED ,  BALDWIN, Ian, Robert ,  DOWN, Kenneth, David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie, Nicole ,  JONES, Paul, Spencer ,  LE, Joelle ,  PARR, Nigel, James ,  RITCHIE, Timothy, John ,  ROBINSON, John, Edward ,  SIMPSON, Juliet, Kay ,  SMETHURST, Christian, Alan, Paul

Inventor： BALDWIN, Ian, Robert ,  DOWN, Kenneth, David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie, Nicole ,  JONES, Paul, Spencer ,  LE, Joelle ,  PARR, Nigel, James ,  RITCHIE, Timothy, John ,  ROBINSON, John, Edward ,  SIMPSON, Juliet, Kay ,  SMETHURST, Christian, Alan, Paul

IPC: A61K31/416 ,  A61P11/00 ,  C07D403/04 ,  C07D403/14

CPC classification number: C07D403/04 ,  C07D401/14 ,  C07D403/14 ,  C07D413/14 ,  C07D471/04

Abstract: The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.

Abstract translation: 本发明涉及某些新化合物。 具体地，本发明涉及式（I）的化合物及其盐。 本发明的化合物是PI3-激酶活性的抑制剂。

公开(公告)号：WO2011067365A1

公开(公告)日：2011-06-09

申请号：PCT/EP2010/068797

申请日：2010-12-03

Applicant: GLAXO GROUP LIMITED ,  BALDWIN, Ian Robert ,  DOWN, Kenneth David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie Nicole ,  JONES, Katherine Louise ,  JONES, Paul Spencer ,  LE, Joelle ,  LUNNISS, Christopher James ,  PARR, Nigel James ,  RITCHIE, Timothy John ,  ROBINSON, John Edward ,  SIMPSON, Juliet Kay ,  SMETHURST, Christian Alan Paul

Inventor： BALDWIN, Ian Robert ,  DOWN, Kenneth David ,  FAULDER, Paul ,  GAINES, Simon ,  HAMBLIN, Julie Nicole ,  JONES, Katherine Louise ,  JONES, Paul Spencer ,  LE, Joelle ,  LUNNISS, Christopher James ,  PARR, Nigel James ,  RITCHIE, Timothy John ,  ROBINSON, John Edward ,  SIMPSON, Juliet Kay ,  SMETHURST, Christian Alan Paul

IPC: C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D417/04 ,  C07D471/04 ,  C07D487/04 ,  A61K31/416 ,  A61P11/00

CPC classification number: C07D487/04 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D417/04 ,  C07D471/04

Abstract: The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of PI3-kinase activity.

Abstract translation: 本发明涉及某些新化合物。 具体地，本发明涉及式（I）的化合物及其盐。 本发明的化合物是PI3-激酶活性的抑制剂。

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：WO2012055846A1

公开(公告)日：2012-05-03

申请号：PCT/EP2011/068604

申请日：2011-10-25

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

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

IPC: C07D413/14 ,  A61K31/422 ,  A61P35/00 ,  A61P37/00 ,  A61P11/00 ,  A61P31/12

CPC classification number: C07D413/14

Abstract: The present invention is directed to a polymorph of a compound of formula (II) and salts and polymorphs thereof, which is an inhibitor of PI3 kinase activity.

Abstract translation: 本发明涉及式（II）化合物及其盐和多晶型物的多晶型物，其是PI3激酶活性的抑制剂。

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：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：WO2005090352A1

公开(公告)日：2005-09-29

申请号：PCT/EP2005/003038

申请日：2005-03-15

Applicant: GLAXO GROUP LIMITED ,  CHRISTENSEN IV, Siegfried, Benjamin ,  COOK, Caroline, Mary ,  EDLIN, Christopher, David ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  SAYANI, Amyn, Pyarali ,  TRIVEDI, Naimisha ,  TROTTET, Lionel

Inventor： CHRISTENSEN IV, Siegfried, Benjamin ,  COOK, Caroline, Mary ,  EDLIN, Christopher, David ,  JOHNSON, Martin, Redpath ,  JONES, Paul, Spencer ,  LINDVALL, Mika, Kristian ,  SAYANI, Amyn, Pyarali ,  TRIVEDI, Naimisha ,  TROTTET, Lionel

IPC: C07D487/04

CPC classification number: C07D471/04

Abstract: The invention provides 4-{[1-(aminocarbonyl)-4-piperidinyl]amino}-N-[(3,4-dimethylphenyl)methyl]-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carb oxamide, which is the compound of formula (I), or a salt thereof. The invention also provides the use of said compound or a pharmaceutically acceptable salt thereof as an inhibitor of phosphodiesterase type IV (PDE4), for example in the treatment and/or prophylaxis of an inflammatory and/or allergic disease, cognitive impairment or depression in a mammal. In particular, the invention provides the use of the compound or pharmaceutically acceptable salt in the treatment and/or prophylaxis of atopic dermatitis in a mammal, for example by external topical administration to the mammal such as a human. Pharmaceutical compositions containing said compound or salt, in particular suitable for external topical administration, are also provided.

Abstract translation: 本发明提供4 - {[1-（氨基羰基）-4-哌啶基]氨基} -N - [（3,4-二甲基苯基）甲基] -1-乙基-1H-吡唑并[3,4-b]吡啶-5 - 肟酰胺，其为式（I）化合物或其盐。 本发明还提供了所述化合物或其药学上可接受的盐作为IV型磷酸二酯酶抑制剂（PDE4）的用途，例如用于治疗和/或预防炎性和/或过敏性疾病，认知障碍或抑郁症 哺乳动物。 特别地，本发明提供了化合物或药学上可接受的盐在哺乳动物治疗和/或预防特应性皮炎中的用途，例如通过外用局部施用于哺乳动物如人。 还提供了含有所述化合物或盐的药物组合物，特别适用于外用局部给药。

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。