公开(公告)号：US20080132536A1

公开(公告)日：2008-06-05

申请号：US12022372

申请日：2008-01-30

申请人： David George Allen ,  Diane Mary Coe ,  Caroline Mary Cook ,  Michael Dennis Dowle ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave ,  John Edward Robinson ,  Naimisha Trivedi

发明人： David George Allen ,  Diane Mary Coe ,  Caroline Mary Cook ,  Michael Dennis Dowle ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave ,  John Edward Robinson ,  Naimisha Trivedi

IPC分类号： A61K31/437 ,  A61P11/00 ,  A61P19/02 ,  A61P37/08 ,  A61P17/00 ,  C07D471/04 ,  A61K31/4545 ,  C07D487/04

CPC分类号： C07D471/04

摘要： The invention provides a compound of formula (I) or a salt thereof: wherein Ar has the sub-formula (x) or (z): and wherein R3 is optionally substituted C3-8cycloalkyl, optionally substituted C5-7cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc), or a bicyclic group (ee); and wherein R4 is H, C1-3alkyl, C1-2fluoroalkyl, cyclopropyl, —CH2OR4a, —CH(Me)OR4a, or —CH2CH2OR4a; and R5 is inter alia H, C1-8alkyl, C1-3fluoroalkyl, C3-8cycloalkyl, certain substituted alkyl groups, —(CH2)n13-Het, or optionally substituted phenyl or —CH2-Ph; or R4 and R5 taken together are —(CH2)p1— or —(CH2)p3—X5—(CH2)p4—; provided that at least one of R4 and R5 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.

摘要翻译： 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个环烷基，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为H，C 1-3烷基，C 1-12氟代烷基，环丙基，-CH 2， -CH（Me）OR 4a或-CH 2 H 2 CH 2或-O SUP > 4a ; 且R 5特别是H，C 1-8烷基，C 1-3烷基，C 3-8 - 某些取代的烷基， - （CH 2）n - ，或任选取代的苯基或-CH 2 - 2 - 或 - （CH 2）2 - - - - （CH 2） 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：US07528148B2

公开(公告)日：2009-05-05

申请号：US10540371

申请日：2003-12-19

申请人： David George Allen ,  Diane Mary Coe ,  Caroline Mary Cook ,  Anthony William James Cooper ,  Michael Dennis Dowle ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave

发明人： David George Allen ,  Diane Mary Coe ,  Caroline Mary Cook ,  Anthony William James Cooper ,  Michael Dennis Dowle ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave

IPC分类号： C07D471/02 ,  C07D491/02 ,  C07D498/02 ,  C07D513/02 ,  C07D515/02 ,  A01N43/42 ,  A61K31/44

CPC分类号： C07D471/04

摘要： The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is C1-4alkyl, C1-3fluoroalkyl or —(CH2)2OH; R2 is a hydrogen atom (H), methyl or C1fluoroalkyl; R3a is a hydrogen atom (H) or C1-3alkyl; R3 is optionally substituted branched C3-6alkyl, optionally substituted C3-8cycloalkyl, optionally substituted mono-unsaturated-C5-7cycloalkenyl, optionally substituted phenyl, or an optionally substituted heterocyclic group of sub-formula (aa), (bb) or (cc): in which n1 and n2 independently are 1 or 2; and Y is O, S, SO2, or NR4; and wherein Het is of sub-formula (i), (ii), (iii), (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.

摘要翻译： 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氟烷基或 - （CH 2）2 OH; R2是氢原子（H），甲基或C1-4烷基; R3a是氢原子（H）或C1-3烷基; R 3是任选取代的支链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），（bb）或（cc） 其中n1和n2独立地为1或2; Y是O，S，SO 2或NR 4; 并且其中Het为亚式（i），（ii），（iii），（iv）或（v）：所述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：US07465743B2

公开(公告)日：2008-12-16

申请号：US10598944

申请日：2005-03-15

申请人： Diane Mary Coe ,  Caroline Mary Cook ,  Anthony William James Cooper ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave ,  John Edward Robinson

发明人： Diane Mary Coe ,  Caroline Mary Cook ,  Anthony William James Cooper ,  Christopher David Edlin ,  Julie Nicole Hamblin ,  Martin Redpath Johnson ,  Paul Spencer Jones ,  Mika Kristian Lindvall ,  Charlotte Jane Mitchell ,  Alison Judith Redgrave ,  John Edward Robinson

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D471/02 ,  C07D491/02 ,  C07D498/02 ,  C07D513/02 ,  C07D515/02

CPC分类号： C07D471/04

摘要： The invention relates to a compound of formula (I) or a salt thereof: wherein: R1 is Et, n-Pr, i-Pr, C2fluoroalkyl, or —CH2CH2OH; R2 is H, Me, Et, n-Pr, i-Pr, C1-2fluoroalkyl, cyclopropyl or (cyclopropyl)methyl-; and NHR3 has the sub-formula (nhr3): wherein R3a is methyl or ethyl; R3b is H, methyl or ethyl; R3c is H, methyl or ethyl, R3d is H, methyl or ethyl, and R3e is H or methyl, provided that: (a) R3b is methyl or ethyl; and/or (b) R3c and R3d are independently methyl or ethyl; and provided that: (c) when R3c is ethyl and/or when R3d is ethyl and/or when R3e is methyl, then: R3a is methyl and/or R3b is hydrogen or methyl. These compounds are PDE4 inhibitors.

摘要翻译： 本发明涉及式（I）化合物或其盐：其中：R 1为Et，n-Pr，i-Pr，C 2 F 2烷基或-CH 2 CH 2 OH; R2是H，Me，Et，n-Pr，i-Pr，C1-2氟烷基，环丙基或（环丙基）甲基; 和NHR 3具有子式（nhr3）：其中R3a是甲基或乙基; R3b是H，甲基或乙基; R3c是H，甲基或乙基，R3d是H，甲基或乙基，R3e是H或甲基，条件是：（a）R3b是甲基或乙基; 和/或（b）R3c和R3d独立地是甲基或乙基; 并且条件是：（c）当R3c是乙基和/或当R3d是乙基和/或当R3e是甲基时，则：R3a是甲基和/或R3b是氢或甲基。 这些化合物是PDE4抑制剂。

公开(公告)号：US08563717B2

公开(公告)日：2013-10-22

申请号：US13058465

申请日：2009-08-07

申请人： Helene Bazin-Lee ,  Diane Mary Coe ,  Linos Lazarides ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

发明人： Helene Bazin-Lee ,  Diane Mary Coe ,  Linos Lazarides ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

IPC分类号： A61K31/522 ,  A61P29/02 ,  A61P37/08 ,  C07D473/16

CPC分类号： C07D473/16 ,  A61K31/522 ,  C07D473/18

摘要： The present invention relates to compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure: 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 —(CH2)n— moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; 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.

摘要翻译： 本发明涉及式（I）的化合物：其中R 1是C 1-6烷基氨基或C 1-6烷氧基; R2是具有以下结构的基团：n是具有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：US08575340B2

公开(公告)日：2013-11-05

申请号：US13578008

申请日：2011-02-08

申请人： Helene Bazin-Lee ,  Diane Mary Coe ,  David A. Johnson ,  Charlotte Jane Mitchell

发明人： Helene Bazin-Lee ,  Diane Mary Coe ,  David A. Johnson ,  Charlotte Jane Mitchell

IPC分类号： A61K31/52 ,  C07D473/18 ,  A61P31/00 ,  A61P35/00 ,  A61P37/08 ,  A61P29/00 ,  A61P37/04 ,  A61P11/06

CPC分类号： C07D473/18 ,  C07D473/16

摘要： The present invention relates to compounds of formula (I): wherein; R1 represents hydrogen or C1-3alkyl; n is an integer having a value of 1 to 5; X represents O or NH; Y represents C or N; or a pharmaceutically acceptable salt thereof, have been shown to be inducers of human interferon and may possess an improved profile with respect to known inducers of human interferon, for example enhanced potency. The compounds of the invention may therefore be useful in the treatment of various disorders, in particular the treatment of infectious diseases, cancer, allergic diseases and other inflammatory conditions, and their use as vaccine adjuvants.

摘要翻译： 本发明涉及式（I）的化合物：其中： R1代表氢或C1-3烷基; n为1〜5的整数， X表示O或NH; Y表示C或N; 已经显示其是人类干扰素的诱导剂，并且相对于人干扰素的已知诱导剂可能具有改进的特征，例如增强的效力。 因此，本发明的化合物可用于治疗各种疾病，特别是治疗感染性疾病，癌症，过敏性疾病和其它炎性病症，以及它们作为疫苗佐剂的用途。

公开(公告)号：US20120315291A1

公开(公告)日：2012-12-13

申请号：US13578008

申请日：2011-02-08

申请人： Helene Bazin-Lee ,  Diane Mary Coe ,  David A. Johnson ,  Charlotte Jane Mitchell

发明人： Helene Bazin-Lee ,  Diane Mary Coe ,  David A. Johnson ,  Charlotte Jane Mitchell

IPC分类号： A61K31/52 ,  A61P31/00 ,  A61P35/00 ,  A61P11/06 ,  A61P29/00 ,  A61K39/00 ,  A61P37/04 ,  C07D473/18 ,  A61P37/08

CPC分类号： C07D473/18 ,  C07D473/16

摘要： The present invention relates to compounds of formula (I): wherein; R1 represents hydrogen or C1-3alkyl; n is an integer having a value of 1 to 5; X represents O or NH; Y represents C or N; or a pharmaceutically acceptable salt thereof, have been shown to be inducers of human interferon and may possess an improved profile with respect to known inducers of human interferon, for example enhanced potency. The compounds of the invention may therefore be useful in the treatment of various disorders, in particular the treatment of infectious diseases, cancer, allergic diseases and other inflammatory conditions, and their use as vaccine adjuvants.

摘要翻译： 本发明涉及式（I）的化合物：其中： R1代表氢或C1-3烷基; n为1〜5的整数， X表示O或NH; Y表示C或N; 已经显示其是人类干扰素的诱导剂，并且相对于人干扰素的已知诱导剂可能具有改进的特征，例如增强的效力。 因此，本发明的化合物可用于治疗各种疾病，特别是治疗感染性疾病，癌症，过敏性疾病和其它炎性病症，以及它们作为疫苗佐剂的用途。

公开(公告)号：US20100075995A1

公开(公告)日：2010-03-25

申请号：US12537392

申请日：2009-08-07

申请人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

发明人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

IPC分类号： A61K31/522 ,  C07D473/18 ,  A61P11/06

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

摘要： Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; 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.

摘要翻译： 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：US09346806B2

公开(公告)日：2016-05-24

申请号：US13272956

申请日：2011-10-13

申请人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

发明人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

IPC分类号： A61K31/522 ,  A61P11/06 ,  C07D473/18 ,  C07D473/16

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

摘要： Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; 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.

摘要翻译： 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：US20120035193A1

公开(公告)日：2012-02-09

申请号：US13272956

申请日：2011-10-13

申请人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

发明人： Keith Biggadike ,  Diane Mary Coe ,  Xiao Qing Lewell ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

IPC分类号： A61K31/522 ,  A61P11/06

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

摘要： Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; 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.

摘要翻译： 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：US20110144136A1

公开(公告)日：2011-06-16

申请号：US13058465

申请日：2009-08-07

申请人： Helene Bazin-Lee ,  Diane Mary Coe ,  Linos Lazarides ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

发明人： Helene Bazin-Lee ,  Diane Mary Coe ,  Linos Lazarides ,  Charlotte Jane Mitchell ,  Stephen Allan Smith ,  Naimisha Trivedi

IPC分类号： A61K31/522 ,  C07D473/18 ,  C07D473/16 ,  A61P29/00 ,  A61P37/08

CPC分类号： C07D473/16 ,  A61K31/522 ,  C07D473/18

摘要： The present invention relates to compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure: 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 —(CH2)n— moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; 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.

摘要翻译： 本发明涉及式（I）的化合物：其中R 1是C 1-6烷基氨基或C 1-6烷氧基; R2是具有以下结构的基团：n是具有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。