公开(公告)号：US20060089375A1

公开(公告)日：2006-04-27

申请号：US10527866

申请日：2003-09-12

Applicant: David Allen ,  Diane Coe ,  Caroline Cook ,  Michael Dowle ,  Christophen Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Richard Knowles ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  Peter Ward

Inventor： David Allen ,  Diane Coe ,  Caroline Cook ,  Michael Dowle ,  Christophen Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Richard Knowles ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  Peter Ward

IPC: C07D471/02 ,  A61K31/4745

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是C 1-4烷基，C 1-3烷基， 氟代烷基，-CH 2 CH 2 OH或-CH 2 CH 2 CO 2， C 1-12烷基; R 2是氢原子（H），甲基或C 1氟代烷基; R 3是任选取代的C 3-8环烷基或任选取代的单不饱和C 5〜5-7环烯基或任选取代的杂环基 子公式（aa），（bb）或（cc）; 其中n 1和n 2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）：其中X是NR 4 R 5或OR 5a 。 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：US20050048024A1

公开(公告)日：2005-03-03

申请号：US10492606

申请日：2002-10-17

Applicant: Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

Inventor： Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

IPC: A61K9/12 ,  A61K9/00 ,  A61K9/72 ,  A61K31/137 ,  A61K31/439 ,  A61K31/522 ,  A61K31/56 ,  A61K31/573 ,  A61K31/58 ,  A61K47/06 ,  A61K47/12 ,  A61K47/34 ,  A61P11/02 ,  A61P11/06 ,  A61P11/08 ,  A61P29/00 ,  A61P37/08 ,  B01F17/00 ,  C07C59/125 ,  C07C59/185 ,  A61L9/04 ,  A61K7/075 ,  A61K7/08 ,  C07C59/10

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

Abstract: 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, as well as pharmaceutical formulations containing such compounds and processes for the manufacture of such compounds are disclosed. Intermediates of such compounds and processes for the manufacture of such intermediates are also disclosed.

Abstract translation: 式（I）化合物或其盐或溶剂合物，其中：n和n独立地表示2-12的整数; m 1和m 2独立地表示1至15的整数; 和R 1和R 2独立地表示 - （CO）x C1-9烷基或 - （CO）xC1-9氟代烷基，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，以及含有这些化合物的药物制剂和制备这些化合物的方法。 还公开了这些化合物的中间体和制备这种中间体的方法。

公开(公告)号：US20080021058A1

公开(公告)日：2008-01-24

申请号：US10598940

申请日：2005-03-15

Applicant: David Allen ,  Diane Coe ,  Caroline Cook ,  Michael Dowle ,  Christopher Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  Naimisha Trivedi

Inventor： David Allen ,  Diane Coe ,  Caroline Cook ,  Michael Dowle ,  Christopher Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  Naimisha Trivedi

IPC: A61K31/437 ,  A61P29/00 ,  A61P37/08 ,  C07D221/04

CPC classification number: C07D471/04

Abstract: The invention provides a compound of formula (I) or a salt thereof: wherein W is Ar, —CR4R5Ar or a group (y) or (y1), wherein Ar is (x) or (z): R1 is C1-4alkyl, C1-3fluoroalkyl or —CH2CH2OH. R2 is C2-6alkyl, C3-6cycloalkyl or —(CH2)n4-C3-6cycloalkyl; and R3 is optionally substituted C3-8cycloalkyl, optionally substituted mono-unsaturated-C5-7cycloalkenyl, an optionally substituted heterocyclic group (aa), (bb) or (cc) (in which Y is O, S, SO2, or NR10), or a bicyclic group (ee): These compounds are PDE4 inhibitors.

Abstract translation: 本发明提供式（I）化合物或其盐：其中W为Ar，-CR 4 R 5或Ar或基团（y）或（y1） 其中Ar是（x）或（z）：R 1是C 1-4烷基，C 1-3 - 氟代烷基或-CH 2 CH 2 OH。 R 2是C 2-6 - 烷基，C 3-6环烷基或 - （CH 2 CH 2） _{n + 4-C 3-6环烷基; 且R 3是任选取代的C 3-8环烷基，任选取代的单不饱和C 5〜5-7环烯基，任意取代的杂环基 （aa），（bb）或（cc）（其中Y为O，S，SO 2或NR 10）或双环基团（ee） 这些化合物是PDE4抑制剂。}

公开(公告)号：US20070049570A1

公开(公告)日：2007-03-01

申请号：US11349701

申请日：2006-02-08

Applicant: Anthony Dean ,  Brian Evans ,  Sharon Gough ,  Christopher Lunniss ,  Alison Redgrave

Inventor： Anthony Dean ,  Brian Evans ,  Sharon Gough ,  Christopher Lunniss ,  Alison Redgrave

IPC: A61K31/56

CPC classification number: C07D401/12 ,  C07D215/54 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D453/02

Abstract: There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 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: 根据本发明提供新的式（I）化合物或其药学上可接受的盐，其中R1，R2，R19，R20和R34如说明书中所述，其制备方法，含有它们的制剂及其在 治疗炎症性疾病。

公开(公告)号：US20050287076A1

公开(公告)日：2005-12-29

申请号：US10506339

申请日：2003-03-04

Applicant: Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

Inventor： Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

IPC: A61K9/12 ,  A61K9/00 ,  A61K9/72 ,  A61K47/06 ,  A61K47/24 ,  C07F9/10 ,  C07F9/11 ,  A61K9/14 ,  C07F9/02

CPC classification number: A61K9/008 ,  C07F9/10

Abstract: Compounds of formula (I): and uses of such compounds are described.

Abstract translation: 描述了式（I）化合物及其用途。

公开(公告)号：US20070167485A1

公开(公告)日：2007-07-19

申请号：US10598944

申请日：2005-03-15

Applicant: Diane Coe ,  Caroline Cook ,  Anthony Cooper ,  Christopher Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  John Robinson

Inventor： Diane Coe ,  Caroline Cook ,  Anthony Cooper ,  Christopher Edlin ,  Julie Hamblin ,  Martin Johnson ,  Paul Jones ,  Mika Lindvall ,  Charlotte Mitchell ,  Alison Redgrave ,  John Robinson

IPC: A61K31/44

CPC classification number: C07D471/04

Abstract: 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.

Abstract translation: 本发明涉及式（I）化合物或其盐：其中：R 1是Et，n-Pr，i-Pr，C 2氟代烷基，或 -CH 2 CH 2 CH 2 OH; R 2是H，Me，Et，n-Pr，i-Pr，C 1-12氟代烷基，环丙基或（环丙基）甲基; 和NHR 3具有子式（nhr3）：其中R 3a是甲基或乙基; 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为乙基时，和/或当R 3d为乙基时，和/或当R 3e为甲基时， 那么：R 3a是甲基，和/或R 3b是氢或甲基。 这些化合物是PDE4抑制剂。

公开(公告)号：US20050163720A1

公开(公告)日：2005-07-28

申请号：US10504252

申请日：2003-02-12

Applicant: Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

Inventor： Brian Looker ,  Christopher Lunniss ,  Alison Redgrave

IPC: A61K9/12 ,  A61K20060101 ,  A61K8/60 ,  A61K8/81 ,  A61K8/92 ,  A61K9/00 ,  A61K47/12 ,  A61K47/14 ,  A61P11/00 ,  A61Q9/04 ,  B01F20060101 ,  C07C20060101 ,  C07C69/63 ,  C09K3/00 ,  A61K31/225 ,  A61L9/04

CPC classification number: A61K8/60 ,  A61K8/8111 ,  A61K8/922 ,  A61K9/008 ,  A61K47/12 ,  A61Q9/04 ,  C07C69/63

Abstract: Compounds of formula (I) or a salt or solvate thereof, wherein: x represents 0 or 1; y represents 0 or 1; R1 and R2 independently represent —C1-9 alkyleneC1-6 fluoroalkyl, which fluoroalkyl moiety contains at least 1 fluorine atom and not more than 3 consecutive perfluorocarbon atoms and wherein the R1 and/or R2 moiety is optionally interrupted by an ether link, processes for their preparation, use of the compounds in the preparation of pharmaceutical formulations and the formulations are described.

Abstract translation: 式（I）化合物或其盐或溶剂合物，其中：x表示0或1; y表示0或1; R 1和R 2独立地代表-C 1-6 - 亚烷基C 1-6 - 氟代烷基，该氟烷基部分含有 至少1个氟原子和不超过3个连续的全氟化碳原子，其中R 1和/或R 2 O 2部分任选地被醚键中断，其制备方法 描述了制备药物制剂和制剂中化合物的用途。

公开(公告)号：US20070191426A1

公开(公告)日：2007-08-16

申请号：US10572913

申请日：2004-09-27

Applicant: Christopher Edlin ,  Colin Eldred ,  Christopher Lunniss ,  Alison Redgrave ,  John Robinson ,  Michael Woodrow

Inventor： Christopher Edlin ,  Colin Eldred ,  Christopher Lunniss ,  Alison Redgrave ,  John Robinson ,  Michael Woodrow

IPC: A61K31/47

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：US20070142373A1

公开(公告)日：2007-06-21

申请号：US10557079

申请日：2004-05-19

Applicant: Ian Baldwin ,  Michael Barker ,  Anthony Dean ,  Colin Eldred ,  Brian Evans ,  Sharon Gough ,  Stephen Guntrip ,  Julie Hamblin ,  Stuart Holman ,  Paul Jones ,  Mika Lindvall ,  Christopher Lunniss ,  Tracy Redfern ,  Alison Redgrave ,  John Robinson ,  Michael Woodrow

Inventor： Ian Baldwin ,  Michael Barker ,  Anthony Dean ,  Colin Eldred ,  Brian Evans ,  Sharon Gough ,  Stephen Guntrip ,  Julie Hamblin ,  Stuart Holman ,  Paul Jones ,  Mika Lindvall ,  Christopher Lunniss ,  Tracy Redfern ,  Alison Redgrave ,  John Robinson ,  Michael Woodrow

IPC: A61K31/5377 ,  A61K31/496 ,  A61K31/4709 ,  C07D413/02 ,  C07D403/02 ,  C07D401/02

CPC classification number: C07D401/12 ,  C07D215/54 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D453/02

Abstract: There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 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: 根据本发明提供新的式（I）化合物或其药学上可接受的盐，其中R 1，R 2，R 19，R 20和R 34如说明书中所述，其制备方法，含有 他们及其在治疗炎症性疾病中的应用。