公开(公告)号：US06936619B2

公开(公告)日：2005-08-30

申请号：US10387106

申请日：2003-03-12

申请人： Julian Blagg ,  Michael Jonathan Fray ,  Mark Llewellyn Lewis ,  John Paul Mathias ,  Mark Henryk Stefaniak ,  Alan Stobie

发明人： Julian Blagg ,  Michael Jonathan Fray ,  Mark Llewellyn Lewis ,  John Paul Mathias ,  Mark Henryk Stefaniak ,  Alan Stobie

IPC分类号： C07D239/95 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/5386 ,  A61P3/06 ,  A61P9/06 ,  A61P9/10 ,  A61P9/12 ,  A61P13/08 ,  A61P15/00 ,  A61P15/08 ,  A61P15/10 ,  A61P27/06 ,  A61P43/00 ,  C07D401/04 ,  C07D401/14 ,  C07D471/04 ,  C07D487/04 ,  C07D519/00

CPC分类号： C07D401/04 ,  C07D471/04 ,  C07D487/04

摘要： Compounds of formula (I): or pharmaceutically acceptable salts or solvates thereof, wherein R1 represents C1-4 alkyl; R2 represents halo, C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyloxy, —SO2(C1-4 alkyl), optionally substituted C1-4 alkyloxy, Het or —OHet; R3 represents a bicyclic group of the formula  wherein X and Y are selected from C and N, provided that at least one is C; Ring A together with X and Y represents a 5- or 6-membered aromatic ring containing 0, 1, 2 or 3 nitrogen atoms in the ring; n is), 1 or 2 L represents a direct link, C1-4 alkylene or C1-4 alkoxyalkylene; R4 represents H, —NR5R6, C3-6 cycloalkyl, —OR7, Het1 or Het4; R5 and R6 are independently selected from H, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-4 alkylene, —SO2(C1-4 alkyl) and optionally substituted C1-4 alkyl R7 is selected from H, C1-4 alkyl, C1-4 alkoxyalkyl, C3-6cycloalkyl, Het2 and C1-4alkyl-Het3; R8 is H or C1-4 alkyl; Het, Het1, Het2 and Het3 independently represent an optionally substituted 4 to 7 membered saturated heterocyclic group which may be mono- or bi-cyclic and which contains one or more heteroatoms selected from N, O or S; Het4 represents an optionally substituted 5 or 6 membered unsaturated heterocyclic group containing one or more heteroatoms selected from N, O or S; R9 is H or C1-4 alkyl; R10 and R11 are independently selected from H and C1-4 alkyl; are useful in the treatment of hypertension, myocardial infarction, male erectile dysfunction (MED), hyperlipidaemia, cardiac arrhythmia, glaucoma and benign prostatic hyperplasia (BPH). They also find utility in the treatment of female sexual arousal dysfunction (FSAD).

公开(公告)号：US20090239899A1

公开(公告)日：2009-09-24

申请号：US12371719

申请日：2009-02-16

申请人： John Paul Mathias ,  David Simon Millan ,  Russell Andrew Lewthwaite ,  Christopher Phillips

发明人： John Paul Mathias ,  David Simon Millan ,  Russell Andrew Lewthwaite ,  Christopher Phillips

IPC分类号： A61K31/437 ,  A61P11/06

CPC分类号： C07D471/04

摘要： A compound of formula (I), or a pharmaceutical acceptable salt and/or solvate (including hydrate) thereof; and the use of a compound of formula (I) in the treatment of a TNF-mediated disease, disorder, or condition, or a p38-mediated disease, disorder, or condition, in particular the allergic and non-allergic airways diseases, more particularly obstructive or inflammatory airways diseases, preferably chronic obstructive pulmonary disease.

摘要翻译： 式（I）化合物或其药学上可接受的盐和/或其溶剂合物（包括水合物）; 和式（I）化合物在治疗TNF介导的疾病，病症或病症或p38介导的疾病，病症或病症，特别是过敏性和非过敏性气道疾病中的用途更多 特别是阻塞性或炎症性气道疾病，优选慢性阻塞性肺疾病。

公开(公告)号：US07176311B2

公开(公告)日：2007-02-13

申请号：US10753199

申请日：2004-01-06

申请人： Mark Edward Bunnage ,  Keith Michael DeVries ,  Laurence James Harris ,  Philip Charles Levett ,  John Paul Mathias ,  Joanna Teresa Negri ,  Stephen Derek Albert Street ,  Albert Shaw Wood

发明人： Mark Edward Bunnage ,  Keith Michael DeVries ,  Laurence James Harris ,  Philip Charles Levett ,  John Paul Mathias ,  Joanna Teresa Negri ,  Stephen Derek Albert Street ,  Albert Shaw Wood

IPC分类号： C07D487/04 ,  C07D401/12

CPC分类号： C07D213/80 ,  A61K31/519 ,  C07D231/38 ,  C07D401/12 ,  C07D487/04

摘要： A process for the preparation of Compounds of the formula (1): wherein R1, R2, R4 and R13 are as defined or a pharmaceutically or veterinarily acceptable salt or polymorph thereof, or a pharmaceutically or veterinarily acceptable solvate or pro-drug thereof: are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiestbrase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).

摘要翻译： 制备式（1）化合物的方法：其中R 1，R 2，R 4和R 13 或其药学上或兽医学上可接受的盐或多晶型物，或其药学上或兽医学上可接受的溶剂合物或前体药物：是5型环鸟苷酸3'，5'-单磷酸磷酸二酯酶的有效和选择性抑制剂 cGMP PDE5），可用于治疗男性勃起功能障碍（MED）和女性性功能障碍（FSD）。

公开(公告)号：US06458951B2

公开(公告)日：2002-10-01

申请号：US09845420

申请日：2001-04-30

申请人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

发明人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

IPC分类号： C07D40112

CPC分类号： C07D213/80 ,  C07D401/12 ,  C07D405/12 ,  C07D487/04

摘要： Compounds of the formulae (IA) and (IB): wherein R1 is C1 to C3 alkyl optionally substituted with phenyl, Het or a N-linked heterocyclic group selected from piperidinyl and morpholinyl; wherein said phenyl group is optionally substituted by one or more substitutents selected from C1 to C4 alkoxy; halo; CN; CF3; OCF3 or C1 to C4 alkyl wherein said C1 to C4 alkyl group is optionally substituted by C1 to C4 haloalkyl or haloalkoxy either of which is substituted by one or more halo atoms; R2 is C1 to C6 alkyl and R13 is OR3 or NR5R6, or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).

摘要翻译： 式（IA）和（IB）的化合物：其中R 1为任选被苯基，Het或选自哌啶基和吗啉基的N-连接的杂环基取代的C 1至C 3烷基; 其中所述苯基任选被一个或多个选自C 1至C 4烷氧基的取代基取代; 光环; CN; CF3; OCF 3或C 1至C 4烷基，其中所述C 1至C 4烷基任选被被一个或多个卤素原子取代的C 1至C 4卤代烷基或卤代烷氧基取代; R2是C1至C6烷基，R13是OR3或NR5R6，或其药学或兽医学上可接受的盐，或任何一个实体的药学上或兽医学上可接受的溶剂合物是5型环鸟嘌呤3'，5'-单磷酸磷酸二酯酶（cGMP）的有效和选择性抑制剂 PDE5），并且可用于治疗男性勃起功能障碍（MED）和女性性功能障碍（FSD）。

公开(公告)号：US20090258861A1

公开(公告)日：2009-10-15

申请号：US12491370

申请日：2009-06-25

申请人： Graham Lunn ,  John Paul Mathias ,  Ross Sinclair Strang

发明人： Graham Lunn ,  John Paul Mathias ,  Ross Sinclair Strang

IPC分类号： A61K31/55 ,  A61K31/506 ,  A61K31/497 ,  A61K31/4436 ,  A61P35/00

CPC分类号： C07D471/04

摘要： The present invention relates to tetrahydronaphthyridine derivatives of the general formula (I): or of the general formula (I′) in which A and R1 are as defined within, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, including the treatment diseases mediated by H3 ligands, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

摘要翻译： 本发明涉及通式（I）的四氢萘并吡啶衍生物：或其中A和R 1如上所定义的通式（I'）的化合物，以及制备用于制备组合物的中间体的方法 包括由H3配体介导的治疗疾病，特别是炎性，过敏性和呼吸道疾病，病症和病症的用途。

公开(公告)号：US20090012079A1

公开(公告)日：2009-01-08

申请号：US12162018

申请日：2007-01-29

申请人： Russell Andrew Lewthwaite ,  John Paul Mathias ,  Christopher Phillips

发明人： Russell Andrew Lewthwaite ,  John Paul Mathias ,  Christopher Phillips

IPC分类号： A61K31/5377 ,  C07D471/02 ,  A61K31/437 ,  A61P11/08 ,  A61P11/00 ,  A61P11/06 ,  C07D413/14

CPC分类号： C07D471/04

摘要： A compound of formula (Ia): or a pharmaceutically acceptable salt and/or solvate (including hydrate) thereof, or a compound of formula (Ib): or a pharmaceutically acceptable salt and/or solvate (including hydrate) thereof, and the use of a compound of formula (Ia) or (Ib) in the treatment of a TNF-mediated disease, disorder, or condition, or a p38-mediated disease, disorder, or condition, in particular the allergic and non-allergic airway diseases, more particularly obstructive or inflammatory airways diseases, preferably chronic obstructive pulmonary disease.

摘要翻译： 式（Ia）化合物或其药学上可接受的盐和/或溶剂化物（包括水合物）或式（Ib）的化合物或其药学上可接受的盐和/或溶剂合物（包括水合物），以及使用 式（Ia）或（Ib）化合物在治疗TNF介导的疾病，病症或病症或p38介导的疾病，病症或病症，特别是过敏性和非过敏性气道疾病中的用途， 更具体地阻塞性或炎症性气道疾病，优选慢性阻塞性肺疾病。

公开(公告)号：US06723719B1

公开(公告)日：2004-04-20

申请号：US09402229

申请日：1999-09-29

申请人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

发明人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

IPC分类号： C07D48704

CPC分类号： C07D487/04 ,  C07D231/40

摘要： Compounds of formulae (IA) and (IB) or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein R1 is C1 to C3 alkyl substituted with C3 to C6 cycloalkyl, CONR5R6 or a N-linked heterocyclic group; (CH2)nHet or (CH2)nAr; R2 is C1 to C6 alkyl; R3 is C1 to C6 alkyl optionally substituted with C1 to C4 alkoxy; R4 is SO2NR7R8; R5 and R6 are each independently selected from H and C1 to C4 alkyl optionally substituted with C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocyclic group; R7 and R8, together with the nitrogen atom to which they are attached, form a 4-R10-piperazinyl group; R10 is H or C1 to C4 alkyl optionally substituted with OH, C1 to C4 alkoxy or CONH2; H is an optionally substituted C-linked 5- or 6-membered heterocyclic group; Ar is optionally substituted phenyl; and n is 0 or 1; are potent and selective cGMP PDE5 inhibitors useful in the treatment of, inter alia, male erectile dysfunction and female sexual dysfunction.

摘要翻译： 式（IA）和（IB）化合物或其药学或兽医学上可接受的盐，或任一实体的药学上或兽医学上可接受的溶剂化物，其中R 1为被C 3至C 6环烷基取代的C 1至C 3烷基，CONR 5 R 6或N-连接的杂环基; （CH2）nHet或（CH2）nAr; R 2是C 1至C 6烷基; R 3是任选被C 1至C 4烷氧基取代的C 1至C 6烷基; R 4是SO 2 NR 7 R 8; R 5和R 6各自独立地选自H和任选被C 1至C 4烷氧基取代的C 1至C 4烷基，或与它们所连接的氮原子一起形成5-或6-元杂环 组; R 7和R 8与它们所连接的氮原子一起形成4-R 10 - 哌嗪基; R 10是H或任选被OH，C 1至C 4烷氧基或CONH 2取代的C 1至C 4烷基; H是任选取代的C连接的5或6元杂环基; Ar是任选取代的苯基; 并且n为0或1; 是用于治疗男性勃起功能障碍和女性性功能障碍的有效和选择性的cGMP PDE5抑制剂。

公开(公告)号：US06916927B2

公开(公告)日：2005-07-12

申请号：US10808027

申请日：2004-03-23

申请人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

发明人： Mark Edward Bunnage ,  John Paul Mathias ,  Stephen Derek Albert Street ,  Anthony Wood

IPC分类号： C07D295/22 ,  A61K20060101 ,  A61K31/415 ,  A61K31/505 ,  A61K31/519 ,  A61K31/5377 ,  A61P1/00 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P9/12 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P13/08 ,  A61P13/10 ,  A61P15/00 ,  A61P15/10 ,  A61P27/06 ,  A61P35/00 ,  A61P37/08 ,  A61P43/00 ,  C07B20060101 ,  C07D231/40 ,  C07D401/06 ,  C07D487/04 ,  C07D295/26 ,  C07D231/02

CPC分类号： C07D487/04 ,  C07D231/40

摘要： Compounds of formulae (IA) and (IB) or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein R1 is C1 to C3 alkyl substituted with C3 to C6 cycloalkyl, CONR5R6 or a N-linked heterocyclic group; (CH2)nHet or (CH2)nAr, R2 is C1 to C6 alkyl; R3 is C1 to C6 alkyl optionally substituted with C1 to C4 alkoxy; R4 is SO2NR7R8; R5 and R6 are each independently selected from H and C1 to C4 alkyl optionally substituted with C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocyclic group; R7 and R8, together with the nitrogen atom to which they are attached, form a 4-R10-piperazinyl group; R10 is H or C1 to C4 alkyl optionally substituted with OH, C1 to C4 alkoxy or CONH2; Het is an optionally substituted C-linked 5- or 6-membered heterocyclic group; Ar is optionally substituted phenyl; and n is 0 or 1; are potent and selective cGMP PDE5 inhibitors useful in the treatment of, inter alia, male erectile dysfunction and female sexual dysfunction

公开(公告)号：US06333330B1

公开(公告)日：2001-12-25

申请号：US09426554

申请日：1999-10-22

申请人： Mark Edward Bunnage ,  John Paul Mathias ,  Graham Nigel Maw ,  David James Rawson ,  Stephen Derek Albert Street ,  Anthony Wood

发明人： Mark Edward Bunnage ,  John Paul Mathias ,  Graham Nigel Maw ,  David James Rawson ,  Stephen Derek Albert Street ,  Anthony Wood

IPC分类号： A61K31505

CPC分类号： C07D401/12 ,  C07D231/14 ,  C07D487/04

摘要： There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, R4 and A have meanings given in the description, which are useful in the curative and prophylactic treatment of medical conditions for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

摘要翻译： 提供式IA和式IB的化合物，其中R 1，R 2，R 3，R 4和A具有在描述中给出的含义，其可用于治疗和预防治疗环状鸟苷3' ，需要5'-单磷酸磷酸二酯酶（例如cGMP PDE5）。

公开(公告)号：US20090035313A1

公开(公告)日：2009-02-05

申请号：US10564693

申请日：2004-07-13

申请人： Christohper Gordon Barber ,  Mark Edward Bunnage ,  John Wilson Harvey ,  John Paul Mathias

发明人： Christohper Gordon Barber ,  Mark Edward Bunnage ,  John Wilson Harvey ,  John Paul Mathias

IPC分类号： A61K39/395 ,  C07D409/12 ,  A61K31/4436 ,  A61P11/00 ,  A61K31/522 ,  A61K31/56

CPC分类号： A61K31/4436 ,  A61K9/2018 ,  A61K9/2866 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/519 ,  C07D213/82 ,  C07D409/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  Y02A50/411

摘要： This invention relates to nicotinamide derivatives of general formula (I): in which R1, Z and R2 have the meanings defined herein, and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of such derivatives.

摘要翻译： 本发明涉及通式（I）的烟酰胺衍生物：其中R1，Z和R2具有本文定义的含义，以及制备用于制备含有此类衍生物的组合物的中间体的方法。