公开(公告)号：US20110130413A1

公开(公告)日：2011-06-02

申请号：US12992990

申请日：2009-05-13

Applicant: Bernard Golding ,  Peter Cicala ,  Richard Franklin ,  Angus Macleod

Inventor： Bernard Golding ,  Peter Cicala ,  Richard Franklin ,  Angus Macleod

IPC: A61K31/517 ,  C07D239/84 ,  A61P7/02

CPC classification number: C07D239/84

Abstract: This invention relates to the discovery of prodrugs of substituted analogues of the selective platelet lowering agent anagrelide which have reduced potential for cardiovascular side-effects and which should therefore lead to improved patient compliance and safety in the treatment of myeloproliferative diseases. More specifically, the present invention relates to prodrugs of certain imidazoquinazoline derivatives which have the general formula (I) shown below wherein the substituents have the meanings defined in claim 1 and which have utility as platelet lowering agents in humans. The compounds of the present invention function by inhibiting the formation of blood platelets.

Abstract translation: 本发明涉及降低选择性血小板降低剂阿那格雷的取代类似物的前药，其具有降低心血管副作用的潜力，因此应该导致改善的患者依从性和治疗骨髓增生性疾病的安全性。 更具体地，本发明涉及具有下面通式（I）的某些咪唑并喹唑啉衍生物的前药，其中取代基具有权利要求1中定义的含义，并且其可用作人血小板降低剂。 本发明化合物通过抑制血小板的形成起作用。

公开(公告)号：US20070238729A1

公开(公告)日：2007-10-11

申请号：US11758332

申请日：2007-06-05

Applicant: Niall Martin ,  Graeme Smith ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Laurent Rigoreau ,  Xiao-ling Cockcroft ,  Vincent Junior Loh ,  Paul Workman ,  Florence Raynaud ,  Bernard Nutley

Inventor： Niall Martin ,  Graeme Smith ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Laurent Rigoreau ,  Xiao-ling Cockcroft ,  Vincent Junior Loh ,  Paul Workman ,  Florence Raynaud ,  Bernard Nutley

IPC: A61K31/351 ,  A61K31/519 ,  A61K31/5377 ,  A61P35/00

CPC classification number: C07D417/04 ,  C07D309/38 ,  C07D311/22 ,  C07D311/92 ,  C07D471/04

Abstract: The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR4 and O, O and CR′4 and NR″4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R3 and R4 or R′4 is an optionally substituted C3-20 heteroaryl or C5-20 aryl group, and the other of R3 and R4 or R′4 is H, or R3 and R4 or R″4 together are -A-B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

Abstract translation: 本发明涉及式（I）化合物及其异构体，盐，溶剂合物，化学保护形式及其前药在制备用于抑制DNA-PK活性的药物中的用途，其中R 1， R 2和R 2各自独立地为氢，任选取代的C 1-7 - 烷基，C 3-20杂环基或C 或者可以与它们所连接的氮原子一起形成具有4至8个环原子的任选取代的杂环; X和Y选自CR 4和O，O和CR'4和NR“4和N，其中不饱和键处于 R 2中的一个是R 3，R 4，R 4和R 4中的一个是任选取代的C 3 -20个杂芳基或C 5-20-20芳基，R 3和R 4中的另一个或R' > 4 是H，或R 3和R 4或R“4”一起是-AB-，它们共同表示 稠合的任选取代的芳环。 与PI3-激酶和/或ATM相比，化合物还选择性地抑制DNA-PK的活性。

公开(公告)号：US20060264427A1

公开(公告)日：2006-11-23

申请号：US11403606

申请日：2006-04-13

Applicant: Graeme Smith ,  Niall Martin ,  Keith Menear ,  Marc Hummersone ,  Xiao-ling Cockcroft ,  Mark Frigerio ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  David Newell ,  HiIary Calvert ,  Nicola Curtin ,  Kappusamy Saravanan ,  Marine Desage-El Murr

Inventor： Graeme Smith ,  Niall Martin ,  Keith Menear ,  Marc Hummersone ,  Xiao-ling Cockcroft ,  Mark Frigerio ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  David Newell ,  HiIary Calvert ,  Nicola Curtin ,  Kappusamy Saravanan ,  Marine Desage-El Murr

IPC: A61K31/541 ,  A61K31/5377 ,  C07D487/02

CPC classification number: C07D413/00 ,  C07D401/14 ,  C07D405/04 ,  C07D407/04 ,  C07D407/14 ,  C07D409/04 ,  C07D471/04

Abstract: Compounds of formula I: wherein A, B and D are respectively selected from the group consisting of: (i) CH, NH, C; (ii) CH, N, N;and (iii) CH, O, C; the dotted lines represent two double bonds in the appropriate locations; and where Z is selected from S, O, C(═O), CH2 and NH are disclosed for use in inhibiting DNA-PK.

Abstract translation: 式I化合物：其中A，B和D分别选自：（i）CH，NH，C; （ii）CH，N，N;和（iii）CH，O，C; 虚线表示适当位置的两个双键; 并且其中Z选自S，O，C（-O），CH 2和NH，用于抑制DNA-PK。

公开(公告)号：US08530651B2

公开(公告)日：2013-09-10

申请号：US13132001

申请日：2009-11-30

Applicant: Bernard Golding

Inventor： Bernard Golding

IPC: C07D487/04

CPC classification number: C07D487/04 ,  C07C201/08 ,  C07C201/12 ,  C07C227/16 ,  C07C227/18 ,  C07C303/28 ,  C07C309/66 ,  C07C229/14 ,  C07C205/44 ,  C07C205/26

Abstract: The present invention relates to a novel process for producing quinazoline compounds which are useful in therapy. More specifically, the compounds produced by the process of the invention are useful in the treatment of a number of cardiovascular diseases. The process of the invention provides 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin 2(3H)-one, more commonly known as anagrelide and its analogues in a clean and efficient manner.

Abstract translation: 本发明涉及可用于治疗的喹唑啉化合物的新方法。 更具体地，通过本发明的方法生产的化合物可用于治疗许多心血管疾病。 本发明的方法以清洁和有效的方式提供了6,7-二氯-1,5-二氢咪唑并[2,1-b]喹唑啉2（3H） - 酮，更通常称为阿那格雷及其类似物。

公开(公告)号：US20110071173A1

公开(公告)日：2011-03-24

申请号：US12993054

申请日：2009-05-13

Applicant: Bernard Golding ,  Richard Franklin ,  Angus Macleod

Inventor： Bernard Golding ,  Richard Franklin ,  Angus Macleod

IPC: A61K31/519 ,  C07D239/00 ,  A61P7/00

CPC classification number: C07D487/04

Abstract: This invention relates to the discovery of substituted analogues of the selective platelet lowering agent anagrelide with reduced potential for cardiovascular side-effects which should lead to improved patient compliance and safety in the treatment of myeloproliferative diseases. More specifically, the present invention relates to certain imidazoquinazoline derivatives which have the general formula shown below wherein the substituents have the meanings defined in claim 1: and which have utility as platelet lowering agents in humans. The compounds of the present invention function by inhibiting megakaryocytopoeisis and hence the formation of blood platelets.

Abstract translation: 本发明涉及具有降低心血管副作用潜力的选择性血小板降低剂阿那格雷的取代类似物的发现，其应该导致改善的患者依从性和治疗骨髓增生性疾病的安全性。 更具体地，本发明涉及具有以下通式的某些咪唑并喹唑啉衍生物，其中取代基具有权利要求1中定义的含义，并且其在人体中可用作血小板降低剂。 本发明的化合物通过抑制巨核细胞吞噬作用并因此起血小板的形成的作用。

公开(公告)号：US20110071171A1

公开(公告)日：2011-03-24

申请号：US12993013

申请日：2009-05-13

Applicant: Bernard Golding ,  Richard Franklin

Inventor： Bernard Golding ,  Richard Franklin

IPC: A61K31/519 ,  C07D487/04 ,  A61P7/02 ,  A61P35/00 ,  A61P7/00

CPC classification number: C07D487/04

Abstract: This invention relates to the discovery of substituted analogues of the selective platelet lowering agent anagrelide with reduced potential for cardiovascular side-effects which should lead to improved patient compliance and safety in the treatment of myeloproliferative diseases. More specifically, the present invention relates to certain imidazoquinazoline derivatives which have the general formula shown below wherein the substituents have the meanings defined in claim 1: and which have utility as platelet lowering agents in humans. The compounds of the present invention function by inhibiting megakaryocytopoeisis and hence the formation of blood platelets.

Abstract translation: 本发明涉及具有降低心血管副作用潜力的选择性血小板降低剂阿那格雷的取代类似物的发现，其应该导致改善的患者依从性和治疗骨髓增生性疾病的安全性。 更具体地，本发明涉及具有以下通式的某些咪唑并喹唑啉衍生物，其中取代基具有权利要求1中定义的含义，并且其在人体中可用作血小板降低剂。 本发明的化合物通过抑制巨核细胞吞噬作用并因此起血小板的形成的作用。

公开(公告)号：US20070238731A1

公开(公告)日：2007-10-11

申请号：US11575606

申请日：2005-09-20

Applicant: Graeme Smith ,  Niall Martin ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  Kappusamy Saravanan ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Keith Menear ,  Marc Hummersone

Inventor： Graeme Smith ,  Niall Martin ,  Roger Griffin ,  Bernard Golding ,  Ian Hardcastle ,  Kappusamy Saravanan ,  David Newell ,  Hilary Calvert ,  Nicola Curtin ,  Keith Menear ,  Marc Hummersone

IPC: A61K31/5355 ,  C07D413/14

CPC classification number: C07D413/14 ,  C07D409/04 ,  C07D409/14

Abstract: A compound of formula I: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein: R1 and R2 are independently selected from hydrogen, an optionally substituted C1-7 alkyl group, C3-20heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; Q is —NH—C(═O)— or —O—; Y is an optionally substituted C1-5 alkylene group; X is selected from SR3 or NR4R5, wherein, R3 or R4 and R5 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R4 and R5 may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; if Q is —O—, X is additionally selected from —C(═O)—NR6R7, wherein R6 and R7 are independently selected from hydrogen, optionally substituted C1-7 alkyl, C5-20 aryl, or C3-20 heterocyclyl groups, or R6 and R7 may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and if Q is —NH—C(═O)—, —Y—X may additionally be selected from C1-7 alkyl.

Abstract translation: 式I化合物及其异构体，盐，溶剂合物，化学保护形式及其前药，其中：R 1和R 2独立地选自氢，任选地 取代的C 1-7烷基，C 3-20杂环基或C 5-20-20芳基，或者可以一起形成 与它们所连接的氮原子一起形成具有4至8个环原子的任选取代的杂环; Q是-NH-C（-O） - 或-O-; Y是任选取代的C 1-5亚烷基; X选自SR 3或NR 4 R 5，其中，R 3或R 4 R 5和R 5独立地选自氢，任选取代的C 1-7 - 烷基，C 5-20芳基或C 3-20个杂环基或R 4和R 5可以一起与它们所连接的氮原子一起形成任选地 具有4至8个环原子的取代杂环; 如果Q是-O-，X另外选自-C（-O）-NR 6 R 7，其中R 6和R 独立地选自氢，任选取代的C 1-7 - 烷基，C 5-20-20芳基或C 3-20 或者R 6和R 7可以与它们所连接的氮原子一起形成任选取代的杂环，其具有4个 至8个环原子; 并且如果Q是-NH-C（-O） - ，-Y-X可另外选自C 1-7烷基。