公开(公告)号：US11975001B2

公开(公告)日：2024-05-07

申请号：US18312333

申请日：2023-05-04

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Michael Karl Bechtold ,  Julie Kay Cahill ,  Katja Maren Fastnacht ,  Kieran James Lennon ,  Bernd Harald Liepold ,  Claudia Bettina Packhaeuser ,  Benedikt Steitz

IPC分类号： A61K31/502 ,  A61K9/20 ,  A61K47/02 ,  A61K47/12 ,  A61K47/20 ,  A61K47/32

CPC分类号： A61K31/502 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2027 ,  A61K9/2095 ,  A61K47/02 ,  A61K47/12 ,  A61K47/20 ,  A61K47/32

摘要： The present invention relates to a pharmaceutical formulation comprising the drug 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, such as copovidone. The invention also relates to a daily pharmaceutical dose of the drug provided by such a formulation. In addition, the invention relates to the use of a matrix polymer that exhibits low hygroscopicity and high softening temperature in solid dispersion with 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one for increasing the bioavailability of the drug.

公开(公告)号：US09717736B2

公开(公告)日：2017-08-01

申请号：US14733257

申请日：2015-06-08

申请人： KuDOS Pharmaceuticals Limited

发明人： Heather Mary Ellen Duggan ,  Frederic Georges Marie Leroux ,  Karine Fabienne Malagu ,  Niall Morrison Barr Martin ,  Keith Menear ,  Graeme Cameron Murray Smith

IPC分类号： C07D413/14 ,  C07D471/04 ,  C07D475/08 ,  C07D475/10 ,  A61K31/5377 ,  A61K31/565 ,  A61K45/06

CPC分类号： A61K31/5377 ,  A61K31/565 ,  A61K45/06 ,  C07D413/14 ,  C07D471/04 ,  C07D475/08 ,  C07D475/10

摘要： There is provided a compound of formula I: or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.

公开(公告)号：US20160067258A1

公开(公告)日：2016-03-10

申请号：US14733257

申请日：2015-06-08

申请人： KuDOS Pharmaceuticals Limited

发明人： Heather Mary Ellen Duggan ,  Frederic Georges Marie Leroux ,  Karine Fabienne Malagu ,  Niall Morrison Barr Martin ,  Keith Menear ,  Graeme Cameron Murray Smith

IPC分类号： A61K31/5377 ,  A61K31/565 ,  A61K45/06

CPC分类号： A61K31/5377 ,  A61K31/565 ,  A61K45/06 ,  C07D413/14 ,  C07D471/04 ,  C07D475/08 ,  C07D475/10

摘要： There is provided a compound of formula I: or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.

摘要翻译： 提供式I化合物或其药学上可接受的盐。 还提供了制备式1化合物的方法和式1化合物作为药物和用于治疗癌症的用途。

公开(公告)号：US20240245643A1

公开(公告)日：2024-07-25

申请号：US18473061

申请日：2023-09-22

申请人： The Institute of Cancer Research: Royal Cancer Hospital ,  Kudos Pharmaceuticals Limited

发明人： Alan Ashworth ,  Stephen Jackson ,  Niall Martin ,  Graeme Cameron Murray Smith

IPC分类号： A61K31/366 ,  A61K31/00 ,  A61K31/405 ,  A61K31/4184 ,  A61K31/4706 ,  A61K31/473 ,  A61K31/502 ,  A61K31/517 ,  A61K31/522 ,  A61K31/675

CPC分类号： A61K31/366 ,  A61K31/00 ,  A61K31/405 ,  A61K31/4184 ,  A61K31/4706 ,  A61K31/473 ,  A61K31/502 ,  A61K31/517 ,  A61K31/522 ,  A61K31/675 ,  Y02A50/30

摘要： The present invention relates to the recognition that inhibition of the base excision repair pathway is selectively lethal in cells which are deficient in HR dependent DNA DSB repair. Methods and means relating to the treatment of cancers which are deficient in HR dependent DNA DSB repair using inhibitors which target base excision repair components, such as PARP, is provided herein.

公开(公告)号：US20230346780A1

公开(公告)日：2023-11-02

申请号：US18312333

申请日：2023-05-04

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Michael Karl Bechtold ,  Julie Kay Cahill ,  Katja Maren Fastnacht ,  Kieran James Lennon ,  Bernd Harald Liepold ,  Claudia Bettina Packhaeuser ,  Benedikt Steitz

IPC分类号： A61K31/502 ,  A61K47/02 ,  A61K47/12 ,  A61K9/20 ,  A61K47/32 ,  A61K47/20

CPC分类号： A61K31/502 ,  A61K47/02 ,  A61K47/12 ,  A61K9/2027 ,  A61K9/2013 ,  A61K47/32 ,  A61K9/2009 ,  A61K9/2095 ,  A61K47/20

摘要： The present invention relates to a pharmaceutical formulation comprising the drug 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, such as copovidone. The invention also relates to a daily pharmaceutical dose of the drug provided by such a formulation. In addition, the invention relates to the use of a matrix polymer that exhibits low hygroscopicity and high softening temperature in solid dispersion with 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one for increasing the bioavailability of the drug.

公开(公告)号：US11160803B2

公开(公告)日：2021-11-02

申请号：US16567892

申请日：2019-09-11

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A61K31/502 ,  A61K31/00 ,  C07D237/32 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D403/10 ,  C07D495/04 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D403/14 ,  A61K31/506 ,  A61N5/10 ,  C07D243/08

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

公开(公告)号：US10034884B2

公开(公告)日：2018-07-31

申请号：US15626282

申请日：2017-06-19

申请人： KuDOS Pharmaceuticals Limited

发明人： Heather Mary Ellen Duggan ,  Frederic Georges Marie Leroux ,  Karine Fabienne Malagu ,  Niall Morrison Barr Martin ,  Keith Menear ,  Graeme Cameron Murray Smith

IPC分类号： A61K31/5377 ,  A61K31/565 ,  A61K45/06 ,  C07D413/14 ,  C07D471/04 ,  C07D475/08 ,  C07D475/10

CPC分类号： A61K31/5377 ,  A61K31/565 ,  A61K45/06 ,  C07D413/14 ,  C07D471/04 ,  C07D475/08 ,  C07D475/10

摘要： There is provided a compound of formula I: or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.

公开(公告)号：US09566276B2

公开(公告)日：2017-02-14

申请号：US14853360

申请日：2015-09-14

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A61K31/502 ,  A61K31/00 ,  C07D237/32 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D403/14 ,  A61K31/506 ,  A61N5/10

CPC分类号： A61K31/502 ,  A61K31/00 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  A61N5/10 ,  C07D237/32 ,  C07D243/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NRX或CRXRY; 如果X = NRX则n为1或2，如果X = CRXRY则n为1; RX选自H，任选取代的C 1-20烷基，C 5-20芳基，C 3-20杂环基，酰氨基，硫代酰氨基，酯，酰基和磺酰基; RY选自H，羟基，氨基; 或RX和RY可以一起形成螺C 3-7环烷基或杂环基; RC1和RC2均为氢，或当X为CRXRY时，RC1，RC2，RX和RY与它们所连接的碳原子一起形成任选取代的稠合芳环; 并且R 1选自H和卤素。

公开(公告)号：US12048695B2

公开(公告)日：2024-07-30

申请号：US18312375

申请日：2023-05-04

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Michael Karl Bechtold ,  Julie Kay Cahill ,  Katja Maren Fastnacht ,  Kieran James Lennon ,  Bernd Harald Liepold ,  Claudia Bettina Packhaeuser ,  Benedikt Steitz

IPC分类号： A61K31/502 ,  A61K9/14 ,  A61K9/20 ,  A61K47/02 ,  A61K47/12 ,  A61K47/20 ,  A61K47/32

CPC分类号： A61K31/502 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2027 ,  A61K9/2095 ,  A61K47/02 ,  A61K47/12 ,  A61K47/20 ,  A61K47/32

摘要： The present invention relates to a pharmaceutical formulation comprising the drug 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, such as copovidone. The invention also relates to a daily pharmaceutical dose of the drug provided by such a formulation. In addition, the invention relates to the use of a matrix polymer that exhibits low hygroscopicity and high softening temperature in solid dispersion with 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one for increasing the bioavailability of the drug.

公开(公告)号：US20230338372A1

公开(公告)日：2023-10-26

申请号：US18312375

申请日：2023-05-04

申请人： KUDOS PHARMACEUTICALS LIMITED

发明人： Michael Karl Bechtold ,  Julie Kay Cahill ,  Katja Maren Fastnacht ,  Kieran James Lennon ,  Bernd Harald Liepold ,  Claudia Bettina Packhaeuser ,  Benedikt Steitz

IPC分类号： A61K9/20 ,  A61K47/12 ,  A61K31/502 ,  A61K47/02 ,  A61K47/20 ,  A61K47/32

CPC分类号： A61K31/502 ,  A61K9/2009 ,  A61K9/2013 ,  A61K9/2027 ,  A61K9/2095 ,  A61K47/02 ,  A61K47/12 ,  A61K47/20 ,  A61K47/32

摘要： The present invention relates to a pharmaceutical formulation comprising the drug 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, such as copovidone. The invention also relates to a daily pharmaceutical dose of the drug provided by such a formulation. In addition, the invention relates to the use of a matrix polymer that exhibits low hygroscopicity and high softening temperature in solid dispersion with 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one for increasing the bioavailability of the drug.