公开(公告)号：US10323028B2

公开(公告)日：2019-06-18

申请号：US15363030

申请日：2016-11-29

Applicant: AstraZeneca AB ,  Cancer Research Technology Limited

Inventor： Johannes Wilhelmus Maria Nissink ,  Maurice Raymond Verschoyle Finlay ,  Mark David Charles

IPC: C07D417/14

Abstract: A compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: Q can be 1,2,4-triazin-3-yl, pyridazin-3-yl, 6-methylpyridazin-3-yl, or 6-fluoropyridazin-3-yl; R1 can be hydrogen, methoxy, trifluoromethoxy, oxetan-3-yl, 3-fluoroazetidin-1-yl, 3-methoxyazetidin-1-yl, or 3,3-difluoroazetidin-1-yl; R2 can be hydrogen or fluoro; R3 can be hydrogen or methoxy; and R4 can be methoxy, ethoxy, or methoxymethyl; provided that when R1 is hydrogen, methoxy or trifluoromethoxy, then R3 is not hydrogen, and/or R4 is methoxymethyl. The compound of formula (I) can inhibit glutaminase, e.g., GLS1.

公开(公告)号：US10294221B2

公开(公告)日：2019-05-21

申请号：US16025455

申请日：2018-07-02

Applicant: AstraZeneca AB ,  Cancer Research Technology Limited

Inventor： Maurice Raymond Verschoyle Finlay ,  Chukuemeka Tennyson Ekwuru ,  Mark David Charles ,  Piotr Antoni Raubo ,  Jonathan James Gordon Winter ,  Johannes Wilhelmus Maria Nissink

IPC: C07D417/14 ,  C07B59/00

Abstract: The specification relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where Q, R, R1 and R2 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent GLS1 mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating GLS1 kinase mediated disease, including cancer, using such compounds and salts.

公开(公告)号：US20190002462A1

公开(公告)日：2019-01-03

申请号：US16064297

申请日：2016-12-20

Applicant: CANCER RESEARCH TECHNOLOGY LIMITED

Inventor： Sebastien Gaston Andre NAUD ,  Julian BLAGG

IPC: C07D471/04 ,  A61P35/00

Abstract: The present invention relates to novel pyrrolo[3,2-c]pyridine-6-amino derivatives that inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases. In particular, the present invention relates to isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and their use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds and to pharmaceutical compositions comprising them.

公开(公告)号：US20180327504A1

公开(公告)日：2018-11-15

申请号：US15773821

申请日：2016-11-04

Applicant: Cancer Research Technology Limited

Inventor： Aymen Al-Shamkhani ,  Hak Tak Claude Chan ,  Mark Steven Cragg ,  Ruth Rosemary French ,  Martin John Glennie ,  Jane Elizabeth Willoughby

IPC: C07K16/28 ,  A61K39/00 ,  A61K45/06 ,  A61K39/395 ,  A61P35/02

CPC classification number: C07K16/2878 ,  A61K39/0011 ,  A61K39/3955 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/545 ,  A61K2039/57 ,  A61K2039/575 ,  A61K2039/80 ,  A61P35/02 ,  C07K16/2818 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/53 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/75

Abstract: The invention relates to antibodies specific for 4-1BB and OX40, as well as to methods for using such antibodies and therapeutic uses thereof.

公开(公告)号：US20180312808A1

公开(公告)日：2018-11-01

申请号：US15771875

申请日：2016-10-31

Applicant: CANCER RESEARCH TECHNOLOGY LIMITED ,  King's College London ,  The Francis Crick Institute Limited

Inventor： Adrian HAYDAY ,  Oliver NUSSBAUMER ,  Richard WOOLF

IPC: C12N5/0783

CPC classification number: C12N5/0638 ,  C12N2501/2302 ,  C12N2501/2315

Abstract: This invention relates to the expansion of non-haematopoietic tissue-resident γδ T cells in vitro by culturing lymphocytes obtained from non-haematopoietic tissue of humans or non-human animals in the presence of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) and the absence of TCR activation or co-stimulation signals, without any direct contact with stromal or epithelial cells. Methods of non-haematopoietic tissue-resident γδ T cell expansion are provided, as well as populations of non-haematopoietic tissue-resident γδ T cells and uses thereof.

公开(公告)号：US20180282418A1

公开(公告)日：2018-10-04

申请号：US15544323

申请日：2016-01-21

Applicant: Cancer Research Technology Limited

Inventor： Roy Bicknell ,  Peter Noy ,  Kabir Ali Khan

IPC: C07K16/28 ,  G01N33/50

Abstract: The invention provides a method of inhibiting angiogenes—is in an individual, the method comprising administering to the individual an agent that inhibits the interaction between CLEC14A and MMNR2. The inhibitor may be an antibody, a polypeptide, a peptide, a polynucleotide, a peptidomimetic, a natural product, a carbohydrate, an aptamer or a small molecule

公开(公告)号：US10040788B2

公开(公告)日：2018-08-07

申请号：US15314562

申请日：2015-05-27

Applicant: AstraZeneca AB ,  Cancer Research Technology Limited

Inventor： Maurice Raymond Verschoyle Finlay ,  Chukuemeka Tennyson Ekwuru ,  Mark David Charles ,  Piotr Antoni Raubo ,  Jonathan James Gordon Winter ,  Johannes Wilhelmus Maria Nissink

IPC: C07D417/14 ,  C07B59/00

Abstract: The specification relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, where Q, R, R1 and R2 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent GLS1 mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating GLS1 kinase mediated disease, including cancer, using such compounds and salts.

公开(公告)号：US20180194782A1

公开(公告)日：2018-07-12

申请号：US15846679

申请日：2017-12-19

Applicant: AstraZeneca AB ,  Cancer Research Technology Limited

Inventor： Maurice Raymond Verschoyle FINLAY ,  Frederick Woolf GOLDBERG ,  Attilla Kuan Tsuei TING

IPC: C07D519/00 ,  A61K31/522 ,  A61P35/00 ,  A61K45/06 ,  A61K31/502

CPC classification number: C07D519/00 ,  A61K31/502 ,  A61K31/522 ,  A61K45/06 ,  A61P35/00 ,  C07D473/18 ,  A61K2300/00

Abstract: The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1 and R2 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.

公开(公告)号：US09914730B2

公开(公告)日：2018-03-13

申请号：US14038915

申请日：2013-09-27

Applicant: Ignyta, Inc. ,  Cancer Research Technology Limited

Inventor： Henry J. Breslin ,  Bruce D. Dorsey ,  Benjamin J Dugan ,  Katherine M. Fowler ,  Robert L Hudkins ,  Eugen F. Mesaros ,  Nathaniel J. T. Monck ,  Emma L. Morris ,  Ikeoluwa Olowoye ,  Gregory R. Ott ,  Gregoire A. Pave ,  Jonathan R. Roffey ,  Christelle N. Soudy ,  Ming Tao ,  Craig A. Zificsak ,  Allison L. Zulli

IPC: A61K31/675 ,  C07D471/04 ,  C07D519/00 ,  C07D493/08 ,  C07D498/04 ,  C07F9/6584

CPC classification number: C07D471/04 ,  C07D493/08 ,  C07D498/04 ,  C07D519/00 ,  C07F9/6584

Abstract: The present application provides azaquinazoline compounds as defined herein. This application further describes compositions comprising the same. These azaquinazoline compounds and their salts have atypical protein kinase C (“aPKC”) inhibitory activity, and may be used to treat proliferative disorders.

公开(公告)号：US09765059B2

公开(公告)日：2017-09-19

申请号：US15191967

申请日：2016-06-24

Applicant: Cancer Research Technology Limited

Inventor： Ian Collins ,  Michael Lainchbury ,  Thomas Peter Matthews ,  John Charles Reader

IPC: A61K31/497 ,  C07D401/14 ,  C07D401/12 ,  A61K45/06 ,  A61N5/10 ,  A61K9/00

CPC classification number: C07D401/14 ,  A61K9/0053 ,  A61K31/497 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1098 ,  C07D401/12

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyridyl-amino-pyrazine carbonitrile compounds that, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; and (e) ionizing radiation.