JP2017519754A5 - - Google Patents
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- JP2017519754A5 JP2017519754A5 JP2016572754A JP2016572754A JP2017519754A5 JP 2017519754 A5 JP2017519754 A5 JP 2017519754A5 JP 2016572754 A JP2016572754 A JP 2016572754A JP 2016572754 A JP2016572754 A JP 2016572754A JP 2017519754 A5 JP2017519754 A5 JP 2017519754A5
- Authority
- JP
- Japan
- Prior art keywords
- disease
- alkyl
- compound according
- lymphoma
- cycloalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 206010025323 Lymphomas Diseases 0.000 claims 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 13
- 201000010099 disease Diseases 0.000 claims 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 13
- 125000005843 halogen group Chemical group 0.000 claims 13
- 150000003839 salts Chemical class 0.000 claims 12
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 10
- 125000002252 acyl group Chemical group 0.000 claims 10
- 208000032839 leukemia Diseases 0.000 claims 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims 9
- 208000003950 B-cell lymphoma Diseases 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 8
- 229910052799 carbon Inorganic materials 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 6
- 208000023275 Autoimmune disease Diseases 0.000 claims 6
- 208000037979 autoimmune inflammatory disease Diseases 0.000 claims 6
- 208000026278 immune system disease Diseases 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 5
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 5
- 125000004429 atom Chemical group 0.000 claims 5
- 210000003719 b-lymphocyte Anatomy 0.000 claims 5
- 125000002837 carbocyclic group Chemical group 0.000 claims 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 5
- 125000000623 heterocyclic group Chemical group 0.000 claims 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 5
- 206010025135 lupus erythematosus Diseases 0.000 claims 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 4
- 206010005949 Bone cancer Diseases 0.000 claims 4
- 208000018084 Bone neoplasm Diseases 0.000 claims 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 208000011231 Crohn disease Diseases 0.000 claims 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 4
- 206010027476 Metastases Diseases 0.000 claims 4
- 208000034578 Multiple myelomas Diseases 0.000 claims 4
- -1 NR b R c Chemical group 0.000 claims 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 4
- 201000000023 Osteosclerosis Diseases 0.000 claims 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims 4
- 206010003246 arthritis Diseases 0.000 claims 4
- 210000000988 bone and bone Anatomy 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 4
- 125000005347 halocycloalkyl group Chemical group 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 230000009401 metastasis Effects 0.000 claims 4
- 208000011580 syndromic disease Diseases 0.000 claims 4
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 229910052801 chlorine Inorganic materials 0.000 claims 3
- 239000000460 chlorine Substances 0.000 claims 3
- 229910052731 fluorine Inorganic materials 0.000 claims 3
- 239000011737 fluorine Substances 0.000 claims 3
- 210000002768 hair cell Anatomy 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 3
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims 3
- 210000003734 kidney Anatomy 0.000 claims 3
- 238000002054 transplantation Methods 0.000 claims 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 2
- 230000002490 cerebral effect Effects 0.000 claims 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
- 230000036210 malignancy Effects 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003367 polycyclic group Chemical group 0.000 claims 2
- 229920006395 saturated elastomer Polymers 0.000 claims 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 230000001413 cellular effect Effects 0.000 claims 1
- 239000013066 combination product Substances 0.000 claims 1
- 229940127555 combination product Drugs 0.000 claims 1
- 150000001925 cycloalkenes Chemical class 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000002831 pharmacologic agent Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
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- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
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| US10611766B2 (en) * | 2015-09-16 | 2020-04-07 | Loxo Oncology Inc. | Pyrazolopyrimidine derivatives as BTK inhibitors for the treatment of cancer |
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Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6660744B1 (en) | 1999-09-17 | 2003-12-09 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidines as therapeutic agents |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| US20030225098A1 (en) | 2002-03-21 | 2003-12-04 | Hirst Gavin C. | Kinase inhibitors |
| EA018573B1 (ru) | 2006-09-22 | 2013-09-30 | Фармасайкликс, Инк. | Ингибиторы тирозинкиназы брутона |
| EP2089391B1 (en) | 2006-11-03 | 2013-01-16 | Pharmacyclics, Inc. | Bruton's tyrosine kinase activity probe and method of using |
| SG10201508035TA (en) * | 2007-03-28 | 2015-10-29 | Pharmacyclics Inc | Inhibitors of bruton's tyrosine kinase |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| BRPI0914682B8 (pt) | 2008-06-27 | 2021-05-25 | Avila Therapeutics Inc | compostos de heteroarila e composições compreendendo os referidos compostos |
| JP5369183B2 (ja) * | 2008-07-16 | 2013-12-18 | ファーマサイクリックス，インク． | 固形腫瘍の治療用のブルートンのチロシンキナーゼの阻害剤 |
| EP2324008B1 (en) | 2008-07-24 | 2012-05-09 | Nerviano Medical Sciences S.R.L. | 3,4-diarylpyrazoles as protein kinase inhibitors |
| US8426428B2 (en) | 2008-12-05 | 2013-04-23 | Principia Biopharma, Inc. | EGFR kinase knockdown via electrophilically enhanced inhibitors |
| US7718662B1 (en) | 2009-10-12 | 2010-05-18 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| US20120087915A1 (en) | 2010-06-03 | 2012-04-12 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
| US9580427B2 (en) | 2011-05-17 | 2017-02-28 | The Regents Of The University Of California | Kinase inhibitors |
| KR102027598B1 (ko) | 2011-05-17 | 2019-10-01 | 프린시피아 바이오파마, 인코퍼레이티드 | 타이로신 키나아제 저해제 |
| CA2841080A1 (en) * | 2011-07-13 | 2013-01-17 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| EP2548877A1 (en) | 2011-07-19 | 2013-01-23 | MSD Oss B.V. | 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors |
| US8377946B1 (en) * | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| WO2013191965A1 (en) | 2012-06-18 | 2013-12-27 | Principia Biopharma Inc. | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for the treatment cancer and autoimmune diseases |
| WO2014022569A1 (en) | 2012-08-03 | 2014-02-06 | Principia Biopharma Inc. | Treatment of dry eye |
| US20150291554A1 (en) | 2012-11-02 | 2015-10-15 | Pfizer Inc. | Bruton's Tyrosine Kinase Inhibitors |
| CN103848810A (zh) | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
| GB201309085D0 (en) | 2013-05-20 | 2013-07-03 | Redx Pharma Ltd | Compounds |
| SI3052476T1 (sl) | 2013-09-30 | 2020-12-31 | Guangzhou Innocare Pharma Tech Co., Ltd. | Substituirani nikotinimidni inhibitorji BTK in njihova priprava in uporaba pri zdravljenju raka, vnetja in avtoimunske bolezni |
| EP3082809B1 (en) | 2013-12-20 | 2021-01-20 | Merck Sharp & Dohme Corp. | Btk inhibitors |
| EP3107544B1 (en) | 2014-02-21 | 2020-10-07 | Principia Biopharma Inc. | Salts and solid form of a btk inhibitor |
| GB201404987D0 (en) | 2014-03-20 | 2014-05-07 | Redx Pharma Ltd | Compounds |
| CN105085474B (zh) | 2014-05-07 | 2018-05-18 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| GB201410430D0 (en) | 2014-06-11 | 2014-07-23 | Redx Pharma Ltd | Compounds |
| US10611766B2 (en) | 2015-09-16 | 2020-04-07 | Loxo Oncology Inc. | Pyrazolopyrimidine derivatives as BTK inhibitors for the treatment of cancer |
| CN114573510B (zh) | 2015-12-16 | 2025-02-25 | 洛克索肿瘤学股份有限公司 | 可用作激酶抑制剂的化合物 |
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