JP2016510745A5 - - Google Patents
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- JP2016510745A5 JP2016510745A5 JP2015561550A JP2015561550A JP2016510745A5 JP 2016510745 A5 JP2016510745 A5 JP 2016510745A5 JP 2015561550 A JP2015561550 A JP 2015561550A JP 2015561550 A JP2015561550 A JP 2015561550A JP 2016510745 A5 JP2016510745 A5 JP 2016510745A5
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- Japan
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- substituted
- heterocyclyl
- compound according
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 34
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 30
- 101000799140 Homo sapiens Activin receptor type-1 Proteins 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 229940124530 sulfonamide Drugs 0.000 claims description 19
- 150000003456 sulfonamides Chemical class 0.000 claims description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 18
- 125000004442 acylamino group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 14
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 150000003384 small molecules Chemical class 0.000 claims description 14
- 150000003462 sulfoxides Chemical class 0.000 claims description 14
- -1 cyano, sulfonyl Chemical group 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 102000054953 human ACVR1 Human genes 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 102100034111 Activin receptor type-1 Human genes 0.000 claims description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 10
- 241000282412 Homo Species 0.000 claims description 9
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 9
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 8
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- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 claims description 6
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 229940112869 bone morphogenetic protein Drugs 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 5
- 229940002612 prodrug Drugs 0.000 claims description 5
- 201000001376 Familial Combined Hyperlipidemia Diseases 0.000 claims description 4
- 101000712674 Homo sapiens TGF-beta receptor type-1 Proteins 0.000 claims description 4
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- 206010027476 Metastases Diseases 0.000 claims description 4
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- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 4
- 102000052842 human TGFBR1 Human genes 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 230000036244 malformation Effects 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 claims description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 2
- 102000006991 Apolipoprotein B-100 Human genes 0.000 claims description 2
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- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
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- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 2
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- 102100025423 Bone morphogenetic protein receptor type-1A Human genes 0.000 claims description 2
- 102100027052 Bone morphogenetic protein receptor type-1B Human genes 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000004434 Calcinosis Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 241000233866 Fungi Species 0.000 claims description 2
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims description 2
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 claims description 2
- 101000934638 Homo sapiens Bone morphogenetic protein receptor type-1A Proteins 0.000 claims description 2
- 101000984546 Homo sapiens Bone morphogenetic protein receptor type-1B Proteins 0.000 claims description 2
- 101000799194 Homo sapiens Serine/threonine-protein kinase receptor R3 Proteins 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 102100025744 Mothers against decapentaplegic homolog 1 Human genes 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000013612 Parathyroid disease Diseases 0.000 claims description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 101700032040 SMAD1 Proteins 0.000 claims description 2
- 208000005475 Vascular calcification Diseases 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 210000004504 adult stem cell Anatomy 0.000 claims description 2
- 201000007930 alcohol dependence Diseases 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- 229940124522 antiretrovirals Drugs 0.000 claims description 2
- 239000003903 antiretrovirus agent Substances 0.000 claims description 2
- 239000002876 beta blocker Substances 0.000 claims description 2
- 229940097320 beta blocking agent Drugs 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 230000002308 calcification Effects 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 230000007211 cardiovascular event Effects 0.000 claims description 2
- 230000024245 cell differentiation Effects 0.000 claims description 2
- 230000001587 cholestatic effect Effects 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims description 2
- 230000007547 defect Effects 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 2
- 208000028208 end stage renal disease Diseases 0.000 claims description 2
- 201000000523 end stage renal failure Diseases 0.000 claims description 2
- 239000000262 estrogen Substances 0.000 claims description 2
- 229940011871 estrogen Drugs 0.000 claims description 2
- 239000003862 glucocorticoid Substances 0.000 claims description 2
- 210000003709 heart valve Anatomy 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
- 235000009200 high fat diet Nutrition 0.000 claims description 2
- 102000049307 human ACVR1B Human genes 0.000 claims description 2
- 102000047644 human ACVRL1 Human genes 0.000 claims description 2
- 208000003532 hypothyroidism Diseases 0.000 claims description 2
- 230000002989 hypothyroidism Effects 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 230000000366 juvenile effect Effects 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 230000002503 metabolic effect Effects 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 244000045947 parasite Species 0.000 claims description 2
- 208000022560 parathyroid gland disease Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000026731 phosphorylation Effects 0.000 claims description 2
- 238000006366 phosphorylation reaction Methods 0.000 claims description 2
- 239000000583 progesterone congener Substances 0.000 claims description 2
- 230000000750 progressive effect Effects 0.000 claims description 2
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims description 2
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
- 230000000276 sedentary effect Effects 0.000 claims description 2
- 230000011664 signaling Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 claims description 2
- 239000003451 thiazide diuretic agent Substances 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 37
- 102000004895 Lipoproteins Human genes 0.000 claims 1
- 108090001030 Lipoproteins Proteins 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 description 27
- 208000014644 Brain disease Diseases 0.000 description 1
- BBDGBGOVJPEFBT-UHFFFAOYSA-N C(C1)NCCN1c(cc1)ccc1-c1c[n]2ncc(-c3cccc4c3cccn4)c2nc1 Chemical compound C(C1)NCCN1c(cc1)ccc1-c1c[n]2ncc(-c3cccc4c3cccn4)c2nc1 BBDGBGOVJPEFBT-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361772465P | 2013-03-04 | 2013-03-04 | |
| US61/772,465 | 2013-03-04 | ||
| PCT/US2014/020360 WO2014138088A1 (en) | 2013-03-04 | 2014-03-04 | Bmp inhibitors and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2016510745A JP2016510745A (ja) | 2016-04-11 |
| JP2016510745A5 true JP2016510745A5 (https=) | 2017-04-06 |
Family
ID=51491878
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015561550A Withdrawn JP2016510745A (ja) | 2013-03-04 | 2014-03-04 | Ｂｍｐ阻害剤およびその使用方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20160115167A1 (https=) |
| EP (1) | EP2964651A4 (https=) |
| JP (1) | JP2016510745A (https=) |
| WO (1) | WO2014138088A1 (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5638961B2 (ja) | 2008-03-13 | 2014-12-10 | ザ ジェネラル ホスピタル コーポレイション | Ｂｍｐシグナル伝達経路のインヒビター |
| EP3721880B1 (en) | 2010-09-01 | 2022-02-02 | Thomas Jefferson University | Composition and method for muscle repair and regeneration |
| JP6430383B2 (ja) | 2012-09-28 | 2018-11-28 | ヴァンダービルト ユニバーシティーＶａｎｄｅｒｂｉｌｔ Ｕｎｉｖｅｒｓｉｔｙ | 選択的ｂｍｐ阻害剤としての縮合複素環化合物 |
| WO2014160203A2 (en) | 2013-03-14 | 2014-10-02 | The Brigham And Women's Hospital, Inc. | Bmp inhibitors and methods of use thereof |
| MX394360B (es) | 2013-03-14 | 2025-03-24 | Sumitomo Pharma Oncology Inc | Inhibidores de jak2 y alk2 y metodos para su uso. |
| US10513521B2 (en) | 2014-07-15 | 2019-12-24 | The Brigham And Women's Hospital, Inc. | Compositions and methods for inhibiting BMP |
| US10179777B2 (en) | 2015-04-16 | 2019-01-15 | Merck Patent Gmbh | 3-(1H-benzimidazol-2-yl)-1H-pyridin-2-one derivatives |
| US10669528B2 (en) | 2015-06-25 | 2020-06-02 | Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance |
| CN105130991B (zh) * | 2015-07-10 | 2017-09-19 | 成都知普莱生物医药科技有限公司 | 一种合成骨形态发生蛋白受体抑制剂的方法 |
| EP4049665B1 (en) | 2016-03-15 | 2025-03-12 | The Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion |
| CN109311889B (zh) * | 2016-04-15 | 2021-11-16 | 缆图药品公司 | 激活素受体样激酶抑制剂 |
| JP7023868B2 (ja) * | 2016-06-08 | 2022-02-22 | クレメンティア ファーマシューティカルズ，インコーポレイテッド | 異所性骨化を治療するための方法 |
| MX388518B (es) * | 2016-07-20 | 2025-03-19 | Novartis Ag | Derivados de aminopiridina y su uso como inhibidores selectivos de alk-2. |
| CA3043807A1 (en) | 2016-11-16 | 2018-05-24 | Clementia Pharmaceuticals Inc. | Methods for treating multiple osteochondroma (mo) |
| WO2018124001A1 (ja) | 2016-12-27 | 2018-07-05 | 国立研究開発法人理化学研究所 | Ｂｍｐシグナル阻害化合物 |
| EP3562827A1 (en) | 2016-12-30 | 2019-11-06 | Frequency Therapeutics, Inc. | 1h-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells |
| EP3615538B1 (en) * | 2017-04-27 | 2024-02-07 | The Brigham and Women's Hospital, Inc. | Novel alk2 inhibitors and methods for inhibiting bmp signaling |
| EP3697786B1 (en) | 2017-10-18 | 2022-08-31 | Blueprint Medicines Corporation | Substituted pyrrolopyridines as inhibitors of activin receptor-like kinase |
| EP3710021A4 (en) | 2017-11-15 | 2021-08-11 | Semma Therapeutics, Inc. | ISLAND CELL MANUFACTURING COMPOSITIONS AND METHOD OF USE |
| WO2019126686A1 (en) | 2017-12-21 | 2019-06-27 | Frequency Therapeutics, Inc. | 1,2-dihydro-3h-pyrazol-3-one compounds and methods of using same |
| WO2019178383A1 (en) | 2018-03-14 | 2019-09-19 | Vanderbilt University | Inhibition of bmp signaling, compounds, compositions and uses thereof |
| AU2019310590A1 (en) | 2018-07-26 | 2021-01-14 | Sumitomo Pharma Oncology, Inc. | Methods for treating diseases associated with abnormal acvr1 expression and acvr1 inhibitors for use in the same |
| EP3870181B1 (en) | 2018-10-26 | 2024-08-14 | Keros Therapeutics, Inc. | Crystal forms of an alk2 inhibitor |
| CN111721932B (zh) * | 2019-03-20 | 2024-08-16 | 复旦大学 | 以cd133为靶点的小分子化合物的筛选方法及其在制药中的应用 |
| US20220372135A1 (en) | 2019-09-27 | 2022-11-24 | Disc Medicine, Inc. | Methods for treating myelofibrosis and related conditions |
| JP7717065B2 (ja) | 2019-11-22 | 2025-08-01 | インサイト コーポレーション | Ａｌｋ２阻害剤及びｊａｋ２阻害剤を含む併用療法 |
| US12508262B2 (en) | 2020-04-30 | 2025-12-30 | Keros Therapeutics, Inc. | Methods of using ALK2 inhibitors |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| WO2021257532A1 (en) | 2020-06-16 | 2021-12-23 | Incyte Corporation | Alk2 inhibitors for the treatment of anemia |
| WO2022098812A1 (en) | 2020-11-04 | 2022-05-12 | Keros Therapeutics, Inc. | Methods of treating iron overload |
| WO2022099166A1 (en) * | 2020-11-09 | 2022-05-12 | Keros Therapeutics, Inc. | Methods of treating cardiovascular-related disease |
| CN114668764A (zh) * | 2022-04-07 | 2022-06-28 | 中南大学 | 化合物在制备治疗糖尿病足的外用药物上的应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2062048A4 (en) * | 2006-09-12 | 2009-12-02 | Gen Hospital Corp | METHOD FOR IDENTIFYING CELL SIGNALING MODULATING COMPOUNDS AND METHOD FOR USING SUCH COMPOSITES |
| JP5638961B2 (ja) * | 2008-03-13 | 2014-12-10 | ザ ジェネラル ホスピタル コーポレイション | Ｂｍｐシグナル伝達経路のインヒビター |
-
2014
- 2014-03-04 EP EP14760191.8A patent/EP2964651A4/en not_active Withdrawn
- 2014-03-04 WO PCT/US2014/020360 patent/WO2014138088A1/en not_active Ceased
- 2014-03-04 US US14/772,630 patent/US20160115167A1/en not_active Abandoned
- 2014-03-04 JP JP2015561550A patent/JP2016510745A/ja not_active Withdrawn
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