RU2019107011A - Композиции апилимода и способы их применения - Google Patents
Композиции апилимода и способы их применения Download PDFInfo
- Publication number
- RU2019107011A RU2019107011A RU2019107011A RU2019107011A RU2019107011A RU 2019107011 A RU2019107011 A RU 2019107011A RU 2019107011 A RU2019107011 A RU 2019107011A RU 2019107011 A RU2019107011 A RU 2019107011A RU 2019107011 A RU2019107011 A RU 2019107011A
- Authority
- RU
- Russia
- Prior art keywords
- agent
- apilimod
- additional active
- lymphoma
- active agent
- Prior art date
Links
- 229950002889 apilimod Drugs 0.000 title claims 8
- HSKAZIJJKRAJAV-KOEQRZSOSA-N n-[(e)-(3-methylphenyl)methylideneamino]-6-morpholin-4-yl-2-(2-pyridin-2-ylethoxy)pyrimidin-4-amine Chemical compound CC1=CC=CC(\C=N\NC=2N=C(OCCC=3N=CC=CC=3)N=C(C=2)N2CCOCC2)=C1 HSKAZIJJKRAJAV-KOEQRZSOSA-N 0.000 title claims 8
- 239000000203 mixture Substances 0.000 title claims 4
- 238000000034 method Methods 0.000 claims 21
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 6
- 239000013543 active substance Substances 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 claims 3
- 229910019142 PO4 Inorganic materials 0.000 claims 3
- 239000002552 dosage form Substances 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 3
- 239000010452 phosphate Substances 0.000 claims 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims 3
- 229960004528 vincristine Drugs 0.000 claims 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229960004679 doxorubicin Drugs 0.000 claims 2
- 201000003444 follicular lymphoma Diseases 0.000 claims 2
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims 2
- 229960001507 ibrutinib Drugs 0.000 claims 2
- 239000006186 oral dosage form Substances 0.000 claims 2
- 229960005205 prednisolone Drugs 0.000 claims 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims 2
- -1 rituximab Chemical compound 0.000 claims 2
- 229960004641 rituximab Drugs 0.000 claims 2
- 229940095064 tartrate Drugs 0.000 claims 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 claims 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 1
- 229920002253 Tannate Polymers 0.000 claims 1
- 102000004243 Tubulin Human genes 0.000 claims 1
- 108090000704 Tubulin Proteins 0.000 claims 1
- 229940009456 adriamycin Drugs 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 229940072107 ascorbate Drugs 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 229940077388 benzenesulfonate Drugs 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 150000001805 chlorine compounds Chemical group 0.000 claims 1
- 229940001468 citrate Drugs 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 229960004397 cyclophosphamide Drugs 0.000 claims 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 1
- 229960005167 everolimus Drugs 0.000 claims 1
- 229940050411 fumarate Drugs 0.000 claims 1
- 229940050410 gluconate Drugs 0.000 claims 1
- 229940097042 glucuronate Drugs 0.000 claims 1
- 229930195712 glutamate Natural products 0.000 claims 1
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 claims 1
- 229960003727 granisetron Drugs 0.000 claims 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims 1
- 239000000138 intercalating agent Substances 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 claims 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 229940049964 oleate Drugs 0.000 claims 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 1
- 229960002131 palonosetron Drugs 0.000 claims 1
- CPZBLNMUGSZIPR-NVXWUHKLSA-N palonosetron Chemical compound C1N(CC2)CCC2[C@@H]1N1C(=O)C(C=CC=C2CCC3)=C2[C@H]3C1 CPZBLNMUGSZIPR-NVXWUHKLSA-N 0.000 claims 1
- 229940014662 pantothenate Drugs 0.000 claims 1
- 235000019161 pantothenic acid Nutrition 0.000 claims 1
- 239000011713 pantothenic acid Substances 0.000 claims 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 claims 1
- 229960002508 pindolol Drugs 0.000 claims 1
- 229960004618 prednisone Drugs 0.000 claims 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims 1
- 229960001534 risperidone Drugs 0.000 claims 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims 1
- 229960001860 salicylate Drugs 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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| BR112016017112A2 (pt) | 2014-01-24 | 2017-08-08 | Ai Therapeutics Inc | Composições de apilimod e métodos de uso das mesmas |
| JP6705828B2 (ja) * | 2014-11-07 | 2020-06-03 | エイアイ・セラピューティクス・インコーポレーテッド | 腎癌の処置に使用するためのアピリモド |
| PT3215157T (pt) | 2014-11-07 | 2019-07-12 | Ai Therapeutics Inc | Apilimod para utilização no tratamento de melanoma |
| US10729694B2 (en) | 2015-01-23 | 2020-08-04 | AI Therapeutics, Inc. | Anti-viral compositions containing PIKfyve inhibitors and use thereof |
| WO2016160102A1 (en) * | 2015-03-31 | 2016-10-06 | Lam Therapeutics, Inc. | Active metabolites of apilimod and uses thereof |
| TWI746449B (zh) | 2015-07-20 | 2021-11-21 | 美商Ａｉ治療公司 | 使用阿吡莫德治療癌症之方法 |
| WO2017127661A1 (en) * | 2016-01-21 | 2017-07-27 | Lam Therapeutics, Inc. | Biomarkers for treating cancer with apilimod |
| KR20180015441A (ko) | 2016-08-03 | 2018-02-13 | 엘지전자 주식회사 | 롤리 키보드 |
| CA3034453A1 (en) * | 2016-08-25 | 2018-03-01 | AI Therapeutics, Inc. | Compositions comprising pikfyve inhibitors and methods related to inhibition of rank signaling |
| WO2019164861A1 (en) * | 2018-02-21 | 2019-08-29 | AI Therapeutics, Inc. | Combination therapy with apilimod and glutamatergic agents |
| CN108743947B (zh) * | 2018-07-04 | 2020-12-15 | 复旦大学附属肿瘤医院 | 一种治疗b细胞淋巴瘤的药物组合物 |
| CN110496128B (zh) * | 2019-09-23 | 2022-09-30 | 吉林大学 | 利培酮或帕潘立酮在制备治疗弥漫性大b细胞淋巴瘤的药物中的应用 |
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| JP2024521449A (ja) * | 2021-06-11 | 2024-05-31 | オルフアイ セラピューティクス インコーポレイテッド | 安定化されたアピリモドの組成物およびその使用方法 |
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| EP1791544A4 (en) * | 2004-09-08 | 2007-09-12 | Chelsea Therapeutics Inc | CHINAZOLINE DERIVATIVES AS METABOLIC INERT ANTIFOLATE |
| US7923557B2 (en) | 2004-11-10 | 2011-04-12 | Synta Pharmaceuticals Corporation | Process for preparing trisubstituted pyrimidine compounds |
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| WO2006128129A2 (en) * | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
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| US8173647B2 (en) | 2007-02-06 | 2012-05-08 | Gordana Atallah | PI 3-kinase inhibitors and methods of their use |
| RU2438664C2 (ru) | 2007-05-15 | 2012-01-10 | Пирамал Лайф Сайнсиз Лимитед | Синергическая фармацевтическая комбинация для лечения рака |
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| JP5258331B2 (ja) * | 2008-03-03 | 2013-08-07 | ロート製薬株式会社 | 光安定性が改善されたニューキノロン系抗菌剤含有医薬組成物 |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
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| CN102844023B (zh) * | 2010-03-08 | 2016-01-20 | 索隆-基特林癌症研究协会 | Cdc7激酶抑制剂以及其用途 |
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| PT3215157T (pt) | 2014-11-07 | 2019-07-12 | Ai Therapeutics Inc | Apilimod para utilização no tratamento de melanoma |
| JP6705828B2 (ja) | 2014-11-07 | 2020-06-03 | エイアイ・セラピューティクス・インコーポレーテッド | 腎癌の処置に使用するためのアピリモド |
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| WO2016160102A1 (en) | 2015-03-31 | 2016-10-06 | Lam Therapeutics, Inc. | Active metabolites of apilimod and uses thereof |
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| AU2019299234A1 (en) | 2018-07-05 | 2021-01-14 | Mayo Foundation For Medical Education And Research | PIKfyve inhibitors |
| AR119934A1 (es) | 2019-09-12 | 2022-01-19 | Ai Therapeutics Inc | Inhibidores de pikfyve para terapia contra el cáncer |
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