RU2017106172A - Применение антагонистов cxcr2 для предотвращения и/или лечения периферической невропатии, вызванной химиотерапией (cipn) - Google Patents

Применение антагонистов cxcr2 для предотвращения и/или лечения периферической невропатии, вызванной химиотерапией (cipn) Download PDF

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RU2017106172A
RU2017106172A RU2017106172A RU2017106172A RU2017106172A RU 2017106172 A RU2017106172 A RU 2017106172A RU 2017106172 A RU2017106172 A RU 2017106172A RU 2017106172 A RU2017106172 A RU 2017106172A RU 2017106172 A RU2017106172 A RU 2017106172A
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cxcr2
chloro
urea
cxcr2 antagonist
hydroxy
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RU2017106172A
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Ебере И. ИГБОКО
Пол Брайан РЕН
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Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед
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Claims (53)

1. Антагонист CXCR2 для применения при предотвращении и/или лечении CIPN.
2. Антагонист CXCR2 по п.1, для применения при предотвращении CIPN.
3. Антагонист CXCR2 по п.1 или п.2, где CIPN вызывается химиотерапевтическим агентом, содержащим платину.
4. Антагонист CXCR2 по п.3, где CIPN вызывается оксалиплатином.
5. Антагонист CXCR2 по любому из предыдущих пунктов, имеющий значение pIC50 по отношению к рецептору CXCR2 равное или большее чем 7,0, как измерено с помощью анализа связывания рецептора CXCR2.
6. Антагонист CXCR2 по любому из пп.1-4, имеющий значение pIC50 по отношению к рецептору CXCR2 равное или большее чем 7,0, как измерено в анализе a).
7. Антагонист CXCR2 по любому из пп.1-4, имеющий значение pA2 по отношению к рецептору CXCR2 равное или большее чем 8,0, как измерено в анализе b).
8. Антагонист CXCR2 по любому из пп.1-4, имеющий значение pIC50 по отношению к рецептору CXCR2 равное или большее чем 8,0, как измерено в анализах c).
9. Антагонист CXCR2 по любому из пп.1-4, имеющий значение pIC50 по отношению к рецептору CXCR2 равное или большее чем 5,0, как измерено в анализе d).
10. Антагонист CXCR2 по любому из пп.1-4, имеющий селективность по отношению к CXCR2, по сравнению с CXCR1, такую же или большую в 29 раз.
11. Антагонист CXCR2 по любому из предыдущих пунктов, имеющий растворимость 10 мкг/мл.
12. Антагонист CXCR2 по любому из предыдущих пунктов, имеющий проницаемость мембраны для него, соответствующую значению Log D7,4 от -2 до +4.
13. Антагонист CXCR2 по любому из пп.1-4, где антагонист выбирают из группы, состоящей из:
1-(4-хлор-2-гидрокси-3-(пиперазин-1-илсульфонил)фенил)-3-(2-хлор-3-фторфенил)мочевины Формулы (A)
Figure 00000001
1-(4-хлор-2-гидрокси-3-(пиперидин-3-илсульфонил)фенил)-3-(3-фтор-2-метилфенил)мочевины Формулы (B)
Figure 00000002
1-(4-хлор-2-гидрокси-3-(((R)-3-метилтетрагидрофуран-3-ил)сульфонил)фенил)-3-((R)-2- метилциклопент-2-ен-1-ил)мочевины Формулы (C)
Figure 00000003
1-(4-хлор-3-((1,4-диметилпиперидин-4-ил)сульфонил)-2-гидроксифенил)-3-(2-хлор-3-фторфенил)мочевины Формулы (D)
Figure 00000004
;
(R)-1-(4-хлор-2-гидрокси-3-((4-метилтетрагидро-2H-пиран-4-ил)сульфонил)фенил)-3-(2-хлорциклопент-2-ен-1-ил)мочевины Формулы (E)
Figure 00000005
(R)-1-(3-(трет-бутилсульфонил)-4-циано-2-гидроксифенил)-3-(2-метилциклопент-2-ен-1-ил)мочевины Формулы (F)
Figure 00000006
1-(4-хлор-2-гидрокси-3-((транс-3-(пирролидин-1-ил)циклобутил)сульфонил)фенил)-3-((R)-2-метилциклопент-2-ен-1-ил)мочевины Формулы (G)
Figure 00000007
1-(4-хлор-3-((транс-3-(диметиламино)циклобутил)сульфонил)-2-гидроксифенил)-3-((R)-2-метилциклопент-2-ен-1-ил)мочевины Формулы (H)
Figure 00000008
(R)-1-(4-хлор-3-((1,1-дифторэтил)сульфонил)-2-гидроксифенил)-3-(2-метилциклопент-2-ен-1-ил)мочевины Формулы (I)
Figure 00000009
1-(4-хлор-2-гидрокси-3-(((S)-3-метилтетрагидрофуран-3-ил)сульфонил)фенил)-3-((R)-2- метилциклопент-2-ен-1-ил)мочевины Формулы (J)
Figure 00000010
1-(4-хлор-2-гидрокси-3-(((S)-3-метилтетрагидрофуран-3-ил)сульфонил)фенил)-3-((R)-2-хлорциклопент-2-ен-1-ил)мочевины Формулы (K)
Figure 00000011
и
1-(4-хлор-2-гидрокси-3-(((R)-3-метилтетрагидрофуран-3-ил)сульфонил)фенил)-3-((R)-2- хлорциклопент-2-ен-1-ил)мочевины Формулы (L)
Figure 00000012
или их фармацевтически приемлемой соли.
14. Антагонист CXCR2 1-(4-хлор-2-гидрокси-3-(пиперазин-1-илсульфонил)фенил)-3-(2-хлор-3-фторфенил)мочевина Формулы (A) по п.13 или его фармацевтически приемлемая соль.
Figure 00000013
15. Антагонист CXCR2 1-(4-хлор-2-гидрокси-3-(пиперидин-3-илсульфонил)фенил)-3-(3- фтор-2-метилфенил)мочевина Формулы (B) по п.13 или его фармацевтически приемлемая соль
Figure 00000014
16. Антагонист CXCR2 1-(4-хлор-2-гидрокси-3-(((S)-3-метилтетрагидрофуран-3-ил)сульфонил)фенил)-3-((R)-2-метилциклопент-2-ен-1-ил)мочевина Формулы (J) по п.13 или ее фармацевтически приемлемая соль
Figure 00000015
17. Фармацевтическая композиция, содержащая a) антагонист CXCR2 по любому из предыдущих пунктов и b) один или несколько фармацевтически приемлемых наполнителей для применения при предотвращении и/или лечении CIPN.
18. Фармацевтическая композиция по п.17, адаптированная для перорального введения.
19. Комбинация, содержащая a) антагонист CXCR2 и b) один или несколько первичных химиотерапевтических агентов, выбранных из группы, состоящей из: соединений платины (например, оксалиплатина), таксанов, алкалоидов винка, талидомида и бортезомиба.
20. Комбинация по п.19, в которой первичный химиотерапевтический агент представляет собой оксалиплатин.
21. Комбинация по п.19 или 20, в которой антагонист CXCR2 вводится до одного или нескольких первичных химиотерапевтических агентов или одновременно с ними.
22. Способ предотвращения и/или лечения CIPN у человека, нуждающегося в этом, включающий введение антагониста CXCR2.
23. Способ по п.22, в котором антагонист CXCR2 определяется в любом из пп.1-16.
24. Применение антагониста CXCR2 при приготовлении лекарственного препарата для предотвращения и/или лечения CIPN.
25. Применение по п.24, в котором антагонист CXCR2 определяется в любом из пп.1-16.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2807067C2 (ru) * 2018-08-01 2023-11-09 Сефалон Ллс Антитела против CXCR2 и их применение
US12018084B2 (en) 2018-08-01 2024-06-25 Cephalon Llc Anti-CXCR2 antibodies and uses thereof

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CR20160557A (es) 2014-05-29 2017-01-20 Glaxosmithkline Ip Dev Ltd Compuestos derivados de 1-(ciclopent-2-en-1-il)-3-(2-hidroxi-3-(arilsulfonil)fenil)urea como inhibidores cxcr2
EP3192504A1 (en) * 2016-01-15 2017-07-19 Dompé farmaceutici S.p.A. Il-8 inhibitors for use in the treatment of chemotherapy-induced peripheral neuropathy
MX2018008614A (es) * 2016-01-15 2018-11-19 Dompe Farm Spa Inhibidores de il-8 para usarse en el tratamiento de neuropatia periferica inducida por quimioterapia.
EP3299032A1 (en) 2016-09-23 2018-03-28 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Inhibitors of gpr132 for use in preventing and/or treating chemotherapy-induced neuropathic pain
EP4252629A3 (en) 2016-12-07 2023-12-27 Biora Therapeutics, Inc. Gastrointestinal tract detection methods, devices and systems
EP3554541B1 (en) 2016-12-14 2023-06-07 Biora Therapeutics, Inc. Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor
CN107779436A (zh) * 2017-10-27 2018-03-09 南京中医药大学 化疗所致周围神经病变细胞模型构建及其检测方法
KR102285938B1 (ko) * 2018-04-19 2021-08-04 한양대학교 산학협력단 이매티닙 또는 이의 약학적으로 허용되는 염을 유효성분으로 포함하는 화학요법유발 말초신경병증의 예방 또는 치료용 조성물
KR20210095165A (ko) 2018-11-19 2021-07-30 프로제너티, 인크. 바이오의약품으로 질환을 치료하기 위한 방법 및 디바이스
EP3998256A4 (en) * 2019-07-11 2023-07-19 Shenzhen Optimum Biological Technology Co., Ltd CRYSTALLINE FORM OF CXCR2 ANTAGONIST AND ITS USE
CN115666704A (zh) 2019-12-13 2023-01-31 比奥拉治疗股份有限公司 用于将治疗剂递送至胃肠道的可摄取装置
BR112023024140A2 (pt) 2021-05-18 2024-02-06 Ltt Bio Pharma Co Ltd Composição farmacêutica que compreende uma superóxido dismutase lecitinizada e uso de uma superóxido dismutase lecitinizada para tratar ou prevenir um distúrbio associado com a administração de um agente anticâncer

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CO5280089A1 (es) * 2000-03-16 2003-05-30 Smithkline Beecham Corp Antagonistas del receptor il-8
ITMI20012434A1 (it) * 2001-11-20 2003-05-20 Dompe Spa Acidi 2-aril-propionici e composizioni farmaceutiche che li contengono
GB0221829D0 (en) * 2002-09-20 2002-10-30 Astrazeneca Ab Novel compound
AR041834A1 (es) * 2002-10-29 2005-06-01 Smithkline Beecham Corp Compuesto de difenilurea sustituido con sulfonamida, composicion farmaceutica que lo comprende y su uso para preparar dicha composicion
US20100256157A1 (en) * 2002-10-29 2010-10-07 Jakob Busch-Petersen Method of treatment
EP1676834A1 (en) * 2004-12-30 2006-07-05 Sanofi-Aventis Deutschland GmbH Fused bicyclic carboxamide derivates for use as CXCR2 inhibitors in the treatment of inflammation
BRPI0710232B8 (pt) * 2006-04-21 2021-05-25 Glaxosmithkline Llc composto antagonista do receptor de il-8, composição farmacêutica que compreende o dito composto e uso do mesmo para o tratamento de uma doença mediada por quimiocina
AU2007253424B2 (en) * 2006-05-18 2013-03-07 Dompe' Farmaceutici S.P.A. (2R)-2-[(4-sulfonyl)aminophenyl]propanamides and pharmaceutical compositions containing them
US20090041753A1 (en) * 2006-09-26 2009-02-12 Miller Robert H Cytokine signaling
EP1925304A1 (en) * 2006-11-15 2008-05-28 Nikem Research S.R.L. Pyrrolo[1,2-a]imidazoledione effective in the treatment of peripheral neurotoxicity induced by chemotherapeutic agents
US20140287021A1 (en) * 2013-03-21 2014-09-25 Panacea Pharmaceuticals Treatment of chemotherapy-induced peripheral neuropathy
CR20160557A (es) * 2014-05-29 2017-01-20 Glaxosmithkline Ip Dev Ltd Compuestos derivados de 1-(ciclopent-2-en-1-il)-3-(2-hidroxi-3-(arilsulfonil)fenil)urea como inhibidores cxcr2

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2807067C2 (ru) * 2018-08-01 2023-11-09 Сефалон Ллс Антитела против CXCR2 и их применение
US12018084B2 (en) 2018-08-01 2024-06-25 Cephalon Llc Anti-CXCR2 antibodies and uses thereof

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