TR201902884T4 - Mmp akti̇f vasküler bozucu ajanlar. - Google Patents

Mmp akti̇f vasküler bozucu ajanlar. Download PDF

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TR201902884T4
TR201902884T4 TR2019/02884T TR201902884T TR201902884T4 TR 201902884 T4 TR201902884 T4 TR 201902884T4 TR 2019/02884 T TR2019/02884 T TR 2019/02884T TR 201902884 T TR201902884 T TR 201902884T TR 201902884 T4 TR201902884 T4 TR 201902884T4
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compound according
compound
agent
desacetylcolchicine
vda
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Andrew Falconer Robert
Gill Jason
Atkinson Jennifer
Loadman Paul
Bibby Michael
Patterson Laurence
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Incanthera Ltd
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Abstract

Buluş, vasküler bozucu ajanların ön ilaçları ve bu tür bileşiklerin, hedeflenen kanser tedavisinde kullanımına ilişkindir.

Claims (32)

ISTEMLER
1. Bir matris metaloproteinaz (MMP) proteolitik bölünme bölgesi içeren bir peptid ile baglantili vasküler bir bozucu ajan (VDA) içeren bir bilesik ya da bunun farmasötik olarak kabul edilebilir bir tuzu olup, özelligi; burada VDA'nin, bir antikanser ve tübülin baglayici ajan olmasi ve MMP proteolitik bölünme bölgesinin, bir amino asit sekansi - Arg-Ser-Cit-GIy-Hof-P2`-Leu- içermesi, burada P2' ifadesinin bir amino asit olmasi ve tirozin olmamasidir.
2. Istem 1'e göre bir bilesik olup, özelligi; burada bilesigin formül (I)'e sahip olmasi X'in, VDA olmasi; ve Y'nin, bir MMP proteolitik bölünme bölgesi içeren peptit olmasidir.
3. Istem 1 ya da 2'ye göre bir bilesik olup, özelligi; burada VDAinin, tübülin üzerindeki kolsisin baglanma bölgesinde tübülin ile etkilesime girmesi ve azademetilkolsisin, kolsisin, azakolsisin, N-metil desasetilkolsisin, desasetilkolsisin, N- asetiIkolsisinoI-O-fosfat, kolsikinoidler, combretastatinler, fenstatin, podofilotoksinler, steganasinler, amfetinil, stilbenler ya da flavonoidler arasindan seçilmesi, istege bagli olarak burada VDA'nin azademetilkolsisin, kolsisin, azakolsisin, N-metil desasetilkolsisin, desasetilkolsisin arasindan seçilmesi ve tercih edilen sekliyle burada VDAinin azademetilkolsisin olmasidir.
4. Istem 1 ya da 2'ye göre bir bilesik olup, özelligi; burada VDAinin tübülin üzerinde, Catharanthus (Vinka) alkaloitleri ile ortak bir baglama bölgesini paylasiyor olmasi; istege bagli olarak burada VDA'nin vinkristin, vinblastin, vinflunini maytansinoidler, phomopsin A, rizoksin, auristatin, auristatin analogu ya da dolastatin arasindan seçilmesidir.
5. Istem 1 ya da 2'ye göre bir bilesik olup, özelligi; burada VDA'nin paklitaksele benzer sekilde stabil mikrotübüllerin olusumunu desteklemesidir.
6. Onceki istemlerden herhangi birine göre bir bilesik olup, özelligi; burada MMP proteolitik bölünme bölgesinin yedi ila on amino asit arasinda bir peptid sekansi olmasidir.
7. Onceki istemlerden herhangi birine göre bir bilesik olup, özelligi; burada P2' ifadesinin: a) polar, degismemis amino asitler ve/ veya bazik amino asitler, ya da b) Asp, Ala, Asn, Pro, Leu ve Arg'den olusan grup arasindan seçilmesidir.
8. Onceki istemlerden herhangi birine göre bir bilesik olup, özelligi; burada P2' ifadesinin metillenmis bir amino asit olmasidir.
9. Onceki istemlerden herhangi birine göre bir bilesik olup, özelligi; burada bir baska antikanser ajaninin bir MT-MMP proteolitik bölünme bölgesi içeren peptide baglanmasidir.
10. istem 9'a göre bir bilesik olup, özelligi; burada antikanser ajaninin bir antimetabolit, bir sitotoksik ajan, bir antiproliferatif ajan, 5-florourasil, antrasiklin, doksorubisin, vinka alkaloid, taksan, bir sitotoksik nükleotit, bir biyotoksin, bir radyoterapötik, bir hormonal ajan, kolsisin, azademetilkolsisin, N-metil desasetilkolsisin ya da desasetilkolsisinden olusan gruptan seçilmesidir.
11. istem 10'a göre bir bilesik olup, özelligi; burada antikanser ajaninin doksorubisin olmasidir.
12. Onceki istemlerden herhangi birine göre bir bilesik olup, özelligi; ayrica peptidin spesifik olmayan bir sekilde bozulmasini önleyen MMP proteolitik bölünme bölgesini içeren, peptit üzerinde bir kapatma grubu içermesidir.
13. istem 2 ila 12'den herhangi birine göre bir bilesik olup, özelligi; burada bilesigin formül (ll)'ye sahip olmasi: burada Crnin bir kapatma grubu olmasidir.
14. istem 13'e göre bir bilesik olup, özelligi; burada C'nin alifatik, aromatik, polisiklik, karbonhidrat ve amino asitlerden olusan gruptan seçilmesi, istege bagli olarak burada C'nin hidrofilik bir grup olmasidir.
15. Istem 13 ya da 14'e göre bir bilesik olup, özelligi; burada cinin formül (C)n ile temsil edilmesi, burada n'nin 1 ila 5 arasinda bir tam sayi olmasi, istege bagli olarak burada crnin dogal olmayan bir amino asit olmasi ve n'nin 3 olmasidir.
16. Istem 2 ila 13'ten herhangi birine göre bir bilesik olup, özelligi; burada bilesigin form'ul (Ill)7e sahip olmasi: burada a'nin X ile dogrudan ya da dolayli olarak iliskili bir baglayici olmasidir.
17. Istem 16'ya göre bir bilesik olup, özelligi; burada baglayicinin birtekli amino asit ya da amino asit sekansi olmasidir.
18. Istem 16'ya göre bir bilesik olup, özelligi; burada bilesigin formül (IV)'e sahip olmasi: X-a-Y-c (IV) burada c'nin istem 13'te tanimlandigi gibi olmasidir.
19. Istem 13'e göre bir bilesik olup, özelligi; burada bilesigin formül (V)'e sahip olmasi: burada b'nin, Y'ye dogrudan ya da dolayli olarak baglanmis bir aralayici grup olmasidir.
20. Istem 19'a göre bir bilesik olup, özelligi; burada aralayicinin bir tekli amino asit, bir amino asit sekansi ve bir s'L'iksiniI grubundan olusan gruptan seçilmesidir.
21. Istem 18'e göre bir bilesik olup, özelligi; burada bilesigin formül (VI)'ya sahip olmasi: X-a-Y-b-c (VI) burada b'nin Y'ye dogrudan ya da dolayli olarak baglanmis bir aralayici grup olmasidir.
22. Istem 2 ila 21'den herhangi birinde ileri sürüld'ugü gibi bir bilesik olup, özelligi; burada bilesigin formül (VII),ye sahip olmasi: burada Zinin bir antikanser ajani olmasidir.
23. Istem 22'ye göre bir bilesik olup, özelligi; burada Z'nin bir vasküler bozucu ajan, bir antimetabolit, bir sitotoksik ajan, bir biyotoksin, bir radyoterapötik ve bir hormonal ajandan olusan gruptan seçilmesi ve tercih edilen sekliyle burada Zrnin sitotoksik ajan doksorubisin olmasidir.
24. Istem 22 ya da 23'e göre bir bilesik olup, özelligi; burada Xiin azademetilkolsisin, kolsisin, azakolsisin, N-metil desasetilkolsisin, desasetilkolsisin arasindan seçilmesidir.
25. Istem 22'ye göre bir bilesik olup, özelligi; burada X ve Z'nin azademetilkolsisin, kolsisin, azakolsisin, N-metil desasetilkolsisin, desasetilkolsisin arasindan seçilmesidir.
26. Onceki istemlerden herhangi birine göre bir bilesik ya da bunun farmasötik olarak kabul edilebilir bir tuzu olup, özelligi; ilaçta kullanima yönelik olmasidir.
27. Bir farmasötik formülasyon olup, özelligi; istem 1-25'ten herhangi birine göre bir bilesik ve en az bir ilave farmasötik olarak kabul edilebilir yardimci madde, seyreltici ya da tasiyici içermesidir.
28. Bir farmasötik formülasyon olup, özelligi; istem 1-25'ten herhangi birine göre bir bilesik ve baska bir terapötik ajan içermesi, istege bagli olarak burada baska bir terapötik ajanin sisplatin, karboplatin, siklofosfamid, melfalan, karmustin, metotreksat, 5-florourasil, sitarabin, merkaptopurin, daunorubisin, doksorubisin, epirubisin, vinblastin, vinkristin, daktinomisin C, taksol, L-asparaginaz, G-CSF, etoposid, kolsisin, deferoksamin mesilat ya da kamptotesin arasindan seçilmesidir.
29. Istem 1-25'ten herhangi birine göre bir bilesik ya da istem 27 ya da 28'e göre bir farmasötik formülasyon olup, özelligi; kansertedavisinde kullanima yönelik olmasidir.
30. Istem 1-25'ten herhangi birine göre bir bilesik ya da istem 27 ya da 28'e göre bir farmasötik formülasyon olup, özelligi; bir enflamatuar bozuklugun tedavisinde kullanima yönelik olmasidir.
31. Istem 1-25'ten herhangi birine göre bir bilesik ya da istem 27 ya da 28'e göre bir farmasötik formülasyon olup, özelligi; kalp yetmezligi tedavisinde kullanima yönelik olmasidir.
32. Istem 1-25'ten herhangi birine göre bir bilesik ya da istem 27 ya da 28'e göre bir farmasötik formülasyon olup, özelligi; bir yaranin tedavisinde kullanima yönelik olmasidir.
TR2019/02884T 2008-10-22 2009-10-20 Mmp akti̇f vasküler bozucu ajanlar. TR201902884T4 (tr)

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GB0707034D0 (en) * 2007-04-12 2007-05-23 St Andrews The Compounds
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EA032515B1 (ru) 2012-11-02 2019-06-28 Марри Энд Пул Энтерпрайзес, Лтд. Лечение или профилактика сердечно-сосудистых явлений с использованием колхицина
US20160081936A1 (en) 2013-04-16 2016-03-24 Murray And Poole Enterprises Limited Sustained-release formulations of colchicine and methods of using same
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CA2925106C (en) * 2013-09-25 2023-11-14 Cytomx Therapeutics, Inc. Matrix metalloproteinase substrates and other cleavable moieties and methods of use thereof
IL270562B (en) 2014-01-31 2022-08-01 Cytomx Therapeutics Inc Polypeptide substrates that activate matriptase and u-plasminogen and other cleavable groups, preparations containing them and their uses
MA41374A (fr) 2015-01-20 2017-11-28 Cytomx Therapeutics Inc Substrats clivables par métalloprotéase matricielle et clivables par sérine protéase et procédés d'utilisation de ceux-ci
GB2545169B (en) * 2015-12-01 2019-10-09 Ellipses Pharma Ltd Taxane Prodrug Comprising A Membrane Type Matrix Metalloproteinase Cleavage Site
MY205459A (en) 2018-12-06 2024-10-22 Cytomx Therapeutics Inc Matrix metalloprotease-cleavable and serine or cysteine protease-cleavable substrates and methods of use thereof
CN115353534B (zh) * 2021-12-31 2024-06-07 郑州大学第一附属医院 一种秋水仙碱衍生物及其制备和其应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US819287A (en) * 1905-09-11 1906-05-01 Caesar Klaus Automatic brake.
US5595756A (en) * 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
HUP0300590A2 (hu) * 2000-03-15 2003-07-28 Bristol-Myers Squibb Pharma Company Peptidázzal hasítható, célzott antineoplasztikus szerek és terápiás alkalmazásuk
GB0018240D0 (en) 2000-07-25 2000-09-13 Pharmacia & Upjohn Spa Polymeric conjugates of antitumor agents
GB0105929D0 (en) 2001-03-09 2001-04-25 Btg Int Ltd Physiologically activated prodrugs
SI1545613T1 (sl) 2002-07-31 2011-11-30 Seattle Genetics Inc Avristatinski konjugati in njihova uporaba za zdravljenje raka avtoimunske bolezni ali infekcijskebolezni
US20050106100A1 (en) 2003-09-03 2005-05-19 Harris Thomas D. Compounds containing matrix metalloproteinase substrates and methods of their use
GB0320691D0 (en) * 2003-09-04 2003-10-01 Smith & Nephew Use of joint lining cells for articular cartilage repair
US8420603B2 (en) * 2004-05-14 2013-04-16 Abraxis Bioscience, Llc SPARC and methods of use thereof
DK1853631T3 (en) 2005-01-24 2016-03-29 Univ Texas Fc-FUSION CONSTRUCTIONS BINDING TO PHOSPHATIDYLSERINE AND THERAPEUTIC APPLICATION THEREOF
EP1862470A4 (en) 2005-02-25 2010-04-21 Univ Hokkaido Nat Univ Corp A BLOODED ELEMENT WHICH IS SELECTLY Degraded in TUMOR TISSUE
US7714016B2 (en) 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
GB0707034D0 (en) 2007-04-12 2007-05-23 St Andrews The Compounds
GB0819287D0 (en) 2008-10-22 2008-11-26 Univ Bradford Compounds

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