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HRP20230455T1 - Antitumorski spojevi - Google Patents

Antitumorski spojevi Download PDF

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Publication number
HRP20230455T1
HRP20230455T1 HRP20230455TT HRP20230455T HRP20230455T1 HR P20230455 T1 HRP20230455 T1 HR P20230455T1 HR P20230455T T HRP20230455T T HR P20230455TT HR P20230455 T HRP20230455 T HR P20230455T HR P20230455 T1 HRP20230455 T1 HR P20230455T1
Authority
HR
Croatia
Prior art keywords
substituted
unsubstituted
cancer
alkyl
butyl
Prior art date
Application number
HRP20230455TT
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English (en)
Inventor
Maria Del Carmen Cuevas Marchante
Andres Francesch Solloso
Valentin MARTINEZ BARRASA
Original Assignee
Pharma Mar S.A.
Priority date (The priority date 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 date listed.)
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Publication date
Application filed by Pharma Mar S.A. filed Critical Pharma Mar S.A.
Publication of HRP20230455T1 publication Critical patent/HRP20230455T1/hr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D515/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D515/22Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains four or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4995Pyrazines or piperazines forming part of bridged ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07Optical isomers
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (17)

1. Spoj sa formulom IC, ili njegova farmaceutski prihvatljiva sol ili ester: [image] pri čemu: X je -NH-; R1 je -OH ili -CN; R2 je -C(=O)Ra grupa; R3 je vodik ili -ORb grupa; R4 je odabran od -CHzOH i -CH2O-(C=O)Rc; Ra je odabran od vodika, supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila; Rb je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila i supstituiranog ili nesupstituiranog C2-C12 alkinila; i Rc je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila.
2. Spoj prema patentnom zahtjevu 1 odabran od formula ICa ili ICb, ili njegova farmaceutski prihvatljiva sol ili ester: [image] pri čemu: X je -NH-; R1 je -OH ili -CN; R2 je -C(=O)Ra grupa; R3 je vodik ili -ORb grupa; R4 je odabran od -CHzOH i -CH2OC(=O)Rc; Ra je odabran od vodika, supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila; i Rb je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila; i Rc je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila.
3. Spoj prema patentnom zahtjevu 1 ili 2, pri čemu R4 je odabran od -CHzOH i - CH2O(C=O)Rc pri čemu Rc je supstituirani ili nesupstituirani C1-C6 alkil; poželjno pri čemu je Rc odabran od supstituiranog ili nesupstituiranog metila, supstituiranog ili nesupstituiranog etila, supstituiranog ili nesupstituiranog n-propila, supstituiranog ili nesupstituiranog izopropila, supstituiranog ili nesupstituiranog n-butila, supstituiranog ili nesupstituiranog izobutila, supstituiranog ili nesupstituiranog sek-butila, i supstituiranog ili nesupstituiranog terc-butila; pri čemu je dalje poželjno Rc metil.
4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 pri čemu R4 je -CHzOH.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4, pri čemu R1 je -OH.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, pri čemu R2 je -C(=O)Ra grupa pri čemu Ra je supstituirani ili nesupstituirani C1-C6 alkil; pri čemu je poželjno Ra odabran od supstituiranog ili nesupstituiranog metila, supstituiranog ili nesupstituiranog etila, supstituiranog ili nesupstituiranog n-propila, supstituiranog ili nesupstituiranog izopropila, supstituiranog ili nesupstituiranog n-butila, supstituiranog ili nesupstituiranog izobutila, supstituiranog ili nesupstituiranog sek-butila i supstituiranog ili nesupstituiranog terc-butila, pri čemu je poželjno R2 acetil.
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6, pri čemu R3 je vodik ili -ORb pri čemu Rb je supstituirani ili nesupstituirani C1-C6 alkil; pri čemu je poželjno Rb odabran od supstituiranog ili nesupstituiranog metila, supstituiranog ili nesupstituiranog etila, supstituiranog ili nesupstituiranog n-propila, supstituiranog ili nesupstituiranog izopropila, supstituiranog ili nesupstituiranog n-butila, supstituiranog ili nesupstituiranog izobutila, supstituiranog ili nesupstituiranog sek-butila i supstituiranog ili nesupstituiranog terc-butila, pri čemu poželjno R3 je vodik.
8. Spoj prema patentnom zahtjevu 7 pri čemu R3 je -ORb pri čemu Rb je supstituirani ili nesupstituirani C1-C6 alkil; pri čemu je poželjno Rb odabran od supstituiranog ili nesupstituiranog metila, supstituiranog ili nesupstituiranog etila, supstituiranog ili nesupstituiranog n-propila, supstituiranog ili nesupstituiranog izopropila, supstituiranog ili nesupstituiranog n-butila, supstituiranog ili nesupstituiranog izobutila, supstituiranog ili nesupstituiranog sek-butila i supstituiranog ili nesupstituiranog terc-butila, poželjno pri čemu R3 je metoksi.
9. Spoj prema patentnom zahtjevu 1 sa formulom: [image] [image] ili njegova farmaceutski prihvatljiva sol ili ester.
10. Spoj prema bilo kojem od patentnih zahtjeva 1 do 9, pri čemu je sol odabrana od hidroklorida, hidrobromida, hidrojodida, sulfata, nitrata, fosfata, acetata, trifluoroacetata, maleata, fumarata, citrata, oksalata, sukcinata, tartrata, malata, mandelata, metan sulfonata, p-toluen sulfonata, natrija, kalija, kalcija, amonija, etilendiamina, etanolamina, N,N-dialkilenetanolamina, trietanolamina i baznih aminokiselina.
11. Farmaceutska kompozicija koja sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 10 ili njegovu farmaceutski prihvatljivu sol ili ester i farmaceutski prihvatljiv nosač.
12. Dozni oblik koji sadrži farmaceutsku kompoziciju prema patentnom zahtjevu 11.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol ili ester, ili kompozicija prema patentnom zahtjevu 11, ili dozni oblik prema patentnom zahtjevu 12, za primjenu kao lijek.
14. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol ili ester, kompozicija prema patentnom zahtjevu 11, ili dozni oblik prema patentnom zahtjevu 12, za primjenu u liječenju raka.
15. Spoj, kompozicija ili dozni oblik za primjenu prema patentnom zahtjevu 14, pri čemu je rak odabran od raka pluća uključujući nesitnostanični rak pluća i sitnostanični rak pluća, raka debelog crijeva, kolorektalnog raka, raka dojke, raka gušterače, sarkoma, raka jajnika, raka prostate i raka želuca; pri čemu je poželjno rak odabran od raka pluća uključujući nesitnostanični rak pluća i sitnostanični rak pluća, raka dojke, raka gušterače i kolorektalnog raka.
16. Proces dobivanja spoja kako je definirano u bilo kojem od patentnih zahtjeva 1 do 10 ili njegove farmaceutski prihvatljive soli ili estera: koji obuhvaća korak reagiranja spoja formule II sa spojem formule III da se dobije spoj formule IV: [image] pri čemu (gdje je dozvoljeno mogućim supstituentnim grupama): X je -NH-; R2 je -C(=O)Ra grupa; R3 je vodik ili -ORb grupa; R4 je odabran od -CHzOH i -CH2OC(=O)Rc; Ra je odabran od vodika, supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, supstituiranog ili nesupstituiranog C2-C12 alkinila; Rb je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila; i Rc je odabran od supstituiranog ili nesupstituiranog C1-C12 alkila, supstituiranog ili nesupstituiranog C2-C12 alkenila, i supstituiranog ili nesupstituiranog C2-C12 alkinila; i koji po izboru obuhvaća dodatni korak zamjene cijano grupe u spoju formule IV sa hidroksi grupom da se dobije spoj formule IC, pri čemu R1 je OH.
17. Komplet koji sadrži terapijski efikasnu količinu spoja prema bilo kojem patentom zahtjevu 1 do 10 ili njegove farmaceutski prihvatljive soli ili estera i farmaceutski prihvatljiv nosač; komplet koji po izboru dalje sadrži uputstva za primjenu spoja u liječenju raka, i poželjnije raka odabranog od raka pluća, uključujući nesitnostanični rak pluća i sitnostanični rak pluća, raka debelog crijeva, raka dojke, raka gušterače, sarkoma, raka jajnika, raka prostate, kolorektalnog raka i raka želuca.
HRP20230455TT 2017-04-27 2018-04-27 Antitumorski spojevi HRP20230455T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP17382228 2017-04-27
EP17382497 2017-07-26
PCT/EP2018/060868 WO2018197663A1 (en) 2017-04-27 2018-04-27 Antitumoral compounds
EP18720255.1A EP3615544B9 (en) 2017-04-27 2018-04-27 Antitumoral compounds

Publications (1)

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HRP20230455T1 true HRP20230455T1 (hr) 2023-07-21

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Family Applications (5)

Application Number Title Priority Date Filing Date
HRP20230455TT HRP20230455T1 (hr) 2017-04-27 2018-04-27 Antitumorski spojevi
HRP20231233TT HRP20231233T1 (hr) 2017-04-27 2018-04-27 Antitumorski spojevi
HRP20230433TT HRP20230433T1 (hr) 2017-04-27 2018-04-27 Antitumorski spojevi
HRP20191442 HRP20191442T1 (hr) 2017-04-27 2019-08-09 Antitumorska sjedinjenja
HRP20191443 HRP20191443T1 (hr) 2017-04-27 2019-08-09 Antitumorska sjedinjenja

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HRP20231233TT HRP20231233T1 (hr) 2017-04-27 2018-04-27 Antitumorski spojevi
HRP20230433TT HRP20230433T1 (hr) 2017-04-27 2018-04-27 Antitumorski spojevi
HRP20191442 HRP20191442T1 (hr) 2017-04-27 2019-08-09 Antitumorska sjedinjenja
HRP20191443 HRP20191443T1 (hr) 2017-04-27 2019-08-09 Antitumorska sjedinjenja

Country Status (38)

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US (5) US11332480B2 (hr)
EP (5) EP3395821B1 (hr)
JP (5) JP6501947B2 (hr)
KR (3) KR102492283B1 (hr)
CN (4) CN114736219B (hr)
AU (4) AU2018260314C1 (hr)
BR (1) BR112019022282A2 (hr)
CA (1) CA3061518A1 (hr)
CL (1) CL2019003057A1 (hr)
CO (1) CO2019011967A2 (hr)
CY (3) CY1121885T1 (hr)
DK (5) DK4101855T3 (hr)
EC (1) ECSP19083967A (hr)
ES (5) ES2944344T3 (hr)
FI (3) FI4101855T3 (hr)
HK (2) HK1255938B (hr)
HR (5) HRP20230455T1 (hr)
HU (5) HUE046109T2 (hr)
IL (3) IL289963B2 (hr)
JO (1) JOP20190254A1 (hr)
LT (5) LT4101855T (hr)
MA (2) MA44020B1 (hr)
MD (5) MD3395821T2 (hr)
ME (2) ME03467B (hr)
MX (3) MX392829B (hr)
MY (1) MY198004A (hr)
PH (1) PH12019550224A1 (hr)
PL (5) PL4101855T3 (hr)
PT (2) PT3395821T (hr)
RS (5) RS59173B1 (hr)
SG (2) SG11201909841RA (hr)
SI (5) SI3395820T1 (hr)
SM (5) SMT202300169T1 (hr)
TN (2) TN2019000211A1 (hr)
TW (3) TWI807411B (hr)
UY (1) UY37706A (hr)
WO (1) WO2018197663A1 (hr)
ZA (1) ZA201907119B (hr)

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TWI824043B (zh) * 2018-10-25 2023-12-01 西班牙商瑪製藥股份有限公司 藥物抗體共軛物
PH12022551216A1 (en) * 2019-11-21 2023-07-17 Pharma Mar Sa Methods of treating small cell lung cancer with lurbinectedin formulations
PE20230785A1 (es) * 2020-04-21 2023-05-11 Pharma Mar Sa Conjugados de anticuerpos de farmacos
TW202144369A (zh) * 2020-04-26 2021-12-01 大陸商江蘇恆瑞醫藥股份有限公司 海鞘素類衍生物及其製備方法與醫藥用途
CN117295499A (zh) 2021-05-19 2023-12-26 法马马有限公司 海鞘素的给药方案
WO2024186263A1 (en) * 2023-03-07 2024-09-12 Axcynsis Therapeutics Pte. Ltd. Antibody-drug conjugates comprising trabectedin and lurbinectedin derivatives
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MD4101855T2 (ro) 2023-12-31
US11339180B2 (en) 2022-05-24
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US20210070775A1 (en) 2021-03-11
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US10538535B2 (en) 2020-01-21
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LT3395821T (lt) 2019-08-12
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CA3061518A1 (en) 2018-11-01

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