ME02630B - Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti - Google Patents

Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti

Info

Publication number
ME02630B
ME02630B MEP-2017-42A MEP201742A ME02630B ME 02630 B ME02630 B ME 02630B ME P201742 A MEP201742 A ME P201742A ME 02630 B ME02630 B ME 02630B
Authority
ME
Montenegro
Prior art keywords
nr9r10
cr5r6
nr9c
alkyl
cycloalkyl
Prior art date
Application number
MEP-2017-42A
Other languages
German (de)
English (en)
French (fr)
Inventor
Simon Bailey
Benjamin Joseph Burke
Michael Raymond Collins
Jingrong Jean Cui
Judith Gail Deal
Robert Louis Hoffman
Qinhua Huang
Ted William Johnson
Robert Steven Kania
John Charles Kath
Phuong Thi Quy Le
Michele Ann Mctigue
Cynthia Louise Palmer
Paul Francis Richardson
Neal William Sach
Original Assignee
Pfizer
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=48142828&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02630(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Pfizer filed Critical Pfizer
Publication of ME02630B publication Critical patent/ME02630B/me

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen 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 three hetero rings
    • C07D513/18—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (17)

1. Spoj formule (I),naznačen time što:X se bira iz skupine koju čine -(CR5R6)qO(CR5R6)r-, -(CR5R6)qN(R1)(CR5R6)r-, -(CR5R6)qC(O)N(R1)(CR5R6)r- i -(CR5R6)qN(R1)C(O)(CR5R6)r-;svako od Y i Z je neovisno N ili CH, uz uvjet da kada je Y N, Z je CH i kada je Z N, Y je CH;A je prsten, kojeg se bira između C6-C12 arila i 5-6-eročlanog heteroarila;R1 se bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10;svakog R2 se neovisno bira iz skupine koju čine halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -S(O)tR7, -S(O)2NR7R8, -S(O)2OR7, -NO2, -(CR5R6)qNR7R8, -N(CR5R6)(CR5R6)qNR7R8, -OR7, -O(CR5R6)(CR5R6)qOR7, -O(CR5R6)(CR5R6)qR7, -CN, -C(O)R7, -OC(O)R7, -O(CR5R6)qR7, -NR7C(O)R8, -(CR5R6)qC(O)OR7, -(CR5R6)qNR7R8, -C(=NR7)NR7R8, -NR7C(O)NR7R8, -NR7S(O)2R8 i -(CR5R6)qC(O)NR7R8; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH,-NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10;svakog od R3 i R4 se neovisno bira između vodika, C1-C6 alkila i C3-C6 cikloalkila, gdje svaki vodik na C1-C6 alkilu i C3-C6 cikloalkilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10;svakog R5 i R6 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 i -C(O)NR9R10; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10;svakog R7 i R8 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10;svakog R9 i R10 se neovisno bira između vodika, C1-C6 alkila, C2-C6 alkenila, C2-C6 alkinila, C3-C6 cikloalkila, C6-C12 arila, 3-12-eročlanog heteroalicikla i 5-6-eročlanog heteroarila;m je 0, 1, 2 ili 3;n je 0, 1, 2 ili 3;p je 0,1,2, 3 ili 4;svaki q je neovisno 0, 1, 2 ili 3;svaki r je neovisno 0, 1, 2 ili 3; isvaki t je neovisno 0, 1 ili 2;ili njegova farmaceutski prihvatljiva sol.
2. Spoj u skladu s patentnim zahtjevom 1 formule (V) , naznačen time što: A je prsten, kojeg se bira između C6-C12 arila i 5-6-eročlanog heteroarila; R1 se bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2R9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, --C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R2 se neovisno bira iz skupine koju čine halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -S(O)tR7, -S(O)2NR7R8, -S(O)2OR7, -NO2, -(CR5R6)qNR7R8, -N(CR5R6)(CR5R6)qNR1R8, -OR7, -O(CR5R6)(CR5R6)qOR7, -O(CR5R6)(CR5R6)qR7, -CN, -C(O)R7, -OC(O)R7, -O(CR5R6)qR7, -NR7C(O)R8, -(CR5R6)qC(O)OR7, -(CR5R6)qNR7R8, -C(=NR7)NR7 R8, -NR7C(O)NR7R8, -NR7S(O)2R8 i -(CR5R6)qC(O)NR7R8; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog od R3 i R4 se neovisno bira između vodika, C1-C6 alkila i C3-C6 cikloalkila, gdje svaki vodik na C1-C6 alkilu i C3-C6 cikloalkilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10); svakog R5 i R6 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 i -C(O)NR9R10; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R7 i R8 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2 -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R9 i R10 se neovisno bira između vodika, C1-C6 alkila, C2-C6 alkenila, C2-C6 alkinila, C3-C6 cikloalkila, C6-C12 arila, 3-12-eročlanog heteroalicikla i 5-6-eročlanog heteroarila; p je 0, 1, 2, 3 ili 4; svaki q je neovisno 0, 1, 2 ili 3; i svaki t je neovisno 0, 1 ili 2; ili njegova farmaceutski prihvatljiva sol.
3. Spoj u skladu s patentnim zahtjevom 1 formule (VI) , naznačen time što: A je prsten, kojeg se bira između C6-C12 arila i 5-6-eročlanog heteroarila; R1 se bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R2 se neovisno bira iz skupine koju čine halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -S(O)tR7, -S(O)2NR7R8, -S(O)3OR7, -NO2, -(CR5R6)qNR7R8, -N(CR5R6)(CR5R6)qNR7R8, -OR7, -O(CR5R6)(CR5R6)qOR7, -O(CR5R6)(CR5R6)qR7, -CN, -C(O)R7, -OC(O)R7, -O(CR5R6)qR7, -NR7C(O)R8, -(CR5R6)qC(O)OR7, -(CR5R6)qNR7R8, -C(=NR7)NR7R8, -NR7C(O)NR7R8, -NR7S(O)2R8 i -(CR5R6)qC(O)NR7R8; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH,-NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog od R3 i R4 se neovisno bira između vodika, C1-C6 alkila i C3-C6 cikloalkila, gdje svaki vodik na C1-C6 alkilu i C3-C6 cikloalkilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R5 i R6 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl, 5-6-eročlani heteroaril, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 i -C(O)NR9R10; gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -CN, -OR9, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R7 i R8 se neovisno bira iz skupine koju čine vodik, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C6 cikloalkil, C6-C12 aril, 3-12-eročlani heteroalicikl i 5-6-eročlani heteroaril, gdje svaki vodik na navedenom C1-C6 alkilu, C2-C6 alkenilu, C2-C6 alkinilu, C3-C6 cikloalkilu, C6-C12 arilu, 3-12-eročlanom heteroaliciklu i 5-6-eročlanom heteroarilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10; svakog R9 i R10 se neovisno bira između vodika, C1-C6 alkila, C2-C6 alkenila, C2-C6 alkinila, C3-C6 cikloalkila, C6-C12 arila, 3-12-eročlanog heteroalicikla i 5-6-eročlanog heteroarila; p je 0, 1, 2, 3 ili 4; svaki q je neovisno 0, 1, 2 ili 3; i svaki t je neovisno 0, 1 ili 2; ili njegova farmaceutski prihvatljiva sol.
4. Spoj u skladu s patentnim zahtjevom 1, 2 ili 3, naznačen time što se R1 bira iz skupine koju čine vodik, C1-C6 alkil i C3-C6 cikloalkil, ili njegova farmaceutski prihvatljiva sol.
5. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što svakog R2 se neovisno bira iz skupine koju čine C1-C6 alkil, C3-C6 cikloalkil, -S(O)tR7, -S(O)2NR7R8, -OR7, -O(CR5R6)(CR5R6)qOR7, -O(CR5R6)(CR5R6)qR7 i -CN; gdje svaki vodik na navedenom C1-C6 alkilu i C3-C6 cikloalkilu može biti neovisno izborno supstituiran halogenom, -OH, -NH2, -S(O)tR9, -S(O)2NR9R10, -S(O)2OR9, -NO2, -OR9, -CN, -C(O)R9, -OC(O)R9, -NR9C(O)R10, -C(O)OR9, -C(=NR9)NR9R10, -NR9C(O)NR9R10, -NR9S(O)2R10 ili -C(O)NR9R10, ili njegova farmaceutski prihvatljiva sol.
6. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što je A prsten kojeg se bira iz skupine koju čine fenil, piridin, pirimidin, piridazin, pirazin, triazin, pirazol, imidazol, triazol, tetrazol, tiazol, izotiazol, oksazol i izoksazol, ili njegova farmaceutski prihvatljiva sol.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što se svakog od R3 i R4 neovisno bira iz skupine koju čine vodik i C1-C6 alkil, ili njegova farmaceutski prihvatljiva sol.
8. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (10R)-7-amino-12-fluor-2,10,16-trimetil-15-okso-10,15,16,17-tetrahidro-2H-8,4-(meteno)pirazolo[4,3-h][2,5,11]benzoksadiazaciklotetradecin-3-karbonitril, ili njegova farmaceutski prihvatljiva sol.
9. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (10R)-7-amino-12-fluor-2,10,16-trimetil-15-okso-10,15,16,17-tetrahidro-2H-8,4-(meteno)pirazolo[4,3-h][2,5,11]benzoksadiazaciklotetradecin-3-karbonitril.
10. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, kao i farmaceutski prihvatljivu podlogu ili pomoćnu tvar.
11. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi kao medikament, po mogućnosti u liječenju raka kod sisavca.
12. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je rak posredovan kinazom iz anaplastičnog limfoma (ALK).
13. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je rak posredovan fuzijskim proteinom EML4-ALK.
14. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je rak posredovan fuzijskim proteinom EML4-ALK, koji ima najmanje jednu mutaciju.
15. Spoj u skladu s patentnim zahtjevom 14, naznačen time što je navedena mutacija L1196M ili C1156Y.
16. Spoj u skladu s bilo kojim od patentnih zahtjeva 11 do 15, naznačen time što se rak bira iz skupine koju čine rak velikih stanica pluća (NSCLC), karcinom pločastih stanica, rak prostate neosjetljiv na hormone, karcinom papilarnih stanica bubrega, kolorektalni adenokarcinom, neuroblastomi, anaplastični limfom velikih stanica (ALCL) i rak želuca.
17. Kombinacija, naznačena time što je kombinacija spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 9, ili njegove farmaceutski prihvatljive soli, s dodatnim sredstvom protiv raka.
MEP-2017-42A 2012-03-06 2013-02-20 Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti ME02630B (me)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261607485P 2012-03-06 2012-03-06
US201361759307P 2013-01-31 2013-01-31
PCT/IB2013/051391 WO2013132376A1 (en) 2012-03-06 2013-02-20 Macrocyclic derivatives for the treatment of proliferative diseases
EP13717555.0A EP2822953B9 (en) 2012-03-06 2013-02-20 Macrocyclic derivatives for the treatment of proliferative diseases

Publications (1)

Publication Number Publication Date
ME02630B true ME02630B (me) 2017-06-20

Family

ID=48142828

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-2017-42A ME02630B (me) 2012-03-06 2013-02-20 Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti

Country Status (45)

Country Link
US (2) US8680111B2 (me)
EP (1) EP2822953B9 (me)
JP (2) JP5823066B2 (me)
KR (1) KR101692600B1 (me)
CN (1) CN104169286B (me)
AP (1) AP2014007881A0 (me)
AR (1) AR090230A1 (me)
AU (1) AU2013229173B2 (me)
BR (1) BR112014022106B1 (me)
CA (1) CA2863892C (me)
CL (1) CL2014002084A1 (me)
CO (1) CO7061081A2 (me)
CR (1) CR20140370A (me)
CY (2) CY1118771T1 (me)
DK (1) DK2822953T5 (me)
DO (1) DOP2014000188A (me)
EA (1) EA026155B9 (me)
ES (1) ES2621220T3 (me)
FR (1) FR19C1062I2 (me)
GE (1) GEP201606560B (me)
GT (1) GT201400187A (me)
HR (1) HRP20170287T2 (me)
HU (2) HUE034118T2 (me)
IL (1) IL234062A (me)
LT (2) LT2822953T (me)
LU (1) LUC00131I2 (me)
MD (1) MD4590C1 (me)
ME (1) ME02630B (me)
MX (1) MX350844B (me)
MY (1) MY169142A (me)
NI (1) NI201400102A (me)
NL (1) NL301006I2 (me)
NO (1) NO2019034I1 (me)
NZ (1) NZ627900A (me)
PE (1) PE20142339A1 (me)
PH (1) PH12014501992B1 (me)
PL (1) PL2822953T3 (me)
PT (1) PT2822953T (me)
RS (1) RS55814B1 (me)
SG (1) SG11201404451TA (me)
SI (1) SI2822953T1 (me)
TW (1) TWI476199B (me)
UY (1) UY34657A (me)
WO (1) WO2013132376A1 (me)
ZA (1) ZA201406244B (me)

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SMT201700256T1 (it) 2013-01-31 2017-09-07 Vertex Pharma Piridone ammidi come modulatori di canali del sodio
US9637500B2 (en) 2013-06-28 2017-05-02 Pfizer Inc. Solid forms of a macrocyclic kinase inhibitor
CN104513253A (zh) * 2013-10-01 2015-04-15 南京波尔泰药业科技有限公司 用于治疗增殖性疾病的大环化合物
JP6463580B2 (ja) 2013-12-13 2019-02-06 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ ナトリウムチャネルの調節剤として有用なピリドンアミドのプロドラッグ
HRP20191283T1 (hr) 2014-01-24 2019-10-18 Turning Point Therapeutics, Inc. Diaril makrocikli kao modulatori protein kinaze
TWI672141B (zh) 2014-02-20 2019-09-21 美商醫科泰生技 投予ｒｏｓ１突變癌細胞之分子
CN103772272A (zh) * 2014-03-04 2014-05-07 定陶县友帮化工有限公司 2-boc-氨基-3-羟基-5-溴吡啶的合成方法
WO2016026423A1 (en) * 2014-08-20 2016-02-25 Teligene Ltd Substituted macrocycles useful as kinases inhibitors and methods of use thereof
CN107207528B (zh) * 2014-08-20 2019-06-21 苏州韬略生物科技有限公司 作为激酶抑制剂的经取代大环及其使用方法
US9663535B2 (en) * 2014-10-13 2017-05-30 Atrin Pharmaceuticals LLC Ataxia telengiectasia and Rad3-related (ATR) protein kinase inhibitors
CN107207471B (zh) 2014-12-02 2020-06-26 伊尼塔公司 用于治疗神经母细胞瘤的组合
US11077093B2 (en) * 2015-01-16 2021-08-03 Chugai Seiyaku Kabushiki Kaisha Combination drug
AU2016287568B2 (en) 2015-07-02 2020-08-20 Turning Point Therapeutics, Inc. Chiral diaryl macrocycles as modulators of protein kinases
EP4397665A3 (en) 2015-07-06 2024-08-21 Turning Point Therapeutics, Inc. Diaryl macrocycle polymorph
DK3325488T3 (da) 2015-07-21 2020-09-14 Turning Point Therapeutics Inc Chiral diaryl-makrocyklus og anvendelse deraf til behandling af cancer
HK1252845A1 (zh) 2015-07-31 2019-06-06 Pfizer Inc. 劳拉替尼游离碱的结晶形式
JP2018529719A (ja) 2015-09-30 2018-10-11 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ Ａｌｋ陰性がんを処置するためのｐｄ−１系結合アンタゴニストおよびａｌｋ阻害剤の組合せ
JP7061068B2 (ja) 2015-12-18 2022-04-27 イグナイタ インコーポレイテッド 癌治療のための併用薬
ES2812336T3 (es) * 2016-03-03 2021-03-16 Shenzhen Targetrx Inc Macrocíclico y composición que comprende el mismo
CN105732355A (zh) * 2016-04-07 2016-07-06 戊言医药科技（上海）有限公司 1-(5-氟-2-碘苯基)乙酮的制备方法
CN105646355A (zh) * 2016-04-07 2016-06-08 戊言医药科技（上海）有限公司 3-(羟甲基)-1-甲基-吡唑-5-甲腈的制备方法
CA3019905C (en) * 2016-04-08 2022-08-23 Pfizer Inc. Crystalline forms of lorlatinib maleate
WO2017180723A1 (en) * 2016-04-12 2017-10-19 Atrin Pharmaceuticals LLC Ataxia telengiectasia and rad3-related (atr) inhibitors and methods of their use
CN105801603B (zh) * 2016-04-13 2018-10-02 成都倍特药业有限公司 一种具有大环结构的alk抑制剂及其制备方法
TW201815799A (zh) 2016-07-28 2018-05-01 美商Ｔｐ生物醫藥公司 巨環激酶抑制劑
TW201831478A (zh) * 2016-12-02 2018-09-01 瑞士商赫孚孟拉羅股份公司 雙環醯胺化合物及其使用方法
WO2018137679A1 (en) * 2017-01-25 2018-08-02 Teligene Ltd Process for the Preparation of (10R) -7- (2-aminoacetyl) amino-12-fluoro-2, 10, 16-trimethyl-15-oxo-10, 15, 16, 17-tetrahydro-2H-8, 4- (metheno) pyrazolo [4, 3-h] [2, 5, 11] -benzoxadiazacyclotetradecine-3-carbonitrile
TWI808958B (zh) 2017-01-25 2023-07-21 美商特普醫葯公司 涉及二芳基巨環化合物之組合療法
BR112019024016A2 (pt) 2017-05-16 2020-06-09 Vertex Pharma amidas de piridona deuteradas e profármacos das mesmas como moduladores de canais de sódio
UA125800C2 (uk) 2017-06-30 2022-06-08 Баєр Енімал Хелс Гмбх Похідні азахіноліну
CN121401264A (zh) 2017-07-19 2026-01-27 伊尼塔公司 包括恩曲替尼的药物组合物
BR112020001695A2 (pt) 2017-07-28 2020-07-21 Turning Point Therapeutics, Inc. compostos macrocíclicos e usos dos mesmos
DK3694863T3 (da) 2017-10-10 2023-07-03 Pfizer Krystallinsk form af frit basehydrat af lorlatinib
WO2019077506A1 (en) 2017-10-17 2019-04-25 Ignyta, Inc. PHARMACEUTICAL COMPOSITIONS AND SOLID GALENIC FORMS
US11179412B2 (en) 2017-12-04 2021-11-23 University of Pittsburgh—of the Commonwealth System of Higher Education Methods of treating conditions involving elevated inflammatory response
CN111511746B (zh) 2017-12-19 2024-01-09 特普医药公司 用于治疗疾病的巨环化合物
EP3752152A1 (en) 2018-02-12 2020-12-23 Vertex Pharmaceuticals Incorporated A method of treating pain
US11760701B2 (en) 2018-02-27 2023-09-19 The Research Foundation For The State University Of New Yrok Difluoromethoxylation and trifluoromethoxylation compositions and methods for synthesizing same
US20210163498A1 (en) 2018-04-23 2021-06-03 Pliva Hrvatska D.O.O. Solid state forms of lorlatinib and their preparation
CN111918868B (zh) * 2018-05-04 2022-12-30 正大天晴药业集团股份有限公司 作为蛋白激酶调节剂的二芳基大环化合物
CN108621206B (zh) * 2018-05-07 2020-08-14 昆山国显光电有限公司 手套箱系统以及手套箱系统的保养方法
JPWO2020059705A1 (ja) * 2018-09-18 2021-08-30 株式会社ヤクルト本社 キノリンカルボキサミド誘導体を用いるがん併用療法
CN109232607A (zh) * 2018-09-20 2019-01-18 沈阳药科大学 劳拉替尼的合成方法
CN109081810A (zh) * 2018-09-20 2018-12-25 沈阳药科大学 1-甲基-3–((甲氨基)甲基)-1h-吡唑-5-腈的合成方法
CN111233833A (zh) 2018-11-28 2020-06-05 深圳市塔吉瑞生物医药有限公司 一种氘代大环化合物的制备方法
US20220040324A1 (en) 2018-12-21 2022-02-10 Daiichi Sankyo Company, Limited Combination of antibody-drug conjugate and kinase inhibitor
CN109651397A (zh) * 2019-01-25 2019-04-19 安庆多辉生物科技有限公司 一种劳拉替尼中间体及制备劳拉替尼的方法
CN109651418A (zh) * 2019-01-25 2019-04-19 安庆多辉生物科技有限公司 一种劳拉替尼原料药合成中间体及有机金属钯催化偶联制备劳拉替尼的方法
CN109651398B (zh) * 2019-01-25 2021-07-30 安庆多辉生物科技有限公司 一种合成劳拉替尼的溴代物中间体及催化合成劳拉替尼的方法
CN111499514B (zh) * 2019-01-31 2024-09-20 连云港润众制药有限公司 一种罗沙司他中间体的制备方法
WO2020190827A1 (en) * 2019-03-21 2020-09-24 Merck Sharp & Dohme Corp. Inhibitors of histone deacetylase useful for the treatment or prevention of hiv infection
ES2958528T3 (es) * 2019-05-14 2024-02-09 Teligene Ltd Macrociclos sustituidos útiles como inhibidores de quinasas
WO2021011345A1 (en) * 2019-07-18 2021-01-21 Pliva Hrvatska D.O.O Crystalline lorlatinib : fumaric acid and solid state form thereof
CN112321604A (zh) * 2019-08-05 2021-02-05 华东理工大学 大环类jak2抑制剂及其应用
CN110483551B (zh) * 2019-08-30 2021-10-22 北京赛思源生物医药技术有限公司 一种劳拉替尼游离碱的晶体
WO2021069571A1 (en) 2019-10-10 2021-04-15 Sandoz Ag Polymorph of lorlatinib
CN112812128B (zh) * 2019-11-18 2024-04-02 正大天晴药业集团股份有限公司 作为alk和ros调节剂的大环化合物
CN112824417A (zh) * 2019-11-21 2021-05-21 上海天慈国际药业有限公司 一种劳拉替尼的制备方法
DK4069691T3 (da) 2019-12-06 2024-10-28 Vertex Pharma Substituerede tetrahydrofuraner som modulatorer af natriumkanaler
CN111170908B (zh) * 2020-01-09 2021-08-17 北京印刷学院 一种2，4-二甲基-3-甲磺酰基卤苯的合成方法
WO2021176349A1 (en) 2020-03-05 2021-09-10 Pfizer Inc. Combination of an anaplastic lymphoma kinase inhibitor and a cyclin dependent kinase inhibitor
MX2022013657A (es) * 2020-05-05 2023-02-01 Nuvalent Inc Quimioterápicos de éter macrocíclico heteroaromático.
EP4146205A4 (en) 2020-05-05 2024-05-29 Nuvalent, Inc. HETEROAROMATIC MACROCYCLIC ETHERS AS CHEMOTHERAPEUTIC AGENTS
JP2023529068A (ja) * 2020-05-18 2023-07-07 深▲チェン▼市塔吉瑞生物医薬有限公司 固体形態の大環状化合物、その調製およびその使用
KR20230037564A (ko) * 2020-07-10 2023-03-16 블로썸힐 테라퓨틱스, 인크. 거대고리 화합물 및 그의 용도
KR20230121773A (ko) * 2020-12-17 2023-08-21 블로썸힐 테라퓨틱스, 인크. 거대고리 화합물 및 그의 용도
CN114805371B (zh) * 2021-01-19 2024-05-24 江苏开元药业有限公司 含2-氨基嘧啶大环类化合物及其制备方法和用途
WO2022182845A1 (en) * 2021-02-25 2022-09-01 Blossomhill Therapeutics, Inc. Macrocycles and their use
WO2022214681A1 (en) 2021-04-09 2022-10-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for the treatment of anaplastic large cell lymphoma
CN115246843A (zh) * 2021-04-26 2022-10-28 苏州东南药业股份有限公司 一类十四元稠环衍生物及其应用
MA64853B1 (fr) 2021-06-04 2025-11-28 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hétéro)aryl) tétrahydrofuran carboxamides utilisés en tant que modulateurs de canaux sodiques
CA3231813A1 (en) * 2021-10-01 2023-04-06 Sibao CHEN Solid forms, pharmaceutical compositions and preparation of heteroaromatic macrocyclic ether compounds
US20250162986A1 (en) 2022-02-21 2025-05-22 Universidade Nov A De Lisboa Compounds and compositions for neurodegenerative diseases
EP4230201A1 (en) 2022-02-21 2023-08-23 Universidade Nova De Lisboa Composition for treating neurodegenerative diseases
AU2023364043A1 (en) * 2022-10-19 2025-04-10 Nuvalent, Inc. Heteroaromatic macrocyclic ether chemotherapeutic agents
CN115746023B (zh) * 2022-10-27 2024-08-09 复旦大学 一种作为蛋白激酶抑制剂的含吲唑结构的杂环大环化合物及其制备方法
WO2024046512A2 (zh) * 2022-12-01 2024-03-07 中国医药研究开发中心有限公司 含氮大环类化合物及其制备方法和医药用途
WO2024146541A1 (en) * 2023-01-03 2024-07-11 Guangdong Newopp Biopharmaceuticals Co., Ltd. Macrocyclic compounds as usp1 inhibitors
WO2025103408A1 (zh) * 2023-11-15 2025-05-22 深圳市塔吉瑞生物医药有限公司 治疗alk阳性或ros1阳性的非小细胞肺癌的方法
WO2025212729A1 (en) * 2024-04-03 2025-10-09 Blossomhill Therapeutics, Inc. Macrocyclic compounds and their use
WO2026008023A1 (zh) * 2024-07-04 2026-01-08 正大天晴药业集团股份有限公司 哒嗪胺类化合物及其医药用途

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR0166088B1 (ko) 1990-01-23 1999-01-15 . 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도
US5376645A (en) 1990-01-23 1994-12-27 University Of Kansas Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof
GB9518953D0 (en) 1995-09-15 1995-11-15 Pfizer Ltd Pharmaceutical formulations
WO2000035298A1 (en) 1996-11-27 2000-06-22 Wm. Wrigley Jr. Company Chewing gum containing medicament active agents
GB9711643D0 (en) 1997-06-05 1997-07-30 Janssen Pharmaceutica Nv Glass thermoplastic systems
DE10239042A1 (de) 2002-08-21 2004-03-04 Schering Ag Makrozyclische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel
GEP20084341B (en) 2003-02-26 2008-03-25 Sugen Inc Aminoheteroaryl compounds as protein kinase inhibitors
WO2004078682A2 (en) 2003-03-05 2004-09-16 Irm Llc Cyclic compounds and compositions as protein kinase inhibitors
PA8603801A1 (es) * 2003-05-27 2004-12-16 Janssen Pharmaceutica Nv Derivados de la quinazolina
RU2346996C2 (ru) 2004-06-29 2009-02-20 ЮРОПИЭН НИКЕЛЬ ПиЭлСи Усовершенствованное выщелачивание основных металлов
MX2007002248A (es) 2004-08-25 2008-10-02 Pfizer Triazolobenzodiazepinas y su uso como antagonistas de vasopresina.
NZ552946A (en) 2004-08-26 2010-09-30 Pfizer Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors
BRPI0513915A (pt) * 2004-08-26 2008-05-20 Pfizer compostos aminoeteroarila enantiomericamente puros como inibidores de proteìna quinase
EP1710246A1 (en) 2005-04-08 2006-10-11 Schering Aktiengesellschaft Sulfoximine-pyrimidine Macrocycles and the salts thereof, a process for making them, and their pharmaceutical use against cancer
RU2387650C2 (ru) 2005-12-05 2010-04-27 Пфайзер Продактс Инк. Полиморфы с-met/hgfr ингибитора
DK1959955T3 (da) 2005-12-05 2011-02-07 Pfizer Prod Inc Fremgangsmåde til behandling af abnorm cellevækst
CA2675755C (en) 2007-01-19 2015-10-06 Xcovery, Inc. Pyridine and pyridazine derivatives as kinase inhibitors
RU2009136343A (ru) 2007-03-01 2011-04-10 Чугаи Сейяку Кабусики Кайся (Jp) Макроциклическое соединение
AU2008224633A1 (en) * 2007-03-13 2008-09-18 Pfizer Products Inc. Erythromycin-based macrolides
EP2265270A1 (en) * 2008-02-04 2010-12-29 OSI Pharmaceuticals, Inc. 2-aminopyridine kinase inhibitors
US8871753B2 (en) * 2008-04-24 2014-10-28 Incyte Corporation Macrocyclic compounds and their use as kinase inhibitors
KR101673886B1 (ko) * 2008-06-06 2016-11-08 사노피 ＴＡＦＩａ의 억제제로서의 마크로사이클릭 우레아 및 술파미드 유도체
AU2009288021B2 (en) * 2008-09-08 2015-06-18 Merck Patent Gmbh Macrocyclics pyrimidines as Aurora kinase inhibitors
WO2010085597A1 (en) 2009-01-23 2010-07-29 Incyte Corporation Macrocyclic compounds and their use as kinase inhibitors
WO2011047926A1 (en) 2009-10-21 2011-04-28 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Non-natural macrocyclic amide hdac6 inhibitor compounds and their uses as therapeutic agents
US8383793B2 (en) 2010-04-15 2013-02-26 St. Jude Children's Research Hospital Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors
EP2566858A2 (en) * 2010-05-04 2013-03-13 Pfizer Inc. Heterocyclic derivatives as alk inhibitors
RU2735545C2 (ru) * 2010-05-20 2020-11-03 Эррэй Биофарма Инк. Макроциклические соединения в качестве ингибиторов киназы trk
US8975232B2 (en) 2010-07-29 2015-03-10 President And Fellows Of Harvard College Macrocyclic kinase inhibitors and uses thereof
EP2686323A1 (en) 2011-03-16 2014-01-22 Cephalon, Inc. Macrocyclic compounds as alk, fak and jak2 inhibitors

Also Published As

Publication number Publication date
RS55814B1 (sr) 2017-08-31
MD4590B1 (ro) 2018-08-31
KR20140137414A (ko) 2014-12-02
US20130252961A1 (en) 2013-09-26
FR19C1062I1 (me) 2019-11-22
US20140135339A1 (en) 2014-05-15
HUE034118T2 (en) 2018-01-29
MD20140086A2 (ro) 2015-01-31
TW201350484A (zh) 2013-12-16
AU2013229173B2 (en) 2017-06-01
EA201491394A1 (ru) 2015-05-29
JP5823066B2 (ja) 2015-11-25
JP2016041709A (ja) 2016-03-31
CO7061081A2 (es) 2014-09-19
PL2822953T3 (pl) 2017-07-31
PH12014501992A1 (en) 2014-11-24
JP6002825B2 (ja) 2016-10-05
LTC2822953I2 (lt) 2020-12-28
EP2822953B9 (en) 2017-06-21
LT2822953T (lt) 2017-04-10
NL301006I2 (nl) 2020-04-14
BR112014022106A2 (pt) 2017-07-11
LUC00131I2 (me) 2020-07-16
US8680111B2 (en) 2014-03-25
BR112014022106B1 (pt) 2022-08-02
HK1199247A1 (zh) 2015-06-26
HRP20170287T1 (hr) 2017-04-21
EP2822953B1 (en) 2017-02-01
LUC00131I1 (me) 2019-10-11
AR090230A1 (es) 2014-10-29
CA2863892A1 (en) 2013-09-12
WO2013132376A1 (en) 2013-09-12
IL234062A (en) 2017-08-31
ZA201406244B (en) 2015-05-27
MX2014010716A (es) 2014-09-22
SG11201404451TA (en) 2014-09-26
SI2822953T1 (sl) 2017-04-26
MX350844B (es) 2017-09-22
CR20140370A (es) 2014-08-21
HUS1900040I1 (hu) 2019-09-30
PT2822953T (pt) 2017-04-06
NZ627900A (en) 2016-08-26
LTPA2019519I1 (lt) 2019-11-11
FR19C1062I2 (fr) 2020-09-04
PH12014501992B1 (en) 2014-11-24
CN104169286A (zh) 2014-11-26
MD4590C1 (ro) 2019-03-31
TWI476199B (zh) 2015-03-11
JP2015510879A (ja) 2015-04-13
CY1118771T1 (el) 2017-07-12
MY169142A (en) 2019-02-18
UY34657A (es) 2013-10-31
AU2013229173A1 (en) 2014-08-21
AP2014007881A0 (en) 2014-08-31
KR101692600B1 (ko) 2017-01-03
EA026155B1 (ru) 2017-03-31
CA2863892C (en) 2016-08-30
ES2621220T3 (es) 2017-07-03
CL2014002084A1 (es) 2014-11-03
HRP20170287T2 (hr) 2017-11-03
ES2621220T9 (es) 2017-11-23
US9133215B2 (en) 2015-09-15
DK2822953T5 (en) 2017-09-11
EP2822953A1 (en) 2015-01-14
GT201400187A (es) 2015-10-15
NO2019034I1 (no) 2019-08-19
NI201400102A (es) 2015-03-05
DK2822953T3 (en) 2017-04-03
PE20142339A1 (es) 2015-01-15
CY2019033I2 (el) 2019-11-27
EA026155B9 (ru) 2017-06-30
CN104169286B (zh) 2016-06-08
GEP201606560B (en) 2016-10-25
CY2019033I1 (el) 2019-11-27
DOP2014000188A (es) 2014-11-16

Similar Documents

Publication Publication Date Title
ME02630B (me) Makrociklički derivati, namijenjeni liječenju proliferativnih bolesti
CN114430739A (zh) Egfr抑制剂、组合物及其制备方法
HRP20191826T4 (hr) Derivati n-piridinil acetamida kao inhibitori wnt signalnog puta
AR080754A1 (es) Derivados de imidazo (1,2-a) pirazina y su uso como inhibidores de pde10
HK1254469A1 (zh) 稠合双环嘧啶衍生物及其用途
HRP20210447T1 (hr) Piridinski spoj
AU2009258115B2 (en) Diazacarbazoles and methods of use
FI4074703T3 (fi) Pyridinyyli-(atsa)indolsulfonamiidit
MY194405A (en) Dihydropyrimidine compounds and uses thereof in medicine
MY204050A (en) Benzolactam compounds as protein kinase inhibitors
PE20090493A1 (es) DERIVADOS DE LA 6-CICLOAMINO-3-(PIRIDAZIN-4-IL)IMIDAZO[1,2-b]-PIRIDAZINA, SU PREPARACION Y SU APLICACION EN TERAPEUTICA
HK1246645A1 (zh) 细胞周期蛋白依赖性激酶的抑制剂
JP2019503337A5 (me)
HK1245260A1 (zh) 细胞周期蛋白依赖性激酶7(cdk7)的抑制剂
HK1202541A1 (en) 2-amino, 6-phenyl substituted pyrido [2, 3 - d] pyrimidine derivatives useful as raf kinase inhibitors
EA023824B1 (ru) ПРОИЗВОДНЫЕ 3,4-ДИГИДРОПИРРОЛО[1,2-a]ПИРАЗИН-1-ИЛАМИНА, ПРИГОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ БЕТА-СЕКРЕТАЗЫ (BACE)
WO2015058163A3 (en) Heteromaromatic compounds useful for the treatment of prolferative diseases
CA2651363A1 (en) Triazolopyrazine derivatives useful as anti-cancer agents
MY192109A (en) Aminopyrimidinyl compounds as jak inhibitors
WO2017044858A3 (en) Inhibitors of cyclin-dependent kinases
JP2016514719A5 (me)
RU2019117356A (ru) Азотсодержащее макроциклическое соединение, способ его получения, фармацевтическая композиция и применение
JP2013542941A5 (me)
AR107042A1 (es) Inhibidores de la tirosina quinasa de bruton y métodos de su uso
JP2019512535A5 (me)