FI114801B - Borester- och -syraföreningar samt syntes och användning därav - Google Patents

Borester- och -syraföreningar samt syntes och användning därav Download PDF

Info

Publication number
FI114801B
FI114801B FI971746A FI971746A FI114801B FI 114801 B FI114801 B FI 114801B FI 971746 A FI971746 A FI 971746A FI 971746 A FI971746 A FI 971746A FI 114801 B FI114801 B FI 114801B
Authority
FI
Finland
Prior art keywords
alkyl
aryl
group
compound according
mmol
Prior art date
Application number
FI971746A
Other languages
English (en)
Finnish (fi)
Other versions
FI971746A0 (sv
FI971746A (sv
Inventor
Julian Adams
Yu-Ting Ma
Ross Stein
Matthew Baevsky
Louis Grenier
Louis Plamondon
Original Assignee
Millennium Pharm Inc
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=26987313&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=FI114801(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Millennium Pharm Inc filed Critical Millennium Pharm Inc
Publication of FI971746A0 publication Critical patent/FI971746A0/sv
Publication of FI971746A publication Critical patent/FI971746A/sv
Application granted granted Critical
Publication of FI114801B publication Critical patent/FI114801B/sv

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/04—Esters of boric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C07K5/06043—Leu-amino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Virology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pyridine Compounds (AREA)

Claims (27)

1. Förening kännetecknad av formeln P--N- -tf-X'- -CH-X2-CH—ΒίΖ’χΖ*) (la) B A' R2 A* JA 5 I eller ett farmaceutiskt godtagbart sait därav; där P betecknar R7-C(0)-, R7-NH-C(0)-, R70-C (O) - eller R7-S02-, där R7 betecknar heteroaryl eller heteroarylalkyl; eller där R7 ocksä kan beteckna N-morfolinyl när P betecknar R7-C(0)-; 10 där Bl vid varje förekomst oberoende betecknar N eller CH; där X1 vid varje förekomst oberoende betecknar -C(0)-NH-, -CH2-NH-, -CH(OH)-CH2, -CH(OH)-CH(OH)-, -CH(OH)-CH2-NH-, -CH~CH-, -C(0)-CH2-, -S02-NH-, —S02—CH2— eller -CH (OH) -CH2-C (O) -NH-, med det förebehället att när B1 betecknar N, sä är den grupp X1 som f 15 är fästad vid Bl -C(0)-NH-; där X2 betecknar -C(0)-NH-, -CH(OH)-CH2-, -CH(OH)-CH(OH-, : -C(0)-CH2-, -SO2-NH-, -S02-CH2- eller -CH (OH) -CH2-C (O) -NH-; där R betecknar väte eller alkyl, eller där R tillsammans med den angränsande R1, eller tillsammans med den angränsande R2 20 när A är lika med noll, bildar ett kväve-innehällande mono-, di- eller tricykliskt, mättat eller partiellt mättat ringsy-:·! stem innehällande 4-14 ringatomer, varvid detta ringsystem .*' > eventuellt kan vara substituerat med en eller tvä ketogrupper, hydroxigrupper, alkylgrupper, arylgrupper, aralkylgrupper, al-25 koxigrupper eller aryloxigrupper; > · ! 114801 där R1 vid varje förekomst oberoende betecknar väte, alkyl, cykloalkyl, aryl, en 5-10-ledad, mättad, partiellt omättad el-ler aromatisk heterocyklisk grupp eller -CH2-R5, där ringdelen av en eventuell arylgrupp, aralkylgrupp, alkarylgrupp eller 5 heterocyklisk grupp eventuellt kan vara substituerad; där R2 betecknar väte, alkyl, cykloalkyl, aryl, en 5-10-ledad, , mättad, partiellt omättad eller aromatisk heterocyklisk grupp eller -CH2-R5, där ringdelen av en eventuell arylgrupp, aralkylgrupp, alkarylgrupp eller heterocyklisk grupp eventuellt 10 kan vara substituerad; där R3 betecknar väte, alkyl, cykloalkyl, aryl, en 5-10-ledad, mättad, partiellt omättad eller aromatisk heterocyklisk grupp eller -CH2-R5, där ringdelen av en eventuell arylgrupp, aralkylgrupp, alkarylgrupp eller heterocyklisk grupp eventuellt 15 kan vara substituerad; där R5 vid varje förekomst betecknar aryl, aralkyl, alkaryl, cykloalkyl, en 5-10-ledad, mättad, partiellt omättad eller • .1 aromatisk heterocyklisk grupp eller W-R6, där W betecknar en kalkogen och R6 betecknar alkyl, varvid ringdelen av en eventu-20 eli arylgrupp, aralkylgrupp, alkarylgrupp eller heterocyklisk grupp eventuellt kan vara substituerad; där Z1 och Z2 oberoende av varandra betecknar alkyl, hydroxi, alkoxi eller aryloxi, eller där Z1 och Z2 tillsammans bildar en grupp härrörande frän en dihydroxiförening med minst tvä hyd-,25 roxigrupper separerade medelst minst tvä sammanbindande atomer i en kedja eller ring, varvid kedjän eller ringen innefattar kolatomer och eventuellt en eller flera heteroatomer valda :·/. bland N, S och O; > och där A betecknar 0, 1 eller 2. 101 1 1 4801
2. Förening enligt krav 1, kännetecknad av att heteroarylgruppen R7 ör vald bland tienyl, benso[b]tienyl, nafto[2,3~b]tienyl, tiantrenyl, furyl, pyranyl, isobensofuranyl, bensoxazolyl, kromenyl, xan-5 tenyl, fenoxatiinyl, 2H-pyrrolyl, pyrrolyl, imidazolyl, pyra-zolyl, pyridyl, pyrazinyl, pyrimidinyl, pyrdazinyl, indolizi-nyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, 4H-kinolizinyl, isokinolyl, kinolyl, ftalazinyl, naftyridinyl, kinazolinyl, cinnolinyl, pteridinyl, 4aH-karbazolyl, karbazo-10 lyl, β-karbolinyl, fenantridinyl, akridinyl, perimidinyl, fe-nantrolinyl, fenazinyl, isotiazolyl, fenotiazinyl, isoxazolyl, furazanyl och fenoxazinyl.
3. Förening enligt krav 1, kännetecknad av att P betecknar kinolinkarbonyl,· pyridinkarbonyl, kinolinsulfonyl, 15 kinoxalinkarbonyl, kinoxalinsulfonyl, pyrazinkarbonyl, pyrazin-sulfonyl, furankarbonyl, ifuransulfonyl eller N-morfolinkarbonyl.
4. Förening enligt krav 1, kanne tecknad av att P betecknar 8-kinolinkarbohyl, 8-kinolinsulfonyl, 2-kinoxalin- j ♦ · | karbonyl, 2-kinoxalinsulfonyl, 2-pyrazinkarbonyl, 2-pyrazinsul-fonyl, 3-furankarbonyl, 3-furansulfonyl eller N-morfolinkarbonyl. ·· 20
5. Förening enligt krav 1, kännetecknad av att A betecknar 0.
6. Förening enligt krav 1, kännetecknad av att B1 vid varje förekomst betecknar CH.
7. Förening enligt krav 6, kännetecknad av att X1 vid varje förekomst betecknar -C(0)-NH-. Γ· . 25
: 8. Förening enligt krav 7rkännetecknad av att X2 betecknar -C(0)-NH-. • * I
] 9. Förening enligt krav 1, kännetecknad av att * * » ’ : R betecknar väte eller Ci-e~ alkyl. t 108 1 1 4801
10 R2, R3 eller R5 eventuellt kan vara substituerad med en eller tvä substituenter oberoende valda bland Ci-6-alkyl, C3-8-cyklo- alkyl, Ci_6-alkyl (C3-8) cykloalkyl, C2-8-alkenyl, C2-e-alkynyl, cy- ano, amino, Ci-6-alkylamino, di (Ci-β) -alkylamino, bensylamino, dibensylamino, nitro, karboxi, karbo(Ci-β)-alkoxi, trifluorme- 15 tyl, halogen, Ci-6-alkoxi, C6-io~aryl, C6-i0-aryl (Ca_6) -alkyl, C6-io-aryl (Ci_6)-alkoxi, hydroxi, Ci-6-alkyltio, Ci-6~alkylsulfi- nyl, Cj-6-alkylsulfonyl, C6-i0-aryltio, C6_io-arylsulfinyl, C6-x0- . arylsulfonyl, C6-io-aryl, Ci-6-alkyl (C6-i0) aryl och halo(C6-io)- • « aryl. 20
11. Förening enligt krav 1, kännetecknad av att A betecknar noll; där X2 betecknar -C(O) -NH-; där R betecknar väte eller Ci-8-alkyl; och där R3 betecknar Ci_6~alkyl. »
10. Förening enligt krav 1, kanne tecknad av att! k1 vid varje förekomst och R2 och R3 oberoende av varandra vardera betecknar väte, Ci-8-alkyl, en 5-, 6-, 9- eller 10-ledad heteroarylgrupp eller -CH2-R5; C3-i0-cykloalkyl, C6-io~aryl, 5 där R5 vid varje förekomst betecknar C6-io-aryl, Ci-io-ar (Ci-β) -alkyl, Ci_6-alk (C6-i0) aryl, C3-i0-cykloalkyl, Ci-8-alkoxi, Ci_8-alkyltio eller en 5-, 6-, 9- eller 10-ledad heteroarylgrupp; varvid ringdelen i en eventuell arylgrupp, aralkylgrupp, alka- rylgrupp eller 5-, 6-, 9- eller 10-ledad heteroarylgrupp R1,
12. Förening enligt krav 1, kännetecknad av att R3 betecknar Ci_i2-alkyl.
13. Förening enligt krav 1, kännetecknad av att R3 betecknar Ci-6-alkyl. 25
14. Förening enligt krav 1, kännetecknad av att R3 betecknar C4-alkyl.
15. Förening enligt krav 1, kännetecknad av att • I : ·' R3 betecknar isobutyl.
16. Förening enligt krav 1, kännetecknad av att R2 betecknar isobutyl, 1-naftylmetyl, 2-naftylmetyl, 3-pyridyl"- 109 11 4801 metyl, 2-pyridylmetyl, 6-kinolinylmetyl, 3-indolylmetyl, bensyl, 4-fluorbensyl, 4-hydroxibensyl, 4-(2'-pyridylmetoxi)-bensyl, 4-(bensyloxi)bensyl, bensylnaftylmety1 eller fenetyl.
17. Förening enligt krav 1, kännetecknad av att 5 Z1 och 7} oberoende av varandra betecknar C1-6—alkyl, hydroxi, Ci-6-alkoxi eller Ci-io-aryloxi .
18. Förening enligt krav 17, kännetecknad av att Z1 och 7? bäda betecknar hydroxi.
19. Förening enligt krav 1, kännetecknad av att 10 Z1 och Z2 tillsammans bildar en grupp härrörande frän en dihyd- roxiförening vald bland pinakol, perfluorpinakol, pinandiol, etylenglykol, dietylenglykol, 1,2-cyklohexandiol, 1,3-propandiol, 2,3-butandiol, glycerol och dietanolamin.
20. Förening enligt krav 1, kännetecknad av att 15 P betecknar kinolinkarbonyl, pyridinkarbonyl, kinolinsulfonyl, kinoxalinkarbonyl, kinoxalinsulfonyl, pyrazinkarbonyl, pyrazin- • sulfonyl, furankarbonyl,furansulfonyl eller N—morfolinkarbonyl; .. där A betecknar noli; ♦ # där X2 betecknar -C(0)-NH-; 20 där R betecknar väte eller Ci-e-alkyl; där R2 och R3 oberoende av varandra vardera betecknar väte, : Ci-e-alkyl, C3-i0-cykloalkyl, C6-io-aryl, C6.10-ar(Ci_6)alkyl, pyri- dylmetyl eller kinolinylmetyl; ;>* och där Z och Z bäda betecknar hydroxi, Ci-6-alkoxi eller
21. Förening enligt krav 1, kännetecknad av att P betecknar 8-kinolinkarbonyl, 8-kinolinsulfonyl, 2-kinoxalin-5 karbonyl, 2-kinoxalinsulfonyl, 2-pyrazinkarbonyl, 2-pyrazin— sulfonyl, .3-pyridinkarbonyl, 3-pyridinsulfonyl, 3-furankarbonyl, 3-furansulfonyl eller N- morfolinkarbonyl; där A betecknar noli; där X2 betecknar -C(0)-NH-; 10 där R betecknar väte eller Ci-e-alkyl; där R3 betecknar isobutyl; där R2 betecknar isobutyl, 1-naftylmetyl, 2-naftylmetyl, 3-pyridylmetyl, 2-pyridylmetyl, 6-kinolinylmetyl, 3-indolyl-metyl, bensyl, 4-fluorbensyl, 4-hydroxibensyl, 4-(2' -pyridyl-15 metoxi)bensyl, 4-(bensyloxi)bensyl, bensylnaftylraetyl eller • · ;* fenetyl; och där Z1 och Z2 oberoende av varandra betecknar hydroxi, Οχ-6~ alkoxi eller C6-io~aryloxi, eller där Z1 och Z2 tillsammans bil-·. dar en grupp härrörande frän en dihydroxiförening vald bland : 20 pinakol, perfluorpinakol, pinandiol, etylenglykol, dietylen- glykol, 1,2-cyklohexandiol, 1,3-propandiol, 2,3-butandiol, :* glycerol och dietanolamin.
22. Förening enligt krav 1, kännetecknad av att den är ; 25 N- (2-pyrazin) karbonyl-L-fenylalanin-L-leucin-boronsyra; N- (2-kinolin) sulfonyl-L-homof enylalanin-L-leucin-boronsyra; N-(3-pyridin)karbonyl-L-fenylalanin-L-leucin-boronsyra; -N-(4-morfolin)karbonyl-L-fenylalanin-L-leucin-boronsyra; ) 114801 m υ u 1 N-(4-morfolin)karbonyl-β-(l-naftyl)-L-alanin-L-leucin-boronsyra; N-(8-kinolin) sulfonyl-β- (1-naftyl) -L-alanin-L-leucon-boronsyra; N-(4-morfoi in)karbonyl-(O-bensyl) -L-tyrosin-L-leucin-5 boronsyra; N-(4-morfolin)karbonyl-L-tyrosin-L-leucin-boronsyra; N-(4-morfolin)karbonyl-[O-(2-pyridylmetyl)]-L-tyrosin-L-leucin-boronsyra; eller ett farmaceutiskt godtagbart sait eller en boronatester 10 därav.
23. Förening enligt krav 22, kännetecknad av att den är N-(2-pyrazin)karbonyl-L-fenylalanin-L-leucin-boronsyra eller ett farmaceutiskt godtagbart sait eller en boronatester därav.
24. Farmaceutisk komposition, kännetecknad av att innefattäden en förening enligt nägot av de föregäende kraven, eller ett farmaceutiskt godtagbart sait därav, och en farma— ceutiskt godtagbar bärare eller ett farmaceutiskt godtagbart * utspädningsmedel. ·* 25. Farmaceutisk komposition enligt krav 24, kanne — * ’ 20 tecknad av att föreningen är närvarande i en mängd som ' hämmar proteasom-funktionen hos ett däggdjur.
25 C6-io~aryloxi, eller där Z1 och Z2 tillsammans bildar en grupp ,‘i härrörande frän en dihydroxiförening vald bland pinakol, per- fluorpinakol, pinandiol, etylenglykol, dietylenglykol, 1,2- „0 114801 cyklohexandiol, 1,3-propandiol, 2,3-butandiol, glycerol och dietanolamin.
26. Användning av en förening enligt nägot av kraven 1-23 ;· för framställning av en farmaceutisk komposition för (a) hämning av en cancercells tillväxt; 25 (b) minskning av den hastighet med vilken muskelprote- in nedbrytes; • · (c) minskning av aktiviteten av NF-κΒ i en cell; 114801 (d) minskning av den hastighet med vilken intracellu-lärt protein nedbrytes; (e) minskning av hastigheten av nedbrytning av p53; (f) hämning av cyklin-nedbrytning i en cell; 5 (g) förhindrande eller behandling av ett inflammato- riskt tillstAnd; (h) hämning av antigenpresentation i en cell; (i) hämning av inducerbar, NF-KB-beroende cellvidhäft-ning; eller 10 <j) hämning av HIV-replikation.
] 27. Användning enligt krav 26, kännetecknad av att en patient har diagnosticerats med eller riskerar att utveckla i ; ett tillständ valt bland avstötning av vävnad, avstötning av organ, artrit, infektioner, dermatoser, inflammatorisk tarmsjukdom, astma, 15 osteoporos, osteoartrit och autoimmuna sjukdomar. » · » »
FI971746A 1994-10-28 1997-04-23 Borester- och -syraföreningar samt syntes och användning därav FI114801B (sv)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US33052594A 1994-10-28 1994-10-28
US33052594 1994-10-28
US08/442,581 US6083903A (en) 1994-10-28 1995-05-16 Boronic ester and acid compounds, synthesis and uses
US44258195 1995-05-16
PCT/US1995/014117 WO1996013266A1 (en) 1994-10-28 1995-10-27 Boronic ester and acid compounds, synthesis and uses
US9514117 1995-10-27

Publications (3)

Publication Number Publication Date
FI971746A0 FI971746A0 (sv) 1997-04-23
FI971746A FI971746A (sv) 1997-06-06
FI114801B true FI114801B (sv) 2004-12-31

Family

ID=26987313

Family Applications (2)

Application Number Title Priority Date Filing Date
FI971746A FI114801B (sv) 1994-10-28 1997-04-23 Borester- och -syraföreningar samt syntes och användning därav
FI20041415A FI120974B (sv) 1994-10-28 2004-11-03 Borester- och -syraföreningar samt användning därav

Family Applications After (1)

Application Number Title Priority Date Filing Date
FI20041415A FI120974B (sv) 1994-10-28 2004-11-03 Borester- och -syraföreningar samt användning därav

Country Status (25)

Country Link
US (16) US6083903A (sv)
EP (4) EP0788360B3 (sv)
JP (1) JP3717934B2 (sv)
KR (1) KR100398944B1 (sv)
CN (2) CN101077875B (sv)
AT (3) ATE314378T1 (sv)
AU (1) AU710564B2 (sv)
CA (2) CA2496538C (sv)
CH (1) CH0788360H1 (sv)
CY (1) CY2484B1 (sv)
DE (5) DE69534727T2 (sv)
DK (3) DK1627880T3 (sv)
ES (3) ES2254803T3 (sv)
FI (2) FI114801B (sv)
FR (1) FR04C0014I2 (sv)
HK (2) HK1002059A1 (sv)
IL (5) IL137726A (sv)
LU (1) LU91083I2 (sv)
MX (1) MX9703063A (sv)
NL (1) NL300151I2 (sv)
NO (2) NO310558B1 (sv)
NZ (2) NZ337211A (sv)
PT (3) PT1312609E (sv)
TW (1) TW318850B (sv)
WO (1) WO1996013266A1 (sv)

Families Citing this family (306)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6083903A (en) * 1994-10-28 2000-07-04 Leukosite, Inc. Boronic ester and acid compounds, synthesis and uses
US6838477B2 (en) * 1995-04-12 2005-01-04 President And Fellows Of Harvard College Lactacystin analogs
FR2758329B1 (fr) * 1997-01-16 1999-02-12 Synthelabo Derives d'imidazole-4-butane boronique, leur preparation et leur utilisation en therapeutique
CA2281224A1 (en) * 1997-02-15 1998-08-20 Proscript, Inc. Treatment of infarcts through inhibition of nf-kappab
US6221888B1 (en) * 1997-05-29 2001-04-24 Merck & Co., Inc. Sulfonamides as cell adhesion inhibitors
CA2304622A1 (en) * 1997-09-25 1999-04-01 Proscript, Inc. Proteasome inhibitors, ubiquitin pathway inhibitors or agents that interfere with the activation of nf-?b via the ubiquitin proteasome pathway to treat inflammatory and autoimmunediseases
BR9813233A (pt) * 1997-09-29 2000-08-22 Point Therapeutics Inc Estimulação de células hematopoéticas in vitro
US6831057B2 (en) * 1997-10-28 2004-12-14 The University Of North Carolina At Chapel Hill Use of NF-κB inhibition in combination therapy for cancer
CA2219867A1 (en) * 1997-10-31 1999-04-30 Jiangping Wu The use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock
DE19802450A1 (de) * 1998-01-23 1999-07-29 Hoechst Marion Roussel De Gmbh Ustilipide, Verfahren zu deren Herstellung sowie deren Verwendung
US6075150A (en) * 1998-01-26 2000-06-13 Cv Therapeutics, Inc. α-ketoamide inhibitors of 20S proteasome
US6617171B2 (en) 1998-02-27 2003-09-09 The General Hospital Corporation Methods for diagnosing and treating autoimmune disease
FR2779653B1 (fr) * 1998-06-11 2002-12-20 Inst Nat Sante Rech Med Utilisation de composes modulateurs du proteasome en therapie
US6462019B1 (en) 1998-07-10 2002-10-08 Osteoscreen, Inc. Inhibitors of proteasomal activity and production for stimulating bone growth
US6838436B1 (en) * 1998-07-10 2005-01-04 Osteoscreen Inc. Inhibitors of proteasomal activity for stimulating bone growth
US6902721B1 (en) 1998-07-10 2005-06-07 Osteoscreen, Inc. Inhibitors of proteasomal activity for stimulating bone growth
US6979697B1 (en) * 1998-08-21 2005-12-27 Point Therapeutics, Inc. Regulation of substrate activity
EP0982317A1 (en) * 1998-08-26 2000-03-01 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Bivalent inhibitors of the proteasome
BR9914648A (pt) * 1998-10-20 2001-11-27 Millennium Pharm Inc Processo para monitorar ação medicamentosa deinibidor de proteasoma
US6492333B1 (en) * 1999-04-09 2002-12-10 Osteoscreen, Inc. Treatment of myeloma bone disease with proteasomal and NF-κB activity inhibitors
US6890904B1 (en) * 1999-05-25 2005-05-10 Point Therapeutics, Inc. Anti-tumor agents
US6649593B1 (en) * 1999-10-13 2003-11-18 Tularik Inc. Modulators of SREBP processing
AU2001287399A1 (en) * 2000-08-16 2002-02-25 University Of Alberta Non-pressurized methods for the preparation of conjugated solid supports for boronic acids
US6919382B2 (en) 2000-08-31 2005-07-19 The Governors Of The University Of Alberta Preparation and uses of conjugated solid supports for boronic acids
DE50110956D1 (de) * 2000-10-12 2006-10-19 Viromics Gmbh Proteasome inhibitoren zur behandlung von hepatitis-virus infektionen
CA2435146C (en) * 2001-01-25 2011-03-29 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Formulation of boronic acid compounds
DK1392355T3 (da) 2001-05-21 2007-04-30 Alcon Inc Anvendelse af proteasominhibitorer tilbehandling af öjentörhedslidelser
US7112588B2 (en) * 2001-05-21 2006-09-26 Alcon, Inc. Use of proteasome inhibitors to treat dry eye disorders
ATE317850T1 (de) * 2001-05-30 2006-03-15 Novartis Pharma Gmbh 2-((n-(2-amino-3-(heteroaryl- oder - aryl)propionyl)aminoacyl)amino)- alkylboronsäurederivate
WO2003033506A1 (fr) * 2001-10-12 2003-04-24 Kyorin Pharmaceutical Co., Ltd. Derive d'acide d'aminoborane et medicament inhibiteur de proteasomes le contenant
JPWO2003033507A1 (ja) * 2001-10-12 2005-02-03 杏林製薬株式会社 ベンジルマロン酸誘導体およびそれを含有するプロテアソーム阻害薬
AU2003219652A1 (en) 2002-01-08 2003-07-30 Eisai Co. Ltd. Eponemycin and epoxomicin analogs and uses thereof
WO2003077928A1 (en) * 2002-03-12 2003-09-25 Ariad Pharmaceuticals, Inc. Peptide analogues and uses thereof
EA007272B1 (ru) * 2002-03-13 2006-08-25 Янссен Фармацевтика Н. В. Новые ингибиторы гистондеацетилазы
EP1485348B1 (en) * 2002-03-13 2008-06-11 Janssen Pharmaceutica N.V. Carbonylamino-derivatives as novel inhibitors of histone deacetylase
US7767679B2 (en) 2002-03-13 2010-08-03 Janssen Pharmaceutica N.V. Sulfonylamino-derivatives as novel inhibitors of histone deacetylase
WO2003076438A1 (en) * 2002-03-13 2003-09-18 Janssen Pharmaceutica N.V. Piperazinyl-, piperidinyl- and morpholinyl-derivatives as novel inhibitors of histone deacetylase
EP1492545B1 (de) * 2002-04-05 2010-09-15 ViroLogik GmbH Mittel zur behandlung von flaviviridae-infektionen
US7514579B2 (en) * 2002-06-13 2009-04-07 Johns Hopkins University Boronic chalcone derivatives and uses thereof
JP2006506442A (ja) * 2002-07-09 2006-02-23 ポイント セラピューティクス， インコーポレイテッド ボロプロリン化合物併用療法
DE60311825T2 (de) * 2002-08-14 2007-12-06 Janssen Pharmaceutica N.V. Verwendung von nf-kappa b hemmern zur behandlung von brustdrüsenentzündung
US7371729B2 (en) * 2002-09-09 2008-05-13 Trigen Limited Boronic acid salts useful in parenteral formulations
US20050282757A1 (en) * 2002-09-09 2005-12-22 Trigen Limited Peptide boronic acid compounds useful in anticoagulation
US20060084592A1 (en) * 2002-09-09 2006-04-20 Trigen Limited Peptide boronic acid inhibitors
PT1396270E (pt) * 2002-09-09 2006-08-31 Trigen Ltd Processo para a preparacao de compostos uteisncomo intermidiarios.
US20050119226A1 (en) * 2003-09-09 2005-06-02 Trigen Limited Methods for synthesizing organoboronic compounds and products thereof
US20050176651A1 (en) * 2002-09-09 2005-08-11 Trigen Limited Peptide boronic acids useful in making salts thereof
AU2003278727A1 (en) * 2002-09-20 2004-04-08 Alcon, Inc. Use of cytokine synthesis inhibitors for the treatment of dry eye disorders
WO2004053066A2 (en) 2002-12-06 2004-06-24 Millennium Pharmaceuticals, Inc. Methods for the identification, assessment, and treatment of patients with proteasome inhibition therapy
CN100341880C (zh) * 2003-02-13 2007-10-10 上海仁虎制药股份有限公司 新型硼酸或硼酸酯类化合物、制备方法及在药学上的应用
WO2005007211A2 (en) * 2003-07-03 2005-01-27 Medtronic Vascular Inc. Medical devices with proteasome inhibitors for the treatment of restenosis
US7223745B2 (en) * 2003-08-14 2007-05-29 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7576206B2 (en) 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
MXPA06005104A (es) 2003-11-05 2007-01-25 Palingen Inc Citotoxicidad de celulas b aumentada en anticuerpos de enlace a cdim.
US20060052390A1 (en) * 2003-12-24 2006-03-09 Scios, Inc. Treatment of multiple myeloma by p38 MAP kinase and proteasome inhibition
RU2379315C2 (ru) * 2004-02-23 2010-01-20 Трастиз Оф Тафтс Колледж Ингибиторы дипептидилпептидазы iv
GB0405272D0 (en) * 2004-03-09 2004-04-21 Trigen Ltd Compounds
US7371875B2 (en) * 2004-03-12 2008-05-13 Miikana Therapeutics, Inc. Cytotoxic agents and methods of use
PT2377869E (pt) * 2004-03-30 2014-04-15 Millennium Pharm Inc Síntese de bortezomib
AU2016202747B2 (en) * 2004-03-30 2017-11-23 Millennium Pharmaceuticals, Inc. Synthesis of boronic ester and acid compounds
CN102174076A (zh) 2004-04-15 2011-09-07 普罗特奥里克斯公司 用于抑制蛋白酶体酶的化合物
US8198270B2 (en) 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
DK2030981T3 (da) 2004-05-10 2014-10-13 Onyx Therapeutics Inc Forbindelser til proteasom-enzymhæmning
CA2571421A1 (en) 2004-06-24 2006-01-05 Nicholas Valiante Compounds for immunopotentiation
ATE553077T1 (de) 2004-07-23 2012-04-15 Nuada Llc Peptidaseinhibitoren
EP1781639B1 (en) * 2004-07-28 2012-01-25 Janssen Pharmaceutica NV Substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase
AU2005295183A1 (en) 2004-10-20 2006-04-27 CAOnyx Therapeutics, Inc. Labeled compounds for proteasome inhibition
TW200618820A (en) * 2004-11-05 2006-06-16 Alza Corp Liposome formulations of boronic acid compounds
US8377435B2 (en) 2004-11-05 2013-02-19 The Board Of Trustees Of The Leland Stanford Junior University Antibody induced cell membrane wounding
US8017395B2 (en) 2004-12-17 2011-09-13 Lifescan, Inc. Seeding cells on porous supports
US20070098685A1 (en) * 2005-01-19 2007-05-03 Brand Stephen J Methods and kits to treat chronic inflammatory immune diseases by administering a proteasome inhibitor and an interleukin 2 receptor agonist
JP5475235B2 (ja) 2005-01-21 2014-04-16 アステックス・セラピューティクス・リミテッド 医薬化合物
CA2595749A1 (en) * 2005-01-27 2006-08-03 Research Development Foundation Combination therapy with triterpenoid compounds and proteasome inhibitors
US7468383B2 (en) * 2005-02-11 2008-12-23 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7767657B2 (en) * 2005-02-16 2010-08-03 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
EP2987796B1 (en) 2005-02-16 2018-08-08 Anacor Pharmaceuticals, Inc. Halogen-substituted boronophthalides for the treatment of infections
US7589066B2 (en) * 2005-03-11 2009-09-15 The University Of North Carolina At Chapel Hill Potent and specific immunoproteasome inhibitors
AU2006242446A1 (en) * 2005-04-29 2006-11-09 Kosan Biosciences Incorporated Method of treating multiple myeloma using 17-AAG or 17-AG or a prodrug of either in combination with a proteasome inhibitor
WO2006122926A1 (en) 2005-05-18 2006-11-23 Janssen Pharmaceutica N.V. Substituted aminopropenyl piperidine or morpholine derivatives as novel inhibitors of histone deacetylase
AU2006202209B2 (en) * 2005-05-27 2011-04-14 Lifescan, Inc. Amniotic fluid derived cells
CN101484575B (zh) * 2005-06-08 2013-10-02 森托科尔公司 用于眼变性的细胞疗法
EP1912664A2 (en) * 2005-07-06 2008-04-23 Biodevelops Pharma Entwicklung GmbH Use of a compound for enhancing the expression of membrane proteins on the cell surface
EP1752467A1 (en) 2005-08-10 2007-02-14 4Sc Ag Inhibitors of cancer cell, t-cell and keratinocyte proliferation
US7531517B2 (en) 2005-08-10 2009-05-12 4Sc Ag Inhibitors of cancer cell, T-cell and keratinocyte proliferation
US20070059382A1 (en) * 2005-09-09 2007-03-15 Board Of Regents, Univ. And Comm. College System Of Nevada... Medical treatment of breast cancer with boric acid materials
PL1948678T3 (pl) 2005-11-09 2013-09-30 Onyx Therapeutics Inc Związki do hamowania enzymów
WO2007067752A2 (en) * 2005-12-08 2007-06-14 Cytokinetics, Inc. Certain compositions and methods of treatment
EP1979327A1 (en) * 2006-01-19 2008-10-15 Janssen Pharmaceutica, N.V. Pyridine and pyrimidine derivatives as inhibitors of histone deacetylase
CN101370790B (zh) 2006-01-19 2015-10-21 詹森药业有限公司 作为组蛋白去乙酰化酶抑制剂的吡啶和嘧啶衍生物
PT1981874E (pt) * 2006-01-19 2009-09-02 Janssen Pharmactuica N V Derivados de aminofenil como novos inibidores de histonadesacetilase
CA2635015C (en) * 2006-01-19 2014-06-03 Janssen Pharmaceutica N.V. Substituted indolyl-alkyl-amino-derivatives as inhibitors of histone deacetylase
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
PE20070978A1 (es) * 2006-02-14 2007-11-15 Novartis Ag COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks)
CN101420854B (zh) 2006-02-16 2013-08-07 安纳考尔医药公司 作为抗炎药的含硼的小分子
TW200808739A (en) * 2006-04-06 2008-02-16 Novartis Vaccines & Diagnostic Quinazolines for PDK1 inhibition
US8741643B2 (en) * 2006-04-28 2014-06-03 Lifescan, Inc. Differentiation of pluripotent stem cells to definitive endoderm lineage
DE102006026464A1 (de) 2006-06-01 2007-12-06 Virologik Gmbh Innovationszentrum Medizintechnik Und Pharma Pharmazeutische Zusammensetzung zur Behandlung von Virusinfektionen und / oder Tumorerkrankungen durch Inhibition der Proteinfaltung und des Proteinabbaus
US7910108B2 (en) * 2006-06-05 2011-03-22 Incyte Corporation Sheddase inhibitors combined with CD30-binding immunotherapeutics for the treatment of CD30 positive diseases
DK2041158T3 (da) 2006-06-19 2013-06-24 Onyx Therapeutics Inc Peptid-epoxidketoner til proteasom inhibering
MX2009002925A (es) * 2006-09-15 2009-03-31 Janssen Pharmaceutica Nv Inhibidores de histona desacetilasa con actividad combinada sobre histona desacetilasas clase i y clase iib en combinacion con inhibidores del proteasoma.
US20090270419A1 (en) * 2006-09-15 2009-10-29 Janine Arts Combinations of class-i specific histone deacetylase inhibitors with proteasome inhibitors
US8916552B2 (en) 2006-10-12 2014-12-23 Astex Therapeutics Limited Pharmaceutical combinations
WO2008044045A1 (en) 2006-10-12 2008-04-17 Astex Therapeutics Limited Pharmaceutical combinations
CA2606634A1 (en) * 2006-12-08 2008-06-08 Centenary Institute Of Cancer Medicine And Cell Biology Assay for response to proteasome inhibitors
JO3396B1 (ar) * 2007-06-20 2019-10-20 Anacor Pharmaceuticals Inc جزيئات صغيرة تحتوي على البورون
US9080145B2 (en) * 2007-07-01 2015-07-14 Lifescan Corporation Single pluripotent stem cell culture
RU2473685C2 (ru) 2007-07-31 2013-01-27 Лайфскен, Инк. Дифференцировка человеческих эмбриональных стволовых клеток
GB0715087D0 (en) 2007-08-03 2007-09-12 Summit Corp Plc Drug combinations for the treatment of duchenne muscular dystrophy
CN101678107A (zh) 2007-08-03 2010-03-24 萨米特公开有限公司 用于治疗杜兴型肌营养不良的药物组合物
AU2016253697A1 (en) * 2007-08-06 2016-11-24 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
EA034601B1 (ru) * 2007-08-06 2020-02-25 Милленниум Фармасьютикалз, Инк. Способ получения бороновых кислот
KR20150010802A (ko) * 2007-08-06 2015-01-28 밀레니엄 파머슈티컬스 인코퍼레이티드 프로테아좀 억제제
US7442830B1 (en) * 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
US20100226597A1 (en) * 2007-09-12 2010-09-09 Dr. Reddy's Laboratories Limited Bortezomib and process for producing same
US20090076031A1 (en) * 2007-09-17 2009-03-19 Protia, Llc Deuterium-enriched bortezomib
KR20150131405A (ko) 2007-10-04 2015-11-24 오닉스 세라퓨틱스, 인크. 결정형 펩티드 에폭시 케톤 프로테아제 저해제 및 아미노산 케토-에폭시드의 합성
US7838673B2 (en) * 2007-10-16 2010-11-23 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
US20090110688A1 (en) * 2007-10-24 2009-04-30 Georg Fertig Combination therapy of type ii anti-cd20 antibody with a proteasome inhibitor
ATE523585T1 (de) * 2007-11-27 2011-09-15 Lifescan Inc Differenzierung menschlicher embryonaler stammzellen
CN101220048B (zh) * 2007-12-14 2012-08-15 江苏先声药物研究有限公司 ZnCl2催化下的蒎烷二醇酯的制备方法
PA8809001A1 (es) 2007-12-20 2009-07-23 Novartis Ag Compuestos organicos
KR20190057164A (ko) 2008-02-21 2019-05-27 얀센 바이오테크 인코포레이티드 세포 부착, 배양 및 탈리를 위한 방법, 표면 개질 플레이트 및 조성물
KR101672511B1 (ko) 2008-03-06 2016-11-03 아나코르 파마슈티칼스 인코포레이티드 소염제로써 붕소가 함유된 소분자
WO2009140309A2 (en) * 2008-05-12 2009-11-19 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
KR101690571B1 (ko) 2008-06-17 2016-12-28 밀레니엄 파머슈티컬스 인코퍼레이티드 보로네이트 에스테르 화합물 및 이의 제약학적 조성물
JP5734183B2 (ja) 2008-06-30 2015-06-17 ヤンセン バイオテツク，インコーポレーテツド 多能性幹細胞の分化
CN101638414B (zh) * 2008-07-30 2014-01-08 江苏先声药物研究有限公司 肽硼酸及其酯类化合物、制备方法及其用途
US20100028307A1 (en) * 2008-07-31 2010-02-04 O'neil John J Pluripotent stem cell differentiation
WO2010028005A1 (en) 2008-09-04 2010-03-11 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
WO2010027975A1 (en) * 2008-09-04 2010-03-11 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
AR075090A1 (es) 2008-09-29 2011-03-09 Millennium Pharm Inc Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden.
US9493489B2 (en) * 2008-10-15 2016-11-15 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as anti-protozoal agents
EP2349313A4 (en) 2008-10-21 2012-08-29 Onyx Therapeutics Inc COMBINATION THERAPY WITH EPOXYCLETON PEPTIDES
CN102272291B (zh) 2008-10-31 2018-01-16 詹森生物科技公司 人胚胎干细胞向胰腺内分泌谱系的分化
RU2528861C2 (ru) * 2008-10-31 2014-09-20 Сентокор Орто Байотек Инк. Дифференцирование человеческих эмбриональных стволовых клеток в линию панкреатических эндокринных клеток
RU2547925C2 (ru) * 2008-11-20 2015-04-10 Сентокор Орто Байотек Инк. Способы и композиции для закрепления и культивирования клеток на плоских носителях
BRPI0920956A2 (pt) 2008-11-20 2015-08-18 Centocor Ortho Biotech Inc Cultura de células-tronco pluripotentes em microveículos
CN101747354B (zh) * 2008-12-04 2014-08-13 江苏先声药物研究有限公司 一类β氨基酸组成的二肽硼酸及其酯类化合物、制备方法及其用途
JP2012512262A (ja) * 2008-12-17 2012-05-31 アナコール ファーマシューティカルズ，インコーポレーテッド （ｓ）−３−アミノメチル−７−（３−ヒドロキシ−プロポキシ）−３ｈ−ベンゾ［ｃ］［１，２］オキサボロール−１−オールの多形体
US9095514B2 (en) 2009-01-09 2015-08-04 Sun Pharma Advanced Research Company Ltd. Pharmaceutical composition
US20120190565A1 (en) 2009-02-20 2012-07-26 Pangea Biosciences, Inc. Method Of Diagnosis Or Prognosis Of A Neoplasm Comprising Determining The Level Of Expression Of A Protein In Stromal Cells Adjacent To The Neoplasm
WO2010105008A2 (en) 2009-03-12 2010-09-16 Genentech, Inc. Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents for the treatment of hematopoietic malignancies
WO2010106135A1 (en) 2009-03-20 2010-09-23 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Combined use for the treatment of ovarian carcinoma
AR075899A1 (es) 2009-03-20 2011-05-04 Onyx Therapeutics Inc Tripeptidos epoxicetonas cristalinos inhibidores de proteasa
HUE027639T2 (en) * 2009-03-24 2016-11-28 Janssen Pharmaceutica Nv Biomarkers for the study of peripheral neuropathy response to treatment with a proteasome inhibitor
CN102378626B (zh) * 2009-03-30 2014-05-14 天蓝制药公司 聚合物-药剂缀合物、颗粒、组合物和相关使用方法
WO2010114770A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
WO2010114768A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-epothilone conjugates, particles, compositions, and related methods of use
WO2010138141A1 (en) * 2009-05-27 2010-12-02 Cephalon, Inc. Combination therapy for the treatment of multiple myeloma
CN101928329B (zh) * 2009-06-19 2013-07-17 北京大学 三肽硼酸(酯)类化合物、其制备方法和应用
EP2280016A1 (en) 2009-07-27 2011-02-02 LEK Pharmaceuticals d.d. New synthetic route for the preparation of alpha-amino boronic esters via substituted alk-1-ynes
WO2010146176A2 (en) 2009-06-19 2010-12-23 Lek Pharmaceuticals D.D. Process for hydrogenation of halogenoalkenes without dehalogenation
EP2270019A1 (en) 2009-06-19 2011-01-05 LEK Pharmaceuticals d.d. New synthetic route for the preparation of alpha-amino boronic esters
US8293753B2 (en) 2009-07-02 2012-10-23 Novartis Ag Substituted 2-carboxamide cycloamino ureas
DE102009027754A1 (de) 2009-07-15 2011-05-05 Schubert, Ulrich, Dr. Verfahren zur Hemmung der Reifung von dendritischen Zellen
GB2485112B (en) * 2009-07-20 2014-02-26 Janssen Biotech Inc Differentiation of human embryonic stem cells
WO2011011300A2 (en) 2009-07-20 2011-01-27 Centocor Ortho Biotech Inc. Differentiation of human embryonic stem cells
SG177416A1 (en) 2009-07-20 2012-02-28 Janssen Biotech Inc Differentiation of human embryonic stem cells
BR112012001987A2 (pt) * 2009-07-28 2015-09-01 Anacor Pharmaceuticals Inc Composto, combinação, formulação farmacêutica, uso de um composto, uma combinação ou um sal farmaceuticamente aceitável dos mesmos, e, métodos para tratar uma infecção bacteriana, para matar ou inibir o crescimento de uma bactéria, e para inibir uma beta-lactamase.
US9440994B2 (en) 2009-08-14 2016-09-13 Anacor Pharmaceuticals, Inc. Boron containing small molecules as antiprotozoal agents
WO2011022502A1 (en) 2009-08-18 2011-02-24 Georgetown University Boronic acid compositions and methods related to cancer
US20110207701A1 (en) * 2009-08-19 2011-08-25 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as antiprotozoal agents
CN102625807B (zh) 2009-09-08 2016-03-09 霍夫曼-拉罗奇有限公司 4-取代的吡啶-3-基-甲酰胺化合物和使用方法
US20110124597A1 (en) * 2009-09-25 2011-05-26 Anacor Pharmaceuticals, Inc. Boron containing small molecules
EP2305285A1 (en) 2009-09-29 2011-04-06 Julius-Maximilians-Universität Würzburg Means and methods for treating ischemic conditions
EP2519231B1 (en) 2009-10-01 2017-03-15 Janssen Pharmaceutica NV Proteasome inhibitors for treating cancer
WO2011049971A1 (en) 2009-10-20 2011-04-28 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as antiprotozoal agents
WO2011060196A1 (en) * 2009-11-11 2011-05-19 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
US8853147B2 (en) 2009-11-13 2014-10-07 Onyx Therapeutics, Inc. Use of peptide epoxyketones for metastasis suppression
AU2010341530B2 (en) 2009-12-22 2016-03-10 Cephalon, Inc. Proteasome inhibitors and processes for their preparation, purification and use
RU2701335C2 (ru) 2009-12-23 2019-09-25 Янссен Байотек, Инк. Способ получения популяции панкреатических эндокринных клеток, соэкспрессирующих nkx6.1 и инсулин, и способ лечения диабета
ES2633648T3 (es) 2009-12-23 2017-09-22 Janssen Biotech, Inc. Diferenciación de células madre embrionarias humanas
WO2011090940A1 (en) 2010-01-19 2011-07-28 Cerulean Pharma Inc. Cyclodextrin-based polymers for therapeutic delivery
WO2011094450A1 (en) 2010-01-27 2011-08-04 Anacor Pharmaceuticals, Inc Boron-containing small molecules
CA2791476C (en) 2010-03-01 2020-06-30 Janssen Biotech, Inc. Methods for purifying cells derived from pluripotent stem cells
MX2012010017A (es) 2010-03-01 2012-10-01 Onyx Therapeutics Inc Compuestos de para la inhibicion de inmunoproteasomas.
NZ602392A (en) * 2010-03-18 2014-03-28 Innopharma Inc Stable bortezomib formulations
US8263578B2 (en) 2010-03-18 2012-09-11 Innopharma, Inc. Stable bortezomib formulations
WO2011116348A1 (en) 2010-03-19 2011-09-22 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as anti-protozoal agent
WO2011119920A2 (en) 2010-03-25 2011-09-29 Oregon Health & Science University Cmv glycoproteins and recombinant vectors
CN102892291A (zh) 2010-03-31 2013-01-23 米伦纽姆医药公司 1-氨基-2-环丙基乙硼酸衍生物
AU2013204868B2 (en) * 2010-03-31 2016-10-13 Millennium Pharmaceuticals, Inc. Derivatives of 1-amino-2-cyclopropylethylboronic acid
CN102946729B (zh) 2010-04-07 2014-11-05 欧尼斯治疗公司 结晶肽环氧酮免疫蛋白酶体抑制剂
CN101812026B (zh) * 2010-04-12 2013-08-28 亚邦医药股份有限公司 一种硼替佐米的合成方法
WO2011133479A2 (en) 2010-04-19 2011-10-27 Niiki Pharma Inc. Combination therapy with a proteasome inhibitor and a gallium complex
WO2011139379A2 (en) 2010-05-06 2011-11-10 Duke University A method of treating patients undergoing protein replacement therapy, gene replacement therapy, or other therapeutic modalities
RU2663339C1 (ru) 2010-05-12 2018-08-03 Янссен Байотек, Инк. Дифференцирование эмбриональных стволовых клеток человека
EP3566719A1 (en) 2010-05-18 2019-11-13 Cerulean Pharma Inc. Compositions and methods for treatment of autoimmune and other diseases
AR082418A1 (es) 2010-08-02 2012-12-05 Novartis Ag Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico
EP2611907B1 (en) 2010-08-31 2016-05-04 Janssen Biotech, Inc. Differentiation of pluripotent stem cells
CN103221536B (zh) 2010-08-31 2016-08-31 詹森生物科技公司 人胚胎干细胞的分化
PL2611910T3 (pl) 2010-08-31 2018-06-29 Janssen Biotech, Inc Różnicowanie ludzkich embrionalnych komórek macierzystych
US9126997B1 (en) 2010-09-07 2015-09-08 Northwestern University Synergistic effect of glucocorticoid receptor agonists in combination with proteosome inhibitors for treating leukemia and myeloma
DK2613788T3 (en) 2010-09-07 2017-08-07 Anacor Pharmaceuticals Inc BENZOXABOROLD DERIVATIVES FOR TREATMENT OF BACTERIA INFECTIONS
CA2813003A1 (en) 2010-10-05 2012-04-12 Fresenius Kabi Usa, Llc Bortezomib formulations stabilised with boric acid
US8884009B2 (en) 2010-10-14 2014-11-11 Synthon Bv Process for making bortezomib and intermediates for the process
KR101928116B1 (ko) 2011-01-31 2018-12-11 노파르티스 아게 신규 헤테로시클릭 유도체
TW201309303A (zh) 2011-03-03 2013-03-01 Cephalon Inc 用於治療狼瘡的蛋白酶體抑制劑
WO2012135528A2 (en) 2011-03-29 2012-10-04 Texas Tech University System Galectin-3c combination therapy for human cancer
AU2012233171B2 (en) 2011-03-31 2015-08-20 Nanocarrier Co., Ltd. Pharmaceutical composition containing block copolymer comprising boronic acid compound
HUE037408T2 (hu) 2011-06-10 2018-08-28 Univ Oregon Health & Science CMV glikoproteinek és rekombináns vektorok
CA2833775A1 (en) * 2011-06-22 2012-12-27 Cephalon, Inc. Proteasome inhibitors and processes for their preparation, purification and use
US8481655B2 (en) 2011-07-27 2013-07-09 Wacker Chemical Corporation Copper complexes of amino-functional organosilicon compounds and their use
JP6002222B2 (ja) 2011-08-11 2016-10-05 ヤンセン ファーマシューティカ エヌ．ベー． がん治療用予測因子
WO2013021032A1 (en) 2011-08-11 2013-02-14 Janssen Pharmaceutica Nv Histone deacetylase inhibitors in combination with proteasome inhibitors and dexamethasone
JP6367712B2 (ja) 2011-08-19 2018-08-01 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ Ｃ型肝炎ウイルス感染の治療のためのベンゾフラン化合物
HUE060305T2 (hu) * 2011-08-30 2023-02-28 Tufts College FAP-aktivált proteaszóma inhibitorok a szolid tumorok kezelésére
US20130189754A1 (en) 2011-09-12 2013-07-25 International Aids Vaccine Initiative Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies
EP2586461A1 (en) 2011-10-27 2013-05-01 Christopher L. Parks Viral particles derived from an enveloped virus
CN104302180B (zh) 2011-10-28 2017-05-17 米伦纽姆医药公司 对nedd8活化酶(nae)抑制剂的反应的生物标记
CA2853256C (en) 2011-10-28 2019-05-14 Novartis Ag Novel purine derivatives and their use in the treatment of disease
WO2013071163A2 (en) 2011-11-11 2013-05-16 Millennium Pharamaceuticals, Inc. Biomarkers of response to proteasome inhibitors
EP2776043B1 (en) 2011-11-11 2018-02-21 Millennium Pharmaceuticals, Inc. Biomarkers of response to proteasome inhibitors
RU2014124333A (ru) 2011-11-17 2015-12-27 Дзе Юниверсити Оф Токио Блок-сополимер, имеющий введенную в него группу фенилбороновой кислоты, и его применение
EP2794857A4 (en) 2011-12-22 2015-07-08 Janssen Biotech Inc DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS IN SINGLE INSULIN POSITIVE CELLS
WO2013110005A1 (en) 2012-01-18 2013-07-25 Wisconsin Alumni Research Foundation Boronate-mediated delivery of molecules into cells
US9732101B2 (en) 2012-01-18 2017-08-15 Wisconsin Alumni Research Foundation Bioreversible boronates for delivery of molecules into cells
CA2862492A1 (en) 2012-01-24 2013-08-01 Millennium Pharmaceuticals, Inc. Methods of treatment of cancer
US10085987B2 (en) 2012-01-27 2018-10-02 Thomas Jefferson University MCT protein inhibitor-related prognostic and therapeutic methods
JP6335796B2 (ja) 2012-02-08 2018-06-06 アイジーエム バイオサイエンシズ インク．Ｉｇｍ Ｂｉｏｓｃｉｅｎｃｅｓ Ｉｎｃ． Ｃｄｉｍ結合タンパク質及びその使用
AU2013227219A1 (en) 2012-03-02 2014-10-23 Dr. Reddy's Laboratories Limited Pharmaceutical compositions comprising boronic acid compounds
CA2866590A1 (en) 2012-03-07 2013-09-12 Janssen Biotech, Inc. Defined media for expansion and maintenance of pluripotent stem cells
CA2784240C (en) 2012-03-27 2014-07-08 Innopharma, Inc. Stable bortezomib formulations
SG11201406550QA (en) 2012-05-16 2014-11-27 Novartis Ag Dosage regimen for a pi-3 kinase inhibitor
EP3450542B1 (en) 2012-06-08 2021-09-01 Janssen Biotech, Inc. Differentiation of human embryonic stem cells into pancreatic endocrine cells
ES2631608T3 (es) 2012-06-27 2017-09-01 International Aids Vaccine Initiative Variante de la glicoproteína Env del VIH-1
US20140105921A1 (en) 2012-07-09 2014-04-17 Onyx Therapeutics, Inc. Prodrugs of Peptide Epoxy Ketone Protease Inhibitors
JP2013006855A (ja) * 2012-09-03 2013-01-10 Millennium Pharmaceuticals Inc プロテアソーム阻害剤
JP2015532915A (ja) * 2012-09-11 2015-11-16 シプラ・リミテッド ボルテゾミブの製造方法
CN104822844B (zh) 2012-10-01 2019-05-07 米伦纽姆医药公司 预测对抑制剂的反应的生物标记物和方法以及其用途
WO2014072985A1 (en) 2012-11-06 2014-05-15 Natco Pharma Limited Novel boronic acid derivatives as anti cancer agents
JP2015536342A (ja) 2012-11-16 2015-12-21 シルパ・メディケア・リミテッドＳｈｉｌｐａ Ｍｅｄｉｃａｒｅ Ｌｉｍｉｔｅｄ 結晶ボルテゾミブの方法
WO2014097306A1 (en) 2012-12-21 2014-06-26 Natco Pharma Limited Stable and pure polymorphic form of bortezomib
CA2896658C (en) 2012-12-31 2021-06-22 Janssen Biotech, Inc. Differentiation of human embryonic stem cells into pancreatic endocrine cells using hb9 regulators
WO2014106141A1 (en) 2012-12-31 2014-07-03 Janssen Biotech, Inc. Suspension and clustering of human pluripotent cells for differentiation into pancreatic endocrine cells
RU2658488C2 (ru) 2012-12-31 2018-06-21 Янссен Байотек, Инк. Способ получения клеток, экспрессирующих маркеры, характерные для панкреатических эндокринных клеток
US10370644B2 (en) 2012-12-31 2019-08-06 Janssen Biotech, Inc. Method for making human pluripotent suspension cultures and cells derived therefrom
AU2014249003A1 (en) 2013-03-13 2015-10-15 Forma Therapeutics, Inc. Novel compounds and compositions for inhibition of FASN
ZA201402789B (en) 2013-04-16 2015-11-25 Cipla Ltd Process for the preparation of bortezomib mannitol ester
US10022372B2 (en) 2013-04-19 2018-07-17 Thomas Jefferson University Caveolin-1 related methods for treating glioblastoma with temozolomide
US9603775B2 (en) 2013-04-24 2017-03-28 Corning Incorporated Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients
WO2015003146A1 (en) 2013-07-03 2015-01-08 Georgetown University Boronic acid derivatives of resveratrol for activating deacetylase enzymes
EP2848937A1 (en) 2013-09-05 2015-03-18 International Aids Vaccine Initiative Methods of identifying novel HIV-1 immunogens
CN105705149A (zh) 2013-10-03 2016-06-22 米伦纽姆医药公司 用于预防或治疗系统性红斑狼疮和/或狼疮性肾炎的方法
US10058604B2 (en) 2013-10-07 2018-08-28 International Aids Vaccine Initiative Soluble HIV-1 envelope glycoprotein trimers
CN104586776B (zh) * 2013-10-30 2017-05-17 扬子江药业集团上海海尼药业有限公司 以硼替佐米为活性成分的制剂及其制备方法
JP6468562B2 (ja) * 2013-11-21 2019-02-13 国立大学法人北海道大学 プロテアソーム阻害性化合物
WO2015085097A1 (en) * 2013-12-05 2015-06-11 The Broad Institute, Inc. Compositions and methods for identifying and treating cachexia or pre-cachexia
KR20160095035A (ko) 2013-12-06 2016-08-10 노파르티스 아게 알파-이소형 선택성 포스파티딜이노시톨 3-키나제 억제제를 위한 투여 요법
CN111116622A (zh) 2014-02-03 2020-05-08 俄亥俄州创新基金会 硼酸酯和其药物制剂
EP2910557A1 (en) * 2014-02-20 2015-08-26 Ikerchem, S.L. Enantiopure tetrasubstituted pyrrolidines as scaffolds for proteasome inhibitors and medicinal applications thereof
JP6566936B2 (ja) 2014-05-08 2019-08-28 国立大学法人 東京大学 医薬組成物
KR102162138B1 (ko) 2014-05-16 2020-10-06 얀센 바이오테크 인코포레이티드 췌장 내분비 세포에서 mafa 발현을 향상시키기 위한 소분자의 용도
KR102481856B1 (ko) 2014-05-20 2022-12-26 밀레니엄 파머슈티컬스 인코퍼레이티드 일차 암 치료법 후 사용하기 위한 붕소-함유 프로테아좀 저해제
WO2016022955A1 (en) 2014-08-07 2016-02-11 Mayo Foundation For Medical Education And Research Compounds and methods for treating cancer
BR112017006349A2 (pt) * 2014-10-01 2017-12-12 Merck Patent Gmbh derivados de ácido borônico
WO2016110870A1 (en) 2015-01-07 2016-07-14 Emcure Pharmaceuticals Limited Pharmaceutical composition of bortezomid
MA41505A (fr) 2015-02-11 2017-12-19 Millennium Pharm Inc Nouvelle forme cristalline d'un inhibiteur de protéasome
EP3270891A1 (en) 2015-03-17 2018-01-24 Leon-Nanodrugs GmbH Nanoparticles comprising a stabilized boronic acid compound
US10174292B2 (en) 2015-03-20 2019-01-08 International Aids Vaccine Initiative Soluble HIV-1 envelope glycoprotein trimers
US9931394B2 (en) 2015-03-23 2018-04-03 International Aids Vaccine Initiative Soluble HIV-1 envelope glycoprotein trimers
WO2016184793A1 (en) 2015-05-15 2016-11-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for treating a patient with vegfr inhibitor-resistant metastatic renal cell carcinoma
WO2016205790A2 (en) 2015-06-19 2016-12-22 Hanlin Scientific, Inc. Chiral specific boron-containing compounds and their use in treating cancer or amyloidosis
EP3120836A1 (de) 2015-07-22 2017-01-25 Stada Arzneimittel Ag Gebrauchsfertige bortezomib-lösung
EP3120837A1 (de) 2015-07-22 2017-01-25 Stada Arzneimittel Ag Verfahren zur herstellung einer bortezomibester-lösung
CN106478700B (zh) * 2015-08-26 2020-12-29 杭州雷索药业有限公司 硼基取代的苯胺类蛋白激酶抑制剂
CN106588965A (zh) 2015-10-15 2017-04-26 北京大学 脲拟肽硼酸化合物及其药物组合物、制备方法和用途
CA3002954A1 (en) 2015-11-02 2017-05-11 Novartis Ag Dosage regimen for a phosphatidylinositol 3-kinase inhibitor
WO2017106196A1 (en) 2015-12-14 2017-06-22 The Broad Institute, Inc. Compositions and methods for treating cardiac dysfunction
CN107151255A (zh) * 2016-03-06 2017-09-12 复旦大学 硼酸类化合物及其制备方法和用途
CN107151254A (zh) * 2016-03-06 2017-09-12 复旦大学 一种作为20s蛋白酶体抑制剂的硼酸类化合物及其制备方法
MA45479A (fr) 2016-04-14 2019-02-20 Janssen Biotech Inc Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen
US11447506B2 (en) 2016-05-09 2022-09-20 Anacor Pharmaceuticals, Inc. Crystal forms of crisaborole in free form and preparation method and use thereof
CN106008572B (zh) * 2016-05-23 2018-08-17 成都千禧莱医药科技有限公司 一类二肽硼酸化合物及制备方法和用途
JP7164521B2 (ja) 2016-06-21 2022-11-01 オリオン・オフサルモロジー・エルエルシー 炭素環式プロリンアミド誘導体
CN114685453A (zh) 2016-06-21 2022-07-01 奥瑞恩眼科有限责任公司 杂环脯氨酰胺衍生物
JP6681284B2 (ja) * 2016-06-23 2020-04-15 信越化学工業株式会社 糖アルコール化合物の金属低減方法
JP6223508B2 (ja) * 2016-06-27 2017-11-01 ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． プロテアソーム阻害剤
WO2018038687A1 (en) 2016-08-22 2018-03-01 Mustafa Nevzat Ilaç Sanayii A.Ş. Pharmaceutical formulations comprising a bortezomib-cyclodextrin complex
WO2018060833A1 (en) 2016-09-27 2018-04-05 Novartis Ag Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib
WO2018073790A1 (en) 2016-10-20 2018-04-26 Pfizer Inc. Therapeutic particles with peptide boronic acid or boronate ester compounds and methods of making and using same
US11584733B2 (en) 2017-01-09 2023-02-21 Shuttle Pharmaceuticals, Inc. Selective histone deacetylase inhibitors for the treatment of human disease
US11034667B2 (en) 2017-01-09 2021-06-15 Shuttle Pharmaceuticals, Inc. Selective histone deacetylase inhibitors for the treatment of human disease
EP3583110A1 (en) 2017-02-17 2019-12-25 Fresenius Kabi Oncology Ltd An improved process for the preparation of boronic acid esters
WO2018160717A1 (en) 2017-02-28 2018-09-07 Mayo Foundation For Medical Education And Research Compounds and methods for treating cancer
WO2019040680A1 (en) 2017-08-23 2019-02-28 Krzar Life Sciences IMMUNOPROTEASOME INHIBITORS AND IMMUNOSUPPRESSANT AGENT IN THE TREATMENT OF AUTOIMMUNE DISORDERS
CN111108125A (zh) 2017-09-14 2020-05-05 葛兰素史密斯克莱知识产权发展有限公司 用于癌症的组合治疗
JP2018024694A (ja) * 2017-10-03 2018-02-15 ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． プロテアソーム阻害剤
HRP20221292T1 (hr) * 2017-11-16 2022-12-23 Principia Biopharma Inc. Inhibitori imunoproteazoma
CA3080949C (en) 2017-11-16 2024-04-16 Principia Biopharma Inc. Immunoproteasome inhibitors
US10537585B2 (en) 2017-12-18 2020-01-21 Dexcel Pharma Technologies Ltd. Compositions comprising dexamethasone
CN112004537A (zh) 2018-01-09 2020-11-27 穿梭药业公司 用于治疗人疾病的选择性组蛋白去乙酰化酶抑制剂
WO2019148181A1 (en) 2018-01-29 2019-08-01 Cognos Therapeutics, Inc. Intratumoral delivery of bortezomib
TW202003553A (zh) 2018-03-15 2020-01-16 美商艾伯維有限公司 用於治療癌症之abbv-621與抗癌劑之組合
US11243207B2 (en) 2018-03-29 2022-02-08 Mayo Foundation For Medical Education And Research Assessing and treating cancer
US10793554B2 (en) 2018-10-29 2020-10-06 Forma Therapeutics, Inc. Solid forms of 4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone
CN109824756B (zh) * 2019-03-19 2022-03-22 山东大学 含有4-(苯磺酰基)哌嗪-2-酮的苯丙氨酸衍生物及其制备方法与应用
CN114437119B (zh) * 2020-10-30 2024-08-09 苏州开拓药业股份有限公司 一种c-Myc蛋白抑制剂及其制备方法和用途
WO2022120039A2 (en) * 2020-12-02 2022-06-09 Steven Hoffman Compositions and methods for modulating cancer in non-human mammals
TW202237143A (zh) * 2020-12-10 2022-10-01 南韓商Ｌｇ化學股份有限公司 酸（Ｂｏｒｏｎｉｃ Ａｃｉｄ）化合物
US11964993B2 (en) 2021-07-03 2024-04-23 Shilpa Pharma Lifesciences Limited Crystalline bortezomib process
EP4134083A1 (en) 2021-08-12 2023-02-15 Extrovis AG Pharmaceutical compositions of bortezomib
CN113957441B (zh) * 2021-10-29 2024-01-02 光华科学技术研究院(广东)有限公司 蚀刻液及其制备方法和应用
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
WO2023220641A2 (en) 2022-05-11 2023-11-16 Juno Therapeutics, Inc. Methods and uses related to t cell therapy and production of same
WO2024097905A1 (en) 2022-11-02 2024-05-10 Celgene Corporation Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4261868A (en) * 1979-08-08 1981-04-14 Lever Brothers Company Stabilized enzymatic liquid detergent composition containing a polyalkanolamine and a boron compound
US4369183A (en) * 1979-09-06 1983-01-18 Merck & Co., Inc. 2-Pyridyl-1,2-benzisothiazolinone-1,1-dioxides and their use as selective protease inhibitors
US4510130A (en) 1983-05-20 1985-04-09 Genetic Diagnostics Corporation Promoting animal and plant growth with leupeptin
US4499082A (en) * 1983-12-05 1985-02-12 E. I. Du Pont De Nemours And Company α-Aminoboronic acid peptides
US4537773A (en) 1983-12-05 1985-08-27 E. I. Du Pont De Nemours And Company α-Aminoboronic acid derivatives
US4537707A (en) * 1984-05-14 1985-08-27 The Procter & Gamble Company Liquid detergents containing boric acid and formate to stabilize enzymes
US4842769A (en) * 1985-07-26 1989-06-27 Colgate-Palmolive Co. Stabilized fabric softening built detergent composition containing enzymes
US4759032A (en) 1987-06-03 1988-07-19 Monsanto Company Electrode seal assembly
US5187157A (en) * 1987-06-05 1993-02-16 Du Pont Merck Pharmaceutical Company Peptide boronic acid inhibitors of trypsin-like proteases
US5250720A (en) * 1987-06-05 1993-10-05 The Dupont Merck Pharmaceutical Company Intermediates for preparing peptide boronic acid inhibitors of trypsin-like proteases
US5242904A (en) * 1987-06-05 1993-09-07 The Dupont Merck Pharmaceutical Company Peptide boronic acid inhibitors of trypsin-like proteases
SE8702550D0 (sv) * 1987-06-18 1987-06-18 Anders Grubb Cysteinproteashemmare
ATE108185T1 (de) 1987-06-19 1994-07-15 Univ California Neue klasse von niedrigkalorischen proteinsüssstoffen.
EP0315574A3 (de) * 1987-11-05 1990-08-22 Hoechst Aktiengesellschaft Renin-Inhibitoren
US5106948A (en) * 1988-05-27 1992-04-21 Mao Foundation For Medical Education And Research Cytotoxic boronic acid peptide analogs
US4963655A (en) * 1988-05-27 1990-10-16 Mayo Foundation For Medical Education And Research Boron analogs of amino acid/peptide protease inhibitors
DE3827340A1 (de) * 1988-08-12 1990-02-15 Hoechst Ag Verwendung von (alpha)-aminoboronsaeure-derivaten zur prophylaxe und behandlung von viruserkrankungen
ZA897515B (en) * 1988-10-07 1990-06-27 Merrell Dow Pharma Novel peptidase inhibitors
US4997929A (en) * 1989-01-05 1991-03-05 Synergen, Inc. Purified ciliary neurotrophic factor
US4959179A (en) * 1989-01-30 1990-09-25 Lever Brothers Company Stabilized enzymes liquid detergent composition containing lipase and protease
JP2701932B2 (ja) * 1989-04-10 1998-01-21 サントリー株式会社 タンパク質分解酵素阻害剤
US5030378A (en) * 1990-01-02 1991-07-09 The Procter & Gamble Company Liquid detergents containing anionic surfactant, builder and proteolytic enzyme
IL97428A0 (en) 1990-03-05 1992-06-21 Cephalon Inc Chymotrypsin-like proteases and their inhibitors
GB9017694D0 (en) * 1990-08-13 1990-09-26 Sandoz Ltd Improvements in or relating to organic chemistry
EP0478050A1 (en) * 1990-09-24 1992-04-01 Unilever N.V. Detergent composition
GB9024129D0 (en) * 1990-11-06 1990-12-19 Thrombosis Research Trust Inhibitors and substrates of thrombin
JPH06504547A (ja) * 1990-12-28 1994-05-26 ジョージア・テック・リサーチ・コーポレーション ペプチドケトアミド、ケト酸およびケトエステル
JP2703408B2 (ja) 1990-12-28 1998-01-26 麒麟麦酒株式会社 １，４‐ベンゾチアゼピン誘導体
CA2098609A1 (en) * 1990-12-28 1992-06-29 Raymond T. Bartus Use of calpain inhibitors in the inhibition and treatment of neurodegeneration
CA2109526C (en) * 1991-04-30 1998-01-20 Dwight M. Peterson Liquid detergents with an aryl boroic acid
ATE136055T1 (de) * 1991-04-30 1996-04-15 Procter & Gamble Gerüstsubstanzhaltige flüssigwaschmittel mit borsäure-polyolkomplex zur ptoteolytischen enzyminhibierung
EP0511456A1 (en) * 1991-04-30 1992-11-04 The Procter & Gamble Company Liquid detergents with aromatic borate ester to inhibit proteolytic enzyme
US5554728A (en) * 1991-07-23 1996-09-10 Nexstar Pharmaceuticals, Inc. Lipid conjugates of therapeutic peptides and protease inhibitors
CA2133658A1 (en) * 1992-04-16 1993-10-28 Peter R. Bernstein Heterocyclic derivatives
EP0636143B1 (en) * 1992-04-16 1997-09-24 Zeneca Limited Alpha-aminoboronic acid peptides and their use as elastase inhibitors
ES2098484T3 (es) 1992-08-14 1997-05-01 Procter & Gamble Detergentes liquidos que contienen un acido alfa-amino-boronico.
CA2155554A1 (en) 1993-02-10 1994-08-18 Alfred L. Goldberg Role of atp-ubiquitin-dependent proteolysis in mhc-1 restricted antigen presentation and inhibitors thereof
US5384410A (en) * 1993-03-24 1995-01-24 The Du Pont Merck Pharmaceutical Company Removal of boronic acid protecting groups by transesterification
DE4311835A1 (de) * 1993-04-07 1994-10-13 Boehringer Ingelheim Int Verfahren zur Inhibierung der Transkription von Genen
US5424904A (en) * 1993-10-04 1995-06-13 Taylor, Sr.; Thomas T. Circuit for electrically controlled intermittent motion
IL111176A0 (en) * 1993-10-07 1994-12-29 Du Pont Merck Pharma Dipeptide boronic acid inhibitors of trypsin-like enzymes and pharmaceutical compositions containing them
US5693617A (en) * 1994-03-15 1997-12-02 Proscript, Inc. Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein
US6660268B1 (en) * 1994-03-18 2003-12-09 The President And Fellows Of Harvard College Proteasome regulation of NF-KB activity
US5574017A (en) 1994-07-05 1996-11-12 Gutheil; William G. Antibacterial agents
US6083903A (en) * 1994-10-28 2000-07-04 Leukosite, Inc. Boronic ester and acid compounds, synthesis and uses
US5550262A (en) * 1994-11-14 1996-08-27 Cephalon, Inc. Multicatalytic protease inhibitors
US5614649A (en) * 1994-11-14 1997-03-25 Cephalon, Inc. Multicatalytic protease inhibitors
CA2435146C (en) 2001-01-25 2011-03-29 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Formulation of boronic acid compounds
PT2377869E (pt) 2004-03-30 2014-04-15 Millennium Pharm Inc Síntese de bortezomib

Also Published As

Publication number Publication date
CA2496538A1 (en) 1996-05-09
US20030199561A1 (en) 2003-10-23
DE69534727D1 (de) 2006-02-02
FI20041415A (sv) 2004-11-03
EP1627880B1 (en) 2008-10-15
US20110306560A1 (en) 2011-12-15
FI971746A0 (sv) 1997-04-23
US8003791B2 (en) 2011-08-23
LU91083I9 (sv) 2018-12-28
HK1087714A1 (en) 2006-10-20
IL115790A0 (en) 1996-01-19
US5780454A (en) 1998-07-14
US20150072942A1 (en) 2015-03-12
DE69530936C5 (de) 2007-02-22
US20040167332A1 (en) 2004-08-26
DK0788360T3 (da) 2003-09-22
MX9703063A (es) 1998-07-31
EP0788360B3 (en) 2009-08-12
US20090247731A1 (en) 2009-10-01
NZ296717A (en) 1999-11-29
US6617317B1 (en) 2003-09-09
JPH10510245A (ja) 1998-10-06
EP0788360B1 (en) 2003-05-28
IL137726A0 (en) 2001-10-31
DE69530936T3 (de) 2010-08-26
US20130310320A1 (en) 2013-11-21
JP3717934B2 (ja) 2005-11-16
CA2203936C (en) 2005-04-12
US6548668B2 (en) 2003-04-15
US7531526B2 (en) 2009-05-12
US6297217B1 (en) 2001-10-02
IL137726A (en) 2004-08-31
US6747150B2 (en) 2004-06-08
NL300151I2 (nl) 2004-09-01
EP1312609A1 (en) 2003-05-21
ES2254803T3 (es) 2006-06-16
US20080132678A1 (en) 2008-06-05
ATE411324T1 (de) 2008-10-15
CY2484B1 (en) 2005-06-03
AU710564C (en) 1996-05-23
LU91083I2 (fr) 2004-08-09
FR04C0014I1 (sv) 2004-09-17
NO971929D0 (no) 1997-04-25
ATE314378T1 (de) 2006-01-15
DE69530936D1 (de) 2003-07-03
ATE241631T1 (de) 2003-06-15
KR100398944B1 (ko) 2004-06-04
ES2314540T3 (es) 2009-03-16
US6066730A (en) 2000-05-23
EP1627880A1 (en) 2006-02-22
US20020173488A1 (en) 2002-11-21
DE122004000025I2 (de) 2006-09-07
US20070282100A1 (en) 2007-12-06
US20060122390A1 (en) 2006-06-08
KR970706824A (ko) 1997-12-01
US6465433B1 (en) 2002-10-15
CA2496538C (en) 2011-08-02
CN101077875A (zh) 2007-11-28
CN101077875B (zh) 2011-01-26
EP0788360A1 (en) 1997-08-13
CN1168633A (zh) 1997-12-24
EP0788360A4 (en) 1998-05-06
PT1312609E (pt) 2006-05-31
ES2199257T7 (es) 2010-03-31
DE69534727T2 (de) 2006-09-14
AU710564B2 (en) 1999-09-23
NO2004004I1 (no) 2004-08-06
DK1627880T3 (da) 2008-12-08
FI120974B (sv) 2010-05-31
NO2004004I2 (no) 2007-09-10
DE69530936T2 (de) 2004-02-26
DE122004000025I1 (de) 2004-09-30
ES2199257T3 (es) 2004-02-16
IL115790A (en) 2002-12-01
US8378099B2 (en) 2013-02-19
FR04C0014I2 (sv) 2005-05-21
DK0788360T5 (da) 2017-09-18
CA2203936A1 (en) 1996-05-09
NO310558B1 (no) 2001-07-23
EP1312609B1 (en) 2005-12-28
FI971746A (sv) 1997-06-06
PT788360E (pt) 2003-10-31
CN1305475C (zh) 2007-03-21
US6083903A (en) 2000-07-04
AU4139896A (en) 1996-05-23
NL300151I1 (nl) 2004-08-02
WO1996013266A1 (en) 1996-05-09
TW318850B (sv) 1997-11-01
PT1627880E (pt) 2009-01-23
EP1997823A1 (en) 2008-12-03
HK1002059A1 (en) 1998-07-31
IL133831A0 (en) 2001-04-30
CH0788360H1 (de) 2006-03-15
IL133831A (en) 2004-03-28
DE69535866D1 (de) 2008-11-27
NO971929L (no) 1997-06-12
DK1312609T3 (da) 2006-05-15
NZ337211A (en) 2000-12-22
US7119080B2 (en) 2006-10-10

Similar Documents

Publication Publication Date Title
FI114801B (sv) Borester- och -syraföreningar samt syntes och användning därav

Legal Events

Date Code Title Description
SPCF Supplementary protection certificate application filed

Spc suppl protection certif: L20050005

MA Patent expired
SPCX Supplementary protection certificate: correction

Spc suppl protection certif: 253

Extension date: 20190428