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NZ736760B2 - Ebna1 inhibitors and methods using same - Google Patents

Ebna1 inhibitors and methods using same Download PDF

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Publication number
NZ736760B2
NZ736760B2 NZ736760A NZ73676016A NZ736760B2 NZ 736760 B2 NZ736760 B2 NZ 736760B2 NZ 736760 A NZ736760 A NZ 736760A NZ 73676016 A NZ73676016 A NZ 73676016A NZ 736760 B2 NZ736760 B2 NZ 736760B2
Authority
NZ
New Zealand
Prior art keywords
lymphoma
solvate
same
salt
cell lymphoma
Prior art date
Application number
NZ736760A
Other versions
NZ736760A (en
Inventor
Marianne Carlsen
Shuai Chen
Paul M Lieberman
Mark E Mcdonnell
Troy E Messick
Allen B Reitz
Garry R Smith
Yan Zhang
Original Assignee
The Wistar Institute Of Anatomy And Biology
Filing date
Publication date
Application filed by The Wistar Institute Of Anatomy And Biology filed Critical The Wistar Institute Of Anatomy And Biology
Priority claimed from PCT/US2016/032574 external-priority patent/WO2016183534A1/en
Publication of NZ736760A publication Critical patent/NZ736760A/en
Publication of NZ736760B2 publication Critical patent/NZ736760B2/en

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    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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    • 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
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

The present invention provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by EBNA1 activity, such as, but not limited to, cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis. The present invention further provides EBNA1 inhibitors, and/or pharmaceutical compositions comprising the same, that are useful for the treatment of diseases caused by latent Epstein-Barr Virus (EBV) infection and/or lytic EBV infection.

Claims (10)

1. The compound 2-(1H-Indolyl)[4-(tetrahydro-pyranyloxymethyl)-phenylethynyl]- benzoic acid; O HN or a tautomer, salt, and/or solvate f.
2. A pharmaceutical composition comprising the compound 2-(1H-Indolyl)[4- (tetrahydro-pyranyloxymethyl)-phenylethynyl]-benzoic acid, or a tautomer, salt, and/or solvate thereof, and at least one pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2, further comprising at least one additional antiviral and/or anticancer agent.
4. Use of the compound 2-(1H-Indolyl)[4-(tetrahydro-pyranyloxymethyl)- ethynyl]-benzoic acid, or a tautomer, salt, and/or solvate thereof, or a pharmaceutical composition comprising same, in the cture of a medicament for the ent and/or prevention a disease or er caused by EBNA1 activity in a subject.
5. The use of claim 4, wherein the e or disorder is at least one selected from the group consisting of cancer, infectious mononucleosis, chronic fatigue syndrome, multiple sclerosis, ic lupus erythematosus, and rheumatoid arthritis.
6. The use of claim 5, wherein the cancer is at least one selected from the group consisting of anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, hepatosplenic T-cell lymphoma, B-cell lymphoma, Burkitt’s lymphoma, reticuloendotheliosis, reticulosis, microglioma, diffuse large B-cell ma, extranodal T/NK lymphoma/angiocentric lymphoma, follicular lymphoma, immunoblastic lymphoma, mucosa-associated lymphatic tissue lymphoma, B-cell chronic lymphocytic leukemia, mantle cell lymphoma, mediastinal large B cell lymphoma, lymphoplasmactic lymphoma, nodal marginal zone B cell lymphoma, splenic marginal zone ma, intravascular large B-cell lymphoma, primary effusion lymphoma, lyphomatoid granulomatosis, angioimmunoblastic lymphadenopathy, leiomyosarcomas, X-linked lymphoproliferative disease, Hodgkin’s lymphoma and breast cancer.
7. The use of claim 5, wherein the cancer is at least one selected from the group ting of aryngeal carcinoma, gastric carcinoma, non-Hodgkin's lymphoma, and a post-transplant lymphoproliferative disorder.
8. Use of the compound 2-(1H-Indolyl)[4-(tetrahydro-pyranyloxymethyl)- phenylethynyl]-benzoic acid, or a tautomer, salt, and/or solvate f, or a ceutical composition comprising same, in the cture of a medicament for the treatment and/or prevention of an Epstein-Barr Virus (EBV) ion, and/or a disease or disorder associated with EBV infection, in a subject.
9. Use of Indolyl)[4-(tetrahydro-pyranyloxymethyl)-phenylethynyl]-benzoic acid, or a er, salt, and/or solvate thereof, or a pharmaceutical composition comprising same, in the manufacture of a medicament for the treatment and/or prevention lytic and/or latent EBV Virus infection in a subject.
10. The use of any of claims 4-9, wherein the compound, or a tautomer, salt, and/or solvate thereof, or a pharmaceutical composition comprising same, is to be administered to the subject by at least one route selected from the group consisting of oral, nasal, inhalational, topical, buccal, rectal, l, peritoneal, vaginal, intramuscular, subcutaneous, transdermal, epidural, intratracheal, otic, intraocular, intrathecal, and intravenous routes. PHILA-#1867603-v17001WO1(00019)_Sequence_Listing.TXT SEQUENCE LISTING <110> The Wistar Institute of y and Biology Messick, Troy M Smith, Garry R Reitz, Allen B Lieberman, Paul M McDonnell, Mark E Zhang, Yan Carlsen, Marianne Chen, Shuai <120> EBNA1 Inhibitors and Methods Using Same <130> 368530-7001WO1 (00019) <150> US
NZ736760A 2016-05-14 Ebna1 inhibitors and methods using same NZ736760B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562161490P 2015-05-14 2015-05-14
PCT/US2016/032574 WO2016183534A1 (en) 2015-05-14 2016-05-14 Ebna1 inhibitors and methods using same

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NZ736760B2 true NZ736760B2 (en) 2025-01-28

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