NZ736630B2 - Bromodomain inhibitor - Google Patents
Bromodomain inhibitor Download PDFInfo
- Publication number
- NZ736630B2 NZ736630B2 NZ736630A NZ73663016A NZ736630B2 NZ 736630 B2 NZ736630 B2 NZ 736630B2 NZ 736630 A NZ736630 A NZ 736630A NZ 73663016 A NZ73663016 A NZ 73663016A NZ 736630 B2 NZ736630 B2 NZ 736630B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- methylsulfonylphenyl
- cyclopropylmethoxy
- pharmaceutical composition
- polymer
- methylisoquinolinone
- Prior art date
Links
- 229940125763 bromodomain inhibitor Drugs 0.000 title abstract 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 22
- 229920000642 polymer Polymers 0.000 claims abstract 22
- 239000011159 matrix material Substances 0.000 claims abstract 10
- 239000007787 solid Substances 0.000 claims abstract 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract 7
- 201000011510 cancer Diseases 0.000 claims abstract 7
- -1 crystalline forms Chemical compound 0.000 claims abstract 6
- 238000010922 spray-dried dispersion Methods 0.000 claims abstract 6
- 201000010099 disease Diseases 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
- SKHDCIZOXSUCKT-UHFFFAOYSA-N O=C1NC=C(CC(C=CC=C2)=C2S(COCC2CC2)(=O)=O)C2=CC=CC=C12 Chemical compound O=C1NC=C(CC(C=CC=C2)=C2S(COCC2CC2)(=O)=O)C2=CC=CC=C12 SKHDCIZOXSUCKT-UHFFFAOYSA-N 0.000 claims 10
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 7
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 5
- 229920002678 cellulose Polymers 0.000 claims 4
- 239000001913 cellulose Substances 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 3
- 102100027086 NUT family member 1 Human genes 0.000 claims 2
- 101710137446 NUT family member 1 Proteins 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 206010004146 Basal cell carcinoma Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
- 101150015280 Cel gene Proteins 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- SPTSIOTYTJZTOG-UHFFFAOYSA-N acetic acid;octadecanoic acid Chemical compound CC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O SPTSIOTYTJZTOG-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 238000001694 spray drying Methods 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- UWZAJPITKGWMFJ-UHFFFAOYSA-N 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one Chemical compound Cn1cc(-c2cc(ccc2OCC2CC2)S(C)(=O)=O)c2ccccc2c1=O UWZAJPITKGWMFJ-UHFFFAOYSA-N 0.000 abstract 4
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 230000001613 neoplastic effect Effects 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
-
- 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
- A61K31/435—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
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
Abstract
Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments the pharmaceutical composition comprises 4 [2 (cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical compositions comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.
Claims (25)
1. A pharmaceutical composition sing a spray dried dispersion or a micronized form of 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone.
2. The pharmaceutical composition of claim 1 comprising a spray dried dispersion or a micronized form of 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl] methylisoquinolinone, characterized as exhibiting XRPD reflection peaks at 7.8, 9.0, 15.7, 18.0, 21.1, 22.0, 23.6 and 24.5 2-theta (2?).
3. The pharmaceutical composition of claim 1 sing a spray dried dispersion or a micronized form of amorphous 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl] methylisoquinolinone.
4. The pharmaceutical composition of claim 1 comprising 4-[2- (cyclopropylmethoxy) methylsulfonylphenyl]methylisoquinolinone, wherein the 4-[2- (cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone is processed by spray .
5. The pharmaceutical ition of claim 1 comprising 4-[2- (cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone, wherein the 4-[2- (cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone is micronized by rapid expansion of ritical CO2 solution (RESS) process.
6. The pharmaceutical composition of any one of claims 1-5, wherein the composition comprises at least one solid matrix polymer.
7. The pharmaceutical composition of claim 6, wherein the solid matrix polymer is polyvinylpyrrolidone or a polyvinylpyrrolidone derivative.
8. The pharmaceutical ition of claim 6, wherein the solid matrix polymer is a cellulose derivative.
9. The ceutical composition of claim 8, wherein the ose derivative is hydroxypropyl methylcellulose.
10. The pharmaceutical composition of claim 8, wherein the cellulose derivative is hydroxypropyl methylcellulose phthalate.
11. The pharmaceutical composition of claim 8, wherein the cellulose derivative is hydroxypropyl methylcellulose acetate stearate.
12.The pharmaceutical composition of claim 8, wherein the cellulose tive is hydroxypropyl methylcellulose e succinate.
13. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical ition is processed by spray drying.
14. The ceutical ition of claim 6, wherein the ratio of 4-[2- (cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone to solid matrix polymer is from 1:1 to 1:9.
15. The pharmaceutical composition of claim 6, wherein the ratio of 4-[2- (cyclopropylmethoxy)methylsulfonylphenyl]methylisoquinolinone to solid matrix polymer is selected from 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, or 1:9.
16. A pharmaceutical composition comprising a solid polymer matrix comprising: (a) an amorphous form of 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl] isoquinolinone; and (b) a polymer selected from polyvinylpyrrolidone or hydroxypropyl methylcellulose; wherein the solid polymer matrix is a spray dried dispersion.
17. The ceutical composition of claim 16, wherein the polymer is hydroxypropyl methylcellulose present in a ratio of 4-[2-(cyclopropylmethoxy) methylsulfonylphenyl]methylisoquinolinone:polymer of 1:3.
18. The pharmaceutical composition of claim 16, wherein the polymer is hydroxypropyl methylcellulose present in ratio of 4-[2-(cyclopropylmethoxy) methylsulfonylphenyl]methylisoquinolinone:polymer of 1:1.
19. The pharmaceutical composition of claim 16, wherein the polymer is nylpyrrolidone in a ratio of 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl] methylisoquinolinone:polymer of 1:3.
20. The pharmaceutical composition of claim 16, wherein the polymer is polyvinylpyrrolidone in a ratio of 4-[2-(cyclopropylmethoxy)methylsulfonylphenyl] methylisoquinolinone:polymer of 1:1.
21. The use of the pharmaceutical composition of any one of the preceding claims for preparation of a medicament for the treatment of cancer or other stic disease.
22. The use of claim 21, wherein the pharmaceutical composition comprises a solid polymer matrix comprising (a) an amorphous form of 4-[2-(cyclopropylmethoxy) methylsulfonylphenyl]methylisoquinolinone; and (b) a polymer selected from polyvinylpyrrolidone or hydroxypropyl methylcellulose; wherein the solid polymer matrix is a spray dried dispersion.
23. The use of claims 21 or 22, wherein the cancer is nuclear protein in testis (NUT), midline carcinoma (NMC), te cancer, breast cancer, r cancer, lung cancer, or melanoma.
24. The use of claims 21 or 22, wherein the cancer is ts lymphoma.
25. The use of claims 21 or 22, wherein the cancer is gliobastoma (GBM), basal cell carcinoma, pancreatic, multiple myeloma, or acute myeloid leukemia (AML). Celgene Quanticel Research, Inc. By the Attorneys for the Applicant N & FERGUSON E-Th?ta-S :31: *3.MR4- . ??mwwi $erWWW ‘ i ii} '30 '38 48 3—313: ‘-1Uteamxx m.?mm~ iEE " » » V1,. » » » » » » » » » » » » r‘“““u“-1.u“uu- v --r .7. u- - u- v ~ru‘““-,- 330 1’50 370 N90 33% Tempemmz‘s °C (96') £3 mgc 6:: 42a. Ch 4 ' ”uuuuttu/Auutuuuunh”?aunt”,AuntuuuuuI;1111111unuuuuu?nuuu1 : wwngwm‘?w~ -. :2‘ 5 C3 I:n m?xmexW‘wx\\\.u.\\\\xxx\ssss\\xx\\\\\\x\\\\\\\\\x.\\\\\\\\\\\\\\\\\x\\\\\\\\\\\\\\\\\\\\\5\\\\\\\\\\\\\\\\\\>~¢\\\\\\\\\\\\\\\\\s1‘\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\»\\\\\\\\\\\\\\\\\\y bumnngggy 3'1} 3C? 3 {3 $3! .53 {3 853 {’1} 8'a?‘ SEQ Riki) EEE . E %\\\\\
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562151205P | 2015-04-22 | 2015-04-22 | |
| PCT/US2016/029029 WO2016172618A1 (en) | 2015-04-22 | 2016-04-22 | Bromodomain inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ736630A NZ736630A (en) | 2024-03-22 |
| NZ736630B2 true NZ736630B2 (en) | 2024-06-25 |
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