CA2577288A1 - Hydrochloride of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile - Google Patents
Hydrochloride of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile Download PDFInfo
- Publication number
- CA2577288A1 CA2577288A1 CA002577288A CA2577288A CA2577288A1 CA 2577288 A1 CA2577288 A1 CA 2577288A1 CA 002577288 A CA002577288 A CA 002577288A CA 2577288 A CA2577288 A CA 2577288A CA 2577288 A1 CA2577288 A1 CA 2577288A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutical composition
- composition according
- formula
- compound
- wetting agent
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract 4
- YIBOMRUWOWDFLG-UHFFFAOYSA-N 4-[[4-[4-(2-cyanoethenyl)-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C=CC#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-UHFFFAOYSA-N 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 15
- 239000004480 active ingredient Substances 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims abstract 3
- 238000002360 preparation method Methods 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 11
- 150000001875 compounds Chemical class 0.000 claims 6
- 239000011230 binding agent Substances 0.000 claims 4
- 239000000080 wetting agent Substances 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 239000003085 diluting agent Substances 0.000 claims 3
- 238000002156 mixing Methods 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 2
- 239000007884 disintegrant Substances 0.000 claims 2
- 239000000314 lubricant Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims 2
- VERWQPYQDXWOGT-LVJNJWHOSA-N 4-amino-5-fluoro-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VERWQPYQDXWOGT-LVJNJWHOSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- 208000031886 HIV Infections Diseases 0.000 claims 1
- 208000037357 HIV infectious disease Diseases 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 239000007888 film coating Substances 0.000 claims 1
- 238000009501 film coating Methods 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 229920000136 polysorbate Polymers 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000007873 sieving Methods 0.000 claims 1
- 239000008247 solid mixture Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 238000005507 spraying Methods 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a pharmaceutical composition comprising as active ingredient the hydrochloric acid salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethyl- phenyl]amino]-2-pyrimidinyl]amino]benzonitrile and to processes for their preparation.
Claims (17)
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and as active ingredient a therapeutically effective amount of a compound of formula (I) a N-oxide or a stereochemically isomeric form thereof.
2. A pharmaceutical composition according to claim 1 wherein the compound of formula (I) is a compound of formula (I-a)
3. A pharmaceutical composition according to claim 2 wherein the compound of formula (I-a) is polymorphic Form A characterized by X-ray powder diffraction peaks at two-theta positions 9.7°~ 0.2°, 13.5°~
0.2° and 15.0°~ 0.2°.
0.2° and 15.0°~ 0.2°.
4. A pharmaceutical composition according to claim 3 wherein the polymorphic Form A is further characterized by X-ray powder diffraction peaks at two-theta positions 9.1°~ 0.2°, 11.0°~ 0.2°, 14.6°~
0.2°, 22.0°~ 0.2°, 25.0°~ 0.2°, 25.3°~ 0.2° and 26.7°~ 0.2°.
0.2°, 22.0°~ 0.2°, 25.0°~ 0.2°, 25.3°~ 0.2° and 26.7°~ 0.2°.
5. A pharmaceutical composition according to any one of the preceding claims wherein the composition is suitable for oral administration.
6. A pharmaceutical composition according to any one of the preceding claims wherein the composition is a solid composition.
7. A pharmaceutical composition according to any one of the preceding claims further comprising a wetting agent.
8. A pharmaceutical composition according to claim 7 wherein the wetting agent is Tween.
9. A pharmaceutical composition according to any one of the preceding claims wherein the composition is in the form of a tablet.
10. A pharmaceutical composition according to claim 9 which is film-coated.
11. A pharmaceutical composition according to any one of the preceding claims having the following composition (a) from 5 to 50% of active ingredient;
(b) from 0.01 to 5% of a wetting agent;
(c) from 40 to 92% of a diluent;
(d) from 0 to 10% of a polymer;
(e) from 2 to 10% of a disintegrant;
(f) from 0.1 to 5% of a glidant;
(g) from 0.1 to 1.5% of a lubricant.
(b) from 0.01 to 5% of a wetting agent;
(c) from 40 to 92% of a diluent;
(d) from 0 to 10% of a polymer;
(e) from 2 to 10% of a disintegrant;
(f) from 0.1 to 5% of a glidant;
(g) from 0.1 to 1.5% of a lubricant.
12. A pharmaceutical composition according to any one of the preceding claims provided that the composition does not contain both emtricitabine and tenofovir diisoproxyl fumarate.
13. A pharmaceutical composition according to any one of claims 1 to11 provided that the composition does not contain one or more nucleoside reverse transcriptase inhibitors and/or one or more nucleotide reverse transcriptase inhibitors.
14. A process for preparing a pharmaceutical composition according to any one of the preceding claims comprising the following steps :
(i) dry blending the active ingredient and part of the diluent;
(ii) preparing a binder solution by dissolving the binder and the wetting agent in the binder solution solvent;
(iii) spraying the binder solution obtained in step (ii) on the mixture obtained in step (i);
(iv) drying the wet powder obtained in step (iii) followed by sieving and optionally mixing;
(v) mixing the remaining part of the diluent, the disintegrant and the optional glidant in the mixture obtained in step (iv);
(vi) optionally adding the lubricant to the mixture obtained in step (v);
(vii) compressing the mixture obtained in step (vi) into a tablet;
(viii)optionally film-coating the tablet obtained in step (vii).
(i) dry blending the active ingredient and part of the diluent;
(ii) preparing a binder solution by dissolving the binder and the wetting agent in the binder solution solvent;
(iii) spraying the binder solution obtained in step (ii) on the mixture obtained in step (i);
(iv) drying the wet powder obtained in step (iii) followed by sieving and optionally mixing;
(v) mixing the remaining part of the diluent, the disintegrant and the optional glidant in the mixture obtained in step (iv);
(vi) optionally adding the lubricant to the mixture obtained in step (v);
(vii) compressing the mixture obtained in step (vi) into a tablet;
(viii)optionally film-coating the tablet obtained in step (vii).
15. Use of a compound of formula (I) as defined in claim 1 or formula (I-a) as defined in claim 2 for the manufacture of a composition according to any one of claims to 13 for the treatment or the prevention of HIV infection.
16. Process for the preparation of a compound of formula (I) as defined in claim 1 characterized by reacting the corresponding free base with hydrochloric acid in the presence of a suitable acid.
17. Process according to claim 16 wherein the suitable acid is acetic acid.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MYPI20043578A MY169670A (en) | 2003-09-03 | 2004-09-02 | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| MYPI20043578 | 2004-09-02 | ||
| PCT/EP2004/052028 WO2005021001A1 (en) | 2003-09-03 | 2004-09-03 | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| EPPCT/EP2004/052028 | 2004-09-03 | ||
| EP05101467.8 | 2005-02-25 | ||
| EP05101467 | 2005-02-25 | ||
| PCT/EP2005/054342 WO2006024668A1 (en) | 2004-09-02 | 2005-09-02 | Hydrochloride of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl] amino]benzonitrile |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2577288A1 true CA2577288A1 (en) | 2006-03-09 |
| CA2577288C CA2577288C (en) | 2010-11-30 |
Family
ID=34940340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2577288A Active CA2577288C (en) | 2004-09-02 | 2005-09-02 | Hydrochloride of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
Country Status (5)
| Country | Link |
|---|---|
| KR (1) | KR101284361B1 (en) |
| AU (1) | AU2005279158C1 (en) |
| CA (1) | CA2577288C (en) |
| PL (1) | PL1632232T6 (en) |
| WO (1) | WO2006024668A1 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY169670A (en) | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| SI1981506T1 (en) * | 2006-01-20 | 2013-08-30 | Janssen R&D Ireland | Long term treatment of hiv- infection with tcm278 |
| AR065720A1 (en) | 2007-03-14 | 2009-06-24 | Tibotec Pharm Ltd | RECONSTITUTION POWERS THAT INCLUDE RILPIVIRINE DISPERSED IN CERTAIN POLYMERS. USE. PROCESS. |
| WO2008154234A2 (en) * | 2007-06-08 | 2008-12-18 | Boehringer Ingelheim International Gmbh | Extended release formulation of nevirapine |
| ES2437331T3 (en) | 2007-07-12 | 2014-01-10 | Janssen R&D Ireland | Crystalline form of 4 - [[4 - [[4- (2-cyanoetenyl) -2,6-dimethylphenyl] amino] -2-pyrimidinyl] amino] benzonitrile |
| US20120295898A1 (en) | 2010-01-27 | 2012-11-22 | Mark Richard Underwood | Antiviral Therapy |
| MX347512B (en) | 2010-11-19 | 2017-04-28 | Gilead Sciences Inc | Therapeutic compositions comprising rilpivirine hcl and tenofovir disoproxil fumarate. |
| WO2012125993A1 (en) | 2011-03-17 | 2012-09-20 | Teva Pharmaceutical Industries Ltd. | Solid state forms of rilpivirine base, and rilipivirine salts |
| WO2013038425A1 (en) * | 2011-09-16 | 2013-03-21 | Hetero Research Foundation | Rilpivirine hydrochloride |
| WO2013087794A1 (en) * | 2011-12-14 | 2013-06-20 | Sandoz Ag | Polymorph of rilpivirine hydrochloride and its use as antiviral |
| EP2604593A1 (en) * | 2011-12-14 | 2013-06-19 | Sandoz AG | Polymorph of Rilpivirine hydrochloride and its use as antiviral |
| KR20240011873A (en) | 2016-10-24 | 2024-01-26 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | Dispersible compositions |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JO3429B1 (en) * | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | Hiv inhibiting pyrimidines derivatives |
| MY169670A (en) * | 2003-09-03 | 2019-05-08 | Tibotec Pharm Ltd | Combinations of a pyrimidine containing nnrti with rt inhibitors |
| WO2004016581A1 (en) * | 2002-08-09 | 2004-02-26 | Janssen Pharmaceutica N.V. | Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
-
2005
- 2005-09-02 KR KR1020077006837A patent/KR101284361B1/en active IP Right Review Request
- 2005-09-02 AU AU2005279158A patent/AU2005279158C1/en active Active
- 2005-09-02 CA CA2577288A patent/CA2577288C/en active Active
- 2005-09-02 WO PCT/EP2005/054342 patent/WO2006024668A1/en active Application Filing
- 2005-09-02 PL PL05108086T patent/PL1632232T6/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL1632232T6 (en) | 2022-06-27 |
| AU2005279158B2 (en) | 2010-06-17 |
| PL1632232T3 (en) | 2011-10-31 |
| CA2577288C (en) | 2010-11-30 |
| KR20070074555A (en) | 2007-07-12 |
| KR101284361B1 (en) | 2013-07-15 |
| AU2005279158A1 (en) | 2006-03-09 |
| AU2005279158C1 (en) | 2010-12-16 |
| WO2006024668A1 (en) | 2006-03-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |