WO2008101613A1 - Nouvelle forme polymorphe de 2-(4-fluorophényl) -4-3-hydroxy-3-méthyl-1-butoxy-5-[4-méthylsulfonyl)phényl]-3(2h)-pyridazinone (fhmp) - Google Patents
Nouvelle forme polymorphe de 2-(4-fluorophényl) -4-3-hydroxy-3-méthyl-1-butoxy-5-[4-méthylsulfonyl)phényl]-3(2h)-pyridazinone (fhmp) Download PDFInfo
- Publication number
- WO2008101613A1 WO2008101613A1 PCT/EP2008/001040 EP2008001040W WO2008101613A1 WO 2008101613 A1 WO2008101613 A1 WO 2008101613A1 EP 2008001040 W EP2008001040 W EP 2008001040W WO 2008101613 A1 WO2008101613 A1 WO 2008101613A1
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- WO
- WIPO (PCT)
- Prior art keywords
- modification
- compound
- formula
- diseases
- fhmp
- Prior art date
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title 1
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000012986 modification Methods 0.000 claims description 44
- 230000004048 modification Effects 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000000725 suspension Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 206010065390 Inflammatory pain Diseases 0.000 claims description 8
- 238000001228 spectrum Methods 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 4
- 208000012659 Joint disease Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 4
- 206010037660 Pyrexia Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 210000004197 pelvis Anatomy 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 3
- 206010036600 Premature labour Diseases 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 208000026440 premature labor Diseases 0.000 claims description 2
- 230000011514 reflex Effects 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 238000001413 far-infrared spectroscopy Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 238000001069 Raman spectroscopy Methods 0.000 description 3
- 238000001237 Raman spectrum Methods 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000001757 thermogravimetry curve Methods 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
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- 241000282832 Camelidae Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700112 Chinchilla Species 0.000 description 1
- 241000272201 Columbiformes Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000283014 Dama Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000004497 NIR spectroscopy Methods 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 241000282330 Procyon lotor Species 0.000 description 1
- 241000283011 Rangifer Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000646 scanning calorimetry Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
- C07D237/14—Oxygen atoms
- C07D237/16—Two oxygen atoms
-
- 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
- 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
- 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
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to a novel polymorphic form of FHMP, processes for their preparation, medicaments containing them and their use in the control of diseases.
- FHMP is described in WO 99/10331 and also in WO 00/24719 and corresponds to the compound of the formula (I):
- the compound is a COX-2 inhibitor which is particularly suitable for the treatment of inflammatory diseases, pain or pain and fever.
- Other indications include, for example: inflammatory joint diseases, rheumatoid arthritis, osteoarthritis, Bechterew's disease, osteoporosis, dysmenorrhea, asthma, premature labor, adhesions, especially of the pelvis and cancers (eg colon cancer).
- the compound of formula (T) can be prepared in the manner described in WO 99/10331 and WO 00/24/719.
- the compound of the formula (I) is obtained in a crystal modification, which is referred to below as modification II.
- Modification II has one by means of differential
- the present invention relates to the compound of the formula (I) in the modification I.
- the modification I is thermodynamically stable and stable even after processing via suspensions, it is therefore particularly suitable for use in pharmaceutical formulations such. As suspensions or creams, but also in other preparations which are prepared via suspended active ingredient, such as. B. in the aqueous granulation or wet grinding.
- the present invention furthermore relates to pharmaceutical formulations which contain FHMP of the formula (T) in the modification I as the active substance.
- the formulation may contain one or more pharmaceutically acceptable excipients, such as. As binders, solvents, fillers, etc. included.
- Modification I of the compound of the formula (T) has a clearly distinguishable X-ray diffractogram, IR spectrum, NER spectrum, FIR spectrum and Raman spectrum compared to the previously known modification (FIGS. 2-6).
- the compound of formula (I) in the modification I melts at 141 0 C and is thus clearly distinguishable from modification II (melting point 136 ° C).
- a pharmaceutical formulation mainly contains the compound of the formula (I) in the modification I and no major proportions of another form such as for example another modification of the compound of the formula (T).
- the drug contains more than 90% by weight, more preferably more than
- Another object of the present invention is the use of the compound of formula (I) in the modification I for the treatment of diseases.
- Preference is given to a use for the treatment and prophylaxis of inflammatory diseases, pain or pain, fever, inflammatory joint diseases, rheumatoid arthritis, osteoarthritis, Bechterew's disease, osteoporosis, dysmenorrhea, asthma, preterm labor, adhesions (especially of the pelvis) and Cancers (eg colon cancer).
- Particularly preferred is the treatment of pain or pain as well as inflammatory
- Another object of the present invention is the use of the compound of formula (I) in the modification I for the preparation of a medicament for the treatment of diseases, in particular the above-mentioned diseases, particularly preferably pain or pain as well as inflammatory diseases.
- Another object of the present invention is a method for the treatment of diseases, in particular the aforementioned diseases, using an effective amount of the compound of formula (I) in the modification I.
- the compound of the formula (I) in the modification I can be suitably applied; In principle, all possible types of application come into question, such as oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, dermal, transdermal, cojunctival, otic or as an implant or stent. Particularly preferred is oral administration.
- the compounds according to the invention can be administered in suitable administration forms.
- the prior art is capable of rapidly and / or modifying the compound of formula (I) in the modification I-releasing forms of administration, e.g. Tablets (uncoated or coated tablets, for example with enteric or delayed-release or insoluble coatings which control the release of the compound of the invention), orally disintegrating tablets or films / wafers, films / lyophilisates, capsules (for example hard or soft gelatin capsules) in the oral cavity , Dragees, granules, pellets, powders, suspensions or aerosols.
- Tablets uncoated or coated tablets, for example with enteric or delayed-release or insoluble coatings which control the release of the compound of the invention
- capsules for example hard or soft gelatin capsules
- Parenteral administration can be carried out bypassing a resorption step (eg intravenously, intraarterially, intracardially, intraspinally or intralumbarly) or using absorption (for example intramuscularly, subcutaneously, intracutaneously, percutaneously or intraperitoneally).
- a resorption step eg intravenously, intraarterially, intracardially, intraspinally or intralumbarly
- absorption for example intramuscularly, subcutaneously, intracutaneously, percutaneously or intraperitoneally.
- parenteral administration are suitable as application forms u.a. Injection and infusion preparations in the form of suspensions, lyophilisates or sterile powders.
- Inhalation medicaments including powder inhalers, nebulizers
- lingual, sublingual or buccal tablets films / wafers or capsules
- suppositories ear or ophthalmic preparations
- vaginal capsules aqueous suspensions (lotions, shaking mixtures)
- lipophilic suspensions ointments
- creams transdermal therapeutic systems (such as patches)
- pastes scattering powders, implants or stents.
- the compounds according to the invention can be converted into the stated administration forms. This can be done in a conventional manner by mixing with inert, non-toxic, pharmaceutically suitable excipients.
- excipients include, among others, excipients, solvents, emulsifiers and dispersants or wetting agents, binders, stabilizers (eg antioxidants), preservatives, dyes, flavors, flavorings and / or perfumes.
- Another object of the present invention sin ⁇ drugs containing at least the compound of formula (I) in the modification I, usually together with one or more inert, non-toxic, pharmaceutically suitable excipients such as binders, fillers, etc., as well as their use in the previously mentioned purposes.
- the compound of formula (I) can also be used in animals. Called were useful, breeding, zoo, laboratory, experimental and hobby animals.
- the livestock and breeding animals include mammals such as e.g. Cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as e.g. Mink, chinchilla, raccoon, birds, e.g. Chickens, geese, turkeys, ducks, pigeons, bird species for home and zoo keeping. It also includes farmed and ornamental fish.
- mice To laboratory and experimental animals belong z. As mice, rats, guinea pigs, golden hamsters, dogs and cats.
- the hobby animals include z. Dogs and cats.
- Particularly preferred is the use in pets, especially the dog.
- Active substance, method of preparation and time or interval to which the application takes place may be sufficient to manage with less than the aforementioned minimum amount, while in other cases, the said upper limit must be exceeded. In the case of the application of larger quantities, it may be advisable to distribute these in several single doses throughout the day.
- the new modification I of the FHMP can be used and used in the same way as has already been described in the prior art for FHMP.
- Another object of the present invention is a process for the preparation of the compound of formula (I) in the modification I, by suspending the compound of formula (I) in the modification II in an inert solvent and until the desired degree of conversion is stirred or shaken in the modification I. The resulting crystals are isolated and dried. This gives the compound of formula (T) in the modification I. It is preferably carried out at a temperature of 15 to 35 ° C, particularly preferably at 20 to 30 0 C.
- Suitable inert solvents for the process described above are, in particular: lower alcohols, in particular C 1 -C 6 -alkanols, such as, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, 1 pentanol;
- lower alcohols in particular C 1 -C 6 -alkanols, such as, for example, methanol, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, 1 pentanol;
- Ketones in particular di- t QG -Alkylketone such as acetone,
- cyclic five- or six-membered ethers such as tetrahydrofuran or 1,4-dioxane
- aromatic solvents such as toluene
- solvents or solvent mixtures may additionally contain water.
- Preferred of these solvents are ethyl acetate, tetrahydrofuran, ethanol or mixtures thereof.
- thermograms were measured using a differential scanning calorimeter DSC 7 or
- Example 3 Approx. 150 mg of FHMP in Mod. II are suspended in 5 ml of toluene: n-heptane (1: 4) and stirred at 7O 0 C at reflux. After one week, the suspension is filtered and the residue is dried at room temperature at ambient humidity. It is examined by X-ray diffractometry and corresponds to the title compound in Mod. I.
- Fig. 1 DSC and TGA thermograms of FHMP
- FIG. 3 IR spectra of FHMP (mod. I above, mod. II below)
- FIG. 4 Raman spectra of FHMP (mod. I above, mod. II below)
- FIG. 5 FER spectra of FHMP (mod. I above, mod. II below)
- FIG. 6 NIR spectra of FHMP (mod. I above, mod. II below)
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne une nouvelle forme polymorphe de FHMP, un procédé pour sa préparation, des médicaments la contenant, et son utilisation pour lutter contre des maladies.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007008840A DE102007008840A1 (de) | 2007-02-23 | 2007-02-23 | Neue polymorphe Form von 2-(4-Fluorophenyl)-4-3-hydroxy-3-methyl-1-butoxy)-5-[4-methylsulfonyl)phenyl]-3(2H)-pyridazinon (FHMP) |
DE102007008840.1 | 2007-02-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008101613A1 true WO2008101613A1 (fr) | 2008-08-28 |
Family
ID=39410305
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2008/001040 WO2008101613A1 (fr) | 2007-02-23 | 2008-02-12 | Nouvelle forme polymorphe de 2-(4-fluorophényl) -4-3-hydroxy-3-méthyl-1-butoxy-5-[4-méthylsulfonyl)phényl]-3(2h)-pyridazinone (fhmp) |
Country Status (2)
Country | Link |
---|---|
DE (1) | DE102007008840A1 (fr) |
WO (1) | WO2008101613A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102007020689A1 (de) | 2007-05-03 | 2008-11-06 | Bayer Healthcare Ag | Neue polymorphe Form von 2-(4-Fluorophenyl)-4-3-hydroxy-3-methyl-1-butoxy-5-[4-methylsulfonyl)phenyl]3/2H)-pyridazinon (FHMP) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999010331A1 (fr) * | 1997-08-22 | 1999-03-04 | Abbott Laboratories | Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase |
WO2000024719A1 (fr) * | 1998-10-27 | 2000-05-04 | Abbott Laboratories | Inhibiteurs de la biosynthese de la prostaglandine endoperoxyde h synthase |
-
2007
- 2007-02-23 DE DE102007008840A patent/DE102007008840A1/de not_active Withdrawn
-
2008
- 2008-02-12 WO PCT/EP2008/001040 patent/WO2008101613A1/fr active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999010331A1 (fr) * | 1997-08-22 | 1999-03-04 | Abbott Laboratories | Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase |
WO2000024719A1 (fr) * | 1998-10-27 | 2000-05-04 | Abbott Laboratories | Inhibiteurs de la biosynthese de la prostaglandine endoperoxyde h synthase |
Also Published As
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