US20190276405A1 - Crystal of quinoline derivative - Google Patents

Crystal of quinoline derivative Download PDF

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US20190276405A1
US20190276405A1 US16/302,553 US201716302553A US2019276405A1 US 20190276405 A1 US20190276405 A1 US 20190276405A1 US 201716302553 A US201716302553 A US 201716302553A US 2019276405 A1 US2019276405 A1 US 2019276405A1
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crystals
ppm
solid
peaks
state
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Inventor
Donald John Daley
John Gary Montana
George Hynd
Mitsuru Teramoto
Takahiro Ito
Taro Tameyama
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Teijin Pharma Ltd
GB001 Inc
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Teijin Pharma Ltd
GB001 Inc
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Assigned to PULMAGEN THERAPEUTICS (ASTHMA) LIMITED reassignment PULMAGEN THERAPEUTICS (ASTHMA) LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DALEY, DONALD JOHN, HYND, GEORGE, MONTANA, JOHN GARY
Assigned to GB001, INC. reassignment GB001, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PULMAGEN THERAPEUTICS (ASTHMA) LIMITED
Assigned to PULMAGEN THERAPEUTICS (ASTHMA) LIMITED reassignment PULMAGEN THERAPEUTICS (ASTHMA) LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: TEIJIN PHARMA LIMITED
Assigned to TEIJIN PHARMA LIMITED reassignment TEIJIN PHARMA LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PULMAGEN THERAPEUTICS (ASTHMA) LIMITED
Assigned to MIDCAP FINANCIAL TRUST, AS AGENT reassignment MIDCAP FINANCIAL TRUST, AS AGENT SECURITY INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GB001, INC., GB002, INC., GB003, INC., GB004, INC., GB005, INC., GB006, INC., GB007, INC., GOSSAMER BIO SERVICES, INC., GOSSAMER BIO, INC.
Assigned to TEIJIN PHARMA LIMITED reassignment TEIJIN PHARMA LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: TERAMOTO, MITSURU, ITO, TAKAHIRO
Publication of US20190276405A1 publication Critical patent/US20190276405A1/en
Assigned to GB005, INC., GB001, INC., GB002, INC., GB003, INC., GB004, INC., GB007, INC., GOSSAMER BIO SERVICES, INC., GOSSAMER BIO, INC., GB008, INC. reassignment GB005, INC. RELEASE OF SECURITY INTEREST IN INTELLECTUAL PROPERTY COLLATERAL AT REEL/FRAME NO. 49081/0335 Assignors: MIDCAP FINANCIAL TRUST, AS AGENT
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • A61P17/04—Antipruritics
    • 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
    • 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

Definitions

  • the present invention relates to crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid L-lysine salt.
  • Patent citation 1 also states that this compound is useful in the treatment and prevention of diseases in which CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) receptors participate, such as bronchial asthma, chronic obstructive pulmonary disease, allergic airway syndrome, bronchitis, cystic fibrosis, emphysema, rhinitis, etc., and psoriasis, atopic and nonatopic dermatitis, Crohn's disease, ulcerative colitis, and irritable bowel disease, etc.
  • diseases in which CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) receptors participate such as bronchial asthma, chronic obstructive pulmonary disease, allergic airway syndrome, bronchitis, cystic fibrosis, emphysema, rhinitis, etc., and psoriasis, atopic and nonatopic dermatitis, Crohn'
  • patent citation 1 does not mention crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid or of the L-lysine salt thereof.
  • Patent citation 1 International patent publication WO2007/036743
  • the aim of the present invention is to provide crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid that are chemically stable and suitable as a pharmaceutical drug substance.
  • the present invention is:
  • [1] crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid L-lysine salt; [2] the crystals described in [1], which are crystals A; [3] the crystals described in [1] (crystals A), which, in their powder X-ray diffraction spectrum, have peaks at diffraction angles 2 ⁇ 6.0°, 10.0°, 10.7°, 12.1°, 18.4°, 19.2°, and 20.1°; [4] the crystals described in [1] (crystals A), which have the powder X-ray diffraction spectrum pattern shown in FIG.
  • the present invention provides crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid L-lysine salt that are chemically stable, have superior thermal stability and physical properties, and are suitable as a pharmaceutical drug substance.
  • FIG. 1 Powder X-ray diffraction spectrum of crystals A of compound (I)
  • FIG. 2 Powder X-ray diffraction spectrum of crystals B of compound (I)
  • FIG. 3 Infrared absorption spectrum of crystals A of compound (I)
  • FIG. 4 Infrared absorption spectrum of crystals B of compound (I)
  • FIG. 5 Solid-state 13 C-NMR spectrum of crystals A of compound (I)
  • FIG. 6 Solid-state 19 F-NMR spectrum of crystals A of compound (I)
  • FIG. 7 Solid-state 15 N-NMR spectrum of crystals A of compound (I)
  • the inventive crystals are characterized by their powder X-ray diffraction spectra, infrared absorption spectra, solid-state NMR spectra, or a combination of these means.
  • the powder X-ray diffraction (XRD) spectra, infrared absorption spectra, and solid-state NMR spectra of these crystals have unique patterns.
  • the infrared absorption spectrum of crystals A of inventive compound (I) has absorption peaks at wavenumbers 673 cm ⁇ 1 , 810 cm ⁇ 1 , 872 cm ⁇ 1 , 1010 cm ⁇ 1 , 1051 cm ⁇ 1 , 1413 cm ⁇ 1 , and 1568 cm ⁇ 1 . Also, the infrared absorption spectrum of crystals A of inventive compound (I) has the pattern shown in FIG. 3 .
  • the solid-state 13 C-NMR spectrum of crystals A of inventive compound (I) has chemical shift peaks at 107.1 ppm, 115.9 ppm, 127.5 ppm, 136.5 ppm, 145.7 ppm, 152.7 ppm, 153.8 ppm, 165.8 ppm, 175.8 ppm, 177.3 ppm, and 179.5 ppm. Also, the solid-state 13 C-NMR spectrum of crystals A of inventive compound (I) has the pattern shown in FIG. 5 .
  • the solid-state 19F-NMR spectrum of crystals A of inventive compound (I) has chemical shift peaks at ⁇ 77.0 ppm and ⁇ 72.3 ppm. Also, the solid-state 19 F-NMR spectrum of crystals A of inventive compound (I) has the pattern shown in FIG. 6 .
  • the solid-state 15 N-NMR spectrum of crystals A of inventive compound (I) has a chemical shift peak at ⁇ 347.2 ppm. Also, the solid-state 15 N-NMR spectrum of crystals A of inventive compound (I) has the pattern shown in FIG. 7 .
  • crystals A of inventive compound (I) have a melting point of 200° C.
  • the infrared absorption spectrum of crystals B of inventive compound (I) has absorption peaks at wavenumbers 667 cm ⁇ 1 , 803 cm ⁇ 1 , 885 cm ⁇ 1 , 1012 cm ⁇ 1 , 1032 cm ⁇ 1 , 1402 cm ⁇ 1 , and 1597 cm ⁇ 1 . Also, the infrared absorption spectrum of crystals B of inventive compound (I) has the pattern shown in FIG. 4 .
  • identification of suspected infringing substance and crystals A or B of inventive compound (I) depends ultimately on “whether the crystal is the same or not”, and this decision is based not on whether all the peaks on the powder X-ray diffraction spectra, infrared absorption spectra or solid-state NMR spectra the are the same, but on whether the overall pattern is the same.
  • the values of the diffraction angle 2 ⁇ peaks on a powder X-ray diffraction spectrum can vary slightly depending on measurement conditions such as the measurement error of the instrument and the condition of the sample being measured and so even if there are small differences in the 2 ⁇ values, whether or not the crystal form is the same should be decided by examining the overall pattern of the appropriate spectrum; crystals within the error range are included the present invention.
  • the 2 ⁇ value error is thought to be ⁇ 0.50. Specifically, for a crystal identified from the abovementioned diffraction angles, within a ⁇ 0.50 range is deemed “the same”.
  • powder X-ray diffraction spectra peaks that are within ⁇ 0.20 can be said to be the same, and this can also be deemed common knowledge to those skilled in the art.
  • a powder X-ray diffraction spectrum obtained under ordinary measurement conditions is said to “have a peak at a diffraction angle 2 ⁇ value of 6.0°” if the diffraction angle 2 ⁇ value is in the range of from 5.5° to 6.5°, i.e., 6.0 ⁇ 0.5°; however a powder X-ray diffraction spectrum obtained under particularly rigorously controlled measurement conditions is said to “have a peak at a diffraction angle 2 ⁇ value of 6.0°” if the diffraction angle 2 ⁇ value is in the range of from 5.8° to 6.2°. The same applies to the other peaks.
  • the relative intensities at diffraction angles 2 ⁇ on powder X-ray diffraction spectra also vary somewhat, in accordance with the error of the measurement instrument used and the effects of low crystallinity due to the size, shape, orientation, and pulverization of the crystal particles in the sample measured; therefore even when the relative intensities of the peaks on the powder X-ray diffraction spectra differ somewhat from those shown in FIG. 1 and FIG. 2 , those skilled in the art can, by making an overall judgement of the positions of the peaks, sometimes verify that these are spectra of crystals A and B of inventive compound (I).
  • the infrared absorption spectra shown in FIG. 3 and FIG. 4 were measured by the total reflection method (ATR method).
  • ATR method The infrared absorption spectra shown in FIG. 3 and FIG. 4 were measured by the total reflection method (ATR method).
  • Known special features of the total reflection method are that, compared to the transmission method and the diffuse reflectance method (referred to as transmission methods; in these measurement methods the sample is often diluted using KBr powder and then measured), there is usually higher absorption intensity on the low wavenumber side, and the absorption peaks shift from several cm ⁇ 1 to several tens of cm ⁇ 1 to the low wavenumber side.
  • total reflection-measuring devices are often provided with a function known as “ATR correction”, which converts total reflection method measurement results to transmission method measurement results based on more data than is used in the total reflection method and transmission methods.
  • absorption peak errors are common even when the same measurement method is used (even when the total reflection measurement method used is the same in terms of whether or not “ATR correction” is applied). These errors are usually in the range of ⁇ 0.5 cm ⁇ 1 . Therefore the crystal form identified from the abovementioned wavenumbers includes those that match in the range of ⁇ 0.5 cm ⁇ 1 .
  • Errors in the chemical shifts in solid-state NMR spectra are also common. These errors are usually in the range of ⁇ 0.5 ppm, and there can be additional ⁇ 0.5 ppm errors depending on the condition of the solid-state sample. Therefore the crystal form identified from the abovementioned chemical shifts includes those that match in the range of from ⁇ 0.5 ppm to ⁇ 1.0 ppm.
  • [8-Chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethyl-quinolin-5-yloxy]acetic acid can be produced by the production method described in abovementioned patent citation 1, for example.
  • Compound (I) is obtained, for example, by adding L-lysine to a mixed solution of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethyl-quinolin-5-yloxy]acetic acid and solvent.
  • melting point refers to that measured using a differential scanning calorimeter.
  • a pharmaceutical drug substance needs to be stable at the temperatures and pressures employed during tabletting, and on long-term storage, and so crystals must have a high melting point and excellent thermal stability.
  • Inventive crystals of compound (I) can be obtained by various production methods; typical examples are shown below.
  • Crystals of compound (I) can be obtained by dissolving or suspending compound (I) in solvent, or dissolving or suspending [8-chloro-3-(4-chlorobenzyl)-4-difluoro-methoxy-2-ethylquinolin-5-yloxy]acetic acid and L-lysine in solvent, and then crystallizing by concentration, refrigeration or the addition of a poor solvent.
  • a solution of compound (I) is obtained, and if the solution is super-saturated the compound may precipitate out directly as crystals or remain in solution, depending on the conditions such as the type, concentration, and temperature of the solvent.
  • the conditions such as solvent, concentration, and temperature in order to obtain a super-saturated or unsaturated solution, as appropriate.
  • Compound (I) can be precipitated out of solution as crystals by methods such as concentrating or cooling the solution, or adding a poor solvent.
  • Stable crystals can be obtained from suspension as described above and by solvent-mediated transition; that is, using the principle of transition to the most stable form of crystals at that solvent composition and temperature.
  • solvents examples include N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, chloroform, acetonitrile, ethanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, isobutyl alcohol, 2-butanol, t-butyl alcohol, 1-pentanol, 3-methyl-1-butanol, neopentyl alcohol, 2-ethoxymethanol, 2-ethoxyethanol, 2,2,2-trifluorodiethyl ether, 1,1,1,3,3,3-hexafluoro-2-propanol, diisopropyl ether, t-butyl methyl ether
  • the more preferred solvents are acetonitrile, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, methanol, ethanol, 1-propanol, 2-propanol, tetrahydrofuran, 1,4-dioxane, acetone, 2-butanone, hexane, heptane, water, and mixed solvents comprising two or more selected from these.
  • 1 ⁇ volume refers to 1 mL of solvent per 1 g of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid or compound (I).
  • Preferred solvents for minimizing the amount of solvent are ethanol, 1-propanol, 2-propanol, tetrahydrofuran, and 1,4-dioxane, which are solvents in which [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid is highly soluble.
  • the amount thereof is usually from around 0.01% by weight to 20% by weight, preferably 0.1% by weight to 10% by weight, of the drug substance [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid or compound (I), and it is preferably already pulverized.
  • the crystals to be obtained are preferably in the region of super-saturation; it is not necessary for them to be already super-saturated at the time of addition, but it is important that the system is such that the added crystals do not all dissolve.
  • Inventive crystals A of compound (I) are relatively easy to obtain, and can be crystallized by the production methods described above under a wide range of conditions (combinations of various solvents).
  • the crystals obtained from the resulting suspension are filtered and dried to obtain crystals A.
  • the filtration can be performed by a common method; examples of methods that can be used are natural filtration, filtration under increased pressure, filtration under reduced pressure, and centrifugation.
  • the drying can be performed by a common method; examples of methods that can be used are natural drying, drying under reduced pressure, heated drying, and heated drying under reduced pressure.
  • Inventive crystals B of compound (I) are hydrate crystals, and can be obtained using a combination of solvents that includes water. Alcohols such as ethanol and 2-propanol are preferred as the solvent used in combination with water.
  • the crystals can be obtained by dissolving compound (I) in a mixed solvent containing ethanol and water at a ratio of 1:1 (80 ⁇ volume), concentrating and then drying.
  • the drying can comprise natural drying, drying under reduced pressure, heated drying, or heated drying under reduced pressure. In heated drying under reduced pressure it is confirmed that no water of crystallization is lost even at 80° C., but at higher temperatures caution is required.
  • inventive crystals of compound (I) can be used as the active ingredient in pharmaceuticals. It is also possible to use not only a single crystal, but also mixtures of two or more crystal forms.
  • inventive crystals of compound (I) are advantageous in terms of ease of handling during production, reproducibility, stability, storage stability, etc., compared to when non-crystalline.
  • inventive crystals of compound (I) are crystals of L-lysine salt and have better storage stability than crystals of the free form.
  • inventive crystals of compound (I) can be used to obtain pharmaceutical compositions using pharmaceutically acceptable carrier.
  • Formulations containing inventive crystals of compound (I) are prepared using additives commonly used in formulation preparation.
  • additives for solid formulations include excipients such as lactose, white sugar, glucose, corn starch, potato starch, crystalline cellulose, light anhydrous silicic acid, synthetic aluminum silicate, magnesium metasilicate aluminate, and calcium hydrogen phosphate; binders such as crystalline cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, carboxymethylcellulose sodium and polyvinylpyrrolidone; disintegrating agents such as starch, carboxymethylcellulose sodium, carboxymethylcellulose calcium, croscarmellose sodium, and carboxymethylstarch sodium; lubricants such as talc and stearates; coatings such as hydroxymethylpropyl cellulose, hydroxypropyl methyl cellulose phthalate, and ethyl cellulose; and colorants.
  • excipients such as lactose, white sugar, glucose, corn starch, potato starch, crystalline cellulose
  • semi-solid formulations they include base such as white vaseline; and for liquid formulations they include solvents such as ethanol; solubilizing agents such as ethanol; preservatives such as para-oxybenzoic acid esters; isotonizing agents such as glucose; buffers such as citrates; antioxidants such as L-ascorbates; chelating agents such as EDTA; and suspending agents and emulsifiers such as polysorbate 80.
  • solvents such as ethanol
  • solubilizing agents such as ethanol
  • preservatives such as para-oxybenzoic acid esters
  • isotonizing agents such as glucose
  • buffers such as citrates
  • antioxidants such as L-ascorbates
  • chelating agents such as EDTA
  • suspending agents and emulsifiers such as polysorbate 80.
  • inventive crystals of compound (I) can be used in any dosage form, such as solid formulations, semi-solid formulations and liquid formulations, and in any appropriate oral or non-oral formulation (injection agent, transdermal agent, eyedrops, suppository, nasal agent, inhalant, etc.).
  • compositions containing inventive crystals of compound (I) as active ingredient can be used as drugs for the treatment or prevention of diseases in which CRTH2 receptors participate, such as bronchial asthma, chronic obstructive pulmonary disease, bronchitis, cystic fibrosis, perennial allergic rhinitis, seasonal allergic rhinitis, chronic eosinophilic rhinosinusitis, chronic noneosinophilic rhinosinusitis, psoriasis, atopic and nonatopic dermatitis, chronic spontaneous urticaria, Crohn's disease, ulcerative colitis, eosinophilic gastrointestinal disease, and irritable bowel disease.
  • prevention refers to the prevention of disease or symptoms in an individual who does not yet exhibit disease or symptoms
  • treatment refers to affecting cure, inhibition or improvement of disease or symptoms in an individual who already exhibits disease or symptoms.
  • the powder X-ray diffraction of the inventive crystals was measured under the following conditions.
  • Measurement conditions Source Cu-K ⁇ , 40 kV-40 mA, scan 5-400, scan time 35 seconds
  • the infrared absorption spectrum of the inventive crystals was measured under the following conditions in accordance with the ATR infrared absorption spectra measurement method described in the common test methods section of the Japanese Pharmacopoeia.
  • Measurement conditions 4000-400 cm ⁇ 1 , resolution 4 cm ⁇ 1 , accumulation 64 times
  • Measurement conditions 4000-400 cm ⁇ 1 , resolution 4 cm ⁇ 1 , accumulation 24 times
  • the solid-state 13 C-NMR of the inventive crystals was measured under the following conditions.
  • Pulse mode CP/MAS measurement Pulse mode CP/MAS measurement, pulse repeat time 20 seconds, chemical shift standard hexamethylbenzene (external standard: 17.35 ppm)
  • the solid-state 19 F-NMR of the inventive crystals was measured under the following conditions.
  • Measurement conditions Pulse mode CP/MAS measurement, pulse repeat time 55 seconds, chemical shift standard hexafluorobenzene (external standard: ⁇ 163.0 ppm)
  • the solid-state 15 N-NMR of the inventive crystals was measured under the following conditions.
  • Pulse mode CP/MAS measurement Pulse mode CP/MAS measurement, pulse repeat time 15 seconds, chemical shift standard ammonium chloride (external standard: ⁇ 341.2 ppm)
  • the melting point of the inventive crystals was measured under the following conditions.
  • Measurement conditions Measurement range 30-320° C., temperature elevation rate 20° C./minute, on set value
  • the solid-state 13 C-NMR spectrum of the resulting crystals is shown in FIG. 5 .
  • Chemical shift peaks were observed at 107.1 ppm, 115.9 ppm, 127.5 ppm, 136.5 ppm, 145.7 ppm, 152.7 ppm, 153.8 ppm, 165.8 ppm, 175.8 ppm, 177.3 ppm, and 179.5 ppm.
  • the melting point was 200° C.
  • the infrared spectrum of the resulting crystals under conditions 2 is shown in FIG. 4 . Peaks were observed at wavenumbers 667 cm ⁇ 1 , 803 cm ⁇ 1 , 885 cm ⁇ 1 , 1012 cm ⁇ 1 , 1032 cm ⁇ 1 , 1402 cm ⁇ 1 , and 1597 cm ⁇ 1 .
  • the crystals were introduced, respectively, into a glass vessel which was then tightly sealed and stored at 40° C., relative humidity 75° C. for 3 months; the amount of related substances before and after storage was measured by liquid chromatography; the results are shown in Table 1.
  • the values are the total amount of related substances, which are produced impurities, as measured to 20.03%.
  • the inventive crystals of compound (I) can be used for the production of pharmaceutical products.

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US (2) US20190276405A1 (ko)
EP (1) EP3476835A4 (ko)
JP (1) JP6906510B2 (ko)
KR (1) KR20190018643A (ko)
CN (1) CN109415323A (ko)
AU (1) AU2017267768A1 (ko)
BR (1) BR112018073667A2 (ko)
CA (1) CA3025049A1 (ko)
MX (1) MX2018013764A (ko)
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EA015358B1 (ru) * 2005-09-30 2011-06-30 Пульмаджен Терапьютикс (Эсме) Лимитед Хинолины и их терапевтическое применение
GB0519969D0 (en) * 2005-09-30 2005-11-09 Argenta Discovery Ltd Quinoline compounds
AU2008236444B2 (en) * 2007-04-05 2012-06-28 Pfizer Products Inc. Crystalline forms of 6- [2- (methylcarbamoyl) phenylsulfanyl] -3-E- [2- (pyridin-2-yl) ethenyl] indazole suitable for the treatment of abnormal cell growth in mammals
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RU2570198C2 (ru) * 2010-02-12 2015-12-10 Пфайзер Инк. СОЛИ И ПОЛИМОРФЫ 8-ФТОР-2-{4-[(МЕТИЛАМИНО)МЕТИЛ]ФЕНИЛ}-1,3,4,5-ТЕТРАГИДРО-6Н-АЗЕПИНО[5,4,3-cd]ИНДОЛ-6-ОНА
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US20200017447A1 (en) 2020-01-16
JPWO2017199903A1 (ja) 2019-02-28
EP3476835A4 (en) 2020-01-01
EP3476835A1 (en) 2019-05-01
CA3025049A1 (en) 2017-11-23
KR20190018643A (ko) 2019-02-25
TW201808910A (zh) 2018-03-16
JP6906510B2 (ja) 2021-07-21
CN109415323A (zh) 2019-03-01
AU2017267768A1 (en) 2019-01-03
BR112018073667A2 (pt) 2019-03-12
MX2018013764A (es) 2019-08-05
WO2017199903A1 (ja) 2017-11-23
US10626089B2 (en) 2020-04-21
RU2018144286A3 (ko) 2020-09-30

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