JPWO2014017515A1 - 4−[5−(ピリジン−4−イル)−1h−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの結晶多形およびその製造方法 - Google Patents
4−[5−(ピリジン−4−イル)−1h−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの結晶多形およびその製造方法 Download PDFInfo
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- JPWO2014017515A1 JPWO2014017515A1 JP2014526956A JP2014526956A JPWO2014017515A1 JP WO2014017515 A1 JPWO2014017515 A1 JP WO2014017515A1 JP 2014526956 A JP2014526956 A JP 2014526956A JP 2014526956 A JP2014526956 A JP 2014526956A JP WO2014017515 A1 JPWO2014017515 A1 JP WO2014017515A1
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- pyridine
- carbonitrile
- triazol
- pyridin
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- UBVZQGOVTLIHLH-UHFFFAOYSA-N 4-[5-pyridin-4-yl-1h-[1,2,4]triazol-3-yl]-pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC(C=2N=C(NN=2)C=2C=CN=CC=2)=C1 UBVZQGOVTLIHLH-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title description 8
- 239000013078 crystal Substances 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims description 20
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 230000003472 neutralizing effect Effects 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- PMGCZWNEPYZLJX-UHFFFAOYSA-N 4-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile hydrate Chemical compound O.N1=CC=C(C=C1)C1=NC(=NN1)C1=CC(=NC=C1)C#N PMGCZWNEPYZLJX-UHFFFAOYSA-N 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000003860 storage Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002076 thermal analysis method Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SMSNPZULVQJKOG-UHFFFAOYSA-N 3-(3-pyridin-4-yl-1H-1,2,4-triazol-5-yl)pyridine-2-carbonitrile Chemical compound N1=CC=C(C=C1)C1=NC(=NN1)C=1C(=NC=CC1)C#N SMSNPZULVQJKOG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 229940116269 uric acid Drugs 0.000 description 2
- QNCSFBSIWVBTHE-UHFFFAOYSA-N 1-oxidopyridin-1-ium-4-carbonitrile Chemical compound [O-][N+]1=CC=C(C#N)C=C1 QNCSFBSIWVBTHE-UHFFFAOYSA-N 0.000 description 1
- OMPBCHVDILLLFU-UHFFFAOYSA-N 3-methyl-1-oxidopyridin-1-ium-4-carboxylic acid Chemical compound CC1=C[N+]([O-])=CC=C1C(O)=O OMPBCHVDILLLFU-UHFFFAOYSA-N 0.000 description 1
- QUKGHTHKDNHSOX-UHFFFAOYSA-N 4-(3-pyridin-4-yl-1h-1,2,4-triazol-5-yl)pyridine Chemical compound C1=NC=CC(C=2N=C(NN=2)C=2C=CN=CC=2)=C1 QUKGHTHKDNHSOX-UHFFFAOYSA-N 0.000 description 1
- HCEPIFBYVFRGOI-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;4-(5-pyridin-4-yl-1h-1,2,4-triazol-3-yl)pyridine-2-carbonitrile Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C1=NC(C#N)=CC(C=2NN=C(N=2)C=2C=CN=CC=2)=C1 HCEPIFBYVFRGOI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- JOCGTRBJVRLAPR-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)O.N1=C(C=CC=C1)C#N Chemical compound CC1=CC=C(C=C1)S(=O)(=O)O.N1=C(C=CC=C1)C#N JOCGTRBJVRLAPR-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- QCWTWMJMLSKQCJ-UHFFFAOYSA-N Isonicotinic acid N-oxide Chemical compound OC(=O)C1=CC=[N+]([O-])C=C1 QCWTWMJMLSKQCJ-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- -1 inorganic acid salts Chemical class 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- ORVHMLCJEKDDAX-UHFFFAOYSA-N methyl 2-cyanopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C#N)=C1 ORVHMLCJEKDDAX-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000005489 p-toluenesulfonic acid group Chemical group 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Pain & Pain Management (AREA)
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- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
[1]粉末X線回折において、回折角2θの値が10.1、16.0、20.4、25.7及び26.7度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのI型結晶。
[2]粉末X線回折において、回折角2θの値が9.9、16.3、18.2、22.4度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのII型結晶。
[3]粉末X線回折において、回折角(2θ)の値が8.1、14.9、16.4、25.3、26.9、27.6度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの水和物。
[4]4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの酸塩を塩基で処理し、次いで酸で中和することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのI型結晶の製造方法。
[5]4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルを有機溶媒で再結晶することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのII型結晶の製造方法。
[6]4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルを加湿条件下に保存することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの水和物の製造方法。
[7][1]記載のI型結晶及び薬学的に許容される担体を含有する医薬組成物。
[8][2]記載のII型結晶及び薬学的に許容される担体を含有する医薬組成物。
[9][3]記載の水和物及び薬学的に許容される担体を含有する医薬組成物。
これらの塩基の使用量は、化合物(1)の酸塩1モルに対して2〜5モルが好ましく、2〜4モルがより好ましい。
また、DSCにおいて、図4に示す327℃付近での吸熱パターンを示す。
また、DSCにおいて、図5及び6に示す273℃及び327℃付近での吸熱パターンを示す。
また、DSCにおいて、図7に示す107℃及び327℃付近での吸熱パターンを示す。
化合物(1)の水和物としては、1水和物が好ましい。
X線光源:Cu
ゴニオメータ:縦型
発散スリット:Variable
散乱スリット:4.2deg
受光スリット:0.3mm
走査モード:連続
スキャンスピード:2°/分
スキャンステップ:0.02°
走査軸:θ/2θ
走査範囲:3〜60°
昇温速度:10℃/分
雰囲気:窒素
測定温度範囲:30〜400℃
経口用固形製剤を調製する場合は、化合物(1)の結晶に、必要に応じて賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、コーティング剤、湿潤剤、糖衣剤、防腐剤、保存剤、抗酸化剤、矯味・矯臭剤等を加えた後、常法により錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等を製造することができる。
本発明の医薬組成物は、尿酸値低下剤、痛風予防治療剤として有用である。
1H−NMR:プロトン核磁気共鳴スペクトル、DMSO−d6:重水素化ジメチルスルホキシド、Hz:ヘルツ、J:カップリング定数、s:シングレット、dd:ダブルダブレット、m:マルチプレット。尚、NMRは270MHz核磁気共鳴スペクトルを示し、内部標準物質としてTMS(テトラメチルシラン)を用いた。
水:2−ブタノール=10:1の混合溶液55mLにp−トルエンスルホン酸一水和物6.62gを加えた後、80℃で4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリル7.85gを加え、同温で1時間撹拌した。反応液を室温まで冷却した後、析出した結晶をろ取し、水:2−ブタノール=10:1の混合溶液40mLで洗浄した。得られた結晶を80℃で10時間減圧乾燥し、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルp−トルエンスルホン酸塩12.6gを得た。
1H−NMR(DMSO−d6)δ(ppm):2.29(s,3H),7.11(m,2H),7.48(dd,2H,J=6.48,1.62Hz),8.32−8.35(m,3H),8.57(dd,1H,J=1.62,0.81Hz),8.94−8.98(m,3H)
水:エタノール=9:1の混合溶液80mLに炭酸カリウム8.22g、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルp−トルエンスルホン酸塩10.0gを溶解した。20℃で6M塩酸15mLを加え5時間撹拌し、析出した結晶をろ取した後、水100mLで洗浄した。80℃で23時間減圧乾燥し、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリル5.78gを得た。得られた結晶は、図1に示す粉末X線回折パターン及び図4に示すDSCを有し、I型結晶であった。
1H−NMR(DMSO−d6)δ(ppm):8.02(dd,2H,J=4.59,1.62Hz),8.32(dd,1H,J=5.13,1.62Hz),8.55(dd,1H,J=1.62,1.08Hz),8.80(dd,2H,J=4.59,1.62Hz),8.93(dd,1H,5.13,1.08Hz)
融点:327℃
4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリル40.0gにN,N−ジメチルホルムアミド300mLを加え、150℃で25分撹拌した。溶解液を室温まで冷却した後、析出した結晶をろ取し、結晶を水200mLで2回洗浄後、80℃で終夜減圧乾燥し4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリル30.4gを得た。得られた結晶は、図2に示す粉末X線回折パターン及び図5に示すDSCを有し、II型結晶であった。
1H−NMR(DMSO−d6)δ(ppm):8.02(dd,2H,J=4.59,1.62Hz),8.32(dd,1H,J=5.13,1.62Hz),8.55(dd,1H,J=1.62,1.08Hz),8.80(dd,2H,J=4.59,1.62Hz),8.93(dd,1H,5.13,1.08Hz)
融点:327℃
4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリル約2gを、25℃、97%相対湿度の条件で14日間保存した。得られた結晶は図3に示す粉末X線回折パターン及び図7に示すDSCを有し、水和物であった。
1H−NMR(DMSO−d6)δ(ppm):8.02(dd,2H,J=4.59,1.62Hz),8.32(dd,1H,J=5.13,1.62Hz),8.55(dd,1H,J=1.62,1.08Hz),8.80(dd,2H,J=4.59,1.62Hz),8.93(dd,1H,5.13,1.08Hz)
融点:327℃
I型結晶、II型結晶、および水和物の水に対する溶解性は、各試料の飽和溶液濃度を、吸光度測定法により算出した。結果を図8に示す。I型結晶の水に対する溶解度は6.2μg/mLであるのに対し、II型結晶は4.2μg/mL、水和物は1.9μg/mLであった。
図8より、I型結晶及びII型結晶の水溶性が良好であり、特にI型結晶の水溶性は良好である。
Claims (9)
- 粉末X線回折において、回折角2θの値が10.1、16.0、20.4、25.7及び26.7度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのI型結晶。
- 粉末X線回折において、回折角2θの値が9.9、16.3、18.2、22.4度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのII型結晶。
- 粉末X線回折において、回折角(2θ)の値が8.1、14.9、16.4、25.3、26.9、27.6度付近に特徴的なピークを有する4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの水和物。
- 4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの酸塩を塩基で処理し、次いで酸で中和することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのI型結晶の製造方法。
- 4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルを有機溶媒で再結晶することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルのII型結晶の製造方法。
- 4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルを加湿条件下に保存することを特徴とする、4−[5−(ピリジン−4−イル)−1H−1,2,4−トリアゾール−3−イル]ピリジン−2−カルボニトリルの水和物の製造方法。
- 請求項1記載のI型結晶及び薬学的に許容される担体を含有する医薬組成物。
- 請求項2記載のII型結晶及び薬学的に許容される担体を含有する医薬組成物。
- 請求項3記載の水和物及び薬学的に許容される担体を含有する医薬組成物。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519698A (ja) * | 2000-01-07 | 2003-06-24 | トランスフォーム ファーマスーティカルズ,インコーポレイテッド | 多様な固体形態のハイスループットでの形成、同定および分析 |
WO2003064410A1 (fr) * | 2002-01-28 | 2003-08-07 | Fuji Yakuhin Co., Ltd. | Nouveau compose 1,2,4-triazole |
WO2005009991A1 (ja) * | 2003-07-24 | 2005-02-03 | Fujiyakuhin Co., Ltd. | 1,2,4−トリアゾール化合物の製造方法及びその中間体 |
JP2005041802A (ja) * | 2003-07-25 | 2005-02-17 | Fujiyakuhin Co Ltd | 1,2,4−トリアゾール化合物の製造方法 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050089923A9 (en) | 2000-01-07 | 2005-04-28 | Levinson Douglas A. | Method and system for planning, performing, and assessing high-throughput screening of multicomponent chemical compositions and solid forms of compounds |
US6977723B2 (en) | 2000-01-07 | 2005-12-20 | Transform Pharmaceuticals, Inc. | Apparatus and method for high-throughput preparation and spectroscopic classification and characterization of compositions |
US20070020662A1 (en) | 2000-01-07 | 2007-01-25 | Transform Pharmaceuticals, Inc. | Computerized control of high-throughput experimental processing and digital analysis of comparative samples for a compound of interest |
US20070021929A1 (en) | 2000-01-07 | 2007-01-25 | Transform Pharmaceuticals, Inc. | Computing methods for control of high-throughput experimental processing, digital analysis, and re-arraying comparative samples in computer-designed arrays |
US7108970B2 (en) | 2000-01-07 | 2006-09-19 | Transform Pharmaceuticals, Inc. | Rapid identification of conditions, compounds, or compositions that inhibit, prevent, induce, modify, or reverse transitions of physical state |
US20050118637A9 (en) | 2000-01-07 | 2005-06-02 | Levinson Douglas A. | Method and system for planning, performing, and assessing high-throughput screening of multicomponent chemical compositions and solid forms of compounds |
US20050095696A9 (en) | 2000-01-07 | 2005-05-05 | Lemmo Anthony V. | Apparatus and method for high-throughput preparation and characterization of compositions |
US6627646B2 (en) * | 2001-07-17 | 2003-09-30 | Sepracor Inc. | Norastemizole polymorphs |
AU2002336457A1 (en) | 2001-09-07 | 2003-03-24 | Transform Pharmaceuticals, Inc. | Apparatus and method for high-throughput preparation and characterization of compositions |
US20060189811A1 (en) | 2004-07-23 | 2006-08-24 | Fujiyakuhin Co., Ltd. | Process for producing 1,2,4-triazole compound and intermediate therefor |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003519698A (ja) * | 2000-01-07 | 2003-06-24 | トランスフォーム ファーマスーティカルズ,インコーポレイテッド | 多様な固体形態のハイスループットでの形成、同定および分析 |
WO2003064410A1 (fr) * | 2002-01-28 | 2003-08-07 | Fuji Yakuhin Co., Ltd. | Nouveau compose 1,2,4-triazole |
WO2005009991A1 (ja) * | 2003-07-24 | 2005-02-03 | Fujiyakuhin Co., Ltd. | 1,2,4−トリアゾール化合物の製造方法及びその中間体 |
JP2005041802A (ja) * | 2003-07-25 | 2005-02-17 | Fujiyakuhin Co Ltd | 1,2,4−トリアゾール化合物の製造方法 |
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