CN110498800A - 游离碱晶体 - Google Patents
游离碱晶体 Download PDFInfo
- Publication number
- CN110498800A CN110498800A CN201910526464.9A CN201910526464A CN110498800A CN 110498800 A CN110498800 A CN 110498800A CN 201910526464 A CN201910526464 A CN 201910526464A CN 110498800 A CN110498800 A CN 110498800A
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- CN
- China
- Prior art keywords
- methyl
- crystal
- crystals
- pyrazolo
- imidazo
- Prior art date
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- Pending
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- 239000013078 crystal Substances 0.000 title claims abstract description 394
- 239000003513 alkali Substances 0.000 title claims description 11
- 238000000034 method Methods 0.000 claims abstract description 88
- 239000000203 mixture Substances 0.000 claims description 133
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 119
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 111
- 239000012453 solvate Substances 0.000 claims description 106
- 229940126062 Compound A Drugs 0.000 claims description 91
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 91
- 150000003839 salts Chemical class 0.000 claims description 79
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 77
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 77
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 60
- 239000012044 organic layer Substances 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 47
- 239000002585 base Substances 0.000 claims description 38
- 239000002904 solvent Substances 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 19
- -1 monophosphate salt Chemical class 0.000 claims description 19
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 16
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 235000019441 ethanol Nutrition 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 12
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 11
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 11
- ZQJUAPPNCFBJJW-UHFFFAOYSA-N 1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,4,6,8,10-pentaene Chemical compound C1=C2C=NN=C2N2CC=NC2=N1 ZQJUAPPNCFBJJW-UHFFFAOYSA-N 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 9
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 9
- 239000001530 fumaric acid Substances 0.000 claims description 8
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 27
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 13
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 238000004090 dissolution Methods 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 238000010521 absorption reaction Methods 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 239000000155 melt Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 239000012458 free base Substances 0.000 abstract description 211
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 32
- 238000001914 filtration Methods 0.000 description 31
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 28
- 239000010949 copper Substances 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 21
- 239000008096 xylene Substances 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 229910052802 copper Inorganic materials 0.000 description 18
- 150000004712 monophosphates Chemical class 0.000 description 18
- 238000001757 thermogravimetry curve Methods 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 238000010926 purge Methods 0.000 description 10
- 238000002411 thermogravimetry Methods 0.000 description 10
- 108010053481 Antifreeze Proteins Proteins 0.000 description 9
- 229910052782 aluminium Inorganic materials 0.000 description 9
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 239000011521 glass Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 238000007789 sealing Methods 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- JTBBWRKSUYCPFY-UHFFFAOYSA-N 2,3-dihydro-1h-pyrimidin-4-one Chemical compound O=C1NCNC=C1 JTBBWRKSUYCPFY-UHFFFAOYSA-N 0.000 description 5
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000012043 crude product Substances 0.000 description 4
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- RHNXMQLPXJSMON-UHFFFAOYSA-N 2-[4-(chloromethyl)phenyl]-6-fluoropyridine Chemical compound FC1=CC=CC(C=2C=CC(CCl)=CC=2)=N1 RHNXMQLPXJSMON-UHFFFAOYSA-N 0.000 description 3
- UNRBJEOYYDGFGE-UHFFFAOYSA-N 2-[[4-(6-fluoropyridin-2-yl)phenyl]methyl]-5-methyl-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=C2C(=O)N(C)C(=O)NC2=NN1CC(C=C1)=CC=C1C1=CC=CC(F)=N1 UNRBJEOYYDGFGE-UHFFFAOYSA-N 0.000 description 3
- NINZAMOQCXMUNF-UHFFFAOYSA-N 6-chloro-1-[(4-methoxyphenyl)methyl]-3-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C=C1Cl NINZAMOQCXMUNF-UHFFFAOYSA-N 0.000 description 3
- YVPGMHIHOYONMU-RTBURBONSA-N Cn1c(N[C@@H]2CCC[C@H]2O)nc2nn(Cc3ccc(cc3)-c3cccc(F)n3)cc2c1=O Chemical compound Cn1c(N[C@@H]2CCC[C@H]2O)nc2nn(Cc3ccc(cc3)-c3cccc(F)n3)cc2c1=O YVPGMHIHOYONMU-RTBURBONSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- TYBWSXXWAKLUNF-UHFFFAOYSA-N OCc1ccc(cc1)-c1cccc(F)n1 Chemical compound OCc1ccc(cc1)-c1cccc(F)n1 TYBWSXXWAKLUNF-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 235000013980 iron oxide Nutrition 0.000 description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000004408 titanium dioxide Substances 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- WOMANHSZQXKFKJ-UHFFFAOYSA-N 2,3-dihydropyrrolo[3,4-d]pyrimidin-4-one Chemical compound N=1CNC(C=2C1C=NC2)=O WOMANHSZQXKFKJ-UHFFFAOYSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- KTTPPSPBNHDDGN-UHFFFAOYSA-N 6-hydrazinyl-1-[(4-methoxyphenyl)methyl]-3-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C=C1NN KTTPPSPBNHDDGN-UHFFFAOYSA-N 0.000 description 2
- JVYBHXSIAJRNGN-UHFFFAOYSA-N 7-[(4-methoxyphenyl)methyl]-5-methyl-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C1NN=C2 JVYBHXSIAJRNGN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
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- 229930195725 Mannitol Natural products 0.000 description 2
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
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- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229920003125 hypromellose 2910 Polymers 0.000 description 2
- 229940031672 hypromellose 2910 Drugs 0.000 description 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 2
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 238000000646 scanning calorimetry Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-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
- ZFSXKSSWYSZPGQ-TYSVMGFPSA-N (1r,2r)-2-aminocyclopentan-1-ol;hydrochloride Chemical compound Cl.N[C@@H]1CCC[C@H]1O ZFSXKSSWYSZPGQ-TYSVMGFPSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
- ZIDIKYIZXMYHAW-UHFFFAOYSA-N 2-bromo-6-fluoropyridine Chemical compound FC1=CC=CC(Br)=N1 ZIDIKYIZXMYHAW-UHFFFAOYSA-N 0.000 description 1
- SGLXGFAZAARYJY-UHFFFAOYSA-N 6-Chloro-3-methyluracil Chemical compound CN1C(=O)C=C(Cl)NC1=O SGLXGFAZAARYJY-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
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- 101100243082 Caenorhabditis elegans pde-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 description 1
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
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- 239000004698 Polyethylene Substances 0.000 description 1
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- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N acetic acid;palladium Chemical compound [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
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- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
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- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical class [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
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- 239000000919 ceramic Substances 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
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- 239000012535 impurity Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 1
- 238000001907 polarising light microscopy Methods 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
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- 230000007781 signaling event Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US201361919424P | 2013-12-20 | 2013-12-20 | |
| US61/919,424 | 2013-12-20 | ||
| CN201480046150.4A CN105658222A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
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| CN201480046150.4A Division CN105658222A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
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|---|---|
| CN110498800A true CN110498800A (zh) | 2019-11-26 |
Family
ID=52105535
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| CN201910526464.9A Pending CN110498800A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
| CN201480046150.4A Pending CN105658222A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
| CN202110144523.3A Pending CN112851683A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201480046150.4A Pending CN105658222A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
| CN202110144523.3A Pending CN112851683A (zh) | 2013-06-21 | 2014-06-20 | 游离碱晶体 |
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| EP (2) | EP3010509B1 (https=) |
| JP (2) | JP6865036B2 (https=) |
| KR (2) | KR20160040522A (https=) |
| CN (3) | CN110498800A (https=) |
| AU (1) | AU2014284224B2 (https=) |
| BR (1) | BR112015032132B1 (https=) |
| CA (1) | CA2916393C (https=) |
| ES (1) | ES2894770T3 (https=) |
| IL (2) | IL267331B2 (https=) |
| MX (2) | MX2015017972A (https=) |
| RU (1) | RU2675851C2 (https=) |
| WO (1) | WO2014205354A2 (https=) |
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| JP6051210B2 (ja) | 2011-06-10 | 2016-12-27 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| AR091507A1 (es) * | 2012-06-21 | 2015-02-11 | Intra Cellular Therapies Inc | SALES DE (6aR,9aS)-5,6a,7,8,9,9a-HEXAHIDRO-5-METIL-3-(FENILAMINO)-2-((4-(6-FLUOROPIRIDIN-2-IL)FENIL)METIL)-CICLOPENT[4,5]IMIDAZO[1,2-a]PIRAZOLO[4,3-e]PIRIMIDIN-4(2H)-ONA |
| US9630971B2 (en) | 2013-06-21 | 2017-04-25 | Intra-Cellular Therapies, Inc. | Free base crystals |
| EP4413980A3 (en) | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel compounds |
| US12435093B2 (en) | 2020-05-06 | 2025-10-07 | Intra-Cellular Therapies, Inc. | Free base crystals |
| WO2022026417A1 (en) * | 2020-07-26 | 2022-02-03 | Intra-Cellular Therapies, Inc. | Novel uses |
| JP2024531548A (ja) * | 2021-09-03 | 2024-08-29 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 共結晶 |
| EP4469052A4 (en) * | 2022-01-27 | 2026-02-11 | Intra Cellular Therapies Inc | NEW COMPOSITIONS |
| EP4472638A4 (en) * | 2022-01-31 | 2026-03-11 | Intra Cellular Therapies Inc | SALT CRYSTALS |
| WO2023233410A1 (en) * | 2022-06-02 | 2023-12-07 | Biosight Ltd. | Crystalline form of aspacytarabine intermediate |
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| CN101970444A (zh) * | 2007-12-06 | 2011-02-09 | 细胞内治疗公司 | 有机化合物 |
| CN104602695A (zh) * | 2012-06-21 | 2015-05-06 | 细胞内治疗公司 | 盐晶体 |
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| GB9412571D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| US5471001A (en) * | 1994-12-15 | 1995-11-28 | E. I. Du Pont De Nemours And Company | Crystallization of adipic acid |
| GB9624615D0 (en) * | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Chrystallisation process |
| TWI265925B (en) * | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
| PL215006B1 (pl) * | 2002-02-08 | 2013-10-31 | Ono Pharmaceutical Co | Krystaliczna postac pochodnej piperydyny oraz jej zastosowanie |
| EP1613747A1 (en) * | 2003-03-31 | 2006-01-11 | Pfizer Products Inc. | Crystal structure of 3 ,5 -cyclic nucleotide phosphodiesterase 1b (pde1b) and uses thereof |
| JP2007504230A (ja) * | 2003-09-02 | 2007-03-01 | メルク エンド カムパニー インコーポレーテッド | ジペプチジルペプチダーゼ−ｉｖ阻害剤のリン酸塩の新規結晶性形態 |
| JP4996467B2 (ja) * | 2004-09-27 | 2012-08-08 | アカディア ファーマシューティカルズ インコーポレイテッド | Ｎ−（４−フルオロベンジル）−ｎ−（１−メチルピペリジン−４−イル）−ｎ’−（４−（２−メチルプロピルオキシ）フェニルメチル）カルバミド、並びにその酒石酸塩及び結晶形態の合成 |
| AU2006255028B2 (en) * | 2005-06-06 | 2012-04-19 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2008063505A1 (en) | 2006-11-13 | 2008-05-29 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2008070095A1 (en) | 2006-12-05 | 2008-06-12 | Intra-Cellular Therapies, Inc. | Novel uses |
| US20120070443A1 (en) | 2008-12-02 | 2012-03-22 | University Of Utah Research Foundation | Pde1 as a target therapeutic in heart disease |
| MA32942B1 (fr) * | 2008-12-06 | 2012-01-02 | Intra Cellular Therapies Inc | Composes organiques |
| KR20110103949A (ko) | 2008-12-06 | 2011-09-21 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| JP5778582B2 (ja) * | 2008-12-06 | 2015-09-16 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| WO2010098839A1 (en) | 2009-02-25 | 2010-09-02 | Intra-Cellular Therapies, Inc. | Pde 1 inhibitors for ophthalmic disorders |
| JP2012526810A (ja) | 2009-05-13 | 2012-11-01 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| WO2011043816A1 (en) | 2009-10-08 | 2011-04-14 | Intra-Cellular Therapies, Inc. | Phosphodiesterase 1-targeting tracers and methods |
| EP2576551A4 (en) | 2010-05-31 | 2014-04-16 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| JP6051210B2 (ja) | 2011-06-10 | 2016-12-27 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| US9630971B2 (en) | 2013-06-21 | 2017-04-25 | Intra-Cellular Therapies, Inc. | Free base crystals |
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2014
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- 2014-06-20 BR BR112015032132-1A patent/BR112015032132B1/pt active IP Right Grant
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2015
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2019
- 2019-06-04 JP JP2019104412A patent/JP2019189618A/ja active Pending
Patent Citations (2)
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|---|---|---|---|---|
| CN101970444A (zh) * | 2007-12-06 | 2011-02-09 | 细胞内治疗公司 | 有机化合物 |
| CN104602695A (zh) * | 2012-06-21 | 2015-05-06 | 细胞内治疗公司 | 盐晶体 |
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