HU187913B - Process for producing alkyl-imidazo-bracket-1,2-c-bracket closed pyrazolo-bracket-3,4-e-bracket closed-pyrimidine derivatives and antipsychotic compositions containing them - Google Patents
Process for producing alkyl-imidazo-bracket-1,2-c-bracket closed pyrazolo-bracket-3,4-e-bracket closed-pyrimidine derivatives and antipsychotic compositions containing them Download PDFInfo
- Publication number
- HU187913B HU187913B HU831811A HU181183A HU187913B HU 187913 B HU187913 B HU 187913B HU 831811 A HU831811 A HU 831811A HU 181183 A HU181183 A HU 181183A HU 187913 B HU187913 B HU 187913B
- Authority
- HU
- Hungary
- Prior art keywords
- pyrazolo
- pyrimidine
- imidazo
- formula
- dihydro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 73
- 230000008569 process Effects 0.000 title claims abstract description 55
- 239000000203 mixture Substances 0.000 title claims description 61
- 230000000561 anti-psychotic effect Effects 0.000 title description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 133
- 238000002360 preparation method Methods 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 239000007858 starting material Substances 0.000 claims description 25
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 claims description 24
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 230000002140 halogenating effect Effects 0.000 claims description 7
- VJTDTMBPCVRULB-UHFFFAOYSA-N 7,8-dihydro-1,3,5,8-tetramethyl-1h-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine Chemical compound CC1=NN(C)C2=C1N=C(C)N1C2=NC(C)C1 VJTDTMBPCVRULB-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 150000002905 orthoesters Chemical class 0.000 claims description 4
- GWSPWPBQMVSEET-UHFFFAOYSA-N 5-ethyl-1,3,8-trimethyl-1h-imidazo(1,2-c)pyrazolo(3,4-e)pyrimidine Chemical compound C12=NC(C)=CN2C(CC)=NC2=C1N(C)N=C2C GWSPWPBQMVSEET-UHFFFAOYSA-N 0.000 claims description 3
- JUSHBJUUSOUAOJ-UHFFFAOYSA-N 7,8-dihydro-1-ethyl-3,5,8-trimethyl-1h-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine Chemical compound N1=C(C)N2CC(C)N=C2C2=C1C(C)=NN2CC JUSHBJUUSOUAOJ-UHFFFAOYSA-N 0.000 claims description 3
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
- PJHFGEPWJCOHCR-UHFFFAOYSA-N chembl141914 Chemical compound C12=NCCN2C(CC)=NC2=C1N(C)N=C2C PJHFGEPWJCOHCR-UHFFFAOYSA-N 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- SAQVKYRGXZWNFW-UHFFFAOYSA-N 7,8-dihydro-1,3,5,7,7-pentamethyl-1h-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine Chemical compound C12=NCC(C)(C)N2C(C)=NC2=C1N(C)N=C2C SAQVKYRGXZWNFW-UHFFFAOYSA-N 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- MYAFETNELZKADZ-UHFFFAOYSA-N chembl140011 Chemical compound N1=C(C)N2CCN=C2C2=C1C(C)=NN2CC MYAFETNELZKADZ-UHFFFAOYSA-N 0.000 claims description 2
- GJCGYZHZLVGGFO-UHFFFAOYSA-N chembl140096 Chemical compound N1=C(C)N2C(C)=C(C)N=C2C2=C1C(C)=NN2C GJCGYZHZLVGGFO-UHFFFAOYSA-N 0.000 claims description 2
- QHJZUFKYZMITNR-UHFFFAOYSA-N chembl141140 Chemical compound C12=NCCN2C=NC2=C1N(C)N=C2C QHJZUFKYZMITNR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims 3
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims 1
- CKUBZOXMAUYEPM-UHFFFAOYSA-N chembl143318 Chemical compound N1=C(C)N2CC(C)N=C2C2=C1C(C)=NN2CCC CKUBZOXMAUYEPM-UHFFFAOYSA-N 0.000 claims 1
- KQZHDUGJLSEGCD-UHFFFAOYSA-N chembl143378 Chemical compound C12=NC(C)CN2C=NC2=C1N(C)N=C2C KQZHDUGJLSEGCD-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 150000003230 pyrimidines Chemical class 0.000 abstract description 3
- 239000000164 antipsychotic agent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 77
- 239000000243 solution Substances 0.000 description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 38
- 235000019341 magnesium sulphate Nutrition 0.000 description 38
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 36
- 239000000047 product Substances 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- 238000010992 reflux Methods 0.000 description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 21
- 239000000908 ammonium hydroxide Substances 0.000 description 20
- 239000003208 petroleum Substances 0.000 description 20
- -1 methyl-1H-imidazo [1,2-c] pyrazolo [3,4-e] pyrimidine Chemical group 0.000 description 19
- 238000003756 stirring Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 12
- 235000009518 sodium iodide Nutrition 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 10
- 150000001408 amides Chemical group 0.000 description 9
- OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 7
- 150000001414 amino alcohols Chemical class 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- BWESROVLRYCPEU-UHFFFAOYSA-N 7-chloro-1,3,5-trimethylpyrazolo[4,3-d]pyrimidine Chemical compound N1=C(C)N=C2C(C)=NN(C)C2=C1Cl BWESROVLRYCPEU-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- BFRNEURRHHIAJV-UHFFFAOYSA-N 4-amino-2,5-dimethylpyrazole-3-carbonitrile Chemical compound CC1=NN(C)C(C#N)=C1N BFRNEURRHHIAJV-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JFZSDNLQDTYVEE-UHFFFAOYSA-N 1,4-dihydropyrazolo[4,3-d]pyrimidin-7-one Chemical class O=C1N=CNC2=C1NN=C2 JFZSDNLQDTYVEE-UHFFFAOYSA-N 0.000 description 3
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 3
- UJUWPEPEBAQVND-UHFFFAOYSA-N 5-cyclopropyl-1,3-dimethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C2C(C)=NN(C)C2=C(O)N=C1C1CC1 UJUWPEPEBAQVND-UHFFFAOYSA-N 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 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
- 239000002552 dosage form Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- XNHLWMBQIPEDQR-UHFFFAOYSA-N 1,3,5-trimethyl-7-(2-methylaziridin-1-yl)pyrazolo[4,3-d]pyrimidine Chemical compound CC1CN1C1=NC(C)=NC2=C1N(C)N=C2C XNHLWMBQIPEDQR-UHFFFAOYSA-N 0.000 description 2
- FJRYEAGYRIQNOK-UHFFFAOYSA-N 1,3-dimethyl-5-propan-2-yl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CC(C)C1=NC(O)=C2N(C)N=C(C)C2=N1 FJRYEAGYRIQNOK-UHFFFAOYSA-N 0.000 description 2
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 2
- KBICTPPJSYFIAZ-UHFFFAOYSA-N 1-ethyl-3,5-dimethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CC1=NC(O)=C2N(CC)N=C(C)C2=N1 KBICTPPJSYFIAZ-UHFFFAOYSA-N 0.000 description 2
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- WFSHABBLBPZOBT-UHFFFAOYSA-N 3,5,8-trimethyl-11-propan-2-yl-3,4,7,9,12-pentazatricyclo[7.3.0.02,6]dodeca-1(12),2(6),4,7-tetraene dihydrochloride Chemical compound Cl.Cl.CC1=NN(C)C2=C1N=C(C)N1C2=NC(C(C)C)C1 WFSHABBLBPZOBT-UHFFFAOYSA-N 0.000 description 2
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- KTKPPWMAKGGVHD-UHFFFAOYSA-N 7,8-dihydro-5-isopropyl-1,3,8-trimethyl-1h-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine Chemical compound C12=NC(C)CN2C(C(C)C)=NC2=C1N(C)N=C2C KTKPPWMAKGGVHD-UHFFFAOYSA-N 0.000 description 2
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- YBGJZYCWGNYUMA-UHFFFAOYSA-M [Cl-].[P+]=O Chemical compound [Cl-].[P+]=O YBGJZYCWGNYUMA-UHFFFAOYSA-M 0.000 description 2
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- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- QTBFPMKWQKYFLR-UHFFFAOYSA-N isobutyl chloride Chemical compound CC(C)CCl QTBFPMKWQKYFLR-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- LTXZONOMJKYYLN-UHFFFAOYSA-N n-(5-cyano-1,3-dimethylpyrazol-4-yl)-2-methylpropanamide Chemical compound CC(C)C(=O)NC=1C(C)=NN(C)C=1C#N LTXZONOMJKYYLN-UHFFFAOYSA-N 0.000 description 1
- VSVNESBKLBHATG-UHFFFAOYSA-N n-(5-cyano-1,3-dimethylpyrazol-4-yl)cyclopropanecarboxamide Chemical compound CC1=NN(C)C(C#N)=C1NC(=O)C1CC1 VSVNESBKLBHATG-UHFFFAOYSA-N 0.000 description 1
- TVWNLBSFNKJQSY-UHFFFAOYSA-N n-(5-cyano-1,3-dimethylpyrazol-4-yl)propanamide Chemical compound CCC(=O)NC=1C(C)=NN(C)C=1C#N TVWNLBSFNKJQSY-UHFFFAOYSA-N 0.000 description 1
- HMWSFFUPLJWSTA-UHFFFAOYSA-N n-(5-cyano-3-methyl-1-propylpyrazol-4-yl)acetamide Chemical compound CCCN1N=C(C)C(NC(C)=O)=C1C#N HMWSFFUPLJWSTA-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- ZNZJJSYHZBXQSM-UHFFFAOYSA-N propane-2,2-diamine Chemical compound CC(C)(N)N ZNZJJSYHZBXQSM-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C07D231/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/381,484 US4469868A (en) | 1982-05-24 | 1982-05-24 | Alkylimidazo[1,2-c]pyrazolo[3,4-e]pyrimidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU187913B true HU187913B (en) | 1986-03-28 |
Family
ID=23505215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU831811A HU187913B (en) | 1982-05-24 | 1983-05-23 | Process for producing alkyl-imidazo-bracket-1,2-c-bracket closed pyrazolo-bracket-3,4-e-bracket closed-pyrimidine derivatives and antipsychotic compositions containing them |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4469868A (enExample) |
| EP (1) | EP0095289B1 (enExample) |
| JP (1) | JPS58210087A (enExample) |
| KR (1) | KR870000931B1 (enExample) |
| AR (1) | AR240941A1 (enExample) |
| AT (1) | ATE24510T1 (enExample) |
| AU (1) | AU553708B2 (enExample) |
| CA (1) | CA1210393A (enExample) |
| DE (1) | DE3368635D1 (enExample) |
| DK (1) | DK161968C (enExample) |
| ES (4) | ES522617A0 (enExample) |
| FI (1) | FI74012C (enExample) |
| GR (1) | GR79262B (enExample) |
| HK (1) | HK102989A (enExample) |
| HU (1) | HU187913B (enExample) |
| IE (1) | IE55111B1 (enExample) |
| IL (1) | IL68360A (enExample) |
| NO (1) | NO160444C (enExample) |
| NZ (1) | NZ204321A (enExample) |
| PH (1) | PH18454A (enExample) |
| PT (1) | PT76745B (enExample) |
| ZA (1) | ZA832637B (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988000192A1 (en) * | 1986-06-26 | 1988-01-14 | Warner-Lambert Company | 5-SUBSTITUTED PYRAZOLO[4,3-d]PYRIMIDIN-7-ONES |
| KR20070118068A (ko) * | 2004-11-23 | 2007-12-13 | 레디 유에스 테라퓨틱스 인코포레이티드 | 신규의 이원 헤테로고리 화합물, 그 제조방법 및 이들을포함하는 조성물 |
| WO2006133261A2 (en) | 2005-06-06 | 2006-12-14 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2008070095A1 (en) | 2006-12-05 | 2008-06-12 | Intra-Cellular Therapies, Inc. | Novel uses |
| EA201170769A1 (ru) | 2008-12-06 | 2012-02-28 | Интра-Селлулар Терапиз, Инк. | Органические соединения |
| EP2434895A4 (en) | 2009-05-13 | 2013-08-07 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| US9763948B2 (en) | 2010-05-31 | 2017-09-19 | Intra-Cellular Therapies, Inc. | PDE1 inhibitory compounds and methods |
| AU2012244550C1 (en) * | 2011-04-21 | 2017-06-22 | Origenis Gmbh | Pyrazolo [4, 3-d] pyrimidines useful as kinase inhibitors |
| WO2014060112A1 (en) | 2012-10-19 | 2014-04-24 | Origenis Gmbh | Pyrazolo[4,3-d]pyrimidines as kinase inhibitors |
| EP2956141A4 (en) | 2013-02-17 | 2016-10-26 | Intra Cellular Therapies Inc | NEW USES |
| DK2970279T3 (da) | 2013-03-15 | 2020-11-30 | Intra Cellular Therapies Inc | Organiske forbindelser |
| ES2717688T3 (es) | 2013-03-15 | 2019-06-24 | Intra Cellular Therapies Inc | Inhibidores de la PDE1 para uso en el tratamiento y/o prevención de lesiones de SNC, y enfermedades, trastornos o lesiones de SNP |
| DK3157926T3 (da) | 2014-06-20 | 2019-08-19 | Intra Cellular Therapies Inc | Organiske forbindelser |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| US10131671B2 (en) | 2014-08-07 | 2018-11-20 | Intra-Cellular Therapies, Inc. | Organic compounds |
| CA2961212C (en) | 2014-09-17 | 2024-02-06 | Intra-Cellular Therapies, Inc. | Compounds and methods |
| US10682354B2 (en) | 2016-03-28 | 2020-06-16 | Intra-Cellular Therapies, Inc. | Compositions and methods |
| US11291666B2 (en) | 2016-09-12 | 2022-04-05 | Intra-Cellular Therapies, Inc. | Uses |
| JP7401442B2 (ja) | 2018-01-31 | 2023-12-19 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規使用 |
| US12410175B2 (en) | 2019-09-03 | 2025-09-09 | Intra-Cellular Therapies, Inc. | Compounds |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH422807A (de) * | 1963-08-16 | 1966-10-31 | Wander Ag Dr A | Verfahren zur Herstellung von Imidazo- und Pyrimidochinazolinen |
| US3313815A (en) * | 1964-05-04 | 1967-04-11 | Sterling Drug Inc | 8-chloropyrazolo-[1, 5-c]quinazoline derivatives and methods of preparing same |
| US3309369A (en) * | 1966-04-11 | 1967-03-14 | Wander Ag Dr A | Imidazo- and pyrimido-quinazolines |
| US3594379A (en) * | 1968-09-16 | 1971-07-20 | Sandoz Ag | 2,3-dihydroimidazo(1,2-c)quinazolines |
| DE2058501A1 (de) * | 1970-11-27 | 1972-05-31 | Bayer Ag | Verfahren zur Herstellung von neuen N-verbrueckten bicyclischen Heteroaromaten |
| GB1347493A (en) * | 1971-02-11 | 1974-02-27 | Aspro Nicholas Ltd | Benzazine derivatives |
| US3984556A (en) * | 1973-01-19 | 1976-10-05 | Sandoz, Inc. | Alkyl-substituted-tricyclic quinazolinones for lowering blood pressure |
| JPS516993A (en) * | 1974-07-05 | 1976-01-20 | Dainippon Pharmaceutical Co | Adeninjudotaino seiho |
| JPS5398997A (en) * | 1977-02-09 | 1978-08-29 | Sumitomo Chem Co Ltd | Fused pyridine derivertives and process for their preparation |
| US4247553A (en) * | 1977-10-31 | 1981-01-27 | The Upjohn Company | Methods of treating psychosis |
| US4206123A (en) * | 1977-10-31 | 1980-06-03 | Mccall John M | Isothiochroman |
| US4250181A (en) * | 1977-10-31 | 1981-02-10 | The Upjohn Company | Methods of treating psychosis |
| US4192803A (en) * | 1978-09-15 | 1980-03-11 | American Cyanamid Company | 5H-Pyrrolo[2,1-c][1,4]benzodiazepine derivatives |
| DK460879A (da) * | 1978-11-01 | 1980-05-02 | Wellcome Found | Fremgangsmaade til fremstilling af 9-(3-(3,5-cisdimethylpiperazino)propyl)carbazol et salt heraf eller et solvat af et saadant salt |
| CH643263A5 (de) * | 1979-05-11 | 1984-05-30 | Sandoz Ag | Benzodiazepine, ihre herstellung und verwendung. |
| HU178523B (en) * | 1979-05-18 | 1982-05-28 | Egyt Gyogyszervegyeszeti Gyar | Process for preparing new pyrazolo-quinazoline derivatives |
| US4230707A (en) * | 1979-08-27 | 1980-10-28 | Warner-Lambert Company | Oxo-pyrido[1,2-a]thienopyrimidine compounds and methods for their production |
| US4358456A (en) * | 1980-05-03 | 1982-11-09 | John Wyeth & Brother Limited | Antipsychotic piperidinomethyl-indole derivatives |
| US4396770A (en) * | 1982-04-09 | 1983-08-02 | Hoechst-Roussel Pharmaceuticals Inc. | 1-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxy-4-phenylpiperidines |
| US4352811A (en) * | 1981-11-12 | 1982-10-05 | Hoechst-Roussel Pharmaceuticals Inc. | 3-(1-Substituted-4-piperidyl)-1,2-benzisoxazoles |
| US4415581A (en) * | 1982-04-09 | 1983-11-15 | Hoechst-Roussel Pharmaceuticals Inc. | 1-[3-6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-hydroxy-4-phenylpiperidines to treat psychoses |
| US4409230A (en) * | 1982-04-09 | 1983-10-11 | Hoechst-Roussel Pharmaceuticals Inc. | Pharmaceutical compositions and methods employing 8-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-1-phenyl-1,3,8-triazaspiro-[4.]decan-4-one and derivatives thereof |
| US4390544A (en) * | 1982-04-09 | 1983-06-28 | Hoechst-Roussel Pharmaceuticals Inc. | {1-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2-oxo-1-benzimidazolinyl}p |
| US4374245A (en) * | 1982-04-09 | 1983-02-15 | Hoechst-Roussel Pharmaceuticals Inc. | 8-[3-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one |
| US5059699A (en) * | 1990-08-28 | 1991-10-22 | Virginia Tech Intellectual Properties, Inc. | Water soluble derivatives of taxol |
-
1982
- 1982-05-24 US US06/381,484 patent/US4469868A/en not_active Expired - Fee Related
-
1983
- 1983-04-11 IE IE822/83A patent/IE55111B1/en unknown
- 1983-04-12 AU AU13427/83A patent/AU553708B2/en not_active Ceased
- 1983-04-12 IL IL68360A patent/IL68360A/xx unknown
- 1983-04-14 ZA ZA832637A patent/ZA832637B/xx unknown
- 1983-04-19 CA CA000426194A patent/CA1210393A/en not_active Expired
- 1983-05-13 EP EP83302715A patent/EP0095289B1/en not_active Expired
- 1983-05-13 DE DE8383302715T patent/DE3368635D1/de not_active Expired
- 1983-05-13 AT AT83302715T patent/ATE24510T1/de not_active IP Right Cessation
- 1983-05-18 FI FI831742A patent/FI74012C/fi not_active IP Right Cessation
- 1983-05-18 PH PH28929A patent/PH18454A/en unknown
- 1983-05-20 NO NO831792A patent/NO160444C/no unknown
- 1983-05-20 DK DK227183A patent/DK161968C/da not_active IP Right Cessation
- 1983-05-23 NZ NZ204321A patent/NZ204321A/en unknown
- 1983-05-23 ES ES522617A patent/ES522617A0/es active Granted
- 1983-05-23 PT PT76745A patent/PT76745B/pt unknown
- 1983-05-23 KR KR1019830002255A patent/KR870000931B1/ko not_active Expired
- 1983-05-23 HU HU831811A patent/HU187913B/hu not_active IP Right Cessation
- 1983-05-23 GR GR71429A patent/GR79262B/el unknown
- 1983-05-24 JP JP58090133A patent/JPS58210087A/ja active Granted
-
1984
- 1984-02-01 ES ES529373A patent/ES8506004A1/es not_active Expired
- 1984-02-01 ES ES529372A patent/ES8506019A1/es not_active Expired
- 1984-02-01 ES ES529371A patent/ES529371A0/es active Granted
-
1985
- 1985-06-26 AR AR300815A patent/AR240941A1/es active
-
1989
- 1989-12-28 HK HK1029/89A patent/HK102989A/xx unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |