CA1210393A - Alkylimidazo¬1,2-c|pyrazolo¬3,4-e|pyrimidines as antipsychotic agents - Google Patents
Alkylimidazo¬1,2-c|pyrazolo¬3,4-e|pyrimidines as antipsychotic agentsInfo
- Publication number
- CA1210393A CA1210393A CA000426194A CA426194A CA1210393A CA 1210393 A CA1210393 A CA 1210393A CA 000426194 A CA000426194 A CA 000426194A CA 426194 A CA426194 A CA 426194A CA 1210393 A CA1210393 A CA 1210393A
- Authority
- CA
- Canada
- Prior art keywords
- general formula
- compound
- defined above
- pyrazolo
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000000164 antipsychotic agent Substances 0.000 title abstract description 3
- 150000003230 pyrimidines Chemical class 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 193
- 239000000203 mixture Substances 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 81
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 99
- 230000008569 process Effects 0.000 claims description 61
- 238000010992 reflux Methods 0.000 claims description 34
- 239000000126 substance Substances 0.000 claims description 31
- 150000002905 orthoesters Chemical class 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000002140 halogenating effect Effects 0.000 claims description 5
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 claims description 4
- 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 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- ZSAHBIKBYRIJNX-UHFFFAOYSA-N 1,3,5,8-tetramethyl-1h-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidine Chemical compound C12=NC(C)=CN2C(C)=NC2=C1N(C)N=C2C ZSAHBIKBYRIJNX-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 3
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- OLDNXXDKTXYRCS-UHFFFAOYSA-N chembl139730 Chemical compound CC1C(C)N=C2N1C(C)=NC1=C2N(C)N=C1C OLDNXXDKTXYRCS-UHFFFAOYSA-N 0.000 claims description 3
- SPSOQRMOBBYQBC-UHFFFAOYSA-N chembl139765 Chemical compound C12=NCC(C)N2C(CC)=NC2=C1N(C)N=C2C SPSOQRMOBBYQBC-UHFFFAOYSA-N 0.000 claims description 3
- UOTREFZLVOZIDS-UHFFFAOYSA-N chembl336472 Chemical compound N=1C(C)CN2C=1C(N(N=C1C)C)=C1N=C2C1CC1 UOTREFZLVOZIDS-UHFFFAOYSA-N 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- CGUNHXWKUSRCQX-UHFFFAOYSA-N 3,5,8-trimethyl-3,4,7,9,12-pentazatricyclo[7.3.0.02,6]dodeca-1(12),2(6),4,7-tetraene Chemical compound C12=NCCN2C(C)=NC2=C1N(C)N=C2C CGUNHXWKUSRCQX-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- YFAVYALYCRERKH-UHFFFAOYSA-N 7,8-dihydro-8-ethyl-1,3,5-trimethyl-1h-imidazo(1,2-c)pyrazolo(3,4-e)pyrimidine Chemical compound CC1=NN(C)C2=C1N=C(C)N1C2=NC(CC)C1 YFAVYALYCRERKH-UHFFFAOYSA-N 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
- KQZHDUGJLSEGCD-UHFFFAOYSA-N chembl143378 Chemical compound C12=NC(C)CN2C=NC2=C1N(C)N=C2C KQZHDUGJLSEGCD-UHFFFAOYSA-N 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- KHLCQAWUFPIFRY-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 Chemical compound CC1=NN(C)C2=C1N=C(C)N1C2=NC(C(C)C)C1 KHLCQAWUFPIFRY-UHFFFAOYSA-N 0.000 claims 1
- AWZFEOKHHUJCEK-UHFFFAOYSA-N 5,8,11-trimethyl-3-(2,2,2-trifluoroethyl)-3,4,7,9,12-pentazatricyclo[7.3.0.02,6]dodeca-1(12),2(6),4,7-tetraene Chemical compound CC1=NN(CC(F)(F)F)C2=C1N=C(C)N1C2=NC(C)C1 AWZFEOKHHUJCEK-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 claims 1
- GPBHMJQWDYNCBP-UHFFFAOYSA-N 8-ethyl-3,5,11-trimethyl-3,4,7,9,12-pentazatricyclo[7.3.0.02,6]dodeca-1(12),2(6),4-triene Chemical compound C12=NC(C)CN2C(CC)NC2=C1N(C)N=C2C GPBHMJQWDYNCBP-UHFFFAOYSA-N 0.000 claims 1
- GJCGYZHZLVGGFO-UHFFFAOYSA-N chembl140096 Chemical compound N1=C(C)N2C(C)=C(C)N=C2C2=C1C(C)=NN2C GJCGYZHZLVGGFO-UHFFFAOYSA-N 0.000 claims 1
- QHJZUFKYZMITNR-UHFFFAOYSA-N chembl141140 Chemical compound C12=NCCN2C=NC2=C1N(C)N=C2C QHJZUFKYZMITNR-UHFFFAOYSA-N 0.000 claims 1
- KEPDTSPQAAEBIC-UHFFFAOYSA-N chembl141163 Chemical compound C12=NC(C)CN2C(CC)=NC2=C1N(C)N=C2C KEPDTSPQAAEBIC-UHFFFAOYSA-N 0.000 claims 1
- PJHFGEPWJCOHCR-UHFFFAOYSA-N chembl141914 Chemical compound C12=NCCN2C(CC)=NC2=C1N(C)N=C2C PJHFGEPWJCOHCR-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
- ZTXGGKAKTFNRJE-UHFFFAOYSA-N chembl143487 Chemical compound C12=NC(C)CN2C(CC)=NC2=C1N(CC)N=C2C ZTXGGKAKTFNRJE-UHFFFAOYSA-N 0.000 claims 1
- RFHURMNANNCRKS-UHFFFAOYSA-N chembl359452 Chemical compound C12=NC(C)(C)CN2C(C)=NC2=C1N(C)N=C2C RFHURMNANNCRKS-UHFFFAOYSA-N 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 75
- 239000000243 solution Substances 0.000 description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 58
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 38
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 21
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 20
- 239000000908 ammonium hydroxide Substances 0.000 description 20
- 229940093499 ethyl acetate Drugs 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- 235000009518 sodium iodide Nutrition 0.000 description 12
- -1 amino acid ester Chemical class 0.000 description 11
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical group ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 150000001408 amides Chemical group 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 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 5
- 241001465754 Metazoa Species 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001311 chemical methods and process Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 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
- 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 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 150000001414 amino alcohols Chemical class 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 3
- 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 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 230000008018 melting Effects 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
- 239000002244 precipitate Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 2
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- OZYRFKZCHSSRST-UHFFFAOYSA-N 1,3,5-trimethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C)N=C2C(C)=NN(C)C2=C1O OZYRFKZCHSSRST-UHFFFAOYSA-N 0.000 description 2
- GQGGWKXTANDKPJ-UHFFFAOYSA-N 1,5-diethyl-3-methyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCC1=NC(O)=C2N(CC)N=C(C)C2=N1 GQGGWKXTANDKPJ-UHFFFAOYSA-N 0.000 description 2
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 2
- JZIBSZJXVQEBEU-UHFFFAOYSA-N 2,5-dimethyl-4-nitropyrazole-3-carboxamide Chemical compound CC1=NN(C)C(C(N)=O)=C1[N+]([O-])=O JZIBSZJXVQEBEU-UHFFFAOYSA-N 0.000 description 2
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 2
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 2
- FPRCATJFABPUHJ-UHFFFAOYSA-N 4-amino-2-ethyl-5-methylpyrazole-3-carboxamide Chemical compound CCN1N=C(C)C(N)=C1C(N)=O FPRCATJFABPUHJ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- HFTQEQBISBYBIA-UHFFFAOYSA-N 5-methyl-4-nitro-2-(2,2,2-trifluoroethyl)pyrazole-3-carboxamide Chemical compound CC1=NN(CC(F)(F)F)C(C(N)=O)=C1[N+]([O-])=O HFTQEQBISBYBIA-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- OEMZJXCVHOFGIL-UHFFFAOYSA-N 7-chloro-1-ethyl-3,5-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound CC1=NC(Cl)=C2N(CC)N=C(C)C2=N1 OEMZJXCVHOFGIL-UHFFFAOYSA-N 0.000 description 2
- UWCFVXWCQGIPER-UHFFFAOYSA-N 7-chloro-5-ethyl-1,3-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound CCC1=NC(Cl)=C2N(C)N=C(C)C2=N1 UWCFVXWCQGIPER-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229920003091 Methocel™ Polymers 0.000 description 2
- 229910017974 NH40H Inorganic materials 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000005698 chloropyrimidines Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 230000006742 locomotor activity Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VVRVZXIIKFLHIH-RUCXOUQFSA-N (2S)-2-aminopropan-1-ol Chemical compound C[C@H](N)CO.C[C@H](N)CO VVRVZXIIKFLHIH-RUCXOUQFSA-N 0.000 description 1
- YLGDJVRFWMZYCX-ZCFIWIBFSA-N (2r)-2-[(1,3,5-trimethylpyrazolo[4,3-d]pyrimidin-7-yl)amino]propan-1-ol Chemical compound OC[C@@H](C)NC1=NC(C)=NC2=C1N(C)N=C2C YLGDJVRFWMZYCX-ZCFIWIBFSA-N 0.000 description 1
- SUZZEFBECOIRIY-NUBCRITNSA-N (2s)-2-amino-3-methylbutan-1-ol;2-amino-3-methylbutan-1-ol Chemical compound CC(C)C(N)CO.CC(C)[C@H](N)CO SUZZEFBECOIRIY-NUBCRITNSA-N 0.000 description 1
- OPCJOXGBLDJWRM-UHFFFAOYSA-N 1,2-diamino-2-methylpropane Chemical compound CC(C)(N)CN OPCJOXGBLDJWRM-UHFFFAOYSA-N 0.000 description 1
- LYSOMTBDUTZQQH-UHFFFAOYSA-N 1,3-dimethyl-5-(5-methyl-4,5-dihydro-1h-imidazol-2-yl)-4-nitropyrazole Chemical compound CC1CNC(C=2N(N=C(C)C=2[N+]([O-])=O)C)=N1 LYSOMTBDUTZQQH-UHFFFAOYSA-N 0.000 description 1
- FHAKAKPNZSTZAL-UHFFFAOYSA-N 1,3-dimethyl-7-(2-methylaziridin-1-yl)-5-propan-2-ylpyrazolo[4,3-d]pyrimidine Chemical compound C=12N(C)N=C(C)C2=NC(C(C)C)=NC=1N1CC1C FHAKAKPNZSTZAL-UHFFFAOYSA-N 0.000 description 1
- GYKXLWGVAGSSGQ-UHFFFAOYSA-N 1,3-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C(C)=NN(C)C2=C1 GYKXLWGVAGSSGQ-UHFFFAOYSA-N 0.000 description 1
- JFZSDNLQDTYVEE-UHFFFAOYSA-N 1,4-dihydropyrazolo[4,3-d]pyrimidin-7-one Chemical compound O=C1N=CNC2=C1NN=C2 JFZSDNLQDTYVEE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- HYSDHMFCQHHFGV-UHFFFAOYSA-N 2,5-dimethyl-4-nitropyrazole-3-carbonitrile Chemical compound CC1=NN(C)C(C#N)=C1[N+]([O-])=O HYSDHMFCQHHFGV-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- WSPMZTMQBFDGEB-UHFFFAOYSA-N 2-[(1-ethyl-3,5-dimethylpyrazolo[4,3-d]pyrimidin-7-yl)amino]ethanol Chemical compound CC1=NC(NCCO)=C2N(CC)N=C(C)C2=N1 WSPMZTMQBFDGEB-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- JCBPETKZIGVZRE-UHFFFAOYSA-N 2-aminobutan-1-ol Chemical compound CCC(N)CO JCBPETKZIGVZRE-UHFFFAOYSA-N 0.000 description 1
- VOPWRBRGIYIIDL-UHFFFAOYSA-N 2-ethyl-5-methyl-4-nitropyrazole-3-carbonyl chloride Chemical compound CCN1N=C(C)C([N+]([O-])=O)=C1C(Cl)=O VOPWRBRGIYIIDL-UHFFFAOYSA-N 0.000 description 1
- FKHAHNSKRYEMMY-UHFFFAOYSA-N 2-ethyl-5-methyl-4-nitropyrazole-3-carboxamide Chemical compound CCN1N=C(C)C([N+]([O-])=O)=C1C(N)=O FKHAHNSKRYEMMY-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- SVJUYRABGPPHJJ-UHFFFAOYSA-N 3,5,7-trimethyl-2h-pyrazolo[4,3-d]pyrimidine Chemical compound CC1=NC(C)=NC2=C(C)NN=C21 SVJUYRABGPPHJJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- CLDBFOAIKANZJK-UHFFFAOYSA-N 3,5-dimethyl-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one Chemical compound CC=1N=C(C2=C(N1)C(=NN2)C)O CLDBFOAIKANZJK-UHFFFAOYSA-N 0.000 description 1
- OLYWGXUJESDUAC-UHFFFAOYSA-N 3-aminobutan-2-one Chemical compound CC(N)C(C)=O OLYWGXUJESDUAC-UHFFFAOYSA-N 0.000 description 1
- URQJLEHTWPIESE-UHFFFAOYSA-N 3-chloro-2h-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C(Cl)=NNC2=C1 URQJLEHTWPIESE-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- MAEONVQIUBKEIF-UHFFFAOYSA-N 4-amino-2,5-dimethylpyrazole-3-carboxamide Chemical compound CC1=NN(C)C(C(N)=O)=C1N MAEONVQIUBKEIF-UHFFFAOYSA-N 0.000 description 1
- BLSWMOIYTDLKTA-UHFFFAOYSA-N 4-nitro-1h-pyrazole-5-carbonitrile Chemical class [O-][N+](=O)C=1C=NNC=1C#N BLSWMOIYTDLKTA-UHFFFAOYSA-N 0.000 description 1
- YXHDKOBPOQJSEK-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-1,3-dimethyl-4-nitropyrazole Chemical compound CC1=NN(C)C(C=2NCCN=2)=C1[N+]([O-])=O YXHDKOBPOQJSEK-UHFFFAOYSA-N 0.000 description 1
- FEHDQUSCGYPXKY-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-1,3-dimethylpyrazol-4-amine Chemical compound CC1=NN(C)C(C=2NCCN=2)=C1N FEHDQUSCGYPXKY-UHFFFAOYSA-N 0.000 description 1
- QLZOKMCVTKBQTI-UHFFFAOYSA-N 5-(4,5-dihydro-1h-imidazol-2-yl)-1h-pyrazol-4-amine Chemical class C1=NNC(C=2NCCN=2)=C1N QLZOKMCVTKBQTI-UHFFFAOYSA-N 0.000 description 1
- IYWJMHNBXPFBQQ-UHFFFAOYSA-N 5-(4,5-dimethyl-4,5-dihydro-1h-imidazol-2-yl)-1,3-dimethylpyrazol-4-amine Chemical compound CC1C(C)NC(C=2N(N=C(C)C=2N)C)=N1 IYWJMHNBXPFBQQ-UHFFFAOYSA-N 0.000 description 1
- NNULKOKAMSLHID-UHFFFAOYSA-N 5-cyclopropyl-1,3-dimethyl-4-(2-methylaziridin-1-yl)-2h-pyrazolo[4,3-d]pyrimidine Chemical compound CC1CN1N1C(C2CC2)=NC=C2N(C)NC(C)=C21 NNULKOKAMSLHID-UHFFFAOYSA-N 0.000 description 1
- NBBPVYPHTGPTAA-UHFFFAOYSA-N 5-ethyl-1,3-dimethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCC1=NC(O)=C2N(C)N=C(C)C2=N1 NBBPVYPHTGPTAA-UHFFFAOYSA-N 0.000 description 1
- STKSMUMKQNNHCS-UHFFFAOYSA-N 5-methyl-2-(2,2,2-trifluoroethyl)pyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(CC(F)(F)F)N=1 STKSMUMKQNNHCS-UHFFFAOYSA-N 0.000 description 1
- OWMIBOBSZYIGPL-UHFFFAOYSA-N 5-methyl-4-nitro-2-propylpyrazole-3-carbonyl chloride Chemical compound CCCN1N=C(C)C([N+]([O-])=O)=C1C(Cl)=O OWMIBOBSZYIGPL-UHFFFAOYSA-N 0.000 description 1
- QYNNDXVLIVEGSC-UHFFFAOYSA-N 5-methyl-4-nitro-2-propylpyrazole-3-carboxamide Chemical compound CCCN1N=C(C)C([N+]([O-])=O)=C1C(N)=O QYNNDXVLIVEGSC-UHFFFAOYSA-N 0.000 description 1
- MZRUFMBFIKGOAL-UHFFFAOYSA-N 5-nitro-1h-pyrazole Chemical class [O-][N+](=O)C1=CC=NN1 MZRUFMBFIKGOAL-UHFFFAOYSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- ZXWYDMNSDIDMQI-UHFFFAOYSA-N 7-(aziridin-1-yl)-1-ethyl-3,5-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound C=12N(CC)N=C(C)C2=NC(C)=NC=1N1CC1 ZXWYDMNSDIDMQI-UHFFFAOYSA-N 0.000 description 1
- HLDZNBHLRMXXHH-UHFFFAOYSA-N 7-(aziridin-1-yl)-5-ethyl-1,3-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound C=12N(C)N=C(C)C2=NC(CC)=NC=1N1CC1 HLDZNBHLRMXXHH-UHFFFAOYSA-N 0.000 description 1
- YHRMDYCTOBUEIB-UHFFFAOYSA-N 7-chloro-1,3-dimethyl-5-propan-2-ylpyrazolo[4,3-d]pyrimidine Chemical compound CC(C)C1=NC(Cl)=C2N(C)N=C(C)C2=N1 YHRMDYCTOBUEIB-UHFFFAOYSA-N 0.000 description 1
- UDAJKLRGHKQVTN-UHFFFAOYSA-N 7-chloro-1,3-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C(C)=NN(C)C2=C1Cl UDAJKLRGHKQVTN-UHFFFAOYSA-N 0.000 description 1
- LHDTXDSGFSJVQF-UHFFFAOYSA-N 7-chloro-5-cyclopropyl-1,3-dimethylpyrazolo[4,3-d]pyrimidine Chemical compound N1=C2C(C)=NN(C)C2=C(Cl)N=C1C1CC1 LHDTXDSGFSJVQF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100030704 Interleukin-21 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910020667 PBr3 Inorganic materials 0.000 description 1
- 229910019201 POBr3 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- PQUGCKBLVKJMNT-UHFFFAOYSA-N SC560 Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(C(F)(F)F)=N1 PQUGCKBLVKJMNT-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Chemical group 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 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
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 229940047889 isobutyramide Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ZOEJGZDMVLLUJW-UHFFFAOYSA-N n-(5-cyano-1,3-dimethylpyrazol-4-yl)formamide Chemical compound CC1=NN(C)C(C#N)=C1NC=O ZOEJGZDMVLLUJW-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
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000028570 negative regulation of locomotion Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 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
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000006201 parenteral dosage form 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
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-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
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- GDYMWVGEHTVXIT-UHFFFAOYSA-N pyrano[3,2-c]pyrazole-3-carboximidamide Chemical compound C1=COC2=C(C(=N)N)N=NC2=C1 GDYMWVGEHTVXIT-UHFFFAOYSA-N 0.000 description 1
- DSKLYHDHQJANOE-UHFFFAOYSA-N pyrazolo[4,3-d]pyrimidine Chemical compound C1=NC=N[C]2C=NN=C21 DSKLYHDHQJANOE-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 102200014657 rs121434437 Human genes 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 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
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US381,484 | 1982-05-24 | ||
| 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 |
|---|---|
| CA1210393A true CA1210393A (en) | 1986-08-26 |
Family
ID=23505215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000426194A Expired CA1210393A (en) | 1982-05-24 | 1983-04-19 | Alkylimidazo¬1,2-c|pyrazolo¬3,4-e|pyrimidines as antipsychotic agents |
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) | ES8407051A1 (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 |
| US20060128729A1 (en) * | 2004-11-23 | 2006-06-15 | Manojit Pal | Novel bicyclic heterocyclic compounds, process for their preparation and compositions containing them |
| CN101248050B (zh) | 2005-06-06 | 2013-07-17 | 武田药品工业株式会社 | 有机化合物 |
| US9006258B2 (en) | 2006-12-05 | 2015-04-14 | Intra-Cellular Therapies, Inc. | Method of treating female sexual dysfunction with a PDE1 inhibitor |
| EP2358204B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| JP5911854B2 (ja) | 2010-05-31 | 2016-04-27 | 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 |
| JP6222776B2 (ja) * | 2011-04-21 | 2017-11-01 | オリゲニス ゲーエムベーハーＯｒｉｇｅｎｉｓ Ｇｍｂｈ | キナ−ゼ・インヒビタ−として有用なピラゾロ［４，３−ｄ］ピリミジン |
| US9637491B2 (en) | 2012-10-19 | 2017-05-02 | Origenis Gmbh | Pyrazolo[4,3-D]pyrimidines as kinase inhibitors |
| US9801882B2 (en) | 2013-02-17 | 2017-10-31 | Intra-Cellular Therapies, Inc. | Phosphodiesterase-1 inhibitors and their use in treatment of cardiovascular diseases |
| ES2836129T3 (es) | 2013-03-15 | 2021-06-24 | Intra Cellular Therapies Inc | Compuestos orgánicos |
| EP2968338B1 (en) | 2013-03-15 | 2019-01-09 | Intra-Cellular Therapies, Inc. | Pde1 inhibitors for use in the treatment and/or prevention of cns injuries, and pns diseases, disorders or injuries |
| US9884872B2 (en) | 2014-06-20 | 2018-02-06 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2745819T3 (es) | 2014-08-07 | 2020-03-03 | Intra Cellular Therapies Inc | Derivados de imidazo[1,2-a]-pirazolo[4,3-e]-pirimidin-4-ona con actividad inhibidora de la PDE1 |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| EP3193878B1 (en) | 2014-09-17 | 2021-01-06 | Intra-Cellular Therapies, Inc. | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | 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． | 新規組成物および方法 |
| JP7134168B6 (ja) | 2016-09-12 | 2024-02-02 | 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 |
| EP3746081A4 (en) | 2018-01-31 | 2021-10-27 | Intra-Cellular Therapies, Inc. | Novel uses |
| EP4413980A3 (en) | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel 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 |
| US4250181A (en) * | 1977-10-31 | 1981-02-10 | The Upjohn Company | Methods of treating psychosis |
| US4206123A (en) * | 1977-10-31 | 1980-06-03 | Mccall John M | Isothiochroman |
| US4247553A (en) * | 1977-10-31 | 1981-01-27 | 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 |
| MC1286A1 (fr) * | 1978-11-01 | 1980-07-22 | Wellcome Found | Preparation de composes heterocycliques utilisables en pharmacie et de medicaments contenant ces composes |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 IL IL68360A patent/IL68360A/xx unknown
- 1983-04-12 AU AU13427/83A patent/AU553708B2/en not_active Ceased
- 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 AT AT83302715T patent/ATE24510T1/de not_active IP Right Cessation
- 1983-05-13 DE DE8383302715T patent/DE3368635D1/de not_active Expired
- 1983-05-18 PH PH28929A patent/PH18454A/en unknown
- 1983-05-18 FI FI831742A patent/FI74012C/fi not_active IP Right Cessation
- 1983-05-20 DK DK227183A patent/DK161968C/da not_active IP Right Cessation
- 1983-05-20 NO NO831792A patent/NO160444C/no unknown
- 1983-05-23 ES ES522617A patent/ES8407051A1/es not_active Expired
- 1983-05-23 KR KR1019830002255A patent/KR870000931B1/ko not_active Expired
- 1983-05-23 NZ NZ204321A patent/NZ204321A/en unknown
- 1983-05-23 GR GR71429A patent/GR79262B/el unknown
- 1983-05-23 PT PT76745A patent/PT76745B/pt unknown
- 1983-05-23 HU HU831811A patent/HU187913B/hu not_active IP Right Cessation
- 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/ES529372A0/es active Granted
- 1984-02-01 ES ES529371A patent/ES8506315A1/es not_active Expired
-
1985
- 1985-06-26 AR AR300815A patent/AR240941A1/es active
-
1989
- 1989-12-28 HK HK1029/89A patent/HK102989A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1210393A (en) | Alkylimidazo¬1,2-c|pyrazolo¬3,4-e|pyrimidines as antipsychotic agents | |
| DE60219672T2 (de) | Imidazopyridine, -pyrimidine und -triazine als gaba-a alpha 5 rezeptor subtyp liganden zur verbesserung kognitiver eigenschaften | |
| JP2001514260A (ja) | Ｃｎｓおよびストレス関連疾患の治療に有用な、副腎皮質刺激ホルモン放出ホルモン拮抗剤としての、複素環基が置換した環縮合ピリジン類およびピリミジン類 | |
| AU607469B2 (en) | Imadazo-quinazolines, imidazo (1-5a) pyrido (2,3-e) pyrazines, imidazo quinolines and imidazo quinoxalines | |
| WO1995001356A1 (en) | 1,2,4-TRIAZOLO[1,5-c]PYRIMIDINE HETEROCYCLIC ANALOGUES HAVING ANTAGONISTIC ACTIVITY ON ADENOSINE A2 RECEPTOR | |
| CA1067491A (en) | Diazepine derivatives | |
| US5231094A (en) | Triazolopyrimidines which are angiotensin II receptor antagonists and pharmaceutical compositions in which they are present | |
| US4124764A (en) | Meso-ionic didehydro derivatives of 1,7-dehydro-1-substituted-3H-pyrazolo[4,]-1,2,4-triazolo[4,3-c]pyrimidine-3-thiones and 3-ones | |
| AU627181B2 (en) | Imidazoquinoxaline compounds and their preparation and use | |
| US4269980A (en) | (Substituted-phenyl)-1,2,4-triazolo[4,3-c]pyrimidines and (substituted-phenyl)-1,2,4-triazolo[1,5-c]pyrimidines | |
| EP0163240A2 (en) | Dihydroimidazo[1,2-a]pyrimidine derivatives, methods of preparing said compounds and pharmaceutical compositions constaining said compounds | |
| US5512590A (en) | 5,6-dihydro-4h-imidazo 2',1':2,3!imidazo- 4,5,1-ij!quinoline and 4,5-dihydroimidazo- 1,2-a!pyrolo 1,2,3-cd!benzimidazole derivatives, their preparation and application in therapeutics | |
| US3993650A (en) | Pyrrolo [3,4-d] pyrimidines | |
| CA1037959A (en) | 3(2)SUBSTITUTED 4-(.alpha.-AMINO-.alpha. PHENYL-O-TOLYL)4H-1,2,4-TRIAZOLES AND IMIDAZOLES | |
| US4075202A (en) | S-triazolo-1,5-benzodiazpine-4-ones | |
| US4016165A (en) | Triazino benzodiazepines | |
| US3772230A (en) | Polyhydro-imidazo(1,5-a)pyrimidine-3(2h)-thione and pyrido(1,2-c)pyrimidine-1-thione | |
| PL102153B1 (pl) | A process of producing new derivatives of 2-/2-phthalimidomethylo/imidazolylo-1/-benzophenone | |
| JPS61227584A (ja) | ポリアザ複素環誘導体 | |
| EP0573659B1 (en) | Pyrazolothiazolopyrimidine derivative | |
| US5021411A (en) | Imidazodiazepine derivatives | |
| US4001261A (en) | Process for the production of 1-[(dimethylamino)methyl]-6-phenyl-4H-imidazo[1,2-a][1,4]-benzodiazepine | |
| US4075221A (en) | Process for preparing triazolobenzodiazepines | |
| US5260298A (en) | Imidazatriazoloquinazoline compounds and their use | |
| Massa et al. | Research on nitrogen heterocyclic compounds. XV. Synthesis of 1H, 4H‐pyrazolo [4, 3f] pyrrolo [1, 2‐a][1, 4] diazepine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |