CA2043640A1 - Pharmacologically active cns compounds - Google Patents
Pharmacologically active cns compoundsInfo
- Publication number
- CA2043640A1 CA2043640A1 CA002043640A CA2043640A CA2043640A1 CA 2043640 A1 CA2043640 A1 CA 2043640A1 CA 002043640 A CA002043640 A CA 002043640A CA 2043640 A CA2043640 A CA 2043640A CA 2043640 A1 CA2043640 A1 CA 2043640A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrimidine
- amino
- compound
- trichlorophenyl
- piperazinyl
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 151
- -1 nitro, amino Chemical group 0.000 claims abstract description 51
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 238000011321 prophylaxis Methods 0.000 claims abstract description 17
- 125000005843 halogen group Chemical group 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 229930195712 glutamate Natural products 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 10
- 239000002858 neurotransmitter agent Substances 0.000 claims abstract description 10
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 208000015114 central nervous system disease Diseases 0.000 claims description 13
- 239000012458 free base Substances 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 208000025966 Neurological disease Diseases 0.000 claims description 5
- VFQQXOLBMUZRLB-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 VFQQXOLBMUZRLB-UHFFFAOYSA-N 0.000 claims description 4
- TUQWAURGVMOVKD-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=NC=C(C=2C=C(Cl)C=C(Cl)C=2)C(N)=N1 TUQWAURGVMOVKD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 claims description 3
- NWAGOKSOHKBDPE-UHFFFAOYSA-N 5-(4-amino-3,5-dichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(N)C(Cl)=C1 NWAGOKSOHKBDPE-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- QADLBUHAWRBSDH-UHFFFAOYSA-N 2-(4-propan-2-ylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(C(C)C)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 QADLBUHAWRBSDH-UHFFFAOYSA-N 0.000 claims description 2
- XTRPWKSHYSVUOO-UHFFFAOYSA-N 5-(3,5-dichloro-2-nitrophenyl)-6-methylpyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1[N+]([O-])=O XTRPWKSHYSVUOO-UHFFFAOYSA-N 0.000 claims description 2
- XMRKIEQREYNGOB-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-methylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 XMRKIEQREYNGOB-UHFFFAOYSA-N 0.000 claims description 2
- KXXCUIBIORBOGC-UHFFFAOYSA-N 5-(4-amino-3,5-dichlorophenyl)-6-(trifluoromethyl)pyrimidine-2,4-diamine Chemical compound FC(F)(F)C1=NC(N)=NC(N)=C1C1=CC(Cl)=C(N)C(Cl)=C1 KXXCUIBIORBOGC-UHFFFAOYSA-N 0.000 claims description 2
- ASDHQAOMMACQGI-UHFFFAOYSA-N 6-methyl-5-(3,4,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=CC(Cl)=C(Cl)C(Cl)=C1 ASDHQAOMMACQGI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- MQRADWWRHVBWHX-UHFFFAOYSA-N 2-(4-propylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CCC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 MQRADWWRHVBWHX-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- RZABVGKFPFSKJP-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound NC1=NC(N2CCN(CC=3C=CC=CC=3)CC2)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl RZABVGKFPFSKJP-UHFFFAOYSA-N 0.000 claims 1
- FWJSVGUOJIKCLH-UHFFFAOYSA-N 2-(4-butylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CCCC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 FWJSVGUOJIKCLH-UHFFFAOYSA-N 0.000 claims 1
- AOQBUGMDTINKNL-UHFFFAOYSA-N 2-(4-cyclopropylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound NC1=NC(N2CCN(CC2)C2CC2)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl AOQBUGMDTINKNL-UHFFFAOYSA-N 0.000 claims 1
- VVEOZRDMKMFVGR-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-5-(2,4,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=CC(Cl)=C(Cl)C=2)Cl)C(N)=N1 VVEOZRDMKMFVGR-UHFFFAOYSA-N 0.000 claims 1
- NIKUMHWLORLHBZ-UHFFFAOYSA-N 5-(2,3-dichlorophenyl)-4-(4-methylpiperazin-1-yl)pyrimidin-2-amine Chemical compound C1CN(C)CCN1C1=NC(N)=NC=C1C1=CC=CC(Cl)=C1Cl NIKUMHWLORLHBZ-UHFFFAOYSA-N 0.000 claims 1
- MFTUNWFXXLKGGG-UHFFFAOYSA-N 5-(2,3-dichlorophenyl)-4-piperidin-1-ylpyrimidin-2-amine Chemical compound N=1C(N)=NC=C(C=2C(=C(Cl)C=CC=2)Cl)C=1N1CCCCC1 MFTUNWFXXLKGGG-UHFFFAOYSA-N 0.000 claims 1
- DTUHEHSZZIELQD-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-ethylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(CC)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 DTUHEHSZZIELQD-UHFFFAOYSA-N 0.000 claims 1
- SRSZUNLFCXBZCK-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-propan-2-ylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(C(C)C)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 SRSZUNLFCXBZCK-UHFFFAOYSA-N 0.000 claims 1
- YJQWLFUYDVSUEX-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyrimidine-2,4-diamine Chemical compound FC(F)(F)C1=NC(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 YJQWLFUYDVSUEX-UHFFFAOYSA-N 0.000 claims 1
- WJJDXHHPQMNMHX-UHFFFAOYSA-N 5-(4-amino-2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(N)C(Cl)=C1Cl WJJDXHHPQMNMHX-UHFFFAOYSA-N 0.000 claims 1
- GFTAALLRHJZQOG-UHFFFAOYSA-N 5-(4-amino-3,5-dichlorophenyl)-6-methylpyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=CC(Cl)=C(N)C(Cl)=C1 GFTAALLRHJZQOG-UHFFFAOYSA-N 0.000 claims 1
- MWMCPPJAMFMRAL-UHFFFAOYSA-N 6-methyl-2-(4-methylpiperazin-1-yl)-5-(3,4,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=NC(C)=C(C=2C=C(Cl)C(Cl)=C(Cl)C=2)C(N)=N1 MWMCPPJAMFMRAL-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 abstract description 9
- 125000003282 alkyl amino group Chemical group 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 162
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
- 239000000203 mixture Substances 0.000 description 97
- 239000000243 solution Substances 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- 239000002904 solvent Substances 0.000 description 49
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000007787 solid Substances 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- 238000010992 reflux Methods 0.000 description 31
- 238000003756 stirring Methods 0.000 description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 239000011734 sodium Substances 0.000 description 23
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 238000001816 cooling Methods 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 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 20
- 229910052708 sodium Inorganic materials 0.000 description 20
- 239000002253 acid Substances 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 150000002084 enol ethers Chemical class 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000004615 ingredient Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 235000011149 sulphuric acid Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 7
- 230000008570 general process Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- ZYSMJCDSMWNIQQ-UHFFFAOYSA-N 3-methoxy-2-(2,3,5-trichlorophenyl)prop-2-enenitrile Chemical compound COC=C(C#N)C1=CC(Cl)=CC(Cl)=C1Cl ZYSMJCDSMWNIQQ-UHFFFAOYSA-N 0.000 description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 6
- 229960004132 diethyl ether Drugs 0.000 description 6
- 238000001665 trituration Methods 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Substances [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 108020001096 dihydrofolate reductase Proteins 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 229960000789 guanidine hydrochloride Drugs 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- ZPOXIYHRYZMGEJ-UHFFFAOYSA-N n'-methylpiperazine-1-carboximidamide Chemical compound CNC(=N)N1CCNCC1 ZPOXIYHRYZMGEJ-UHFFFAOYSA-N 0.000 description 4
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000001117 sulphuric acid Substances 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- DLAKEJZPXICNSC-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)acetonitrile Chemical compound ClC1=CC(Cl)=CC(CC#N)=C1 DLAKEJZPXICNSC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000001154 acute effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000007963 capsule composition Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 229910052681 coesite Inorganic materials 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 229910052906 cristobalite Inorganic materials 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
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- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 229960004698 dichlorobenzyl alcohol Drugs 0.000 description 1
- 229960003887 dichlorophen Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- CANXLAXDRLYESO-UHFFFAOYSA-N ethyl 2-(2,3-dichlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Cl)=C1Cl CANXLAXDRLYESO-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 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
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
- 208000000747 high pressure neurological syndrome Diseases 0.000 description 1
- LFXAECSQJSRSTP-UHFFFAOYSA-N hydron;methyl carbamimidothioate;iodide Chemical compound I.CSC(N)=N LFXAECSQJSRSTP-UHFFFAOYSA-N 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 229940080428 lactose 200 mg Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical class [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
- UIICPZFWHBJNIG-UHFFFAOYSA-N sodium;2-methoxyethanolate Chemical compound [Na+].COCC[O-] UIICPZFWHBJNIG-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 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
- 230000008733 trauma Effects 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two 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
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Liquid Crystal Substances (AREA)
- Paper (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9012316.7 | 1990-06-01 | ||
| GB909012316A GB9012316D0 (en) | 1990-06-01 | 1990-06-01 | Pharmacologically active cns compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2043640A1 true CA2043640A1 (en) | 1991-12-02 |
Family
ID=10676964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002043640A Abandoned CA2043640A1 (en) | 1990-06-01 | 1991-05-31 | Pharmacologically active cns compounds |
Country Status (25)
| Country | Link |
|---|---|
| EP (2) | EP0679645A1 (enExample) |
| JP (1) | JPH06340634A (enExample) |
| KR (1) | KR920000733A (enExample) |
| AT (1) | ATE141263T1 (enExample) |
| AU (2) | AU652753B2 (enExample) |
| CA (1) | CA2043640A1 (enExample) |
| CZ (1) | CZ281070B6 (enExample) |
| DE (1) | DE69121317T2 (enExample) |
| DK (1) | DK0459819T3 (enExample) |
| ES (1) | ES2093078T3 (enExample) |
| FI (1) | FI912623A7 (enExample) |
| GB (1) | GB9012316D0 (enExample) |
| GR (1) | GR3021237T3 (enExample) |
| HU (2) | HUT58707A (enExample) |
| IE (1) | IE911861A1 (enExample) |
| IL (2) | IL113599A (enExample) |
| MY (2) | MY136248A (enExample) |
| NO (1) | NO180375C (enExample) |
| NZ (3) | NZ248501A (enExample) |
| PL (2) | PL166656B1 (enExample) |
| PT (1) | PT97827B (enExample) |
| RU (1) | RU2091374C1 (enExample) |
| SK (1) | SK278444B6 (enExample) |
| TW (1) | TW224460B (enExample) |
| ZA (1) | ZA914165B (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI895821A7 (fi) * | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| US5629016A (en) * | 1991-01-30 | 1997-05-13 | Glaxo Wellcome Inc. | Water-dispersible tablets |
| UA37214C2 (uk) * | 1991-01-30 | 2001-05-15 | Дзе Веллкам Фаундейшн Лімітед | Таблетки, що диспергуються у воді, та спосіб їх виготовлення |
| GB9215908D0 (en) * | 1992-07-27 | 1992-09-09 | Wellcome Found | Water dispersible tablets |
| GB9226377D0 (en) * | 1992-12-18 | 1993-02-10 | Babbedge Rachel C | Pharmaceutical compositions |
| EP0674627A1 (en) * | 1992-12-18 | 1995-10-04 | The Wellcome Foundation Limited | Pyrimidine, pyridine, pteridinone and indazole derivatives as enzyme inhibitors |
| US5698226A (en) * | 1993-07-13 | 1997-12-16 | Glaxo Wellcome Inc. | Water-dispersible tablets |
| GB9319341D0 (en) * | 1993-09-17 | 1993-11-03 | Wellcome Found | Novel process |
| FR2741879A1 (fr) * | 1995-12-05 | 1997-06-06 | Esteve Labor Dr | Derives de fluorophenyl-triazines et pyrimidines, leur preparation et leur application en tant que medicament |
| US6440965B1 (en) | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| DE19751949A1 (de) * | 1997-11-24 | 1999-05-27 | Bayer Ag | Verwendung von substituierten Aminomethyl-Chromanen zur Verhinderung der neuronalen Degeneration und zur Förderung der neuronalen Regeneration |
| GB9726987D0 (en) | 1997-12-22 | 1998-02-18 | Glaxo Group Ltd | Compounds |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| DE19918325A1 (de) * | 1999-04-22 | 2000-10-26 | Euro Celtique Sa | Verfahren zur Herstellung von Arzneiformen mit regulierter Wirkstofffreisetzung mittels Extrusion |
| CA2383466C (en) | 1999-09-16 | 2009-08-25 | Tanabe Seiyaku Co., Ltd. | Aromatic nitrogen-containing 6-membered cyclic compounds |
| YU63802A (sh) * | 2000-02-25 | 2005-06-10 | F. Hoffmann-La Roche Ag. | Modulatori adenozinskih receptora |
| KR100711042B1 (ko) | 2000-04-28 | 2007-04-24 | 다나베 세이야꾸 가부시키가이샤 | 환상 화합물 |
| US7273868B2 (en) | 2000-04-28 | 2007-09-25 | Tanabe Seiyaku Co., Ltd. | Pyrazine derivatives |
| JP5154728B2 (ja) * | 2000-07-24 | 2013-02-27 | クレニツキー・ファーマシューティカルズ，インコーポレイテッド | 神経栄養活性を有する置換５−アルキニルピリミジン |
| EP1364950A4 (en) | 2001-02-26 | 2005-03-09 | Tanabe Seiyaku Co | Pyridopyrimidine and naphthyridine derivatives |
| PL372390A1 (en) * | 2002-02-05 | 2005-07-25 | Novo Nordisk A/S | Novel aryl- and heteroarylpiperazines |
| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| CN103110635A (zh) | 2005-07-04 | 2013-05-22 | 海波因特制药有限责任公司 | 组胺h3受体拮抗剂 |
| CA2653062A1 (en) | 2006-05-23 | 2007-11-29 | Transtech Pharma, Inc. | 6- (4-cyclopropylpiperazin-1-yl) -2 ' -methyl- [3, 4 ' ] -bipyridine and its use as a medicament |
| ATE538116T1 (de) | 2006-05-29 | 2012-01-15 | High Point Pharmaceuticals Llc | 3-(1,3-benyodioxol-5-yl)-6- (4- cyclopropylpiperazin-1-yl)-pyridazin, dessen salze und solvate und dessen verwendung als histamin-h3-rezeptorantagonist |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| US9073947B2 (en) | 2011-06-10 | 2015-07-07 | Merck Patent Gmbh | Compositions and methods for the production of pyrimidine and pyridine compounds with BTK inhibitory activity |
| ES2699351T3 (es) | 2014-01-17 | 2019-02-08 | Novartis Ag | Derivados de 1-piridazin/triazin-3-il-piper(-azina)/idina/pirolidina y composiciones de las mismas para inhibir la actividad de SHP2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| PT3468972T (pt) | 2016-06-14 | 2020-08-21 | Novartis Ag | Compostos e composições para inibir a atividade da shp2 |
| CN110730678B (zh) | 2017-01-10 | 2022-07-15 | 诺华股份有限公司 | 包含alk抑制剂和shp2抑制剂的药物组合 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE518622A (enExample) * | ||||
| FI895821A7 (fi) * | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| US5136080A (en) * | 1989-12-04 | 1992-08-04 | Burroughs Wellcome Co. | Nitrile compounds |
-
1990
- 1990-06-01 GB GB909012316A patent/GB9012316D0/en active Pending
-
1991
- 1991-05-30 ZA ZA914165A patent/ZA914165B/xx unknown
- 1991-05-31 CA CA002043640A patent/CA2043640A1/en not_active Abandoned
- 1991-05-31 AT AT91304935T patent/ATE141263T1/de not_active IP Right Cessation
- 1991-05-31 MY MYPI95001459A patent/MY136248A/en unknown
- 1991-05-31 TW TW080104285A patent/TW224460B/zh active
- 1991-05-31 IL IL113599A patent/IL113599A/xx not_active IP Right Cessation
- 1991-05-31 IE IE186191A patent/IE911861A1/en unknown
- 1991-05-31 HU HU911826A patent/HUT58707A/hu unknown
- 1991-05-31 EP EP95111314A patent/EP0679645A1/en not_active Withdrawn
- 1991-05-31 NZ NZ248501A patent/NZ248501A/en unknown
- 1991-05-31 PT PT97827A patent/PT97827B/pt not_active IP Right Cessation
- 1991-05-31 RU SU914895583A patent/RU2091374C1/ru active
- 1991-05-31 DK DK91304935.9T patent/DK0459819T3/da active
- 1991-05-31 ES ES91304935T patent/ES2093078T3/es not_active Expired - Lifetime
- 1991-05-31 KR KR1019910009010A patent/KR920000733A/ko not_active Ceased
- 1991-05-31 CZ CS911643A patent/CZ281070B6/cs unknown
- 1991-05-31 NZ NZ238360A patent/NZ238360A/en unknown
- 1991-05-31 MY MYPI91000962A patent/MY109958A/en unknown
- 1991-05-31 SK SK1643-91A patent/SK278444B6/sk unknown
- 1991-05-31 PL PL91290496A patent/PL166656B1/pl unknown
- 1991-05-31 PL PL91305331A patent/PL170373B1/pl unknown
- 1991-05-31 EP EP91304935A patent/EP0459819B1/en not_active Expired - Lifetime
- 1991-05-31 DE DE69121317T patent/DE69121317T2/de not_active Expired - Fee Related
- 1991-05-31 NZ NZ272001A patent/NZ272001A/en unknown
- 1991-05-31 JP JP3235334A patent/JPH06340634A/ja active Pending
- 1991-05-31 FI FI912623A patent/FI912623A7/fi not_active Application Discontinuation
- 1991-05-31 IL IL9833091A patent/IL98330A/en active IP Right Grant
- 1991-05-31 AU AU78097/91A patent/AU652753B2/en not_active Ceased
- 1991-05-31 NO NO912100A patent/NO180375C/no unknown
-
1994
- 1994-07-13 AU AU67455/94A patent/AU680252B2/en not_active Expired - Fee Related
-
1995
- 1995-06-30 HU HU95P/P00669P patent/HU211649A9/hu unknown
-
1996
- 1996-10-03 GR GR960402585T patent/GR3021237T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |