RU2091374C1 - Способ получения замещенных 5-арил-пиримидинов - Google Patents
Способ получения замещенных 5-арил-пиримидинов Download PDFInfo
- Publication number
- RU2091374C1 RU2091374C1 SU914895583A SU4895583A RU2091374C1 RU 2091374 C1 RU2091374 C1 RU 2091374C1 SU 914895583 A SU914895583 A SU 914895583A SU 4895583 A SU4895583 A SU 4895583A RU 2091374 C1 RU2091374 C1 RU 2091374C1
- Authority
- RU
- Russia
- Prior art keywords
- amino
- pyrimidine
- trichlorophenyl
- piperazinyl
- dichlorophenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 239000012458 free base Substances 0.000 claims abstract description 14
- 125000006239 protecting group Chemical group 0.000 claims abstract description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 6
- 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 abstract description 5
- -1 4-iodo-2,3,5-trichlorophenyl Chemical group 0.000 claims description 62
- 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 claims description 8
- 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 description 7
- 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 6
- 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 6
- 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 5
- 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 description 4
- 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 description 4
- 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 4
- 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 description 3
- 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 description 3
- XYMFQPCVHNYLAW-UHFFFAOYSA-N 2-n,2-n-diethyl-5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N(CC)CC)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl XYMFQPCVHNYLAW-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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 description 3
- 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 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 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 description 2
- KULFIMRKKQDMMW-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-(methoxymethyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine Chemical compound COCC1=NC(N2CCN(C)CC2)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 KULFIMRKKQDMMW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- DJVCFHRVCZHWME-UHFFFAOYSA-N n-propylpiperazine-1-carboxamide Chemical compound CCCNC(=O)N1CCNCC1 DJVCFHRVCZHWME-UHFFFAOYSA-N 0.000 claims 2
- PEDBWYZDQIQHNH-UHFFFAOYSA-N 2-(2,3,5-trichlorophenyl)pyrimidine Chemical compound ClC1=CC(Cl)=C(Cl)C(C=2N=CC=CN=2)=C1 PEDBWYZDQIQHNH-UHFFFAOYSA-N 0.000 claims 1
- SDNJAOPJUODMJN-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-methylpyrimidine Chemical compound CC1=CC=NC(C=2C=C(Cl)C=C(Cl)C=2)=N1 SDNJAOPJUODMJN-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 178
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 137
- 239000000243 solution Substances 0.000 description 121
- 239000000203 mixture Substances 0.000 description 115
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
- 239000000047 product Substances 0.000 description 81
- 235000019441 ethanol Nutrition 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000002904 solvent Substances 0.000 description 59
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 238000010992 reflux Methods 0.000 description 43
- 239000007787 solid Substances 0.000 description 43
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- 238000003756 stirring Methods 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 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 28
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- 239000011734 sodium Substances 0.000 description 28
- 229910052708 sodium Inorganic materials 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 25
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 25
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 150000002084 enol ethers Chemical class 0.000 description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- 238000010828 elution Methods 0.000 description 12
- 229930195712 glutamate Natural products 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 210000003169 central nervous system Anatomy 0.000 description 10
- 229940098779 methanesulfonic acid Drugs 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- XEFKJVPJBULCGW-UHFFFAOYSA-N 6-methyl-5-(2,3,6-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=C(Cl)C=CC(Cl)=C1Cl XEFKJVPJBULCGW-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000000354 decomposition reaction Methods 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000007429 general method Methods 0.000 description 7
- 229960000789 guanidine hydrochloride Drugs 0.000 description 7
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 238000001665 trituration Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- DLAKEJZPXICNSC-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)acetonitrile Chemical compound ClC1=CC(Cl)=CC(CC#N)=C1 DLAKEJZPXICNSC-UHFFFAOYSA-N 0.000 description 5
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000002858 neurotransmitter agent Substances 0.000 description 5
- 239000012265 solid product Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 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 4
- 241000124008 Mammalia Species 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 238000000465 moulding Methods 0.000 description 4
- ZPOXIYHRYZMGEJ-UHFFFAOYSA-N n'-methylpiperazine-1-carboximidamide Chemical compound CNC(=N)N1CCNCC1 ZPOXIYHRYZMGEJ-UHFFFAOYSA-N 0.000 description 4
- 230000000626 neurodegenerative effect Effects 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- MVGPEGIFSAFHOU-UHFFFAOYSA-N 2-(2,3,5-trichlorophenyl)acetonitrile Chemical compound ClC1=CC(Cl)=C(Cl)C(CC#N)=C1 MVGPEGIFSAFHOU-UHFFFAOYSA-N 0.000 description 3
- AYAOPGPQSPECQN-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-oxobutanenitrile Chemical compound FC(F)(F)C(=O)C(C#N)C1=CC(Cl)=CC(Cl)=C1 AYAOPGPQSPECQN-UHFFFAOYSA-N 0.000 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 description 3
- KGTZOXFQDVEJFW-UHFFFAOYSA-N 3-methoxy-2-(3,4,5-trichlorophenyl)but-2-enenitrile Chemical compound COC(C)=C(C#N)C1=CC(Cl)=C(Cl)C(Cl)=C1 KGTZOXFQDVEJFW-UHFFFAOYSA-N 0.000 description 3
- AVXAKOOMSXYVJS-UHFFFAOYSA-N 4-chloro-5-(2,3-dichlorophenyl)pyrimidin-2-amine Chemical compound ClC1=NC(N)=NC=C1C1=CC=CC(Cl)=C1Cl AVXAKOOMSXYVJS-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- HKUWHJSPPDFLNG-UHFFFAOYSA-N I.CNC(=N)N1CCNCC1 Chemical compound I.CNC(=N)N1CCNCC1 HKUWHJSPPDFLNG-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- QHJPGANWSLEMTI-UHFFFAOYSA-N aminomethylideneazanium;iodide Chemical compound I.NC=N QHJPGANWSLEMTI-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 208000037765 diseases and disorders Diseases 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- HZKGTRUEBFRMNO-UHFFFAOYSA-N (3,4,5-trichlorophenyl)methanol Chemical compound OCC1=CC(Cl)=C(Cl)C(Cl)=C1 HZKGTRUEBFRMNO-UHFFFAOYSA-N 0.000 description 2
- ZFLRKAMKGYNFPH-UHFFFAOYSA-N 1,3-dichloro-5-(chloromethyl)benzene Chemical compound ClCC1=CC(Cl)=CC(Cl)=C1 ZFLRKAMKGYNFPH-UHFFFAOYSA-N 0.000 description 2
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 2
- YKSVXVKIYYQWBB-UHFFFAOYSA-N 1-butylpiperazine Chemical compound CCCCN1CCNCC1 YKSVXVKIYYQWBB-UHFFFAOYSA-N 0.000 description 2
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
- OXPDQFOKSZYEMJ-UHFFFAOYSA-N 2-phenylpyrimidine Chemical class C1=CC=CC=C1C1=NC=CC=N1 OXPDQFOKSZYEMJ-UHFFFAOYSA-N 0.000 description 2
- ICUICNRYLHKQGS-UHFFFAOYSA-N 3,4,5-trichlorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=C(Cl)C(Cl)=C1 ICUICNRYLHKQGS-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- WZCFBHAQBXXDOT-UHFFFAOYSA-N 3-methoxy-2-(2,3,5-trichlorophenyl)but-2-enenitrile Chemical compound COC(C)=C(C#N)C1=CC(Cl)=CC(Cl)=C1Cl WZCFBHAQBXXDOT-UHFFFAOYSA-N 0.000 description 2
- CPYMVMUGLSWQCG-UHFFFAOYSA-N 3-oxo-2-(2,3,5-trichlorophenyl)propanenitrile Chemical compound ClC1=CC(Cl)=C(Cl)C(C(C=O)C#N)=C1 CPYMVMUGLSWQCG-UHFFFAOYSA-N 0.000 description 2
- IZOGBRQJQXBKNR-UHFFFAOYSA-N 3-oxo-2-(3,4,5-trichlorophenyl)butanenitrile Chemical compound CC(=O)C(C#N)C1=CC(Cl)=C(Cl)C(Cl)=C1 IZOGBRQJQXBKNR-UHFFFAOYSA-N 0.000 description 2
- UHXYYTSWBYTDPD-UHFFFAOYSA-N 4-amino-3,5-dichlorobenzoic acid Chemical compound NC1=C(Cl)C=C(C(O)=O)C=C1Cl UHXYYTSWBYTDPD-UHFFFAOYSA-N 0.000 description 2
- XKIPLNIHBKSYNB-UHFFFAOYSA-N 5-(2,3,4,5-tetrachlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(Cl)C(Cl)=C1Cl XKIPLNIHBKSYNB-UHFFFAOYSA-N 0.000 description 2
- IFJADSSDUPQVPC-UHFFFAOYSA-N 5-(2,3,5-trichloro-4-iodophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(I)C(Cl)=C1Cl IFJADSSDUPQVPC-UHFFFAOYSA-N 0.000 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 description 2
- 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 description 2
- 241000220479 Acacia Species 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- 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 2
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MHLCXRDAVJFBLW-UHFFFAOYSA-N N'-ethylpiperazine-1-carboximidamide hydroiodide Chemical compound I.C(C)NC(=N)N1CCNCC1 MHLCXRDAVJFBLW-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- SOCHGDVNAPHZNI-UHFFFAOYSA-N [O-]CC.[Na+].C(C)(=O)OCC Chemical compound [O-]CC.[Na+].C(C)(=O)OCC SOCHGDVNAPHZNI-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WUPZNKGVDMHMBS-UHFFFAOYSA-N azane;dihydrate Chemical compound [NH4+].[NH4+].[OH-].[OH-] WUPZNKGVDMHMBS-UHFFFAOYSA-N 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 229960004698 dichlorobenzyl alcohol Drugs 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 229940071870 hydroiodic acid Drugs 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 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 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 description 2
- VRNFXUOQGOAQBZ-DYXAMGHASA-N veratrin Chemical compound C1[C@@H](C)CC[C@H]2[C@](O)(C)[C@@]3(O)[C@@H](O)C[C@@]4(O)[C@@H]5CC[C@H]6[C@]7(C)CC[C@H](OC(=O)C(\C)=C/C)[C@@]6(O)O[C@@]75C[C@@]4(O)[C@@H]3CN21.C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 VRNFXUOQGOAQBZ-DYXAMGHASA-N 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- MKERQGLKSFEKAE-UHFFFAOYSA-N (2,3,5-trichlorophenyl)methanol Chemical compound OCC1=CC(Cl)=CC(Cl)=C1Cl MKERQGLKSFEKAE-UHFFFAOYSA-N 0.000 description 1
- VSNNLLQKDRCKCB-UHFFFAOYSA-N (3,5-dichlorophenyl)methanol Chemical compound OCC1=CC(Cl)=CC(Cl)=C1 VSNNLLQKDRCKCB-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- BUFXTZQKWHOGPE-UHFFFAOYSA-N 1,1-diethylguanidine;hydrochloride Chemical compound Cl.CCN(CC)C(N)=N BUFXTZQKWHOGPE-UHFFFAOYSA-N 0.000 description 1
- ZZBPVECKHPGPAQ-UHFFFAOYSA-N 1,2,3-trichloro-5-(chloromethyl)benzene Chemical compound ClCC1=CC(Cl)=C(Cl)C(Cl)=C1 ZZBPVECKHPGPAQ-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- IPFQCETYZRPQAM-UHFFFAOYSA-N 1-(bromomethyl)-2,3,5-trichlorobenzene Chemical compound ClC1=CC(Cl)=C(Cl)C(CBr)=C1 IPFQCETYZRPQAM-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- HNZJIWIXRPBFAN-UHFFFAOYSA-N 1-cyclopropylpiperazine Chemical compound C1CC1N1CCNCC1 HNZJIWIXRPBFAN-UHFFFAOYSA-N 0.000 description 1
- VZOPVKZLLGMDDG-UHFFFAOYSA-N 1-oxido-4-phenylpyridin-1-ium Chemical compound C1=C[N+]([O-])=CC=C1C1=CC=CC=C1 VZOPVKZLLGMDDG-UHFFFAOYSA-N 0.000 description 1
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
- QLEIDMAURCRVCX-UHFFFAOYSA-N 1-propylpiperazine Chemical compound CCCN1CCNCC1 QLEIDMAURCRVCX-UHFFFAOYSA-N 0.000 description 1
- YTPQLWVHCBATKO-UHFFFAOYSA-N 1-propylpiperazine;dihydrobromide Chemical compound Br.Br.CCCN1CCNCC1 YTPQLWVHCBATKO-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- DJYRZTCLVDKWBL-UHFFFAOYSA-N 2,3,5-trichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=C(Cl)C(C=O)=C1 DJYRZTCLVDKWBL-UHFFFAOYSA-N 0.000 description 1
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 1
- ZUZLGSONCFESPE-UHFFFAOYSA-N 2-(2,3,6-trichlorophenyl)acetonitrile Chemical compound ClC1=CC=C(Cl)C(CC#N)=C1Cl ZUZLGSONCFESPE-UHFFFAOYSA-N 0.000 description 1
- YWMXEUIQZOQESD-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1Cl YWMXEUIQZOQESD-UHFFFAOYSA-N 0.000 description 1
- CZLINJDTCHACEH-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)acetonitrile Chemical compound ClC1=CC=CC(CC#N)=C1Cl CZLINJDTCHACEH-UHFFFAOYSA-N 0.000 description 1
- DJJLDMJERKJSCW-UHFFFAOYSA-N 2-(3,4,5-trichlorophenyl)acetonitrile Chemical compound ClC1=CC(CC#N)=CC(Cl)=C1Cl DJJLDMJERKJSCW-UHFFFAOYSA-N 0.000 description 1
- LVGHKSGBRIJLFM-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-3-oxopropanenitrile Chemical compound ClC1=CC(Cl)=CC(C(C=O)C#N)=C1 LVGHKSGBRIJLFM-UHFFFAOYSA-N 0.000 description 1
- UOSKHQDLNDZDNA-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-4-methoxy-3-oxobutanenitrile Chemical compound COCC(=O)C(C#N)C1=CC(Cl)=CC(Cl)=C1 UOSKHQDLNDZDNA-UHFFFAOYSA-N 0.000 description 1
- NAUFYMSKMDDQLL-UHFFFAOYSA-N 2-(4-cyclopropylpiperazin-1-yl)-5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound NC1=NC(N2CCN(CC2)C2CC2)=NC(C(F)(F)F)=C1C1=CC(Cl)=CC(Cl)=C1 NAUFYMSKMDDQLL-UHFFFAOYSA-N 0.000 description 1
- ATLRODNPYMJLSF-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)-4-(trifluoromethyl)pyrimidine Chemical compound CN1CCN(CC1)C1=NC(=C(C=N1)C1=C(C(=CC(=C1)Cl)Cl)Cl)C(F)(F)F ATLRODNPYMJLSF-UHFFFAOYSA-N 0.000 description 1
- QDFFJNGACGVHDB-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl QDFFJNGACGVHDB-UHFFFAOYSA-N 0.000 description 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 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- YUGYNZRHQHRZHO-UHFFFAOYSA-N 2-amino-5-(2,3-dichlorophenyl)-1h-pyrimidin-6-one Chemical compound N1C(N)=NC(=O)C(C=2C(=C(Cl)C=CC=2)Cl)=C1 YUGYNZRHQHRZHO-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- XMIWFFMIJCOJLR-UHFFFAOYSA-N 2-propan-2-ylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)N=C(N)N XMIWFFMIJCOJLR-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- ZWURCFAKSCIVOW-UHFFFAOYSA-N 3-methoxy-2-phenylprop-2-enenitrile Chemical compound COC=C(C#N)C1=CC=CC=C1 ZWURCFAKSCIVOW-UHFFFAOYSA-N 0.000 description 1
- YMLCJRGESQDAPZ-UHFFFAOYSA-N 3-oxo-2-(2,3,6-trichlorophenyl)butanenitrile Chemical compound CC(=O)C(C#N)C1=C(Cl)C=CC(Cl)=C1Cl YMLCJRGESQDAPZ-UHFFFAOYSA-N 0.000 description 1
- WBZZBMPQKBOKRX-UHFFFAOYSA-N 4,4,4-trifluoro-3-methoxy-2-(2,3,5-trichlorophenyl)but-2-enenitrile Chemical compound COC(C(F)(F)F)=C(C#N)C1=CC(Cl)=CC(Cl)=C1Cl WBZZBMPQKBOKRX-UHFFFAOYSA-N 0.000 description 1
- KAZSERADNVUUNY-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxo-2-(2,3,5-trichlorophenyl)butanenitrile Chemical compound FC(F)(F)C(=O)C(C#N)C1=CC(Cl)=CC(Cl)=C1Cl KAZSERADNVUUNY-UHFFFAOYSA-N 0.000 description 1
- OILYRDUBYLFIOE-UHFFFAOYSA-N 5-(2,3,5-trichloro-4-nitrophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C([N+]([O-])=O)C(Cl)=C1Cl OILYRDUBYLFIOE-UHFFFAOYSA-N 0.000 description 1
- WKJFILILEWPMQF-UHFFFAOYSA-N 5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl WKJFILILEWPMQF-UHFFFAOYSA-N 0.000 description 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 description 1
- OLQCNVSVYCXXDC-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-(methoxymethyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.COCc1nc(nc(N)c1-c1cc(Cl)cc(Cl)c1)N1CCN(C)CC1 OLQCNVSVYCXXDC-UHFFFAOYSA-N 0.000 description 1
- GQPQMQLXQKNBBC-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-methylpyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 GQPQMQLXQKNBBC-UHFFFAOYSA-N 0.000 description 1
- HOCAJXHETZRTQB-UHFFFAOYSA-N 6-methyl-5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound CC1=NC(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl HOCAJXHETZRTQB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 241000222455 Boletus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- CGVJZSPGGPGGNB-UHFFFAOYSA-N C(C)(=O)O.C(C)NC(=N)N1CCNCC1 Chemical compound C(C)(=O)O.C(C)NC(=N)N1CCNCC1 CGVJZSPGGPGGNB-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 206010020994 Hypoglycaemia neonatal Diseases 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HWIGTYVHKLPILE-UHFFFAOYSA-N N'-benzylpiperazine-1-carboximidamide hydroiodide Chemical compound I.C(C1=CC=CC=C1)NC(=N)N1CCNCC1 HWIGTYVHKLPILE-UHFFFAOYSA-N 0.000 description 1
- 206010050081 Neonatal hypoxia Diseases 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- LWSORMOSGWPDDS-UHFFFAOYSA-N S(=O)(=O)(O)O.C(CCC)NC(=N)N1CCNCC1 Chemical compound S(=O)(=O)(O)O.C(CCC)NC(=N)N1CCNCC1 LWSORMOSGWPDDS-UHFFFAOYSA-N 0.000 description 1
- PDOCBJADCWMDGL-UHFFFAOYSA-N Sipatrigine Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 PDOCBJADCWMDGL-UHFFFAOYSA-N 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 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
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 108020001096 dihydrofolate reductase Proteins 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical compound CCOC(=O)COC JLEKJZUYWFJPMB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 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
- 239000011521 glass Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 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
- 150000004678 hydrides Chemical class 0.000 description 1
- LFXAECSQJSRSTP-UHFFFAOYSA-N hydron;methyl carbamimidothioate;iodide Chemical compound I.CSC(N)=N LFXAECSQJSRSTP-UHFFFAOYSA-N 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 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
- 208000014674 injury Diseases 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- LBEKFAUAYVGHFP-UHFFFAOYSA-N methyl 4-amino-3,5-dichlorobenzoate Chemical compound COC(=O)C1=CC(Cl)=C(N)C(Cl)=C1 LBEKFAUAYVGHFP-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-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
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007932 molded tablet Substances 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 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
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000004094 surface-active agent Substances 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
- 238000010998 test method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 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
- 230000007704 transition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Images
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)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (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 |
|---|---|---|---|
| GB909012316A GB9012316D0 (en) | 1990-06-01 | 1990-06-01 | Pharmacologically active cns compounds |
| GB90123167 | 1990-06-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2091374C1 true RU2091374C1 (ru) | 1997-09-27 |
Family
ID=10676964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU914895583A RU2091374C1 (ru) | 1990-06-01 | 1991-05-31 | Способ получения замещенных 5-арил-пиримидинов |
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) | MY109958A (enExample) |
| NO (1) | NO180375C (enExample) |
| NZ (3) | NZ238360A (enExample) |
| PL (2) | PL170373B1 (enExample) |
| PT (1) | PT97827B (enExample) |
| RU (1) | RU2091374C1 (enExample) |
| SK (1) | SK278444B6 (enExample) |
| TW (1) | TW224460B (enExample) |
| ZA (1) | ZA914165B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2208436C2 (ru) * | 1999-04-22 | 2003-07-20 | Еуроселтик С.А. | Способ изготовления фармацевтических лекарственных форм и их предшественников и фармацевтическая лекарственная форма |
| RU2217140C2 (ru) * | 1997-11-24 | 2003-11-27 | Байер Акциенгезелльшафт | Применение замещенных аминометил-хроманов для предотвращения дегенерации и для ускорения регенерации нервных клеток |
| RU2277911C2 (ru) * | 2000-02-25 | 2006-06-20 | Ф.Хоффманн-Ля Рош Аг | Модуляторы аденозиновых рецепторов |
Families Citing this family (28)
| 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 |
| FI20021701L (fi) * | 1991-01-30 | 2002-09-24 | Wellcome Found | Veteen dispergoituvia tabletteja |
| 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 |
| JPH08504798A (ja) * | 1992-12-18 | 1996-05-21 | ザ ウエルカム ファウンデーション リミテッド | 酵素阻害薬としての，ピリミジン，ピリジン，プテリジノンおよびインダゾール誘導体 |
| 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 |
| 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 |
| ES2283315T3 (es) | 1999-09-16 | 2007-11-01 | Tanabe Seiyaku Co., Ltd. | Compuestos ciclicos de 6 miembros que contienen nitrogeno aromatico. |
| 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 |
| WO2002068419A1 (en) | 2001-02-26 | 2002-09-06 | Tanabe Seiyaku Co., Ltd. | Pyridopyrimidine or naphthyridine derivative |
| AU2003203148A1 (en) * | 2002-02-05 | 2003-09-02 | High Point Pharmaceuticals, Llc | Novel aryl- and heteroarylpiperazines |
| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| EP2386554A1 (en) | 2005-07-04 | 2011-11-16 | High Point Pharmaceuticals, LLC | Compounds active at the histamine H3 receptor |
| JP2009537596A (ja) | 2006-05-23 | 2009-10-29 | ハイ ポイント ファーマシューティカルズ，リミティド ライアビリティ カンパニー | ６−（４−シクロプロピルピペリジン−１−イル）−２’−メチル−［３，４’］−ビピリジン及びその医薬としての使用 |
| EP2079732B9 (en) | 2006-05-29 | 2012-03-21 | High Point Pharmaceuticals, LLC | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| EA031153B1 (ru) | 2011-06-10 | 2018-11-30 | Мерк Патент Гмбх | Применение пиримидиновых соединений с btk ингибирующей активностью |
| EP3094627B1 (en) | 2014-01-17 | 2018-08-22 | Novartis AG | 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| AU2017283769B2 (en) | 2016-06-14 | 2019-08-15 | Novartis Ag | Compounds and compositions for inhibiting the activity of SHP2 |
| EP3568204B1 (en) | 2017-01-10 | 2023-08-30 | Novartis AG | Pharmaceutical combination comprising an alk inhibitor and an shp2 inhibitor |
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 NZ NZ238360A patent/NZ238360A/en unknown
- 1991-05-31 KR KR1019910009010A patent/KR920000733A/ko not_active Ceased
- 1991-05-31 MY MYPI91000962A patent/MY109958A/en unknown
- 1991-05-31 PL PL91305331A patent/PL170373B1/pl unknown
- 1991-05-31 FI FI912623A patent/FI912623A7/fi not_active Application Discontinuation
- 1991-05-31 EP EP95111314A patent/EP0679645A1/en not_active Withdrawn
- 1991-05-31 NO NO912100A patent/NO180375C/no unknown
- 1991-05-31 NZ NZ248501A patent/NZ248501A/en unknown
- 1991-05-31 EP EP91304935A patent/EP0459819B1/en not_active Expired - Lifetime
- 1991-05-31 IL IL113599A patent/IL113599A/xx not_active IP Right Cessation
- 1991-05-31 PL PL91290496A patent/PL166656B1/pl unknown
- 1991-05-31 TW TW080104285A patent/TW224460B/zh active
- 1991-05-31 IL IL9833091A patent/IL98330A/en active IP Right Grant
- 1991-05-31 MY MYPI95001459A patent/MY136248A/en unknown
- 1991-05-31 JP JP3235334A patent/JPH06340634A/ja active Pending
- 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 RU SU914895583A patent/RU2091374C1/ru active
- 1991-05-31 SK SK1643-91A patent/SK278444B6/sk unknown
- 1991-05-31 PT PT97827A patent/PT97827B/pt not_active IP Right Cessation
- 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 DE DE69121317T patent/DE69121317T2/de not_active Expired - Fee Related
- 1991-05-31 HU HU911826A patent/HUT58707A/hu unknown
- 1991-05-31 AU AU78097/91A patent/AU652753B2/en not_active Ceased
- 1991-05-31 NZ NZ272001A patent/NZ272001A/en unknown
- 1991-05-31 IE IE186191A patent/IE911861A1/en unknown
- 1991-05-31 CZ CS911643A patent/CZ281070B6/cs 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
Non-Patent Citations (1)
| Title |
|---|
| ЕР, патент, 0372934, кл. A 61 K 31/585, 1990. * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2217140C2 (ru) * | 1997-11-24 | 2003-11-27 | Байер Акциенгезелльшафт | Применение замещенных аминометил-хроманов для предотвращения дегенерации и для ускорения регенерации нервных клеток |
| RU2208436C2 (ru) * | 1999-04-22 | 2003-07-20 | Еуроселтик С.А. | Способ изготовления фармацевтических лекарственных форм и их предшественников и фармацевтическая лекарственная форма |
| RU2277911C2 (ru) * | 2000-02-25 | 2006-06-20 | Ф.Хоффманн-Ля Рош Аг | Модуляторы аденозиновых рецепторов |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0459819A2 (en) | Pharmacologically active CNS compound | |
| JP2795498B2 (ja) | 薬理学的に活性な中枢神経系化合物 | |
| US8372854B2 (en) | Pyrrolo[2,3-D]pyrimidine compounds | |
| DE69434721T2 (de) | Pharmacologisch wirksame pyrimidinderivate und verfahren zu deren herstellung | |
| US5589477A (en) | Pyrimidine derivatives and drugs | |
| AU2021389180A1 (en) | Heteroaryl carboxamide compound | |
| BG65159B1 (bg) | Хетероциклични производни на уреа, полезни като противовъзпалителни средства | |
| US10682358B2 (en) | Substituted 2, 3-dihydro-1H-inden-1-one retinoic acid-related orphan nuclear receptor antagonists for treating multiple sclerosis | |
| JP5124471B2 (ja) | 置換二環式ピリミドン誘導体 | |
| WO2022084741A1 (en) | Cftr modulator compounds, compositions, and uses thereof | |
| JP2003524595A (ja) | 薬 剤 | |
| NZ206906A (en) | Substituted pyridazines and pyrimidines and pharmaceutical compositions | |
| US4540696A (en) | 1-Piperazinyl 4-phenylquinazoline compounds having antidepressant properties and drugs containing same | |
| DE102004022672A1 (de) | Substituierte Azachinazoline | |
| US6235738B1 (en) | Diphenyl-substituted heterocycles with 6-membered ring, processes for the preparation thereof and the use thereof as medicaments | |
| CN120607491A (zh) | 2,4-二氨基嘧啶类化合物及其用途 | |
| SI9010607A (en) | Pharmacologically active cns compounds | |
| HK1003928A (en) | Substitutd phenylpyrimidine derivatives, useful in the treatment of prevention of cns disorders |