SK9692001A3 - Utilization of pyrimidine derivatives for preventing and treating cerebral ischaemia - Google Patents

Utilization of pyrimidine derivatives for preventing and treating cerebral ischaemia Download PDF

Info

Publication number: SK9692001A3
Authority: SK; Slovakia
Prior art keywords: pyrimidin; ethyl; thieno; piperazin; hexahydro
Prior art date: 1999-01-11

Application number

SK969-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Gerd Steiner

Kurt Schellhaas

Wilfried Lubisch

Uta Holzenkamp

Dorothea Starck

Monika Knopp

Laszlo Szabo

Franz Emling

Francisco Javier Garcia-Ladona

Hans-Peter Hofmann

Liliane Unger

Original Assignee

Basf Ag

Priority date (The priority date 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 date listed.)

1999-01-11

Filing date

1999-12-24

Publication date

2002-05-09

1999-12-24 Application filed by Basf Ag filed Critical Basf Ag

2002-05-09 Publication of SK9692001A3 publication Critical patent/SK9692001A3/sk

Links

229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title claims abstract description 11
150000003230 pyrimidines Chemical class 0.000 title claims abstract description 6
206010008120 Cerebral ischaemia Diseases 0.000 title claims abstract description 5
150000003839 salts Chemical class 0.000 claims abstract description 13
239000003814 drug Substances 0.000 claims abstract description 5
208000006011 Stroke Diseases 0.000 claims abstract description 3
-1 or C 1 -C 4 -alkyl Chemical group 0.000 claims description 182
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
229910052757 nitrogen Inorganic materials 0.000 claims description 34
125000004093 cyano group Chemical group *C#N 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 19
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
238000011321 prophylaxis Methods 0.000 claims description 4
201000006474 Brain Ischemia Diseases 0.000 claims description 3
206010008118 cerebral infarction Diseases 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 171
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 162
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 105
JEDVKUHCDPPWNR-UHFFFAOYSA-N 3h-thieno[2,3-d]pyrimidin-4-one Chemical compound O=C1NC=NC2=C1C=CS2 JEDVKUHCDPPWNR-UHFFFAOYSA-N 0.000 description 102
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
239000000203 mixture Substances 0.000 description 81
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
239000000047 product Substances 0.000 description 58
239000011541 reaction mixture Substances 0.000 description 51
238000010992 reflux Methods 0.000 description 46
239000012043 crude product Substances 0.000 description 40
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 40
238000000354 decomposition reaction Methods 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
239000002253 acid Substances 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
238000004440 column chromatography Methods 0.000 description 28
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
150000001875 compounds Chemical class 0.000 description 27
238000002844 melting Methods 0.000 description 27
230000008018 melting Effects 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 26
239000012074 organic phase Substances 0.000 description 26
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
238000001035 drying Methods 0.000 description 24
239000000741 silica gel Substances 0.000 description 24
229910002027 silica gel Inorganic materials 0.000 description 24
239000003480 eluent Substances 0.000 description 23
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 20
238000003756 stirring Methods 0.000 description 20
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
DYTQGJLVGDSCLF-UHFFFAOYSA-N thieno[2,3-d]pyrimidin-4-amine Chemical compound NC1=NC=NC2=C1C=CS2 DYTQGJLVGDSCLF-UHFFFAOYSA-N 0.000 description 17
239000003960 organic solvent Substances 0.000 description 16
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 15
239000008096 xylene Substances 0.000 description 15
MMLLKVQSPFYOFR-UHFFFAOYSA-N 3h-pyrido[2,3]thieno[2,4-d]pyrimidin-4-one Chemical compound S1C2=CN=CC=C2C2=C1N=CNC2=O MMLLKVQSPFYOFR-UHFFFAOYSA-N 0.000 description 14
229910000027 potassium carbonate Inorganic materials 0.000 description 14
239000007787 solid Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
239000008346 aqueous phase Substances 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
229910021529 ammonia Inorganic materials 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
208000000044 Amnesia Diseases 0.000 description 8
208000019901 Anxiety disease Diseases 0.000 description 8
208000027534 Emotional disease Diseases 0.000 description 8
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
208000026139 Memory disease Diseases 0.000 description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000007795 chemical reaction product Substances 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 8
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
NDVVQPVEUGLAPX-UHFFFAOYSA-N 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethanamine Chemical compound COC1=CC=CC=C1N1CCN(CCN)CC1 NDVVQPVEUGLAPX-UHFFFAOYSA-N 0.000 description 7
125000004185 ester group Chemical group 0.000 description 7
239000005457 ice water Substances 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
VNICFCQJUVFULD-UHFFFAOYSA-N 1-(1-naphthalenyl)piperazine Chemical compound C1CNCCN1C1=CC=CC2=CC=CC=C12 VNICFCQJUVFULD-UHFFFAOYSA-N 0.000 description 5
PGDXRLBWSZDHQV-UHFFFAOYSA-N 1-(2-methylnaphthalen-1-yl)piperazine Chemical compound CC1=CC=C2C=CC=CC2=C1N1CCNCC1 PGDXRLBWSZDHQV-UHFFFAOYSA-N 0.000 description 5
KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 5
238000009835 boiling Methods 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 5
150000003141 primary amines Chemical class 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
DLKQHBOKULLWDQ-UHFFFAOYSA-N 1-bromonaphthalene Chemical compound C1=CC=C2C(Br)=CC=CC2=C1 DLKQHBOKULLWDQ-UHFFFAOYSA-N 0.000 description 4
SCRBSGZBTHKAHU-UHFFFAOYSA-N 4-bromoisoquinoline Chemical compound C1=CC=C2C(Br)=CN=CC2=C1 SCRBSGZBTHKAHU-UHFFFAOYSA-N 0.000 description 4
NIBZKHUIJGTBOX-UHFFFAOYSA-N 4-piperazin-1-ylisoquinoline Chemical compound C1CNCCN1C1=CN=CC2=CC=CC=C12 NIBZKHUIJGTBOX-UHFFFAOYSA-N 0.000 description 4
UHFQDUNSYUAETO-UHFFFAOYSA-N 7-thia-4,9,11-triazatricyclo[6.4.0.02,6]dodeca-1,3,5,8,10-pentaen-12-one Chemical compound N=1C=NC(C=2C=1SC=1C=2C=NC=1)=O UHFQDUNSYUAETO-UHFFFAOYSA-N 0.000 description 4
208000031091 Amnestic disease Diseases 0.000 description 4
206010012289 Dementia Diseases 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
208000030814 Eating disease Diseases 0.000 description 4
208000019454 Feeding and Eating disease Diseases 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
206010033664 Panic attack Diseases 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000006986 amnesia Effects 0.000 description 4
230000036506 anxiety Effects 0.000 description 4
239000002585 base Substances 0.000 description 4
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
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238000004090 dissolution Methods 0.000 description 4
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XZWUIISYMCVLKK-UHFFFAOYSA-N ethyl n-(3-cyano-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl)methanimidate Chemical compound C1N(C)CCC2=C1SC(N=COCC)=C2C#N XZWUIISYMCVLKK-UHFFFAOYSA-N 0.000 description 4
239000001530 fumaric acid Substances 0.000 description 4
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230000002140 halogenating effect Effects 0.000 description 4
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VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
239000011976 maleic acid Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
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YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
208000019906 panic disease Diseases 0.000 description 4
150000004885 piperazines Chemical class 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
230000001107 psychogenic effect Effects 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
238000002390 rotary evaporation Methods 0.000 description 4
230000001932 seasonal effect Effects 0.000 description 4
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 4
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 4
239000003826 tablet Substances 0.000 description 4
239000011975 tartaric acid Substances 0.000 description 4
235000002906 tartaric acid Nutrition 0.000 description 4
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 4
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
JMBLSGAXSMOKPN-UHFFFAOYSA-N 2-methylnaphthalen-1-amine Chemical compound C1=CC=CC2=C(N)C(C)=CC=C21 JMBLSGAXSMOKPN-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 3
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125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
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QGUCNTXSZPKULH-UHFFFAOYSA-N ethyl 2-(1-ethoxyethylideneamino)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1N(C)CCC2=C1SC(N=C(C)OCC)=C2C(=O)OCC QGUCNTXSZPKULH-UHFFFAOYSA-N 0.000 description 1
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NQZDSKAMKJVOMW-UHFFFAOYSA-N ethyl 2-amino-5-(dimethylcarbamoyl)-5-methyl-2h-thiophene-3-carboxylate Chemical compound CCOC(=O)C1=CC(C)(C(=O)N(C)C)SC1N NQZDSKAMKJVOMW-UHFFFAOYSA-N 0.000 description 1
LVFGODMUVKPRMQ-UHFFFAOYSA-N ethyl 2-amino-5-ethyl-6,7-dihydro-4h-thieno[3,2-c]pyridine-3-carboxylate Chemical compound C1CN(CC)CC2=C1SC(N)=C2C(=O)OCC LVFGODMUVKPRMQ-UHFFFAOYSA-N 0.000 description 1
HKOALYPIWRPOFQ-UHFFFAOYSA-N ethyl 2-amino-6-(3-phenylpropyl)-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CCCC1=CC=CC=C1 HKOALYPIWRPOFQ-UHFFFAOYSA-N 0.000 description 1
QDUCRSRYRSKSIR-UHFFFAOYSA-N ethyl 2-amino-6-[(4-chlorophenyl)methyl]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CC1=CC=C(Cl)C=C1 QDUCRSRYRSKSIR-UHFFFAOYSA-N 0.000 description 1
KGLCQGBRPOKMGN-UHFFFAOYSA-N ethyl 2-amino-6-[2-(4-chlorophenyl)ethyl]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CCC1=CC=C(Cl)C=C1 KGLCQGBRPOKMGN-UHFFFAOYSA-N 0.000 description 1
JYMONQGGDHUGEJ-UHFFFAOYSA-N ethyl 2-amino-6-[2-(4-methoxyphenyl)ethyl]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CCC1=CC=C(OC)C=C1 JYMONQGGDHUGEJ-UHFFFAOYSA-N 0.000 description 1
HLWOSVMLHPRGML-UHFFFAOYSA-N ethyl 2-amino-6-ethyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1N(CC)CCC2=C1SC(N)=C2C(=O)OCC HLWOSVMLHPRGML-UHFFFAOYSA-N 0.000 description 1
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NSZLYSNOVADDDI-UHFFFAOYSA-N ethyl 6-acetyl-2-(ethoxymethylideneamino)-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1N(C(C)=O)CCC2=C1SC(N=COCC)=C2C(=O)OCC NSZLYSNOVADDDI-UHFFFAOYSA-N 0.000 description 1
OHUWMXNZLVSOKK-UHFFFAOYSA-N ethyl 7-(2-hydroxyethyl)-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound N1=CN(CCO)C(=O)C2=C1SC1=C2CN(C(=O)OCC)C1 OHUWMXNZLVSOKK-UHFFFAOYSA-N 0.000 description 1
YDOXKFQSOLLULC-UHFFFAOYSA-N ethyl 7-[2-[4-(2,3-dihydro-1h-inden-4-yl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=CC=CC2=C1CCC2 YDOXKFQSOLLULC-UHFFFAOYSA-N 0.000 description 1
XTIVWXPNPMQFNA-UHFFFAOYSA-N ethyl 7-[2-[4-(2-chlorophenyl)piperazin-1-yl]propyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CC(C)N(CC1)CCN1C1=CC=CC=C1Cl XTIVWXPNPMQFNA-UHFFFAOYSA-N 0.000 description 1
BHMNSLZNBAYYIF-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methoxynaphthalen-1-yl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC=5CN(CC=5C=4C3=O)C(=O)OCC)=C(OC)C=CC2=C1 BHMNSLZNBAYYIF-UHFFFAOYSA-N 0.000 description 1
JSLFYTRQZBOSOY-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methoxyphenyl)piperidin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCC1C1=CC=CC=C1OC JSLFYTRQZBOSOY-UHFFFAOYSA-N 0.000 description 1
AXADUMDRJYXYOG-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methylnaphthalen-1-yl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC=5CN(CC=5C=4C3=O)C(=O)OCC)=C(C)C=CC2=C1 AXADUMDRJYXYOG-UHFFFAOYSA-N 0.000 description 1
BVKMTRLDZGMOLA-UHFFFAOYSA-N ethyl 7-[2-[4-(2-methylphenyl)piperazin-1-yl]ethyl]-8-oxo-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=C1C BVKMTRLDZGMOLA-UHFFFAOYSA-N 0.000 description 1
XMWAOPAJYZCFRW-UHFFFAOYSA-N ethyl 8-oxo-7-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]-1,3-dihydropyrrolo[2,3]thieno[2,4-d]pyrimidine-2-carboxylate Chemical compound O=C1C=2C=3CN(C(=O)OCC)CC=3SC=2N=CN1CCN(CC1)CCN1C1=NC=CC=N1 XMWAOPAJYZCFRW-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000005826 halohydrocarbons Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
208000014674 injury Diseases 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
238000000034 method Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
UWEPBKQSRBGRKA-UHFFFAOYSA-N n,n,5-trimethyl-3-[2-(4-naphthalen-1-ylpiperazin-1-yl)ethyl]-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(C)C)=CC=CC2=C1 UWEPBKQSRBGRKA-UHFFFAOYSA-N 0.000 description 1
FASHPBRQNGGLFP-UHFFFAOYSA-N n,n,5-trimethyl-3-[2-(4-naphthalen-1-ylpiperidin-1-yl)ethyl]-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=C2C(C3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(C)C)=CC=CC2=C1 FASHPBRQNGGLFP-UHFFFAOYSA-N 0.000 description 1
WKRRFYPVVNFKPT-UHFFFAOYSA-N n,n,5-trimethyl-3-[2-[4-(2-methylnaphthalen-1-yl)piperazin-1-yl]ethyl]-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(C)C)=C(C)C=CC2=C1 WKRRFYPVVNFKPT-UHFFFAOYSA-N 0.000 description 1
NPKKGWGXXOOTNH-UHFFFAOYSA-N n,n,5-trimethyl-3-[2-[4-(2-methylphenyl)piperazin-1-yl]ethyl]-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(C)C)SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=C1C NPKKGWGXXOOTNH-UHFFFAOYSA-N 0.000 description 1
PIQWXARZZCBWFP-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[2-(4-pyridin-2-ylpiperazin-1-yl)ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(C)C)SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=N1 PIQWXARZZCBWFP-UHFFFAOYSA-N 0.000 description 1
ONVXSSZJXDPWNC-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(C)C)SC=2N=CN1CCN(CC1)CCN1C1=NC=CC=N1 ONVXSSZJXDPWNC-UHFFFAOYSA-N 0.000 description 1
FIIJBVBIBLPBDU-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[2-(4-quinazolin-4-ylpiperazin-1-yl)ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(C)C)=NC=NC2=C1 FIIJBVBIBLPBDU-UHFFFAOYSA-N 0.000 description 1
PPBMVGNRSFJPKL-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[2-(4-quinolin-2-ylpiperazin-1-yl)ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=CC2=NC(N3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(C)C)=CC=C21 PPBMVGNRSFJPKL-UHFFFAOYSA-N 0.000 description 1
QWOKFGQGYWLWRP-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[2-[4-(5,6,7,8-tetrahydronaphthalen-1-yl)piperazin-1-yl]ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CCCC2=C1C=CC=C2N(CC1)CCN1CCN1C=NC(SC(=C2C)C(=O)N(C)C)=C2C1=O QWOKFGQGYWLWRP-UHFFFAOYSA-N 0.000 description 1
LQBSVOMSOKTDNG-UHFFFAOYSA-N n,n,5-trimethyl-4-oxo-3-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(C)C)SC=2N=CN1CCCN(CC1)CCN1C1=NC=CC=N1 LQBSVOMSOKTDNG-UHFFFAOYSA-N 0.000 description 1
BFQYVGOYWUGPAJ-UHFFFAOYSA-N n,n-diethyl-3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-5-methyl-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(CC)CC)SC=2N=CN1CCN(CC1)CCN1C1=CC=CC=C1OC BFQYVGOYWUGPAJ-UHFFFAOYSA-N 0.000 description 1
SWBLQWYHCNJGMH-UHFFFAOYSA-N n,n-diethyl-5-methyl-3-[2-(4-naphthalen-1-ylpiperazin-1-yl)ethyl]-4-oxothieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC=C2C(N3CCN(CC3)CCN3C=NC=4SC(=C(C=4C3=O)C)C(=O)N(CC)CC)=CC=CC2=C1 SWBLQWYHCNJGMH-UHFFFAOYSA-N 0.000 description 1
IURUXISVEIKINP-UHFFFAOYSA-N n,n-diethyl-5-methyl-4-oxo-3-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound O=C1C=2C(C)=C(C(=O)N(CC)CC)SC=2N=CN1CCN(CC1)CCN1C1=NC=CC=N1 IURUXISVEIKINP-UHFFFAOYSA-N 0.000 description 1
AGGRSWOSWVRSTN-UHFFFAOYSA-N n-[2-[3-[2-[4-(6-methylpyridin-2-yl)piperazin-1-yl]ethyl]-4-oxo-6,8-dihydro-5h-pyrido[2,3]thieno[2,4-d]pyrimidin-7-yl]ethyl]pyridine-3-carboxamide Chemical compound CC1=CC=CC(N2CCN(CCN3C(C=4C=5CCN(CCNC(=O)C=6C=NC=CC=6)CC=5SC=4N=C3)=O)CC2)=N1 AGGRSWOSWVRSTN-UHFFFAOYSA-N 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
230000004112 neuroprotection Effects 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229960001779 pargyline Drugs 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
239000003340 retarding agent Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
239000002356 single layer Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 1
PFENFDGYVLAFBR-UHFFFAOYSA-N tinoridine Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CC1=CC=CC=C1 PFENFDGYVLAFBR-UHFFFAOYSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- 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)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK969-2001A 1999-01-11 1999-12-24 Utilization of pyrimidine derivatives for preventing and treating cerebral ischaemia SK9692001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19900545A DE19900545A1 (de)	1999-01-11	1999-01-11	Verwendung von Pyrimidinderivaten zur Prophylaxe und Therapie der zerebralen Ischämie
PCT/EP1999/010369 WO2000041695A1 (de)	1999-01-11	1999-12-24	Verwendung von pyrimidinderivaten zur prophylaxe und therapie der zerebralen ischämie

Publications (1)

Publication Number	Publication Date
SK9692001A3 true SK9692001A3 (en)	2002-05-09

Family

ID=7893836

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK969-2001A SK9692001A3 (en)	1999-01-11	1999-12-24	Utilization of pyrimidine derivatives for preventing and treating cerebral ischaemia

Country Status (24)

Country	Link
US (1)	US6387912B1 (cs)
EP (1)	EP1140096A1 (cs)
JP (1)	JP2002534465A (cs)
KR (1)	KR20010101442A (cs)
CN (1)	CN1334732A (cs)
AU (1)	AU2433800A (cs)
BG (1)	BG105689A (cs)
BR (1)	BR9916887A (cs)
CA (1)	CA2359253A1 (cs)
CZ (2)	CZ20012484A3 (cs)
DE (1)	DE19900545A1 (cs)
HK (1)	HK1042649A1 (cs)
HU (1)	HUP0201149A3 (cs)
ID (1)	ID30022A (cs)
IL (1)	IL144146A0 (cs)
MX (1)	MXPA01006967A (cs)
MY (1)	MY133107A (cs)
NO (1)	NO20013409L (cs)
NZ (1)	NZ512767A (cs)
PL (1)	PL348920A1 (cs)
SK (1)	SK9692001A3 (cs)
TR (1)	TR200102008T2 (cs)
WO (1)	WO2000041695A1 (cs)
ZA (1)	ZA200105475B (cs)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19900673A1 (de)	1999-01-11	2000-07-13	Basf Ag	Verwendung von Bindungspartnern für 5-HT5-Rezeptoren zur Behandlung neurodegenerativer und neuropsychiatrischer Störungen
US6988199B2 (en) *	2000-07-07	2006-01-17	Message Secure	Secure and reliable document delivery
JP4548882B2 (ja) *	1999-11-30	2010-09-22	興和創薬株式会社	４，５，６，７−テトラヒドロチエノ〔２，３−ｃ〕ピリジン化合物
DE10031389A1 (de) *	2000-07-03	2002-01-17	Knoll Ag	Pyrimidinderivate und ihre Verwendung zur Prophylaxe und Therapie der zerebralen Ischämie
DE10031390A1 (de) *	2000-07-03	2002-01-17	Knoll Ag	Pyrimidinderivate und ihre Verwendung zur Prophylaxe und Therapie der zerebralen Ischämie
DE10259382A1 (de) *	2002-12-18	2004-07-01	Abbott Gmbh & Co. Kg	3-Substituierte 3,4-Dihydro-thieno[2,3-d]pyrimidin-4-on-Derivate, ihre Herstellung und Verwendung
WO2008138126A1 (en) *	2007-05-09	2008-11-20	Neuromed Pharmaceuticals Ltd.	Bicyclic pyrimidine derivatives as calcium channel blockers
US8927718B2 (en)	2009-08-26	2015-01-06	Takeda Pharmaceutical Company Limited	Fused heterocyclic ring derivative and use thereof
WO2021257857A1 (en)	2020-06-19	2021-12-23	Incyte Corporation	Naphthyridinone compounds as jak2 v617f inhibitors
WO2021257863A1 (en)	2020-06-19	2021-12-23	Incyte Corporation	Pyrrolotriazine compounds as jak2 v617f inhibitors
SMT202500271T1 (it)	2020-07-02	2025-09-12	Incyte Corp	Composti di urea triciclici come inibitori di v617f di jak2
US11767323B2 (en)	2020-07-02	2023-09-26	Incyte Corporation	Tricyclic pyridone compounds as JAK2 V617F inhibitors
US11661422B2 (en)	2020-08-27	2023-05-30	Incyte Corporation	Tricyclic urea compounds as JAK2 V617F inhibitors
WO2022140231A1 (en)	2020-12-21	2022-06-30	Incyte Corporation	Deazaguaine compounds as jak2 v617f inhibitors
AR125273A1 (es)	2021-02-25	2023-07-05	Incyte Corp	Lactamas espirocíclicas como inhibidores de jak2 v617f
CN119173514A (zh)	2022-03-17	2024-12-20	因赛特公司	作为jak2 v617f抑制剂的三环脲化合物

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4670560A (en)	1986-04-28	1987-06-02	Ortho Pharmaceutical Corporation	Thienopyrimidine-2,4-dione derivatives and intermediates thereof
DE19636769A1 (de)	1996-09-10	1998-03-12	Basf Ag	3-Substituierte Pyrido [4',3':4,5]thieno[2,3-d]pyrimidin-Derivate, ihre Herstellung und Verwendung
DE19724980A1 (de)	1997-06-13	1998-12-17	Basf Ag	3-Substituierte 3,4-Dihydro-thieno[2,3-d]pyrimidin-Derivate, ihre Herstellung und Verwendung
DE19724979A1 (de)	1997-06-13	1998-12-17	Basf Ag	3-substituierte Pyrido [3,4,5]thieno[2,3-d]pyrimidin-Derivate, ihre Herstellung und Verwendung

1999
- 1999-01-11 DE DE19900545A patent/DE19900545A1/de not_active Withdrawn
- 1999-12-22 CZ CZ20012484A patent/CZ20012484A3/cs unknown
- 1999-12-22 ID IDW00200101717A patent/ID30022A/id unknown
- 1999-12-24 TR TR2001/02008T patent/TR200102008T2/xx unknown
- 1999-12-24 US US09/889,162 patent/US6387912B1/en not_active Expired - Fee Related
- 1999-12-24 BR BR9916887-1A patent/BR9916887A/pt not_active IP Right Cessation
- 1999-12-24 CZ CZ20012485A patent/CZ20012485A3/cs unknown
- 1999-12-24 CN CN99816172A patent/CN1334732A/zh active Pending
- 1999-12-24 JP JP2000593306A patent/JP2002534465A/ja active Pending
- 1999-12-24 IL IL14414699A patent/IL144146A0/xx unknown
- 1999-12-24 HK HK02104075.8A patent/HK1042649A1/zh unknown
- 1999-12-24 AU AU24338/00A patent/AU2433800A/en not_active Abandoned
- 1999-12-24 PL PL99348920A patent/PL348920A1/xx not_active Application Discontinuation
- 1999-12-24 KR KR1020017008692A patent/KR20010101442A/ko not_active Ceased
- 1999-12-24 EP EP99967980A patent/EP1140096A1/de not_active Withdrawn
- 1999-12-24 HU HU0201149A patent/HUP0201149A3/hu unknown
- 1999-12-24 CA CA002359253A patent/CA2359253A1/en not_active Abandoned
- 1999-12-24 SK SK969-2001A patent/SK9692001A3/sk unknown
- 1999-12-24 MX MXPA01006967A patent/MXPA01006967A/es not_active Application Discontinuation
- 1999-12-24 NZ NZ512767A patent/NZ512767A/en unknown
- 1999-12-24 WO PCT/EP1999/010369 patent/WO2000041695A1/de not_active Ceased
2000
- 2000-01-11 MY MYPI20000084A patent/MY133107A/en unknown
2001
- 2001-07-03 ZA ZA200105475A patent/ZA200105475B/en unknown
- 2001-07-10 NO NO20013409A patent/NO20013409L/no not_active Application Discontinuation
- 2001-07-10 BG BG105689A patent/BG105689A/xx unknown

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Publication number	Publication date
US6387912B1 (en)	2002-05-14
JP2002534465A (ja)	2002-10-15
CA2359253A1 (en)	2000-07-20
HUP0201149A3 (en)	2003-07-28
BG105689A (en)	2002-02-28
HK1042649A1 (zh)	2002-08-23
ID30022A (id)	2001-11-01
CZ20012484A3 (cs)	2002-05-15
KR20010101442A (ko)	2001-11-14
HUP0201149A2 (hu)	2002-07-29
CN1334732A (zh)	2002-02-06
MXPA01006967A (es)	2002-04-10
CZ20012485A3 (cs)	2002-04-17
IL144146A0 (en)	2002-05-23
MY133107A (en)	2007-10-31
AU2433800A (en)	2000-08-01
PL348920A1 (en)	2002-06-17
BR9916887A (pt)	2001-11-20
NZ512767A (en)	2003-05-30
TR200102008T2 (tr)	2001-12-21
EP1140096A1 (de)	2001-10-10
DE19900545A1 (de)	2000-07-13
NO20013409D0 (no)	2001-07-10
WO2000041695A1 (de)	2000-07-20
NO20013409L (no)	2001-08-30
ZA200105475B (en)	2002-10-03

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