UA78035C2 - Piperazine benzothiazole for treatment of cerebral ischemic disorders or cns disorders - Google Patents

Piperazine benzothiazole for treatment of cerebral ischemic disorders or cns disorders Download PDF

Info

Publication number: UA78035C2
Authority: UA; Ukraine
Prior art keywords: group; benzothiazol; pyrimidin; ylidene; piperazinebenzothiazole
Prior art date: 2002-04-25

Application number

UA20041008647A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Applied Research Systems

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.)

2002-04-25

Filing date

2003-04-25

Publication date

2007-02-15

2003-04-25 Application filed by Applied Research Systems filed Critical Applied Research Systems

2007-02-15 Publication of UA78035C2 publication Critical patent/UA78035C2/uk

Links

238000011282 treatment Methods 0.000 title claims abstract description 13
230000000302 ischemic effect Effects 0.000 title claims abstract description 12
230000002490 cerebral effect Effects 0.000 title claims abstract description 9
NZORAUGSDRBBBH-UHFFFAOYSA-N 1,3-benzothiazole;piperazine Chemical compound C1CNCCN1.C1=CC=C2SC=NC2=C1 NZORAUGSDRBBBH-UHFFFAOYSA-N 0.000 title abstract 2
238000000034 method Methods 0.000 claims abstract description 24
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
208000035475 disorder Diseases 0.000 claims abstract description 16
208000015114 central nervous system disease Diseases 0.000 claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 76
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 53
-1 C.-Cv-alkylacyl Chemical group 0.000 claims description 52
125000003118 aryl group Chemical group 0.000 claims description 24
125000001072 heteroaryl group Chemical group 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 14
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 11
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000003277 amino group Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
125000004442 acylamino group Chemical group 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 5
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 5
150000004702 methyl esters Chemical class 0.000 claims description 5
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
229940126601 medicinal product Drugs 0.000 claims description 4
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 2
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 2
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims 2
DQGMASZUGMDEFA-UHFFFAOYSA-N 1-methyl-2-nitrosoimidazole Chemical compound CN1C=CN=C1N=O DQGMASZUGMDEFA-UHFFFAOYSA-N 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 17
238000011321 prophylaxis Methods 0.000 abstract 1
239000000243 solution Substances 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
239000000203 mixture Substances 0.000 description 23
238000012360 testing method Methods 0.000 description 22
238000005481 NMR spectroscopy Methods 0.000 description 18
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 16
210000004556 brain Anatomy 0.000 description 16
229910052700 potassium Inorganic materials 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
230000008499 blood brain barrier function Effects 0.000 description 14
210000001218 blood-brain barrier Anatomy 0.000 description 14
230000035945 sensitivity Effects 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
125000001424 substituent group Chemical group 0.000 description 11
102000043136 MAP kinase family Human genes 0.000 description 10
108091054455 MAP kinase family Proteins 0.000 description 10
239000002904 solvent Substances 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
239000007788 liquid Substances 0.000 description 9
239000000843 powder Substances 0.000 description 9
239000000047 product Substances 0.000 description 9
238000005070 sampling Methods 0.000 description 9
230000004913 activation Effects 0.000 description 8
238000002347 injection Methods 0.000 description 8
239000007924 injection Substances 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
238000001914 filtration Methods 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
239000007787 solid Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
206010002091 Anaesthesia Diseases 0.000 description 6
102000040945 Transcription factor Human genes 0.000 description 6
108091023040 Transcription factor Proteins 0.000 description 6
230000037005 anaesthesia Effects 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
210000003169 central nervous system Anatomy 0.000 description 6
239000012043 crude product Substances 0.000 description 6
125000000753 cycloalkyl group Chemical group 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
238000001990 intravenous administration Methods 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
230000037361 pathway Effects 0.000 description 6
239000011347 resin Substances 0.000 description 6
229920005989 resin Polymers 0.000 description 6
ZMZSYUSDGRJZNT-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)acetonitrile Chemical compound C1=CC=C2SC(CC#N)=NC2=C1 ZMZSYUSDGRJZNT-UHFFFAOYSA-N 0.000 description 5
101100287730 Arabidopsis thaliana UMK2 gene Proteins 0.000 description 5
241000700159 Rattus Species 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
201000010099 disease Diseases 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
230000026731 phosphorylation Effects 0.000 description 5
238000006366 phosphorylation reaction Methods 0.000 description 5
125000004076 pyridyl group Chemical group 0.000 description 5
230000019491 signal transduction Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000000126 substance Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
241000699800 Cricetinae Species 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241000282414 Homo sapiens Species 0.000 description 4
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
210000001320 hippocampus Anatomy 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
QSSJZLPUHJDYKF-UHFFFAOYSA-N methyl 4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C=C1 QSSJZLPUHJDYKF-UHFFFAOYSA-N 0.000 description 4
210000002569 neuron Anatomy 0.000 description 4
239000003921 oil Substances 0.000 description 4
LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000002265 prevention Effects 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
125000003396 thiol group Chemical group [H]S* 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
208000023275 Autoimmune disease Diseases 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 3
102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 3
102000001708 Protein Isoforms Human genes 0.000 description 3
108010029485 Protein Isoforms Proteins 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
238000013459 approach Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
239000008187 granular material Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
230000002757 inflammatory effect Effects 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 3
UMYOUNGBUSQMCP-UHFFFAOYSA-N methyl 4-[(3-methylpiperazin-1-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1CC(C)NCC1 UMYOUNGBUSQMCP-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
230000004770 neurodegeneration Effects 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
125000004433 nitrogen atom Chemical group N* 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
239000000758 substrate Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 2
108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
108091000080 Phosphotransferase Proteins 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
238000010171 animal model Methods 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
229940001468 citrate Drugs 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000034994 death Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
230000016273 neuron death Effects 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
102000020233 phosphotransferase Human genes 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000008569 process Effects 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
238000000746 purification Methods 0.000 description 2
150000003230 pyrimidines Chemical class 0.000 description 2
238000010992 reflux Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
230000010410 reperfusion Effects 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000002195 soluble material Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
230000032258 transport Effects 0.000 description 2
238000005303 weighing Methods 0.000 description 2
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 1
125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 1
QVMKLKBODZHJDK-UHFFFAOYSA-N 2-(1,3-benzothiazol-2-yl)-2-(2-chloropyrimidin-4-yl)acetonitrile Chemical compound ClC1=NC=CC(C(C#N)C=2SC3=CC=CC=C3N=2)=N1 QVMKLKBODZHJDK-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
YSNKGJCEHOJIDK-UHFFFAOYSA-N 3-(chloromethyl)-1,2,4-oxadiazole Chemical compound ClCC=1N=CON=1 YSNKGJCEHOJIDK-UHFFFAOYSA-N 0.000 description 1
VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
101100492689 Arabidopsis thaliana ATE2 gene Proteins 0.000 description 1
102100033891 Arylsulfatase I Human genes 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
239000004342 Benzoyl peroxide Substances 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 description 1
206010048964 Carotid artery occlusion Diseases 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
208000018152 Cerebral disease Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
241000632511 Daviesia arborea Species 0.000 description 1
102000010170 Death domains Human genes 0.000 description 1
108050001718 Death domains Proteins 0.000 description 1
YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 1
102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
206010015548 Euthanasia Diseases 0.000 description 1
206010015719 Exsanguination Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000925544 Homo sapiens Arylsulfatase I Proteins 0.000 description 1
101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 1
101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
108010075654 MAP Kinase Kinase Kinase 1 Proteins 0.000 description 1
108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
235000006679 Mentha X verticillata Nutrition 0.000 description 1
235000002899 Mentha suaveolens Nutrition 0.000 description 1
235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
102000005741 Metalloproteases Human genes 0.000 description 1
108010006035 Metalloproteases Proteins 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
102100033115 Mitogen-activated protein kinase kinase kinase 1 Human genes 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
239000006057 Non-nutritive feed additive Substances 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
229920002230 Pectic acid Polymers 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000009056 active transport Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
150000007854 aminals Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
230000007503 antigenic stimulation Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
238000010241 blood sampling Methods 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
230000006931 brain damage Effects 0.000 description 1
231100000874 brain damage Toxicity 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000003139 buffering effect Effects 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
210000001715 carotid artery Anatomy 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000030833 cell death Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
210000004720 cerebrum Anatomy 0.000 description 1
238000000451 chemical ionisation Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid Chemical compound OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
229960002069 diamorphine Drugs 0.000 description 1
AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
210000003989 endothelium vascular Anatomy 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
230000003628 erosive effect Effects 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000005454 flavour additive Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
150000005694 halopyrimidines Chemical class 0.000 description 1
238000011553 hamster model Methods 0.000 description 1
210000002216 heart Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000002008 hemorrhagic effect Effects 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
238000010562 histological examination Methods 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
125000005990 isobenzothienyl group Chemical group 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
229960002725 isoflurane Drugs 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
229950006874 kainic acid Drugs 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229920006008 lipopolysaccharide Polymers 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
102000006240 membrane receptors Human genes 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
229940012189 methyl orange Drugs 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
210000004498 neuroglial cell Anatomy 0.000 description 1
230000009223 neuronal apoptosis Effects 0.000 description 1
230000000324 neuroprotective effect Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229960005010 orotic acid Drugs 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229960002695 phenobarbital Drugs 0.000 description 1
239000002953 phosphate buffered saline Substances 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
238000004262 preparative liquid chromatography Methods 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
229940001470 psychoactive drug Drugs 0.000 description 1
239000004089 psychotropic agent Substances 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
238000011403 purification operation Methods 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000016515 regulation of signal transduction Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
230000035939 shock Effects 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
210000001578 tight junction Anatomy 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
230000007723 transport mechanism Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
102000003390 tumor necrosis factor Human genes 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- 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)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

UA20041008647A 2002-04-25 2003-04-25 Piperazine benzothiazole for treatment of cerebral ischemic disorders or cns disorders UA78035C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02100417		2002-04-25
PCT/EP2003/004323 WO2003091249A1 (en)	2002-04-25	2003-04-25	Piperazine benzothiazoles as agents for the treatment of cerebral ischemic disorders or cns disorders

Publications (1)

Publication Number	Publication Date
UA78035C2 true UA78035C2 (en)	2007-02-15

Family

ID=29265991

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20041008647A UA78035C2 (en)	2002-04-25	2003-04-25	Piperazine benzothiazole for treatment of cerebral ischemic disorders or cns disorders

Country Status (22)

Country	Link
US (1)	US7314878B2 (sr)
EP (1)	EP1501828B1 (sr)
JP (1)	JP4523289B2 (sr)
KR (1)	KR100948469B1 (sr)
CN (1)	CN1310911C (sr)
AT (1)	ATE383356T1 (sr)
AU (1)	AU2003233067B2 (sr)
BR (1)	BRPI0309594A8 (sr)
CA (1)	CA2481763C (sr)
CY (1)	CY1107204T1 (sr)
DE (1)	DE60318567T2 (sr)
DK (1)	DK1501828T3 (sr)
EA (1)	EA009682B1 (sr)
ES (1)	ES2297165T3 (sr)
IL (2)	IL164796A0 (sr)
MX (1)	MXPA04010474A (sr)
PT (1)	PT1501828E (sr)
RS (1)	RS51407B (sr)
SI (1)	SI1501828T1 (sr)
UA (1)	UA78035C2 (sr)
WO (1)	WO2003091249A1 (sr)
ZA (1)	ZA200408023B (sr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RS51407B (sr)	2002-04-25	2011-02-28	Laboratoires Serono Sa	Piperazinski benzotijazoli kao agensi za lečenje cerabralnih ishemičnih poremećaja ili poremećaja cns
EP1696909B1 (en) *	2003-09-12	2007-11-14	Laboratoires Serono SA	Benzothiazole derivatives for the treatment of diabetes
WO2005118543A1 (ja) *	2004-06-03	2005-12-15	Ono Pharmaceutical Co., Ltd.	キナーゼ阻害薬およびその用途
US7838522B2 (en)	2004-11-17	2010-11-23	Ares Trading S.A.	Benzothiazole formulations and use thereof
ATE411817T1 (de) *	2004-11-17	2008-11-15	Ares Trading Sa	Benzothiazolformulierungen und ihre verwendung
BRPI0613042A2 (pt) *	2005-07-15	2010-12-14	Serono Lab	inibidores de jnk para o tratamento de endometriose
KR20080044836A (ko)	2005-07-15	2008-05-21	라보라뚜와르 세로노 에스. 에이.	자궁내막증 치료용 ｊｎｋ 억제제
WO2008125518A2 (en) *	2007-04-17	2008-10-23	Merck Serono S.A.	Process for the preparation of piperazine benzothiazoles
BRPI0912564A2 (pt) *	2008-05-16	2019-09-24	F. Hoffman-La Roche Ag	inibidores de jnk
ES2567828T3 (es) *	2010-06-04	2016-04-26	F. Hoffmann-La Roche Ag	Derivados 2-aminopirimidina útiles como inhibidores de JNK
US8471027B2 (en) *	2011-04-06	2013-06-25	Hoffmann-La Roche Inc.	Adamantyl compounds
CN104903331A (zh) *	2013-01-24	2015-09-09	山东亨利医药科技有限责任公司	Jnk抑制剂

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4153574B2 (ja) *	1997-09-10	2008-09-24	トーアエイヨー株式会社	新規なピペリジン誘導体、その製造法およびそれを含有する循環器官用剤
EP1110957A1 (en) *	1999-12-24	2001-06-27	Applied Research Systems ARS Holding N.V.	Benzazole derivatives and their use as JNK modulators
EP1193256A1 (en) *	2000-09-27	2002-04-03	Applied Research Systems ARS Holding N.V.	Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins
RS51407B (sr)	2002-04-25	2011-02-28	Laboratoires Serono Sa	Piperazinski benzotijazoli kao agensi za lečenje cerabralnih ishemičnih poremećaja ili poremećaja cns

2003
- 2003-04-25 RS YUP-928/04A patent/RS51407B/sr unknown
- 2003-04-25 EP EP03727365A patent/EP1501828B1/en not_active Expired - Lifetime
- 2003-04-25 CA CA2481763A patent/CA2481763C/en not_active Expired - Fee Related
- 2003-04-25 IL IL16479603A patent/IL164796A0/xx unknown
- 2003-04-25 US US10/511,438 patent/US7314878B2/en not_active Expired - Lifetime
- 2003-04-25 KR KR1020047016871A patent/KR100948469B1/ko not_active Expired - Fee Related
- 2003-04-25 DK DK03727365T patent/DK1501828T3/da active
- 2003-04-25 PT PT03727365T patent/PT1501828E/pt unknown
- 2003-04-25 AU AU2003233067A patent/AU2003233067B2/en not_active Ceased
- 2003-04-25 WO PCT/EP2003/004323 patent/WO2003091249A1/en not_active Ceased
- 2003-04-25 JP JP2003587807A patent/JP4523289B2/ja not_active Expired - Fee Related
- 2003-04-25 EA EA200401423A patent/EA009682B1/ru not_active IP Right Cessation
- 2003-04-25 CN CNB03814493XA patent/CN1310911C/zh not_active Expired - Fee Related
- 2003-04-25 UA UA20041008647A patent/UA78035C2/uk unknown
- 2003-04-25 BR BRPI0309594A patent/BRPI0309594A8/pt not_active IP Right Cessation
- 2003-04-25 MX MXPA04010474A patent/MXPA04010474A/es active IP Right Grant
- 2003-04-25 IL IL164796A patent/IL164796A/en not_active IP Right Cessation
- 2003-04-25 DE DE60318567T patent/DE60318567T2/de not_active Expired - Lifetime
- 2003-04-25 SI SI200331114T patent/SI1501828T1/sl unknown
- 2003-04-25 AT AT03727365T patent/ATE383356T1/de active
- 2003-04-25 ES ES03727365T patent/ES2297165T3/es not_active Expired - Lifetime
2004
- 2004-10-05 ZA ZA2004/08023A patent/ZA200408023B/en unknown
2008
- 2008-02-18 CY CY20081100199T patent/CY1107204T1/el unknown

Also Published As

Publication number	Publication date
JP2006504631A (ja)	2006-02-09
EA009682B1 (ru)	2008-02-28
RS92804A (sr)	2006-12-15
CA2481763C (en)	2011-06-14
EA200401423A1 (ru)	2005-04-28
AU2003233067A1 (en)	2003-11-10
US7314878B2 (en)	2008-01-01
EP1501828B1 (en)	2008-01-09
ES2297165T3 (es)	2008-05-01
HK1075664A1 (en)	2005-12-23
DE60318567T2 (de)	2009-02-19
BRPI0309594A2 (pt)	2016-11-16
CN1310911C (zh)	2007-04-18
ZA200408023B (en)	2005-11-30
DK1501828T3 (da)	2008-03-10
WO2003091249A1 (en)	2003-11-06
KR100948469B1 (ko)	2010-03-17
EP1501828A1 (en)	2005-02-02
CN1662528A (zh)	2005-08-31
SI1501828T1 (sl)	2008-04-30
CY1107204T1 (el)	2012-11-21
RS51407B (sr)	2011-02-28
IL164796A (en)	2013-02-28
US20050261304A1 (en)	2005-11-24
JP4523289B2 (ja)	2010-08-11
AU2003233067B2 (en)	2009-01-08
CA2481763A1 (en)	2003-11-06
KR20040104572A (ko)	2004-12-10
IL164796A0 (en)	2005-12-18
MXPA04010474A (es)	2004-12-13
BRPI0309594A8 (pt)	2017-04-11
ATE383356T1 (de)	2008-01-15
PT1501828E (pt)	2008-02-11
DE60318567D1 (de)	2008-02-21

Publication	Publication Date	Title
CN101925301B (zh)	2014-09-17	作为TNF-α合成调节剂和作为PDE4抑制剂的三环化合物
KR102216284B1 (ko)	2021-02-18	Dna-pk 억제제
JP5283336B2 (ja)	2013-09-04	選択的キナーゼ阻害剤
EP3597649B1 (en)	2021-10-13	Compositions containing substituted [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compounds as pde2 inhibitors
WO2021258010A1 (en)	2021-12-23	Oxime compounds useful as t cell activators
CN101163694A (zh)	2008-04-16	作为抑制细胞增殖药物的4-（咪唑-5-基）-2-氨基-嘧啶类
CA2883894A1 (en)	2014-03-13	Compounds and methods for kinase modulation, and indications therefor
CN101472915A (zh)	2009-07-01	吲唑化合物和抑制cdc7的方法
UA78035C2 (en)	2007-02-15	Piperazine benzothiazole for treatment of cerebral ischemic disorders or cns disorders
US12145923B2 (en)	2024-11-19	Tetrahydroisoquinoline compound, preparation method therefor, pharmaceutical composition containing same, and use thereof
WO2018170204A1 (en)	2018-09-20	9,10,11,12-tetrahydro-8h-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one compounds and uses thereof
EP3586848A1 (en)	2020-01-01	Pharmaceutical composition comprising compound capable of penetrating blood-brain barrier as effective ingredient for preventing or treating brain cancer
CA2524161C (en)	2013-01-15	Pyridinyl acetonitriles
CN108929312A (zh)	2018-12-04	具有cdk或hdac抑制活性的新型苯并杂环联嘧啶抑制剂
CN110467610A (zh)	2019-11-19	一种取代嘧啶化合物、其制备方法和用途
EA014083B1 (ru)	2010-08-30	Новые производные индолкарбоксамида, содержащая их фармацевтическая композиция и способ лечения
CN110467629B (zh)	2022-04-08	苯醌衍生物、其药物组合物及应用
CN111848605B (zh)	2023-05-02	一种取代吡啶并[3,4-b]吡嗪-2(1H)-酮化合物、其制备方法和用途
US20220213059A1 (en)	2022-07-07	Inhibiting usp19
US11633415B2 (en)	2023-04-25	Compounds and methods useful for treating or preventing cancers
HK40083035B (zh)	2024-11-29	Parp7抑制剂及其用途
WO2024153143A1 (zh)	2024-07-25	含氮并环类化合物及其应用
CN109942562A (zh)	2019-06-28	含芳基结构的五元杂环联三嗪类化合物及其制备方法和应用