AU2002302419B2 - Substituted Pyrazolopyrimidines and thiazolopyrimidines used as analgesics - Google Patents
Substituted Pyrazolopyrimidines and thiazolopyrimidines used as analgesics Download PDFInfo
- Publication number
- AU2002302419B2 AU2002302419B2 AU2002302419A AU2002302419A AU2002302419B2 AU 2002302419 B2 AU2002302419 B2 AU 2002302419B2 AU 2002302419 A AU2002302419 A AU 2002302419A AU 2002302419 A AU2002302419 A AU 2002302419A AU 2002302419 B2 AU2002302419 B2 AU 2002302419B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- aryl
- denotes
- cycloalkyl
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 5
- 150000008634 thiazolopyrimidines Chemical class 0.000 title description 4
- 229940035676 analgesics Drugs 0.000 title 1
- 239000000730 antalgic agent Substances 0.000 title 1
- -1 thiazolo-pyrimidine compounds Chemical class 0.000 claims abstract description 209
- 125000003118 aryl group Chemical group 0.000 claims abstract description 168
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 69
- 239000002253 acid Substances 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 42
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 27
- 229910004013 NO 2 Inorganic materials 0.000 claims abstract description 23
- 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 abstract description 22
- 108020003175 receptors Proteins 0.000 claims abstract description 13
- 239000003446 ligand Substances 0.000 claims abstract description 12
- 102000019055 Nucleoside Transport Proteins Human genes 0.000 claims abstract description 10
- 108010012315 Nucleoside Transport Proteins Proteins 0.000 claims abstract description 10
- 150000004677 hydrates Chemical class 0.000 claims abstract description 10
- 239000012453 solvate Substances 0.000 claims abstract description 10
- OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 102100032534 Adenosine kinase Human genes 0.000 claims abstract description 8
- 108010076278 Adenosine kinase Proteins 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims abstract description 7
- 102000055025 Adenosine deaminases Human genes 0.000 claims abstract description 7
- 230000000241 respiratory effect Effects 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 101150009274 nhr-1 gene Proteins 0.000 claims abstract 4
- 150000003254 radicals Chemical class 0.000 claims description 143
- 229910052739 hydrogen Inorganic materials 0.000 claims description 84
- 229910052799 carbon Inorganic materials 0.000 claims description 66
- 239000000460 chlorine Substances 0.000 claims description 62
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 125000004429 atom Chemical group 0.000 claims description 55
- BFKYQYMHJANOTR-UHFFFAOYSA-N 2h-pyrimidine-1-carbonitrile Chemical compound N#CN1CN=CC=C1 BFKYQYMHJANOTR-UHFFFAOYSA-N 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 45
- 125000004494 ethyl ester group Chemical group 0.000 claims description 41
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 41
- 229910052801 chlorine Inorganic materials 0.000 claims description 36
- 229910052794 bromium Inorganic materials 0.000 claims description 34
- 229910052731 fluorine Inorganic materials 0.000 claims description 33
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 25
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 25
- 239000011737 fluorine Substances 0.000 claims description 25
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 21
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 21
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 20
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 20
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 150000001336 alkenes Chemical class 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- QOKLSVOEHNDZCY-UHFFFAOYSA-N 9h-fluorene-3-carbonitrile Chemical compound C1=CC=C2C3=CC(C#N)=CC=C3CC2=C1 QOKLSVOEHNDZCY-UHFFFAOYSA-N 0.000 claims description 15
- 206010021143 Hypoxia Diseases 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 15
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 208000018737 Parkinson disease Diseases 0.000 claims description 13
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
- 230000000626 neurodegenerative effect Effects 0.000 claims description 13
- 229960004889 salicylic acid Drugs 0.000 claims description 13
- 201000000980 schizophrenia Diseases 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 208000023105 Huntington disease Diseases 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 206010015037 epilepsy Diseases 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
- XHUWDDXMORFULQ-UHFFFAOYSA-N ethyl 2h-pyrimidine-1-carboxylate Chemical compound CCOC(=O)N1CN=CC=C1 XHUWDDXMORFULQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 238000011321 prophylaxis Methods 0.000 claims description 10
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 229960001867 guaiacol Drugs 0.000 claims description 9
- 208000030507 AIDS Diseases 0.000 claims description 8
- 241000976983 Anoxia Species 0.000 claims description 8
- 206010048962 Brain oedema Diseases 0.000 claims description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 8
- 206010012289 Dementia Diseases 0.000 claims description 8
- 206010028923 Neonatal asphyxia Diseases 0.000 claims description 8
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 claims description 8
- 208000028017 Psychotic disease Diseases 0.000 claims description 8
- 208000009205 Tinnitus Diseases 0.000 claims description 8
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 8
- 208000016620 Tourette disease Diseases 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 230000007953 anoxia Effects 0.000 claims description 8
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 201000002491 encephalomyelitis Diseases 0.000 claims description 8
- 230000007954 hypoxia Effects 0.000 claims description 8
- 230000007574 infarction Effects 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
- 208000033300 perinatal asphyxia Diseases 0.000 claims description 8
- 231100000886 tinnitus Toxicity 0.000 claims description 8
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010002660 Anoxia Diseases 0.000 claims description 7
- 206010008118 cerebral infarction Diseases 0.000 claims description 7
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims description 7
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 6
- UGSCIXIGNBKLBH-UHFFFAOYSA-N 2,3,3a,6-tetrahydro-1h-pyrazolo[4,3-d]pyrimidine Chemical compound N1C=NC2CNNC2=C1 UGSCIXIGNBKLBH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 206010050081 Neonatal hypoxia Diseases 0.000 claims description 5
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- 206010003119 arrhythmia Diseases 0.000 claims description 5
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
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- 230000004968 inflammatory condition Effects 0.000 claims description 5
- 208000014674 injury Diseases 0.000 claims description 5
- 201000006370 kidney failure Diseases 0.000 claims description 5
- 230000007257 malfunction Effects 0.000 claims description 5
- 230000037361 pathway Effects 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 230000036303 septic shock Effects 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 230000025747 negative regulation of nucleoside transport Effects 0.000 claims description 4
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- RFWWOHKMHRVFDD-UHFFFAOYSA-N diethyl 9H-fluorene-3,5-dicarboxylate Chemical compound C(C)OC(=O)C=1C=CC=2CC=3C=CC=C(C=3C=2C=1)C(=O)OCC RFWWOHKMHRVFDD-UHFFFAOYSA-N 0.000 claims description 3
- BYGYIGUYLXZWPE-UHFFFAOYSA-N ethyl 9h-fluorene-3-carboxylate Chemical compound C1=CC=C2C3=CC(C(=O)OCC)=CC=C3CC2=C1 BYGYIGUYLXZWPE-UHFFFAOYSA-N 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 claims description 2
- 101100294104 Caenorhabditis elegans nhr-34 gene Proteins 0.000 claims description 2
- LZMSCOOAVVUPKJ-UHFFFAOYSA-N OC1=NN2C3C=CCC3C(C(=O)OCC)N=C2C1N=NC1=CC=CC=C1 Chemical compound OC1=NN2C3C=CCC3C(C(=O)OCC)N=C2C1N=NC1=CC=CC=C1 LZMSCOOAVVUPKJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- GVGCDHFBWGHAPY-UHFFFAOYSA-N ethyl 5-benzoyl-7-(3-fluorophenyl)-1,2,3,3a-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound CCOC(=O)C1CNN2C1N=C(C(=O)C=1C=CC=CC=1)C=C2C1=CC=CC(F)=C1 GVGCDHFBWGHAPY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 238000005580 one pot reaction Methods 0.000 claims description 2
- HWKXCHCGEBXUFJ-UHFFFAOYSA-N phenanthrene-3-carbonitrile Chemical compound C1=CC=C2C3=CC(C#N)=CC=C3C=CC2=C1 HWKXCHCGEBXUFJ-UHFFFAOYSA-N 0.000 claims description 2
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- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 3
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- SMDJWMDYFAQYJZ-UHFFFAOYSA-N 1-(2-phenylethyl)-3,3a-dihydro-2h-pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound N12C=CC=NC2C(C#N)CN1CCC1=CC=CC=C1 SMDJWMDYFAQYJZ-UHFFFAOYSA-N 0.000 claims 1
- NZTUTBNYSZXHHP-UHFFFAOYSA-N C(C)OC(=O)C=1C(=NN2C3OCCC3CNC12)C1CCCCC1 Chemical compound C(C)OC(=O)C=1C(=NN2C3OCCC3CNC12)C1CCCCC1 NZTUTBNYSZXHHP-UHFFFAOYSA-N 0.000 claims 1
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- BPUCGEOUUDXRTH-UHFFFAOYSA-N ethyl 2-[3-bromo-7-(4-bromophenyl)-1,2,3,3a-tetrahydropyrazolo[1,5-a]pyrimidin-5-yl]cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1C(C=C1C=2C=CC(Br)=CC=2)=NC2N1NCC2Br BPUCGEOUUDXRTH-UHFFFAOYSA-N 0.000 claims 1
- SPSMBUPGPMHVGS-UHFFFAOYSA-N ethyl 7-cyclopropyl-3-oxa-1,8,12-triazatricyclo[7.3.0.02,6]dodeca-8,11-diene-10-carboxylate Chemical compound N1=C2C(C(=O)OCC)C=NN2C2OCCC2C1C1CC1 SPSMBUPGPMHVGS-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 125000006501 nitrophenyl group Chemical group 0.000 claims 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
- 230000027455 binding Effects 0.000 abstract description 14
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- CJPCIJLKUZKGER-UHFFFAOYSA-N 4-(4-methylphenyl)-2-(4-nitrophenyl)-3,4-dihydro-2h-pyrimido[2,1-b][1,3]benzothiazole Chemical compound C1=CC(C)=CC=C1C1N2C3=CC=CC=C3SC2=NC(C=2C=CC(=CC=2)[N+]([O-])=O)C1 CJPCIJLKUZKGER-UHFFFAOYSA-N 0.000 abstract description 2
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- 125000004981 cycloalkylmethyl group Chemical group 0.000 abstract 5
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 abstract 3
- 101150065749 Churc1 gene Proteins 0.000 abstract 3
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- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- General Health & Medical Sciences (AREA)
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- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
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- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
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- Pulmonology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2001112197 DE10112197A1 (de) | 2001-03-14 | 2001-03-14 | Substituierte Pyrazolo- und Thiazolopyrimidine |
| DE10112197.0 | 2001-03-14 | ||
| DE2001153344 DE10153344A1 (de) | 2001-10-29 | 2001-10-29 | Verwendung von substituierten Pyrazolopyrimidinen als Liganden von Nucleosid-Transport-Proteinen und/oder von Purinorezeptoren |
| DE10153344.6 | 2001-10-29 | ||
| PCT/EP2002/002722 WO2002072585A2 (de) | 2001-03-14 | 2002-03-13 | Substituierte pyrazolo- und thiazolopyrimidine als analgetika |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002302419A1 AU2002302419A1 (en) | 2003-03-20 |
| AU2002302419B2 true AU2002302419B2 (en) | 2007-01-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002302419A Ceased AU2002302419B2 (en) | 2001-03-14 | 2002-03-13 | Substituted Pyrazolopyrimidines and thiazolopyrimidines used as analgesics |
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| EP (2) | EP1637533B1 (enExample) |
| JP (1) | JP2004527508A (enExample) |
| KR (1) | KR20030082982A (enExample) |
| CN (1) | CN1318422C (enExample) |
| AT (2) | ATE328886T1 (enExample) |
| AU (1) | AU2002302419B2 (enExample) |
| BR (1) | BR0208244A (enExample) |
| CA (1) | CA2440760C (enExample) |
| CY (1) | CY1105507T1 (enExample) |
| CZ (1) | CZ20032474A3 (enExample) |
| DE (2) | DE50212652D1 (enExample) |
| DK (1) | DK1368355T3 (enExample) |
| ES (2) | ES2263779T3 (enExample) |
| HU (1) | HUP0401211A3 (enExample) |
| IL (2) | IL157895A0 (enExample) |
| MX (1) | MXPA03008291A (enExample) |
| NO (1) | NO20034031L (enExample) |
| NZ (2) | NZ540574A (enExample) |
| PL (1) | PL364388A1 (enExample) |
| PT (1) | PT1368355E (enExample) |
| RU (1) | RU2003129060A (enExample) |
| SK (1) | SK11542003A3 (enExample) |
| WO (1) | WO2002072585A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003265585B2 (en) * | 2002-08-26 | 2008-07-03 | Takeda Pharmaceutical Company Limited | Calcium receptor modulating compound and use thereof |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004076450A1 (en) * | 2003-02-27 | 2004-09-10 | J. Uriach Y Compañia S.A. | Pyrazolopyridine derivates |
| GB0404434D0 (en) | 2004-02-27 | 2004-03-31 | Novartis Ag | Organic compounds |
| WO2005112936A1 (en) * | 2004-05-14 | 2005-12-01 | The Regents Of The University Of Michigan | Compositions and methods relating to protein kinase inhibitors |
| TW200618800A (en) * | 2004-08-03 | 2006-06-16 | Uriach Y Compania S A J | Heterocyclic compounds |
| EP1736475A1 (en) * | 2005-06-21 | 2006-12-27 | Ferrer Internacional, S.A. | Halogenated pyrazolo[1,5-a]pyrimidines, processes, uses, compositions and intermediates |
| KR100838692B1 (ko) | 2007-07-11 | 2008-06-16 | 한국화학연구원 | 7-(3′,4′-디알콕시페닐)-4,5,6,7-테트라히드로피라졸로[1,5-ａ]피리미딘 화합물, 이의 제조방법 및 이를 포함하는천식 및 만성폐쇄성 폐질환을 포함한 염증관련 질환,관절염, 아토피 피부염, 암 및 뇌질환의 치료 및 예방을위한 약제학적 조성물 |
| WO2009093210A2 (ru) * | 2008-01-24 | 2009-07-30 | Alla Chem, Llc | ЗАМЕЩЕННЫЕ ЦИKЛOAЛKAHO[e ИЛИ d]ПИPAЗOЛO[l,5-a]ПИPИMИДИHЫ - АНТАГОНИСТЫ СЕРОТОНИНОВЫХ 5-HT6 РЕЦЕПТОРОВ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| RU2376291C1 (ru) * | 2008-05-07 | 2009-12-20 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ 3,5-ДИАМИНО-4-СУЛЬФОНИЛ-ПИРАЗОЛЫ И 2-АМИНО-3-СУЛЬФОНИЛ-ПИРАЗОЛО[1,5-a]ПИРИМИДИНЫ - АНТАГОНИСТЫ СЕРОТОНИНОВЫХ 5-HT6 РЕЦЕПТОРОВ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| RU2369600C1 (ru) * | 2008-01-24 | 2009-10-10 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ 4-СУЛЬФОНИЛ-ПИРАЗОЛЫ И 3-СУЛЬФОНИЛ-ПИРАЗОЛО[1,5-a]ПИРИМИДИНЫ - АНТАГОНИСТЫ СЕРОТОНИНОВЫХ5-HT6 РЕЦЕПТОРОВ, АКТИВНЫЙ КОМПОНЕНТ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ЛЕКАРСТВЕННОЕ СРЕДСТВО И СПОСОБЫ ИХ ПОЛУЧЕНИЯ |
| JP5584626B2 (ja) * | 2008-01-24 | 2014-09-03 | アンドレイ・アレクサンドロビッチ・イワシェンコ | ２−アルキルアミノ−３−（アリールスルホニル）−シクロアルキル［ｅ又はｄ］ピラゾロ［１，５−ａ］ピリミジン−セロトニン５−ＨＴ６受容体アンタゴニスト、その調製の方法及び使用 |
| RU2374249C1 (ru) * | 2008-09-17 | 2009-11-27 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ ЦИКЛОАЛКАНО[е ИЛИ d]ПИРАЗОЛО[1,5-а]ПИРИМИДИНЫ - АНТАГОНИСТЫ СЕРОТОНИНОВЫХ 5-НТ6 РЕЦЕПТОРОВ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| US8618114B2 (en) | 2008-10-06 | 2013-12-31 | Andrey Alexandrovich Ivashchenko | Substituted 3-arylsulfonyl-pyrazolo[1,5-A]pyrimidines, serotonin 5-HT6 receptor antagonists and methods for the production and use thereof |
| AR074702A1 (es) * | 2008-12-22 | 2011-02-02 | Schering Corp | Moduladores de gamma secretasa y composiciones farmaceuticas que los contienen |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| CN102775412B (zh) * | 2012-08-21 | 2013-05-01 | 四川大学 | 一种镇静催眠的化合物及其制备方法和用途 |
| CN102977106B (zh) * | 2012-12-12 | 2014-12-10 | 中国药科大学 | 一类具有外周镇痛作用的κ阿片受体激动剂 |
| ES2687481T3 (es) * | 2013-03-15 | 2018-10-25 | Chromocell Corporation | Moduladores del canal de sodio para el tratamiento del dolor |
| KR20160054570A (ko) * | 2013-09-10 | 2016-05-16 | 크로모셀 코포레이션 | 통증과 당뇨병의 치료를 위한 나트륨 통로 조절인자 |
| WO2016123629A1 (en) * | 2015-01-30 | 2016-08-04 | Vanderbilt University | Indazole and azaindazole substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| AU2016338679B2 (en) | 2015-10-16 | 2021-05-06 | Eisai R&D Management Co., Ltd. | EP4 antagonists |
| WO2018133835A1 (en) * | 2017-01-20 | 2018-07-26 | National Institute Of Biological Sciences, Beijing | Nucleoside analogue regulating mammalian circadian rhythm |
| WO2018199236A1 (ja) | 2017-04-27 | 2018-11-01 | 武田薬品工業株式会社 | 複素環化合物 |
| US10919891B2 (en) * | 2017-04-27 | 2021-02-16 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| CN113354644B (zh) * | 2020-03-04 | 2023-07-04 | 烟台药物研究所 | 一类用作dpp-iv抑制剂的吡唑并嘧啶结构的化合物及应用 |
| CN116023382B (zh) * | 2023-02-22 | 2025-09-23 | 北京师范大学 | 一种合成手性四氢吡唑并[1,5-a]嘧啶的方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0264773A1 (en) | 1986-10-16 | 1988-04-27 | American Cyanamid Company | 4,5-dihydro and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidines |
| US4847256A (en) * | 1986-10-16 | 1989-07-11 | American Cyanamid Company | 4,5-dihydro and 4,5,6,7-tetrahydropyrazolo(1,5-A)-pyrimidines |
| ZA903588B (en) * | 1989-05-16 | 1991-02-27 | Merrell Dow Pharma | Excitatory amino acid antagonists |
| GB9206266D0 (en) * | 1992-03-23 | 1992-05-06 | Merck Sharp & Dohme | Therapeutic agents |
| FR2717812B1 (fr) * | 1994-03-28 | 1996-05-10 | Rhone Poulenc Rorer Sa | Indeno[1,2-e]pyrazine-4-ones, leur préparation et les médicaments les contenant. |
| FR2722786B1 (fr) * | 1994-07-20 | 1996-08-23 | Rhone Poulenc Rorer Sa | Derives de 4-hydroxy-3-phenyl-indeno(1,2-b)pyridine-2(1h)- one, leur preparation et les medicaments les contenant |
| DE4444815A1 (de) * | 1994-12-15 | 1996-06-20 | Merck Patent Gmbh | Thienopyridone |
| JP2003288537A (ja) | 2000-09-25 | 2003-10-10 | Everyd.Com:Kk | 商品宅配システムおよび方法 |
| DE10112197A1 (de) | 2001-03-14 | 2002-09-19 | Gruenenthal Gmbh | Substituierte Pyrazolo- und Thiazolopyrimidine |
-
2002
- 2002-03-13 NZ NZ540574A patent/NZ540574A/en unknown
- 2002-03-13 PT PT02729998T patent/PT1368355E/pt unknown
- 2002-03-13 CZ CZ20032474A patent/CZ20032474A3/cs unknown
- 2002-03-13 WO PCT/EP2002/002722 patent/WO2002072585A2/de not_active Ceased
- 2002-03-13 DE DE50212652T patent/DE50212652D1/de not_active Expired - Lifetime
- 2002-03-13 DE DE50207103T patent/DE50207103D1/de not_active Expired - Lifetime
- 2002-03-13 KR KR10-2003-7011953A patent/KR20030082982A/ko not_active Withdrawn
- 2002-03-13 DK DK02729998T patent/DK1368355T3/da active
- 2002-03-13 AT AT02729998T patent/ATE328886T1/de not_active IP Right Cessation
- 2002-03-13 JP JP2002571501A patent/JP2004527508A/ja active Pending
- 2002-03-13 PL PL02364388A patent/PL364388A1/xx not_active Application Discontinuation
- 2002-03-13 SK SK1154-2003A patent/SK11542003A3/sk unknown
- 2002-03-13 ES ES02729998T patent/ES2263779T3/es not_active Expired - Lifetime
- 2002-03-13 CA CA2440760A patent/CA2440760C/en not_active Expired - Fee Related
- 2002-03-13 EP EP05026811A patent/EP1637533B1/de not_active Expired - Lifetime
- 2002-03-13 IL IL15789502A patent/IL157895A0/xx unknown
- 2002-03-13 HU HU0401211A patent/HUP0401211A3/hu unknown
- 2002-03-13 AT AT05026811T patent/ATE404568T1/de not_active IP Right Cessation
- 2002-03-13 AU AU2002302419A patent/AU2002302419B2/en not_active Ceased
- 2002-03-13 MX MXPA03008291A patent/MXPA03008291A/es active IP Right Grant
- 2002-03-13 BR BR0208244-6A patent/BR0208244A/pt not_active Application Discontinuation
- 2002-03-13 RU RU2003129060/04A patent/RU2003129060A/ru not_active Application Discontinuation
- 2002-03-13 NZ NZ528639A patent/NZ528639A/en unknown
- 2002-03-13 ES ES05026811T patent/ES2311920T3/es not_active Expired - Lifetime
- 2002-03-13 CN CNB028096886A patent/CN1318422C/zh not_active Expired - Fee Related
- 2002-03-13 EP EP02729998A patent/EP1368355B1/de not_active Expired - Lifetime
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2003
- 2003-09-11 NO NO20034031A patent/NO20034031L/no not_active Application Discontinuation
- 2003-09-11 IL IL157895A patent/IL157895A/en not_active IP Right Cessation
- 2003-09-12 US US10/660,794 patent/US7135568B2/en not_active Expired - Fee Related
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003265585B2 (en) * | 2002-08-26 | 2008-07-03 | Takeda Pharmaceutical Company Limited | Calcium receptor modulating compound and use thereof |
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