CA2532505A1 - 5-ht2b receptor antagonists - Google Patents
5-ht2b receptor antagonists Download PDFInfo
- Publication number
- CA2532505A1 CA2532505A1 CA002532505A CA2532505A CA2532505A1 CA 2532505 A1 CA2532505 A1 CA 2532505A1 CA 002532505 A CA002532505 A CA 002532505A CA 2532505 A CA2532505 A CA 2532505A CA 2532505 A1 CA2532505 A1 CA 2532505A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- alkyl
- group
- phenyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000006969 5-HT2B Serotonin Receptor Human genes 0.000 title claims abstract description 19
- 108010072584 5-HT2B Serotonin Receptor Proteins 0.000 title claims abstract description 15
- 229940044551 receptor antagonist Drugs 0.000 title description 4
- 239000002464 receptor antagonist Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 308
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 230000008485 antagonism Effects 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims description 141
- 125000000217 alkyl group Chemical group 0.000 claims description 123
- -1 3,5-diacetyl-phenyl Chemical group 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 51
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000005488 carboaryl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 9
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 9
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 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
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 8
- 125000006267 biphenyl group Chemical group 0.000 claims 3
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 239000007787 solid Substances 0.000 description 162
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 124
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 101
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
- 238000005160 1H NMR spectroscopy Methods 0.000 description 92
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 74
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
- 239000000203 mixture Substances 0.000 description 64
- 230000002829 reductive effect Effects 0.000 description 58
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 39
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 35
- 238000001819 mass spectrum Methods 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 125000006413 ring segment Chemical group 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 125000000753 cycloalkyl group Chemical group 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 102000005962 receptors Human genes 0.000 description 24
- 108020003175 receptors Proteins 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 24
- 101150041968 CDC13 gene Proteins 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 125000001072 heteroaryl group Chemical group 0.000 description 19
- 125000003277 amino group Chemical group 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000001257 hydrogen Substances 0.000 description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 18
- YMXFJTUQQVLJEN-UHFFFAOYSA-N pyrimidine Chemical compound C1=CN=CN=C1.C1=CN=CN=C1 YMXFJTUQQVLJEN-UHFFFAOYSA-N 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 125000003545 alkoxy group Chemical group 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 14
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 14
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 13
- 239000006071 cream Substances 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 125000000524 functional group Chemical group 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 230000027455 binding Effects 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- GHCAUEMXBSLMGU-UHFFFAOYSA-N oxadiazole;1,2,5-oxadiazole Chemical compound C=1C=NON=1.C1=CON=N1 GHCAUEMXBSLMGU-UHFFFAOYSA-N 0.000 description 12
- HUUBMTMJIQHAEN-UHFFFAOYSA-N triazole-1,4-diamine Chemical class NC1=CN(N)N=N1 HUUBMTMJIQHAEN-UHFFFAOYSA-N 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 11
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 238000004007 reversed phase HPLC Methods 0.000 description 11
- 235000015096 spirit Nutrition 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 125000000304 alkynyl group Chemical group 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 8
- 125000003368 amide group Chemical group 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- ZNGSQFZFQNTPEX-UHFFFAOYSA-N 5-(3-phenylphenyl)-1,3-oxazol-2-amine Chemical class O1C(N)=NC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 ZNGSQFZFQNTPEX-UHFFFAOYSA-N 0.000 description 7
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- NKZDYLNPYDZBGW-UHFFFAOYSA-N 4-(3-bromophenyl)-5-methyl-1,3-oxazol-2-amine Chemical compound O1C(N)=NC(C=2C=C(Br)C=CC=2)=C1C NKZDYLNPYDZBGW-UHFFFAOYSA-N 0.000 description 6
- DUFYLMWYIOZYQZ-UHFFFAOYSA-N 5-(3-bromophenyl)-4-methyl-1,3-oxazol-2-amine Chemical compound N1=C(N)OC(C=2C=C(Br)C=CC=2)=C1C DUFYLMWYIOZYQZ-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 0 CN(*)c1nc(*)c(*)c(**)n1 Chemical compound CN(*)c1nc(*)c(*)c(**)n1 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical group 0.000 description 6
- 239000012131 assay buffer Substances 0.000 description 6
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-M carbamimidothioate Chemical compound NC([S-])=N UMGDCJDMYOKAJW-UHFFFAOYSA-M 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
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- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- UOMDLCVGPUNXQV-UHFFFAOYSA-N 2-bromo-1-(2-phenylphenyl)ethanone Chemical compound BrCC(=O)C1=CC=CC=C1C1=CC=CC=C1 UOMDLCVGPUNXQV-UHFFFAOYSA-N 0.000 description 5
- KOLBVAJFUNZULQ-UHFFFAOYSA-N 5-(2-phenylphenyl)-1,3-oxazol-2-amine Chemical compound O1C(N)=NC=C1C1=CC=CC=C1C1=CC=CC=C1 KOLBVAJFUNZULQ-UHFFFAOYSA-N 0.000 description 5
- KNXIHOLLWXXRDZ-UHFFFAOYSA-N 5-(3-phenylphenyl)-1h-imidazol-2-amine Chemical compound N1C(N)=NC(C=2C=C(C=CC=2)C=2C=CC=CC=2)=C1 KNXIHOLLWXXRDZ-UHFFFAOYSA-N 0.000 description 5
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
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- 238000001514 detection method Methods 0.000 description 5
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- SCQRELOVXUWDGP-UHFFFAOYSA-N n-[5-(3-phenylphenyl)-1h-imidazol-2-yl]acetamide Chemical compound N1C(NC(=O)C)=NC(C=2C=C(C=CC=2)C=2C=CC=CC=2)=C1 SCQRELOVXUWDGP-UHFFFAOYSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
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- RSWPGWSYMLTIOH-UHFFFAOYSA-N 1-(3-bromophenyl)-2-hydroxyethanone Chemical compound OCC(=O)C1=CC=CC(Br)=C1 RSWPGWSYMLTIOH-UHFFFAOYSA-N 0.000 description 4
- AAEFSLHKSBUQLK-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-2-hydroxyethanone Chemical compound COC1=CC=C(Br)C=C1C(=O)CO AAEFSLHKSBUQLK-UHFFFAOYSA-N 0.000 description 4
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- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
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- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/48—Nitrogen atoms not forming part of a nitro radical
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic 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
- C07D417/12—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 chain containing hetero atoms as chain links
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- Pregnancy & Childbirth (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0317346.5 | 2003-07-24 | ||
| GB0317346A GB0317346D0 (en) | 2003-07-24 | 2003-07-24 | 5-ht2b receptor antagonists |
| US49028603P | 2003-07-28 | 2003-07-28 | |
| US60/490,286 | 2003-07-28 | ||
| PCT/GB2004/003184 WO2005012263A1 (en) | 2003-07-24 | 2004-07-23 | 5-ht2b receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2532505A1 true CA2532505A1 (en) | 2005-02-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA002532505A Abandoned CA2532505A1 (en) | 2003-07-24 | 2004-07-23 | 5-ht2b receptor antagonists |
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| EP (1) | EP1648876A1 (enExample) |
| JP (1) | JP2006528617A (enExample) |
| CA (1) | CA2532505A1 (enExample) |
| WO (1) | WO2005012263A1 (enExample) |
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| WO2005097113A2 (en) * | 2004-04-08 | 2005-10-20 | Pharmagene Laboratories Limited | 5-ht2b receptor antagonists |
| MX2008000141A (es) | 2005-06-27 | 2008-04-07 | Exelixis Inc | Moduladores de lxr basados en imidazol. |
| CN101248048B (zh) * | 2005-06-27 | 2013-08-28 | 埃克塞利希斯专利有限责任公司 | 吡唑基lxr调节剂 |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| EP2121621B1 (en) | 2006-12-08 | 2014-05-07 | Exelixis Patent Company LLC | Lxr and fxr modulators |
| US7906544B2 (en) | 2007-01-26 | 2011-03-15 | North Carolina State University | Inhibition of bacterial biofilms with imidazole derivatives |
| JO2784B1 (en) | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| JP2011500625A (ja) | 2007-10-18 | 2011-01-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | トリ置換された1,2,4−トリアゾール |
| US8278340B2 (en) | 2007-11-27 | 2012-10-02 | North Carolina State University | Inhibition of biofilms in plants with imidazole derivatives |
| NZ587669A (en) | 2008-03-19 | 2011-07-29 | Janssen Pharmaceutica Nv | Trisubstituted 1, 2, 4 -triazoles as nicotinic acetylcholine receptor modulators |
| US9005643B2 (en) | 2008-04-04 | 2015-04-14 | North Carolina State University | Inhibition of bacterial biofilms with imidazole-phenyl derivatives |
| US7897631B2 (en) | 2008-04-21 | 2011-03-01 | North Carolina State University | Inhibition and dispersion of bacterial biofilms with imidazole-triazole derivatives |
| EP2280945B1 (en) | 2008-05-09 | 2014-09-03 | Janssen Pharmaceutica, N.V. | Trisubstituted pyrazoles as acetylcholine receptor modulators |
| CN102186809A (zh) * | 2008-08-14 | 2011-09-14 | 拜尔农作物科学股份公司 | 杀虫性的4-苯基-1h-吡唑 |
| US20110294668A1 (en) | 2008-12-08 | 2011-12-01 | North Carolina State University | Inhibition and dispersion of biofilms in plants with imidazole-triazole derivatives |
| US9221765B2 (en) | 2009-06-10 | 2015-12-29 | North Carolina State University | Inhibition and dispersion of bacterial biofilms with benzimidazole derivatives |
| WO2011015524A2 (en) * | 2009-08-03 | 2011-02-10 | Bayer Cropscience Ag | Fungicide heterocycles derivatives |
| WO2011080132A2 (en) * | 2009-12-17 | 2011-07-07 | Katholieke Universiteit Leuven, K.U. Leuven R&D | Compounds, compositions and methods for controlling biofilms |
| WO2012135016A2 (en) | 2011-03-25 | 2012-10-04 | North Carolina State University | Inhibition of bacterial biofilms and microbial growth with imidazole derivatives |
| US20140010783A1 (en) * | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
| JP2016510050A (ja) * | 2013-03-05 | 2016-04-04 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 抗ウイルス性化合物 |
| BR112015020952A2 (pt) | 2013-03-06 | 2017-07-18 | Hoffmann La Roche | compostos antivirais |
| WO2015143240A2 (en) * | 2014-03-19 | 2015-09-24 | Curza Global, Llc | Compositions and methods comprising 2-(acylamino)imidazoles |
| CA2950952C (en) | 2014-06-10 | 2023-01-10 | Sanford-Burnham Medical Research Institute | Metabotropic glutamate receptor negative allosteric modulators (nams) and uses thereof |
| JP2020512981A (ja) | 2017-03-31 | 2020-04-30 | カーザ グローバル,リミティド ライアビリティ カンパニー | 置換2−アミノイミダゾールを含む組成物と方法 |
| AR122450A1 (es) * | 2020-05-08 | 2022-09-14 | Lilly Co Eli | Compuestos de (trifluorometil)pirimidin-2-amina |
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| BE492033A (enExample) * | 1948-11-05 | |||
| GB696692A (en) * | 1950-12-06 | 1953-09-09 | Ici Ltd | New quinazoline derivatives |
| US3464987A (en) * | 1966-02-21 | 1969-09-02 | Upjohn Co | 1,2-dihydro-1-hydroxy-2-imino-6-(lower alkyl)pyrimidines |
| EP0658559A1 (de) * | 1993-12-14 | 1995-06-21 | Chemisch Pharmazeutische Forschungsgesellschaft m.b.H. | Thienothiazinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als 5-dipoxygenase und Cyclooxygenaseinhibitoren |
| US5733932A (en) * | 1995-01-06 | 1998-03-31 | The Picower Institute For Medical Research | Compounds and methods of use to derivatize neighboring lysine residues in proteins under physiological conditions |
| US5952331A (en) * | 1996-05-23 | 1999-09-14 | Syntex (Usa) Inc. | Aryl pyrimidine derivatives |
| US5958934A (en) * | 1996-05-23 | 1999-09-28 | Syntex (U.S.A.) Inc. | Aryl pyrimidine derivatives and uses thereof |
| TW440563B (en) * | 1996-05-23 | 2001-06-16 | Hoffmann La Roche | Aryl pyrimidine derivatives and a pharmaceutical composition thereof |
| JP2004530690A (ja) * | 2001-05-16 | 2004-10-07 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 抗炎症性薬剤として有用なジアリールウレア誘導体 |
| GB0203412D0 (en) * | 2002-02-13 | 2002-04-03 | Pharmagene Lab Ltd | 5-HT 2B receptor antagonists |
| JP2006508042A (ja) * | 2002-07-18 | 2006-03-09 | ブリストル−マイヤーズ スクイブ カンパニー | グルココルチコイド受容体の修飾物質および方法 |
| EP1575502B1 (en) * | 2002-07-18 | 2010-01-20 | Bristol-Myers Squibb Company | Compositions and methods involving nuclear hormone receptor site ii |
| US7365079B2 (en) * | 2002-11-29 | 2008-04-29 | Banyu Pharmaceutical Co., Ltd. | Azole derivatives |
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- 2004-07-23 US US10/564,010 patent/US20090018150A1/en not_active Abandoned
- 2004-07-23 EP EP04743517A patent/EP1648876A1/en not_active Withdrawn
- 2004-07-23 CA CA002532505A patent/CA2532505A1/en not_active Abandoned
- 2004-07-23 WO PCT/GB2004/003184 patent/WO2005012263A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
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| JP2006528617A (ja) | 2006-12-21 |
| US20090018150A1 (en) | 2009-01-15 |
| WO2005012263A1 (en) | 2005-02-10 |
| EP1648876A1 (en) | 2006-04-26 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |