CN100338063C - 7-苯基吡唑并吡啶化合物 - Google Patents
7-苯基吡唑并吡啶化合物 Download PDFInfo
- Publication number
- CN100338063C CN100338063C CNB2003801014177A CN200380101417A CN100338063C CN 100338063 C CN100338063 C CN 100338063C CN B2003801014177 A CNB2003801014177 A CN B2003801014177A CN 200380101417 A CN200380101417 A CN 200380101417A CN 100338063 C CN100338063 C CN 100338063C
- Authority
- CN
- China
- Prior art keywords
- methyl
- group
- compound
- pyrazolo
- salt
- 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.)
- Expired - Lifetime
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- FMVFEDWZIRSTGL-UHFFFAOYSA-N 7-phenyl-1h-pyrazolo[4,3-b]pyridine Chemical class C1=CN=C2C=NNC2=C1C1=CC=CC=C1 FMVFEDWZIRSTGL-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 273
- -1 methyltio Chemical group 0.000 claims abstract description 179
- 150000003839 salts Chemical class 0.000 claims abstract description 121
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 23
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 claims abstract description 15
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims abstract description 10
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims abstract description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 321
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 159
- 238000002360 preparation method Methods 0.000 claims description 93
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 89
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 75
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 39
- 208000035475 disorder Diseases 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 22
- 208000019901 Anxiety disease Diseases 0.000 claims description 18
- 230000036506 anxiety Effects 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 11
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 208000019899 phobic disease Diseases 0.000 claims description 10
- 239000005864 Sulphur Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 9
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 claims description 9
- 125000005936 piperidyl group Chemical group 0.000 claims description 9
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 7
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 7
- 208000016620 Tourette disease Diseases 0.000 claims description 7
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- 206010003805 Autism Diseases 0.000 claims description 6
- 208000020706 Autistic disease Diseases 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 206010010774 Constipation Diseases 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 206010026749 Mania Diseases 0.000 claims description 6
- 206010034912 Phobia Diseases 0.000 claims description 6
- 206010054048 Postoperative ileus Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 206010047700 Vomiting Diseases 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 208000026725 cyclothymic disease Diseases 0.000 claims description 6
- 230000008673 vomiting Effects 0.000 claims description 6
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 230000001419 dependent effect Effects 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 3
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 230000000994 depressogenic effect Effects 0.000 claims description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- 230000036269 ulceration Effects 0.000 claims 1
- 230000008485 antagonism Effects 0.000 abstract description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 344
- 239000002904 solvent Substances 0.000 description 203
- 238000006243 chemical reaction Methods 0.000 description 165
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 149
- 239000000243 solution Substances 0.000 description 139
- 239000011541 reaction mixture Substances 0.000 description 128
- 238000005160 1H NMR spectroscopy Methods 0.000 description 120
- 235000019439 ethyl acetate Nutrition 0.000 description 115
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
- 239000007788 liquid Substances 0.000 description 98
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
- 239000002994 raw material Substances 0.000 description 94
- 230000002829 reductive effect Effects 0.000 description 94
- 239000000284 extract Substances 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 89
- 239000003153 chemical reaction reagent Substances 0.000 description 83
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 78
- 102100021752 Corticoliberin Human genes 0.000 description 77
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical group C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 77
- 238000001035 drying Methods 0.000 description 76
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 70
- 238000003810 ethyl acetate extraction Methods 0.000 description 69
- 230000000452 restraining effect Effects 0.000 description 64
- 238000010898 silica gel chromatography Methods 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- 238000005406 washing Methods 0.000 description 60
- 239000003513 alkali Substances 0.000 description 57
- 238000001914 filtration Methods 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
- 238000003756 stirring Methods 0.000 description 50
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 239000002585 base Substances 0.000 description 44
- 239000003795 chemical substances by application Substances 0.000 description 44
- 239000003921 oil Substances 0.000 description 44
- 235000019198 oils Nutrition 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- 239000012046 mixed solvent Substances 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- 239000013078 crystal Substances 0.000 description 40
- 239000012043 crude product Substances 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
- 238000012360 testing method Methods 0.000 description 37
- 239000002253 acid Substances 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- 239000012266 salt solution Substances 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 28
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 23
- 239000007864 aqueous solution Substances 0.000 description 23
- 239000003814 drug Substances 0.000 description 23
- DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical group C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000003054 catalyst Substances 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 16
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
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- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 13
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- 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 13
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 13
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
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- 229910017053 inorganic salt Inorganic materials 0.000 description 10
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
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- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 7
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
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- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
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- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
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- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
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- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
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- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- CPRPKIMXLHBUGA-UHFFFAOYSA-N triethyltin Chemical compound CC[Sn](CC)CC CPRPKIMXLHBUGA-UHFFFAOYSA-N 0.000 description 1
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- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract
Description
原材料 | 目的 | 0.5mg片剂 | 5mg片剂 | 25mg片剂 |
本发明中的化合物*1 | 主成分 | 0.675 | 6.75 | 33.75 |
甘露醇 | 赋形剂 | 170.925 | 164.85 | 137.85 |
交聚维酮 | 崩解剂 | 10 | 10 | 10 |
羟丙基纤维素 | 粘合剂 | 6 | 6 | 6 |
纯净水 | 溶剂 | q.s. | q.s. | q.s. |
小计 | - | 187.6 | 187.6 | 187.6 |
交聚维酮 | 崩解剂 | 10 | 10 | 10 |
硬脂酸镁 | 润滑剂 | 2.4 | 2.4 | 2.4 |
小计 | - | 200 | 200 | 200 |
包衣剂*2 | 涂覆剂 | 8 | 8 | 8 |
纯净水 | q.s. | q.s. | q.s. | |
合计 | - | 208 | 208 | 208 |
化合物编号(实施例编号) | CRF1受体结合亲合力IC50(nM) | cAMP产生活性IC50(nM) |
例1 | 71 | 4 |
例3 | 49 | 5.1 |
例13 | 90 | 11 |
例23 | 50 | 6 |
例47 | 50 | 50 |
例59 | 52 | 3.5 |
例60 | 30 | 3.5 |
同工酶 | GenBank# | 引物 | 名称 | 序列 |
CYP3A4 | NM017460 | FR | HCYP3A4_F3HCYP3A4_R3 | TAGCTGAGGATGAAGAATGGGTGGATTGTTGAGAGAGTCG |
GAPDH | M_33197 | FR | hGAPDH_FhGAPDH_R | GAAGGTGAAGGTCGGAGTCGAAGATGGTGATGGGATTTC |
温度 | 时间 | |
95 | 10min | |
945672 | 15s15s30s | 变性退火延伸 |
试验浓度实施例 | 阳性对照的百分比(%) | |||||
0.03μM | 0.1μM | 0.3μM | 1μM | 3μM | 10μM | |
实施例59 | 2 | 3 | 11 | 25 | 49 | 59 |
实施例1 | 6 | 7 | 12 | 20 | 36 | 65 |
实施例3 | 3 | 3 | 7 | 25 | 23 | 34 |
利福平(阳性对照) | - | - | - | - | - | 100 |
Claims (16)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP306695/2002 | 2002-10-22 | ||
JP2002306695 | 2002-10-22 | ||
US60/421,071 | 2002-10-25 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200710128111A Division CN100579979C (zh) | 2002-10-22 | 2003-10-22 | 7-苯基吡唑并吡啶化合物 |
CNA2007101281125A Division CN101081853A (zh) | 2002-10-22 | 2003-10-22 | 4-(羟甲基)-2,6-二甲氧基苯基硼酸化合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1705665A CN1705665A (zh) | 2005-12-07 |
CN100338063C true CN100338063C (zh) | 2007-09-19 |
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CN200710128111A Expired - Lifetime CN100579979C (zh) | 2002-10-22 | 2003-10-22 | 7-苯基吡唑并吡啶化合物 |
CNA2007101281125A Pending CN101081853A (zh) | 2002-10-22 | 2003-10-22 | 4-(羟甲基)-2,6-二甲氧基苯基硼酸化合物 |
CNB2003801014177A Expired - Lifetime CN100338063C (zh) | 2002-10-22 | 2003-10-22 | 7-苯基吡唑并吡啶化合物 |
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CN200710128111A Expired - Lifetime CN100579979C (zh) | 2002-10-22 | 2003-10-22 | 7-苯基吡唑并吡啶化合物 |
CNA2007101281125A Pending CN101081853A (zh) | 2002-10-22 | 2003-10-22 | 4-(羟甲基)-2,6-二甲氧基苯基硼酸化合物 |
Country Status (3)
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US (1) | US7176216B2 (zh) |
CN (3) | CN100579979C (zh) |
ZA (1) | ZA200501310B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US8431603B2 (en) | 2008-04-15 | 2013-04-30 | Eisai R&D Management Co., Ltd. | 3-phenylpyrazolo[5,1-b]thiazole compounds |
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TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
NZ529333A (en) * | 2001-04-27 | 2005-01-28 | Eisai Co Ltd | Pyrazolo[1,5-a]pyridines and medicines containing the same |
SI1555265T1 (sl) * | 2002-10-22 | 2009-06-30 | Eisai R&D Man Co Ltd | 7-fenil pirazolopiridinske spojine |
CA2562578C (en) * | 2004-04-12 | 2013-04-02 | Eisai R&D Management Co., Ltd. | Process for production of pyrazole-fused ring derivatives |
AR078521A1 (es) | 2009-10-08 | 2011-11-16 | Eisai R&D Man Co Ltd | Compuesto pirazolotiazol |
JPWO2011043387A1 (ja) * | 2009-10-08 | 2013-03-04 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ピラゾロオキサゾール化合物 |
US8487102B2 (en) * | 2010-04-20 | 2013-07-16 | Hoffmann-La Roche Inc. | Pyrrazolopyridine compounds as dual NK1/NK3 receptor antagonists |
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-
2003
- 2003-10-21 US US10/689,088 patent/US7176216B2/en not_active Expired - Lifetime
- 2003-10-22 CN CN200710128111A patent/CN100579979C/zh not_active Expired - Lifetime
- 2003-10-22 CN CNA2007101281125A patent/CN101081853A/zh active Pending
- 2003-10-22 CN CNB2003801014177A patent/CN100338063C/zh not_active Expired - Lifetime
-
2005
- 2005-02-14 ZA ZA200501310A patent/ZA200501310B/en unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8431603B2 (en) | 2008-04-15 | 2013-04-30 | Eisai R&D Management Co., Ltd. | 3-phenylpyrazolo[5,1-b]thiazole compounds |
Also Published As
Publication number | Publication date |
---|---|
CN1705665A (zh) | 2005-12-07 |
US20040224974A1 (en) | 2004-11-11 |
ZA200501310B (en) | 2006-09-27 |
CN101081850A (zh) | 2007-12-05 |
CN100579979C (zh) | 2010-01-13 |
CN101081853A (zh) | 2007-12-05 |
US7176216B2 (en) | 2007-02-13 |
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