CN1805939A - 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 - Google Patents
用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 Download PDFInfo
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- CN1805939A CN1805939A CNA2004800167803A CN200480016780A CN1805939A CN 1805939 A CN1805939 A CN 1805939A CN A2004800167803 A CNA2004800167803 A CN A2004800167803A CN 200480016780 A CN200480016780 A CN 200480016780A CN 1805939 A CN1805939 A CN 1805939A
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- alkyl
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- 238000011282 treatment Methods 0.000 title abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 7
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 title description 2
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 title description 2
- 150000008038 benzoazepines Chemical class 0.000 title description 2
- 201000010099 disease Diseases 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 612
- 230000008569 process Effects 0.000 claims abstract description 330
- 150000003839 salts Chemical class 0.000 claims abstract description 230
- 150000003254 radicals Chemical class 0.000 claims description 645
- 150000001875 compounds Chemical class 0.000 claims description 345
- 125000005843 halogen group Chemical group 0.000 claims description 328
- 125000001072 heteroaryl group Chemical group 0.000 claims description 269
- -1 C2-C8Alkenyl radical Chemical class 0.000 claims description 261
- 125000003118 aryl group Chemical group 0.000 claims description 251
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 185
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 156
- 125000000217 alkyl group Chemical group 0.000 claims description 149
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 109
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 108
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 107
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 106
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 105
- 125000002883 imidazolyl group Chemical group 0.000 claims description 103
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 98
- 125000003545 alkoxy group Chemical group 0.000 claims description 93
- 238000006243 chemical reaction Methods 0.000 claims description 93
- 239000002904 solvent Substances 0.000 claims description 91
- 125000004650 C1-C8 alkynyl group Chemical group 0.000 claims description 84
- 239000003795 chemical substances by application Substances 0.000 claims description 83
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 75
- 229910052799 carbon Inorganic materials 0.000 claims description 73
- 229910052736 halogen Inorganic materials 0.000 claims description 70
- 150000002367 halogens Chemical class 0.000 claims description 70
- 239000003638 chemical reducing agent Substances 0.000 claims description 69
- 239000002253 acid Substances 0.000 claims description 68
- 125000004429 atom Chemical group 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 67
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 66
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 65
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 62
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 62
- 150000001721 carbon Chemical group 0.000 claims description 62
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 60
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 60
- 125000001188 haloalkyl group Chemical group 0.000 claims description 59
- 239000003153 chemical reaction reagent Substances 0.000 claims description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 41
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 41
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 41
- 238000000926 separation method Methods 0.000 claims description 41
- 125000002541 furyl group Chemical group 0.000 claims description 40
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
- 239000002841 Lewis acid Substances 0.000 claims description 37
- 150000007517 lewis acids Chemical class 0.000 claims description 37
- 239000002244 precipitate Substances 0.000 claims description 33
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 31
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 28
- 229910000085 borane Inorganic materials 0.000 claims description 28
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 27
- 238000006467 substitution reaction Methods 0.000 claims description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 26
- 230000002140 halogenating effect Effects 0.000 claims description 26
- 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 26
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 23
- 150000003557 thiazoles Chemical class 0.000 claims description 23
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 150000002460 imidazoles Chemical class 0.000 claims description 22
- 150000007979 thiazole derivatives Chemical class 0.000 claims description 22
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 21
- 125000005418 aryl aryl group Chemical group 0.000 claims description 21
- 125000001544 thienyl group Chemical group 0.000 claims description 21
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 20
- 125000005336 allyloxy group Chemical group 0.000 claims description 20
- 125000001475 halogen functional group Chemical group 0.000 claims description 20
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 18
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims description 18
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 229910052782 aluminium Inorganic materials 0.000 claims description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 229910052987 metal hydride Inorganic materials 0.000 claims description 11
- 150000004681 metal hydrides Chemical class 0.000 claims description 11
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 239000012454 non-polar solvent Substances 0.000 claims description 10
- 239000011975 tartaric acid Substances 0.000 claims description 10
- 235000002906 tartaric acid Nutrition 0.000 claims description 10
- 239000001358 L(+)-tartaric acid Substances 0.000 claims description 8
- 235000011002 L(+)-tartaric acid Nutrition 0.000 claims description 8
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 8
- 150000003892 tartrate salts Chemical class 0.000 claims description 7
- 230000001376 precipitating effect Effects 0.000 claims description 6
- 229910006121 SOBr2 Inorganic materials 0.000 claims description 5
- 229910006124 SOCl2 Inorganic materials 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000000717 retained effect Effects 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 claims description 3
- 229910020667 PBr3 Inorganic materials 0.000 claims description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 2
- 150000007980 azole derivatives Chemical class 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 30
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 22
- 239000000543 intermediate Substances 0.000 abstract description 9
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical class C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 abstract description 8
- 208000008589 Obesity Diseases 0.000 abstract description 6
- 235000020824 obesity Nutrition 0.000 abstract description 6
- 208000015114 central nervous system disease Diseases 0.000 abstract description 4
- 239000000018 receptor agonist Substances 0.000 abstract description 3
- 229940044601 receptor agonist Drugs 0.000 abstract description 3
- 229940076279 serotonin Drugs 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 239000000047 product Substances 0.000 description 37
- 239000000243 solution Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000010410 layer Substances 0.000 description 23
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
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- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
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- 239000012044 organic layer Substances 0.000 description 15
- 229910015900 BF3 Inorganic materials 0.000 description 14
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 14
- 238000007363 ring formation reaction Methods 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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- 239000007858 starting material Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
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- 230000009467 reduction Effects 0.000 description 9
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 7
- 239000000463 material Substances 0.000 description 7
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000001294 propane Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XTTZERNUQAFMOF-UHFFFAOYSA-N 7-chloro-5-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound CC1CNCCC2=CC=C(Cl)C=C12 XTTZERNUQAFMOF-UHFFFAOYSA-N 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
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- YAFMYKFAUNCQPU-UHFFFAOYSA-N 1-(2-bromoethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CCBr)C=C1 YAFMYKFAUNCQPU-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
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- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
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- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical group [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- JGHYBJVUQGTEEB-UHFFFAOYSA-M dimethylalumanylium;chloride Chemical compound C[Al](C)Cl JGHYBJVUQGTEEB-UHFFFAOYSA-M 0.000 description 4
- UAIZDWNSWGTKFZ-UHFFFAOYSA-L ethylaluminum(2+);dichloride Chemical compound CC[Al](Cl)Cl UAIZDWNSWGTKFZ-UHFFFAOYSA-L 0.000 description 4
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- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 3
- GWMXBSJNHZORGS-UHFFFAOYSA-N 7-chloro-5-methyl-1,2,3,5-tetrahydro-3-benzazepin-4-one Chemical compound C1CNC(=O)C(C)C2=CC(Cl)=CC=C21 GWMXBSJNHZORGS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 3
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
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Abstract
Description
Claims (642)
Applications Claiming Priority (5)
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US47928003P | 2003-06-17 | 2003-06-17 | |
US60/479,280 | 2003-06-17 | ||
US51296703P | 2003-10-21 | 2003-10-21 | |
US60/512,967 | 2003-10-21 | ||
PCT/US2004/019279 WO2005019179A2 (en) | 2003-06-17 | 2004-06-16 | Benzazepine derivatives useful for the treatment of 5ht2c receptor associated diseases |
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CN2008100073149A Division CN101274911B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 |
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CN1805939A true CN1805939A (zh) | 2006-07-19 |
CN1805939B CN1805939B (zh) | 2010-10-13 |
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CN2004800167803A Expired - Lifetime CN1805939B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 |
CN201010003763A Pending CN101792417A (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物 |
CN2008100073149A Expired - Fee Related CN101274911B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 |
CN2004800167733A Expired - Fee Related CN1805938B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物 |
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CN201010003763A Pending CN101792417A (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物 |
CN2008100073149A Expired - Fee Related CN101274911B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 |
CN2004800167733A Expired - Fee Related CN1805938B (zh) | 2003-06-17 | 2004-06-16 | 用于治疗5ht2c受体相关疾病的苯并氮杂卓衍生物 |
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US (3) | US7704993B2 (zh) |
EP (2) | EP2332920A3 (zh) |
JP (2) | JP4782003B2 (zh) |
KR (1) | KR101152521B1 (zh) |
CN (4) | CN1805939B (zh) |
AU (1) | AU2004253888B2 (zh) |
BR (1) | BRPI0411470A (zh) |
CA (2) | CA2888392A1 (zh) |
EA (1) | EA016558B1 (zh) |
IL (1) | IL172334A (zh) |
MX (1) | MXPA05013366A (zh) |
NZ (1) | NZ578503A (zh) |
WO (1) | WO2005003096A1 (zh) |
ZA (2) | ZA200510194B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105693610A (zh) * | 2014-11-28 | 2016-06-22 | 四川省宜宾五粮液集团宜宾制药有限责任公司 | 氯卡色林中间体(r,s)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓的制备方法 |
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US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
CN1805939B (zh) | 2003-06-17 | 2010-10-13 | 艾尼纳制药公司 | 用于治疗5ht2c受体相关病症的苯并氮杂卓衍生物 |
HUE028976T2 (en) | 2003-06-17 | 2017-02-28 | Arena Pharm Inc | 8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105693610A (zh) * | 2014-11-28 | 2016-06-22 | 四川省宜宾五粮液集团宜宾制药有限责任公司 | 氯卡色林中间体(r,s)-8-氯-1-甲基-2,3,4,5-四氢-1h-3-苯并氮杂卓的制备方法 |
CN105693610B (zh) * | 2014-11-28 | 2019-01-11 | 国药集团宜宾制药有限责任公司 | 氯卡色林中间体的制备方法 |
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