HU226059B1 - Novel disubstituted trans-3,4,4a,5,6,10b-hexahydro-2h-naphto[1,2-b][1,4]oxazine derivatives, process for producing them and pharmaceutical compositions containing them - Google Patents

Novel disubstituted trans-3,4,4a,5,6,10b-hexahydro-2h-naphto[1,2-b][1,4]oxazine derivatives, process for producing them and pharmaceutical compositions containing them Download PDF

Info

Publication number: HU226059B1
Authority: HU; Hungary
Prior art keywords: ppm; compound; formula; trans; defined above
Prior art date: 1997-09-01

Application number

HU9801951A

Other languages

English (en)

Hungarian (hu)

Inventor

Jean-Christophe Harmange

Francoise Lejeune

Mark Millan

Jean-Louis Peglion

Original Assignee

Servier Lab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-09-01

Filing date

1998-08-31

Publication date

2008-04-28

1998-08-31 Application filed by Servier Lab filed Critical Servier Lab

1998-11-30 Publication of HU9801951D0 publication Critical patent/HU9801951D0/hu

2000-02-28 Publication of HUP9801951A2 publication Critical patent/HUP9801951A2/hu

2000-04-28 Publication of HUP9801951A3 publication Critical patent/HUP9801951A3/hu

2008-04-28 Publication of HU226059B1 publication Critical patent/HU226059B1/hu

Links

238000000034 method Methods 0.000 title claims description 16
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
230000008569 process Effects 0.000 title claims description 5
150000004893 oxazines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 81
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 39
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
239000000203 mixture Substances 0.000 claims description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
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 claims description 6
238000011282 treatment Methods 0.000 claims description 6
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
230000036506 anxiety Effects 0.000 claims description 3
230000003197 catalytic effect Effects 0.000 claims description 3
230000003287 optical effect Effects 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 2
QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 claims description 2
230000016571 aggressive behavior Effects 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000000304 alkynyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
201000000980 schizophrenia Diseases 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
238000009835 boiling Methods 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
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 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
241001465754 Metazoa Species 0.000 description 18
230000000694 effects Effects 0.000 description 18
239000000047 product Substances 0.000 description 18
108020003175 receptors Proteins 0.000 description 18
102000005962 receptors Human genes 0.000 description 18
239000000243 solution Substances 0.000 description 18
241000700159 Rattus Species 0.000 description 17
238000012360 testing method Methods 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
238000005160 1H NMR spectroscopy Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
210000004027 cell Anatomy 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
239000003136 dopamine receptor stimulating agent Substances 0.000 description 8
229940052760 dopamine agonists Drugs 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
230000003291 dopaminomimetic effect Effects 0.000 description 6
239000012071 phase Substances 0.000 description 5
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 4
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
238000011534 incubation Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012528 membrane Substances 0.000 description 4
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 3
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000012317 TBTU Substances 0.000 description 3
239000000556 agonist Substances 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
230000027455 binding Effects 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
210000003523 substantia nigra Anatomy 0.000 description 3
-1 trans-3,4,4a, 5,6,10b-hexahydro-9 - [(trifluoromethyl) sulfonyl] -4-propyl-2H-naphtho [1,2-b] -1 , 4-oxazine Chemical compound 0.000 description 3
238000002604 ultrasonography Methods 0.000 description 3
238000005303 weighing Methods 0.000 description 3
XKTRZPQOQOCNJU-HUUCEWRRSA-N (4ar,10br)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C1=C(C(N)=O)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 XKTRZPQOQOCNJU-HUUCEWRRSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 2
108010022394 Threonine synthase Proteins 0.000 description 2
210000000683 abdominal cavity Anatomy 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
230000001430 anti-depressive effect Effects 0.000 description 2
230000000949 anxiolytic effect Effects 0.000 description 2
229960004046 apomorphine Drugs 0.000 description 2
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000000872 buffer Substances 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
229960002327 chloral hydrate Drugs 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000007423 decrease Effects 0.000 description 2
238000013461 design Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
102000004419 dihydrofolate reductase Human genes 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000012894 fetal calf serum Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
229960003878 haloperidol Drugs 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
238000011835 investigation Methods 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000003446 ligand Substances 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000010534 mechanism of action Effects 0.000 description 2
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
238000000527 sonication Methods 0.000 description 2
239000002594 sorbent Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000012549 training Methods 0.000 description 2
SRQHWWYGAZAWQB-HZPDHXFCSA-N (4ar,10br)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carbonitrile Chemical compound C1=C(C#N)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 SRQHWWYGAZAWQB-HZPDHXFCSA-N 0.000 description 1
FHBDOQKURPGEEG-CTHHTMFSSA-N (4ar,10br)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxylic acid;hydrochloride Chemical compound Cl.C1=C(C(O)=O)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 FHBDOQKURPGEEG-CTHHTMFSSA-N 0.000 description 1
UDEAASQJJIGOTN-IAGOWNOFSA-N (4ar,10br)-n,n-dimethyl-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C1=C(C(=O)N(C)C)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 UDEAASQJJIGOTN-IAGOWNOFSA-N 0.000 description 1
HBXAUVWJLFTKDA-FGZHOGPDSA-N (4ar,10br)-n-(4-methoxyphenyl)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C([C@@H]1[C@@H](C2=C3)OCCN1CCC)CC2=CC=C3C(=O)NC1=CC=C(OC)C=C1 HBXAUVWJLFTKDA-FGZHOGPDSA-N 0.000 description 1
NTVSBHFQAIUFRR-DHIUTWEWSA-N (4ar,10br)-n-[(4-methoxyphenyl)methyl]-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C([C@@H]1[C@@H](C2=C3)OCCN1CCC)CC2=CC=C3C(=O)NCC1=CC=C(OC)C=C1 NTVSBHFQAIUFRR-DHIUTWEWSA-N 0.000 description 1
PAZHMMYMPVTXLZ-RTBURBONSA-N (4ar,10br)-n-butyl-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C12=CC(C(=O)NCCCC)=CC=C2CC[C@@H]2[C@@H]1OCCN2CCC PAZHMMYMPVTXLZ-RTBURBONSA-N 0.000 description 1
GVOGXTVYHLDSDH-HZPDHXFCSA-N (4ar,10br)-n-methyl-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxamide Chemical compound C1=C(C(=O)NC)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 GVOGXTVYHLDSDH-HZPDHXFCSA-N 0.000 description 1
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
QGRZOKIURVWFKN-IAGOWNOFSA-N 1-[(4ar,10br)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-yl]ethanone Chemical compound C1=C(C(C)=O)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 QGRZOKIURVWFKN-IAGOWNOFSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical class C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
QEQVCPKISCKMOQ-UHFFFAOYSA-N 3h-benzo[f][1,2]benzoxazine Chemical class C1=CC=CC2=C(C=CNO3)C3=CC=C21 QEQVCPKISCKMOQ-UHFFFAOYSA-N 0.000 description 1
GJLQYNALOOKSLR-UHFFFAOYSA-N 6-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-2-ol Chemical compound OC1=CC=C2CC(N(CCC)CCC)CCC2=C1 GJLQYNALOOKSLR-UHFFFAOYSA-N 0.000 description 1
206010001928 Amenorrhoea Diseases 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000031872 Body Remains Diseases 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
102000015554 Dopamine receptor Human genes 0.000 description 1
108050004812 Dopamine receptor Proteins 0.000 description 1
238000001061 Dunnett's test Methods 0.000 description 1
241001269524 Dura Species 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
238000007341 Heck reaction Methods 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
208000016285 Movement disease Diseases 0.000 description 1
101710138657 Neurotoxin Proteins 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
206010043118 Tardive Dyskinesia Diseases 0.000 description 1
102000004142 Trypsin Human genes 0.000 description 1
108090000631 Trypsin Proteins 0.000 description 1
HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000006267 biphenyl group Chemical group 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
238000013480 data collection Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
229960003914 desipramine Drugs 0.000 description 1
238000010586 diagram Methods 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
210000004002 dopaminergic cell Anatomy 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000035622 drinking Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
DTNBLXRAVILHMO-IAGOWNOFSA-N ethyl (4ar,10br)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazine-9-carboxylate Chemical compound C1=C(C(=O)OCC)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 DTNBLXRAVILHMO-IAGOWNOFSA-N 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
210000003191 femoral vein Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
238000005243 fluidization Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
208000031424 hyperprolactinemia Diseases 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000009940 knitting Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000003902 lesion Effects 0.000 description 1
210000003715 limbic system Anatomy 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
239000000463 material Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000005906 menstruation Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
JCSREICEMHWFAY-HUUCEWRRSA-N naxagolide Chemical compound C1=C(O)C=C2[C@H]3OCCN(CCC)[C@@H]3CCC2=C1 JCSREICEMHWFAY-HUUCEWRRSA-N 0.000 description 1
230000007433 nerve pathway Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
239000002581 neurotoxin Substances 0.000 description 1
231100000618 neurotoxin Toxicity 0.000 description 1
239000002547 new drug Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
239000008055 phosphate buffer solution Substances 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
230000001242 postsynaptic effect Effects 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
NNOBHPBYUHDMQF-UHFFFAOYSA-N propylphosphine Chemical compound CCCP NNOBHPBYUHDMQF-UHFFFAOYSA-N 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000033764 rhythmic process Effects 0.000 description 1
239000000523 sample Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000002295 serotoninergic effect Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000035939 shock Effects 0.000 description 1
210000003625 skull Anatomy 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000009182 swimming Effects 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000001890 transfection Methods 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
210000001364 upper extremity Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Neurology (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Psychology (AREA)
Pain & Pain Management (AREA)
Anesthesiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

HU9801951A 1997-09-01 1998-08-31 Novel disubstituted trans-3,4,4a,5,6,10b-hexahydro-2h-naphto[1,2-b][1,4]oxazine derivatives, process for producing them and pharmaceutical compositions containing them HU226059B1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR9710852A FR2767825A1 (fr)	1997-09-01	1997-09-01	Nouvelles trans-3,4,4a,5,6,10b-hexahydro-2h-napht°1,2-b!-1, 4-oxazines disubstituees, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (4)

Publication Number	Publication Date
HU9801951D0 HU9801951D0 (en)	1998-11-30
HUP9801951A2 HUP9801951A2 (hu)	2000-02-28
HUP9801951A3 HUP9801951A3 (en)	2000-04-28
HU226059B1 true HU226059B1 (en)	2008-04-28

Family

ID=9510643

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU9801951A HU226059B1 (en)	1997-09-01	1998-08-31	Novel disubstituted trans-3,4,4a,5,6,10b-hexahydro-2h-naphto[1,2-b][1,4]oxazine derivatives, process for producing them and pharmaceutical compositions containing them

Country Status (18)

Country	Link
US (1)	US6025356A (2)
EP (1)	EP0899267B1 (2)
JP (1)	JP4417451B2 (2)
CN (1)	CN1088064C (2)
AT (1)	ATE229513T1 (2)
AU (1)	AU740928C (2)
BR (1)	BR9803933A (2)
CA (1)	CA2246482C (2)
DE (1)	DE69810034T2 (2)
DK (1)	DK0899267T3 (2)
ES (1)	ES2189108T3 (2)
FR (1)	FR2767825A1 (2)
HU (1)	HU226059B1 (2)
NO (1)	NO311218B1 (2)
NZ (1)	NZ331637A (2)
PL (1)	PL194533B1 (2)
PT (1)	PT899267E (2)
ZA (1)	ZA987963B (2)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0130219D0 (en) *	2001-12-18	2002-02-06	Pfizer Ltd	Compounds for the treatment of sexual dysfunction
AU2003268292A1 (en) *	2002-08-30	2004-03-19	Biostratum, Inc.	Inhibitors of post-amadori advanced glycation end products
BRPI0409492A (pt) *	2003-04-18	2006-05-02	Pharmacia & Up John Company Ll	terapias de combinação
FR2906249B1 (fr) *	2006-09-26	2008-12-19	Servier Lab	Composes tetracycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP2098511A1 (en)	2008-03-07	2009-09-09	Solvias AG	Process for preparing compounds containing a hydronaphtalene structure with an unsymmetrically substituted benzene ring
JP2011525893A (ja) *	2008-06-27	2011-09-29	ハー・ルンドベック・アクチエゼルスカベット	新規のフェノールアミン類およびカテコールアミン類ならびにそのプロドラッグ

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1204745A (en) *	1981-11-20	1986-05-20	Merck Co.	Hexahydronaphth (1,2-b) -1,4 -oxazines
US4420480A (en) *	1981-11-20	1983-12-13	Merck & Co., Inc.	Hexahydronaphth[1,2-b]-1,4-oxazines
US4540691A (en) *	1984-04-13	1985-09-10	Nelson Research & Development Co.	Dopamine agonists and use thereof
US5486611A (en) *	1989-07-13	1996-01-23	The Upjohn Company	Carboxamido-(1,2N)-carbocyclic-2-aminotetralin derivatives
CA2083146A1 (en) *	1990-06-15	1991-12-16	Gevork Minaskanian	Substituted naphthoxazines useful as dopaminergics

1997
- 1997-09-01 FR FR9710852A patent/FR2767825A1/fr active Pending
1998
- 1998-08-31 US US09/144,025 patent/US6025356A/en not_active Expired - Lifetime
- 1998-08-31 HU HU9801951A patent/HU226059B1/hu not_active IP Right Cessation
- 1998-08-31 PL PL328285A patent/PL194533B1/pl not_active IP Right Cessation
- 1998-08-31 CA CA002246482A patent/CA2246482C/fr not_active Expired - Fee Related
- 1998-08-31 CN CN98119987A patent/CN1088064C/zh not_active Expired - Fee Related
- 1998-08-31 NO NO19984007A patent/NO311218B1/no not_active IP Right Cessation
- 1998-08-31 BR BR9803933-4A patent/BR9803933A/pt not_active Application Discontinuation
- 1998-08-31 NZ NZ331637A patent/NZ331637A/xx not_active IP Right Cessation
- 1998-09-01 DE DE69810034T patent/DE69810034T2/de not_active Expired - Lifetime
- 1998-09-01 ES ES98402155T patent/ES2189108T3/es not_active Expired - Lifetime
- 1998-09-01 PT PT98402155T patent/PT899267E/pt unknown
- 1998-09-01 ZA ZA987963A patent/ZA987963B/xx unknown
- 1998-09-01 JP JP24691098A patent/JP4417451B2/ja not_active Expired - Fee Related
- 1998-09-01 AU AU83024/98A patent/AU740928C/en not_active Ceased
- 1998-09-01 AT AT98402155T patent/ATE229513T1/de active
- 1998-09-01 EP EP98402155A patent/EP0899267B1/fr not_active Expired - Lifetime
- 1998-09-01 DK DK98402155T patent/DK0899267T3/da active

Also Published As

Publication number	Publication date
ATE229513T1 (de)	2002-12-15
PT899267E (pt)	2003-04-30
JP4417451B2 (ja)	2010-02-17
EP0899267B1 (fr)	2002-12-11
NO984007D0 (no)	1998-08-31
CN1088064C (zh)	2002-07-24
EP0899267A1 (fr)	1999-03-03
ES2189108T3 (es)	2003-07-01
US6025356A (en)	2000-02-15
AU740928B2 (en)	2001-11-15
DE69810034D1 (de)	2003-01-23
HK1020340A1 (en)	2000-04-14
NO984007L (no)	1999-03-02
AU8302498A (en)	1999-03-11
CA2246482C (fr)	2002-11-26
HU9801951D0 (en)	1998-11-30
CN1222516A (zh)	1999-07-14
FR2767825A1 (fr)	1999-02-26
NZ331637A (en)	1999-07-29
AU740928C (en)	2002-05-16
CA2246482A1 (fr)	1999-03-01
BR9803933A (pt)	2001-04-24
PL328285A1 (en)	1999-03-15
DK0899267T3 (da)	2003-03-10
ZA987963B (en)	1999-03-04
JPH11130759A (ja)	1999-05-18
HUP9801951A2 (hu)	2000-02-28
PL194533B1 (pl)	2007-06-29
HUP9801951A3 (en)	2000-04-28
NO311218B1 (no)	2001-10-29
DE69810034T2 (de)	2003-08-14

Legal Events

Date	Code	Title	Description
2013-05-28	MM4A	Lapse of definitive patent protection due to non-payment of fees

Publication	Publication Date	Title
JP2000500786A (ja)	2000-01-25	エーテルムスカリン様アンタゴニスト
EP2164328B1 (en)	2013-08-07	Therapeutic pyrazoloquinoline urea derivatives
RU2347776C2 (ru)	2009-02-27	Производное циклического амина или его соль
DE69736890T2 (de)	2007-09-06	Kondensierte heterozyklische verbindungen und ihre pharmazeutische anwendung
CZ51694A3 (en)	1994-10-19	Benzoxazine derivatives, process of their preparation and pharmaceutical composition in which said derivatives are comprised
KR101463190B1 (ko)	2014-11-18	５ｈｔ６ 수용체 리간드인 술폰 화합물
JPH037257A (ja)	1991-01-14	ピリジン誘導体及びそれを有効成分とする向精神剤
JP3884177B2 (ja)	2007-02-21	新規インダノール化合物、それらの製法及びそれらを含む医薬組成物
RS55362B1 (sr)	2017-03-31	Jedinjenje benzazepina
EP1400510A1 (en)	2004-03-24	Cyclic diamine compounds having fused-ring groups
US6025356A (en)	2000-02-15	Disubstituted trans-3,4,4a,5,6,10b-hexahydro-2H-naphth[1,2-b]-1,4-oxazines
CN116478134B (zh)	2025-07-25	Ssri/5-ht1a双靶点抗抑郁甲酰哌啶类化合物及其制备方法和应用
EP4501926A1 (en)	2025-02-05	N-substituted quinolinone compound, preparation method therefor and use thereof
TWI564300B (zh)	2017-01-01	經取代之［（５Ｈ－吡咯［２，１－ｃ］［１，４］苯二氮呯－１１－基）哌嗪－１－基］－２，２－二甲基丙酸化合物作為雙重活性Ｈ１反向促進劑／５－ＨＴ2Ａ拮抗劑
JPH11130759A5 (2)	2005-11-04
JP2021104931A (ja)	2021-07-26	含窒素複素環を有するジベンゾアゼピン誘導体
US5229387A (en)	1993-07-20	Decahydro-8H-isoquino[2,1-g][1,6]naphthyridine and decahydrobenzo[a]pyrrolo [2,3-e]quinolizine derivatives
AU597187B2 (en)	1990-05-24	2-{ (4-piperidyl)methyl}benzofuro{2,3-c}pyridine derivatives, their preparation and their application in therapy
TW202134231A (zh)	2021-09-16	蕈毒受體4拮抗劑及使用方法
WO2025131045A1 (zh)	2025-06-26	一种taar1配体激动剂的盐型、晶型及其制备方法和应用
CZ211094A3 (en)	1995-03-15	Naphthoxazines, process of their preparation, their use as medicaments and pharmaceutical compositions containing those naphthoxazines
TWI457341B (zh)	2014-10-21	胺基亞丙基衍生物
EP0726257A1 (en)	1996-08-14	1-(Hetero)Arylvinyl-5H-2,3-benzodiazepine derivatives useful for the treatment of central nervous system disorders, and benzopyrylium intermediates for their preparation
HK1142496B (en)	2014-04-04	Therapeutic pyrazoloquinoline urea derivatives
NZ561905A (en)	2009-01-31	Tetracyclic compounds, a process for their preparation and pharmaceutical compositions containing them