IL108356A - Synergistic mixture of compounds with antagonistic effect on KN1 and KN2 receptors - Google Patents
Synergistic mixture of compounds with antagonistic effect on KN1 and KN2 receptorsInfo
- Publication number
- IL108356A IL108356A IL10835694A IL10835694A IL108356A IL 108356 A IL108356 A IL 108356A IL 10835694 A IL10835694 A IL 10835694A IL 10835694 A IL10835694 A IL 10835694A IL 108356 A IL108356 A IL 108356A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- radical
- substituted
- receptors
- phenyl
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title claims abstract description 52
- 230000000694 effects Effects 0.000 title claims abstract description 24
- 108010040722 Neurokinin-2 Receptors Proteins 0.000 title claims abstract description 22
- 102100037342 Substance-K receptor Human genes 0.000 title claims abstract description 21
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 title claims abstract description 9
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 title claims description 11
- 239000011885 synergistic combination Substances 0.000 title claims description 5
- -1 2-substituted-3-aminoquinuclidine Chemical class 0.000 claims description 132
- 102000005962 receptors Human genes 0.000 claims description 19
- 108020003175 receptors Proteins 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical class C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 claims description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 150000003053 piperidines Chemical class 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- KYHMFVRVHASKGM-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindol-4-ol Chemical compound OC1CCCC2CNCC12 KYHMFVRVHASKGM-UHFFFAOYSA-N 0.000 claims description 3
- 150000003975 aryl alkyl amines Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- UALFYMMGEYDHHJ-UHFFFAOYSA-N 1-azabicyclo[3.2.2]nonan-3-amine Chemical class C1C(N)CC2CCN1CC2 UALFYMMGEYDHHJ-UHFFFAOYSA-N 0.000 claims 1
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 abstract description 13
- 102100024304 Protachykinin-1 Human genes 0.000 abstract description 13
- 101800003906 Substance P Proteins 0.000 abstract description 13
- 238000011282 treatment Methods 0.000 abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 description 160
- 125000004432 carbon atom Chemical group C* 0.000 description 91
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 74
- 150000003254 radicals Chemical class 0.000 description 63
- 125000003545 alkoxy group Chemical group 0.000 description 54
- 229910052736 halogen Inorganic materials 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 38
- 150000002367 halogens Chemical class 0.000 description 35
- 239000000243 solution Substances 0.000 description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 28
- 125000001544 thienyl group Chemical group 0.000 description 28
- 239000000203 mixture Substances 0.000 description 23
- 125000004076 pyridyl group Chemical group 0.000 description 23
- 125000005843 halogen group Chemical group 0.000 description 22
- 125000001424 substituent group Chemical group 0.000 description 21
- 229960002504 capsaicin Drugs 0.000 description 19
- 235000017663 capsaicin Nutrition 0.000 description 19
- 125000001624 naphthyl group Chemical group 0.000 description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 125000000753 cycloalkyl group Chemical group 0.000 description 16
- 229910052760 oxygen Inorganic materials 0.000 description 16
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 15
- 125000001153 fluoro group Chemical group F* 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 13
- 125000004663 dialkyl amino group Chemical group 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 125000003884 phenylalkyl group Chemical group 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 102400000097 Neurokinin A Human genes 0.000 description 12
- 101800000399 Neurokinin A Proteins 0.000 description 12
- HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
- 125000003282 alkyl amino group Chemical group 0.000 description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 12
- 235000019000 fluorine Nutrition 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 229910052717 sulfur Inorganic materials 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 125000002541 furyl group Chemical group 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 125000001041 indolyl group Chemical group 0.000 description 9
- 229910003827 NRaRb Inorganic materials 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 8
- 125000004423 acyloxy group Chemical group 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 208000009079 Bronchial Spasm Diseases 0.000 description 7
- 208000014181 Bronchial disease Diseases 0.000 description 7
- 206010006482 Bronchospasm Diseases 0.000 description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 6
- 235000010290 biphenyl Nutrition 0.000 description 6
- 239000004305 biphenyl Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910052701 rubidium Inorganic materials 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- DXXUGBPKQDTBQW-UHFFFAOYSA-L chlorisondamine Chemical compound [Cl-].[Cl-].ClC1=C(Cl)C(Cl)=C(Cl)C2=C1C[N+](CC[N+](C)(C)C)(C)C2 DXXUGBPKQDTBQW-UHFFFAOYSA-L 0.000 description 5
- 229950002565 chlorisondamine Drugs 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 125000003831 tetrazolyl group Chemical group 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 125000004442 acylamino group Chemical group 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 125000002971 oxazolyl group Chemical group 0.000 description 4
- LFDLEAOOBNTQGK-USVPWNMWSA-N (3as,4s,7as)-4-(2-methoxyphenyl)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-ol;hydrochloride Chemical compound Cl.COC1=CC=CC=C1[C@@]1(O)[C@@H]2CNC[C@@H]2C(C=2C=CC=CC=2)(C=2C=CC=CC=2)CC1 LFDLEAOOBNTQGK-USVPWNMWSA-N 0.000 description 3
- CIJLMNDNUOEELM-URBRKQAFSA-N (3as,7as)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-one;hydrochloride Chemical compound Cl.O=C([C@@H]1CNC[C@@H]11)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 CIJLMNDNUOEELM-URBRKQAFSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108090000189 Neuropeptides Proteins 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 125000001326 naphthylalkyl group Chemical group 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 125000005493 quinolyl group Chemical group 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- GRZXYQUMNHMMSP-RTWAWAEBSA-N tert-butyl (3as,7as)-7-oxo-4,4-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound C=1C=CC=CC=1C1([C@@H]2[C@H](C(CC1)=O)CN(C2)C(=O)OC(C)(C)C)C1=CC=CC=C1 GRZXYQUMNHMMSP-RTWAWAEBSA-N 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- NUSLQDOXLCYVTQ-ZETCQYMHSA-N (2s)-2-(2-methoxyphenyl)propanoic acid Chemical compound COC1=CC=CC=C1[C@H](C)C(O)=O NUSLQDOXLCYVTQ-ZETCQYMHSA-N 0.000 description 2
- VQNFYEUNEWZIKV-JVQKHHOQSA-N (3aS,7aS)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1H-isoindol-4-one (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O=C1CCC([C@H]2CNC[C@@H]12)(c1ccccc1)c1ccccc1 VQNFYEUNEWZIKV-JVQKHHOQSA-N 0.000 description 2
- AWWGCTHFNOCGCA-SCLBCKFNSA-N (4s,5s)-3-[2-(2-methoxyphenyl)acetyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one Chemical compound COC1=CC=CC=C1CC(=O)N1C(=O)O[C@@H](C=2C=CC=CC=2)[C@@H]1C AWWGCTHFNOCGCA-SCLBCKFNSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000689227 Cora <basidiomycete fungus> Species 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 241000036848 Porzana carolina Species 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 102000003141 Tachykinin Human genes 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 2
- 125000005336 allyloxy group Chemical group 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
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- 239000004006 olive oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- NPIJXCQZLFKBMV-YTGGZNJNSA-L pancuronium bromide Chemical compound [Br-].[Br-].C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 NPIJXCQZLFKBMV-YTGGZNJNSA-L 0.000 description 1
- 229960003379 pancuronium bromide Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- PMOBWAXBGUSOPS-UHFFFAOYSA-N selenium tetrafluoride Chemical compound F[Se](F)(F)F PMOBWAXBGUSOPS-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 230000003033 spasmogenic effect Effects 0.000 description 1
- YCFJXOFFQLPCHD-YFKPBYRVSA-N spinacine Chemical compound C1N[C@H](C(=O)O)CC2=C1NC=N2 YCFJXOFFQLPCHD-YFKPBYRVSA-N 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QTJXVIKNLHZIKL-UHFFFAOYSA-N sulfur difluoride Chemical compound FSF QTJXVIKNLHZIKL-UHFFFAOYSA-N 0.000 description 1
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- XIRDWFIDMQZDEU-UHFFFAOYSA-N tetrafluoro(phenyl)-$l^{5}-phosphane Chemical compound FP(F)(F)(F)C1=CC=CC=C1 XIRDWFIDMQZDEU-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- UFXIRMVZNARBDL-UHFFFAOYSA-N trifluoro(morpholin-4-yl)-$l^{4}-sulfane Chemical compound FS(F)(F)N1CCOCC1 UFXIRMVZNARBDL-UHFFFAOYSA-N 0.000 description 1
- AECHPKVYOLOZLF-UHFFFAOYSA-N trifluoro(phenyl)-$l^{4}-sulfane Chemical compound FS(F)(F)C1=CC=CC=C1 AECHPKVYOLOZLF-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- 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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Soil Working Implements (AREA)
- Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Electrotherapy Devices (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9300451A FR2700472B1 (fr) | 1993-01-19 | 1993-01-19 | Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL108356A0 IL108356A0 (en) | 1994-04-12 |
| IL108356A true IL108356A (en) | 1998-09-24 |
Family
ID=9443143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10835694A IL108356A (en) | 1993-01-19 | 1994-01-17 | Synergistic mixture of compounds with antagonistic effect on KN1 and KN2 receptors |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6177450B1 (it) |
| EP (1) | EP0680323B1 (it) |
| JP (1) | JP4341783B2 (it) |
| KR (1) | KR100342152B1 (it) |
| AT (1) | ATE150972T1 (it) |
| AU (1) | AU682166B2 (it) |
| BE (1) | BE1006705A3 (it) |
| CA (1) | CA2152401C (it) |
| CH (1) | CH687503A5 (it) |
| DE (1) | DE69402411T2 (it) |
| DK (1) | DK0680323T3 (it) |
| ES (2) | ES2091712B1 (it) |
| FR (1) | FR2700472B1 (it) |
| GB (1) | GB2274777B (it) |
| GR (1) | GR3023021T3 (it) |
| IE (1) | IE940035A1 (it) |
| IL (1) | IL108356A (it) |
| IT (1) | IT1269185B (it) |
| LU (1) | LU88442A1 (it) |
| NO (1) | NO315077B1 (it) |
| NZ (1) | NZ259728A (it) |
| PT (1) | PT101444A (it) |
| TW (1) | TW381021B (it) |
| WO (1) | WO1994016697A1 (it) |
| ZA (1) | ZA94333B (it) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2287404A (en) * | 1994-03-15 | 1995-09-20 | Pfizer | Antiinflammatory and analgesic compositions |
| EP0790825A1 (en) * | 1994-11-10 | 1997-08-27 | Pfizer Inc. | Nk-1 receptor antagonists for the treatment of eye disorders |
| US5688960A (en) * | 1995-05-02 | 1997-11-18 | Schering Corporation | Substituted oximes, hydrazones and olefins useful as neurokinin antagonists |
| US5696267A (en) * | 1995-05-02 | 1997-12-09 | Schering Corporation | Substituted oximes, hydrazones and olefins as neurokinin antagonists |
| FR2738245B1 (fr) * | 1995-08-28 | 1997-11-21 | Sanofi Sa | Nouveaux derives de piperidine, procede pour leur obtention et compositions pharmaceutiques les contenant |
| US5691362A (en) * | 1996-06-05 | 1997-11-25 | Schering-Plough Corporation | Substituted benzene-fused hetero- and carbocyclics as nuerokinin antagonists |
| US5789422A (en) * | 1996-10-28 | 1998-08-04 | Schering Corporation | Substituted arylalkylamines as neurokinin antagonists |
| AU734872B2 (en) * | 1996-12-02 | 2001-06-21 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating movement disorders |
| US6156749A (en) * | 1997-12-01 | 2000-12-05 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating movement disorders |
| GB9816897D0 (en) * | 1998-08-04 | 1998-09-30 | Merck Sharp & Dohme | Therapeutic use |
| FR2792835B3 (fr) * | 1999-04-27 | 2001-05-25 | Sanofi Sa | Utilisation du saredutant pour la preparation de medicaments utiles dans le traitement ou la prevention de l'ensemble des troubles de l'humeur, des troubles de l'adaptation ou des troubles mixtes anxiete-depression |
| US20100189797A1 (en) | 2002-06-10 | 2010-07-29 | Julien Mendlewicz | Oral antidepressant formulation |
| EP1686985A2 (en) * | 2003-10-27 | 2006-08-09 | Novartis AG | Use of neurokinin antagonists in the treatment of urinary incontinence |
| JP2008514612A (ja) * | 2004-09-23 | 2008-05-08 | ミシャロウ、アレクサンダー | 対抗適応を誘発することにより神経伝達物質系を調節する方法 |
| US20080045610A1 (en) * | 2004-09-23 | 2008-02-21 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5164372A (en) | 1989-04-28 | 1992-11-17 | Fujisawa Pharmaceutical Company, Ltd. | Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same |
| FI97540C (fi) | 1989-11-06 | 1997-01-10 | Sanofi Sa | Menetelmä terapeuttisesti käyttökelpoisten, aromaattisesti substituoitujen piperidiini- ja piperatsiinijohdannaisten valmistamiseksi |
| GB8929070D0 (en) | 1989-12-22 | 1990-02-28 | Fujisawa Pharmaceutical Co | Peptide compounds,processes for preparation thereof and pharmaceutical composition comprising the same |
| US5232929A (en) | 1990-11-28 | 1993-08-03 | Pfizer Inc. | 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use |
| FR2678267B1 (fr) | 1991-06-25 | 1994-02-04 | Elf Sanofi | Arylalkylamines, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| IL99320A (en) | 1990-09-05 | 1995-07-31 | Sanofi Sa | Arylalkylamines, their preparation and pharmaceutical compositions containing them |
| GB9023116D0 (en) | 1990-10-24 | 1990-12-05 | Fujisawa Pharmaceutical Co | Peptide compounds,processes for preparation thereof and pharmaceutical composition comprising the same |
| EP0499313B1 (en) | 1991-02-11 | 1997-06-11 | MERCK SHARP & DOHME LTD. | Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy |
| FR2677361A1 (fr) * | 1991-06-04 | 1992-12-11 | Adir | Nouveaux peptides et pseudopeptides, derives de tachykinines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| CA2106764A1 (en) | 1991-04-24 | 1992-10-25 | David C. Horwell | Ó-substituted polypeptides having therapeutic activity |
| FR2676053B1 (fr) | 1991-05-03 | 1993-08-27 | Sanofi Elf | Nouveaux composes dialkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FR2676055B1 (fr) | 1991-05-03 | 1993-09-03 | Sanofi Elf | Composes polycycliques amines et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FR2676054B1 (fr) | 1991-05-03 | 1993-09-03 | Sanofi Elf | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FI990419A7 (fi) | 1991-06-20 | 1999-02-26 | Pfizer | Typpeä sisältävien hetrosyklisten yhdisteiden fluorialkoksibentsyyliaminojohdannaiset |
| TW202432B (it) | 1991-06-21 | 1993-03-21 | Pfizer | |
| US5288730A (en) | 1991-06-24 | 1994-02-22 | Merck Sharp & Dohme Limited | Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy |
| US5472978A (en) | 1991-07-05 | 1995-12-05 | Merck Sharp & Dohme Ltd. | Aromatic compounds, pharmaceutical compositions containing them and their use in therapy |
| EP0536817A1 (en) | 1991-07-05 | 1993-04-14 | MERCK SHARP & DOHME LTD. | Azabicyclic compounds as tachykinin antagonists |
| JPH06509332A (ja) | 1991-07-05 | 1994-10-20 | メルク シヤープ エンド ドーム リミテツド | 芳香族化合物、それらを含む医薬組成物、及び治療におけるそれらの使用 |
| WO1993001165A2 (en) | 1991-07-10 | 1993-01-21 | Merck Sharp & Dohme Limited | Aromatic compounds, compositions containing them and their use in therapy |
| US5495047A (en) | 1991-07-10 | 1996-02-27 | Merck, Sharp & Dohme (Ltd.) | Fused tricyclic compounds, pharmaceutical compositions containing them and their use in therapy |
| MY110227A (en) | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
| EP0600952B1 (en) | 1991-08-20 | 1996-04-17 | MERCK SHARP & DOHME LTD. | Azacyclic compounds, processes for their preparation and pharmaceutical compositions containing them |
| DE69231395T3 (de) | 1991-09-20 | 2005-07-21 | Glaxo Group Ltd., Greenford | Neue medizinische Indikation für Tachykinin-Antagonisten |
| CZ59394A3 (en) | 1991-09-26 | 1994-11-16 | Pfizer | Condensed tricyclic heterocycles containing nitrogen as antagonists of p substance receptor, process of their preparation, intermediates, pharmaceutical preparations in which they are comprised and use |
| JP2553020B2 (ja) | 1991-11-07 | 1996-11-13 | 吉富製薬株式会社 | キヌクリジン化合物およびその医薬用途 |
| DK0613458T3 (da) | 1991-11-12 | 1998-02-09 | Pfizer | Acykliske ethylendiaminderivater som substans P receptorantagonister |
| CA2083891A1 (en) | 1991-12-03 | 1993-06-04 | Angus Murray Macleod | Heterocyclic compounds, compositions containing them and their use in therapy |
| GB9201179D0 (en) | 1992-01-21 | 1992-03-11 | Glaxo Group Ltd | Chemical compounds |
| US5328927A (en) | 1992-03-03 | 1994-07-12 | Merck Sharpe & Dohme, Ltd. | Hetercyclic compounds, processes for their preparation and pharmaceutical compositions containing them |
| FR2688219B1 (fr) | 1992-03-03 | 1994-07-08 | Sanofi Elf | Sels d'ammonium quaternaires de composes aromatiques amines, leur preparation et compositions pharmaceutiques les contenant. |
| JP2656702B2 (ja) | 1992-03-23 | 1997-09-24 | ファイザー製薬株式会社 | ペプチド性キヌクリジン |
| FR2689888B1 (fr) | 1992-04-10 | 1994-06-10 | Rhone Poulenc Rorer Sa | Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent. |
| EP0636130A1 (en) | 1992-04-15 | 1995-02-01 | Merck Sharp & Dohme Ltd. | Azacyclic compounds |
| EP0641328B1 (en) | 1992-05-18 | 2001-11-21 | Pfizer Inc. | Bridged aza-bicyclic derivatives as substance p antagonists |
-
1993
- 1993-01-19 FR FR9300451A patent/FR2700472B1/fr not_active Expired - Fee Related
- 1993-12-22 LU LU88442A patent/LU88442A1/fr unknown
-
1994
- 1994-01-14 GB GB9400691A patent/GB2274777B/en not_active Revoked
- 1994-01-14 IT ITMI940039A patent/IT1269185B/it active IP Right Grant
- 1994-01-17 IL IL10835694A patent/IL108356A/en not_active IP Right Cessation
- 1994-01-18 PT PT101444A patent/PT101444A/pt not_active Application Discontinuation
- 1994-01-18 CA CA002152401A patent/CA2152401C/fr not_active Expired - Fee Related
- 1994-01-18 EP EP94904685A patent/EP0680323B1/fr not_active Expired - Lifetime
- 1994-01-18 AU AU58627/94A patent/AU682166B2/en not_active Ceased
- 1994-01-18 US US08/448,403 patent/US6177450B1/en not_active Expired - Fee Related
- 1994-01-18 ZA ZA94333A patent/ZA94333B/xx unknown
- 1994-01-18 AT AT94904685T patent/ATE150972T1/de active
- 1994-01-18 DK DK94904685.8T patent/DK0680323T3/da active
- 1994-01-18 KR KR1019950702980A patent/KR100342152B1/ko not_active Expired - Fee Related
- 1994-01-18 ES ES09400092A patent/ES2091712B1/es not_active Expired - Fee Related
- 1994-01-18 TW TW083100392A patent/TW381021B/zh not_active IP Right Cessation
- 1994-01-18 WO PCT/FR1994/000055 patent/WO1994016697A1/fr not_active Ceased
- 1994-01-18 JP JP51672894A patent/JP4341783B2/ja not_active Expired - Fee Related
- 1994-01-18 ES ES94904685T patent/ES2100689T3/es not_active Expired - Lifetime
- 1994-01-18 NZ NZ259728A patent/NZ259728A/en not_active IP Right Cessation
- 1994-01-18 CH CH00144/94A patent/CH687503A5/fr not_active IP Right Cessation
- 1994-01-18 IE IE003594A patent/IE940035A1/en not_active IP Right Cessation
- 1994-01-18 DE DE69402411T patent/DE69402411T2/de not_active Expired - Lifetime
- 1994-01-19 BE BE9400063A patent/BE1006705A3/fr not_active IP Right Cessation
-
1995
- 1995-07-17 NO NO19952828A patent/NO315077B1/no not_active IP Right Cessation
-
1997
- 1997-04-03 GR GR960403642T patent/GR3023021T3/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |