JP2003525274A - α２−アンタゴニストとしてのキノリン誘導体 - Google Patents
α２−アンタゴニストとしてのキノリン誘導体Info
- Publication number
- JP2003525274A JP2003525274A JP2001563488A JP2001563488A JP2003525274A JP 2003525274 A JP2003525274 A JP 2003525274A JP 2001563488 A JP2001563488 A JP 2001563488A JP 2001563488 A JP2001563488 A JP 2001563488A JP 2003525274 A JP2003525274 A JP 2003525274A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- phenyl
- compound
- alkoxy
- mono
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 title abstract description 15
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 139
- 150000002148 esters Chemical class 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 174
- -1 1-imidazolyl Chemical group 0.000 claims description 105
- 229910052736 halogen Inorganic materials 0.000 claims description 66
- 150000002367 halogens Chemical class 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 51
- 125000003282 alkyl amino group Chemical group 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 40
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 239000005557 antagonist Substances 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 208000015114 central nervous system disease Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- YEGLCEJPSSYEQE-UHFFFAOYSA-N 3-ethyl-2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 YEGLCEJPSSYEQE-UHFFFAOYSA-N 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- GZPDMTWJWCKXNJ-UHFFFAOYSA-N 2-[4-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)phenyl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC=C12 GZPDMTWJWCKXNJ-UHFFFAOYSA-N 0.000 claims description 2
- JLIOUCZCOQHOPO-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-3-propan-2-ylquinolin-4-amine Chemical compound CC(C)C1=C(C)N=C2C=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 JLIOUCZCOQHOPO-UHFFFAOYSA-N 0.000 claims description 2
- BXVCYRBPPBQKEN-UHFFFAOYSA-N 4-[4-(4-methylpiperazin-1-yl)anilino]quinoline-3-carbonitrile Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(C#N)C=NC2=CC=CC=C12 BXVCYRBPPBQKEN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 241000577218 Phenes Species 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 150000001555 benzenes Chemical group 0.000 claims description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 2
- VBDVCLHMPVSOQZ-UHFFFAOYSA-N 2-[4-[4-(acridin-9-ylamino)phenyl]piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 VBDVCLHMPVSOQZ-UHFFFAOYSA-N 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 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
- 229940126585 therapeutic drug Drugs 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- HSWPZIDYAHLZDD-UHFFFAOYSA-N atipamezole Chemical compound C1C2=CC=CC=C2CC1(CC)C1=CN=CN1 HSWPZIDYAHLZDD-UHFFFAOYSA-N 0.000 description 17
- 229960003002 atipamezole Drugs 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- 229940125904 compound 1 Drugs 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- MOZNZNKHRXRLLF-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1 MOZNZNKHRXRLLF-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 7
- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 7
- 229960004253 dexmedetomidine Drugs 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-UHFFFAOYSA-N 0.000 description 6
- 102100025983 Alpha-2C adrenergic receptor Human genes 0.000 description 6
- 101710149275 Alpha-2C adrenergic receptor Proteins 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 102100022815 Alpha-2A adrenergic receptor Human genes 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- KPFJTEFGYBEBOJ-UHFFFAOYSA-N 9-(4-piperazin-1-ylphenyl)acridin-1-amine Chemical compound Nc1cccc2nc3ccccc3c(-c3ccc(cc3)N3CCNCC3)c12 KPFJTEFGYBEBOJ-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 description 3
- 101710106858 Alpha-2A adrenergic receptor Proteins 0.000 description 3
- 102100036666 Alpha-2B adrenergic receptor Human genes 0.000 description 3
- 101710175728 Alpha-2B adrenergic receptor Proteins 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 210000004556 brain Anatomy 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
- 238000001816 cooling Methods 0.000 description 3
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000006742 locomotor activity Effects 0.000 description 3
- MQWCXKGKQLNYQG-UHFFFAOYSA-N methyl cyclohexan-4-ol Natural products CC1CCC(O)CC1 MQWCXKGKQLNYQG-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GZNDUKANJZIZOT-UHFFFAOYSA-N 1-methyl-4-(4-nitrophenyl)piperazine Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C=C1 GZNDUKANJZIZOT-UHFFFAOYSA-N 0.000 description 2
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 description 2
- OQJMHUOCLRCSED-UHFFFAOYSA-N 3,3,5,5-tetramethylcyclohexan-1-one Chemical group CC1(C)CC(=O)CC(C)(C)C1 OQJMHUOCLRCSED-UHFFFAOYSA-N 0.000 description 2
- KPJBXWZOABNBLN-UHFFFAOYSA-N 4-chloro-2-methyl-3-propan-2-ylquinoline Chemical compound C1=CC=CC2=C(Cl)C(C(C)C)=C(C)N=C21 KPJBXWZOABNBLN-UHFFFAOYSA-N 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- TWLLPUMZVVGILS-UHFFFAOYSA-N Ethyl 2-aminobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N TWLLPUMZVVGILS-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
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- 206010039897 Sedation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000004559 acridin-9-yl group Chemical group C1=CC=CC2=NC3=CC=CC=C3C(=C12)* 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 2
- 102000015006 alpha2-adrenergic receptor activity proteins Human genes 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
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- 238000001035 drying Methods 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000012048 forced swim test Methods 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
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- 239000003446 ligand Substances 0.000 description 2
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- 230000001404 mediated effect Effects 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
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- 150000003248 quinolines Chemical class 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
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- 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
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/08—Nitrogen atoms
- C07D219/10—Nitrogen atoms attached in position 9
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI20000480 | 2000-03-01 | ||
| FI20000480A FI20000480A0 (fi) | 2000-03-01 | 2000-03-01 | Kinoliini- ja naftaleenijohdannaisia alfa-2 antagonisteina |
| PCT/FI2001/000203 WO2001064645A2 (fr) | 2000-03-01 | 2001-02-28 | Derives de quinoline utilises comme antagonistes alpha2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003525274A true JP2003525274A (ja) | 2003-08-26 |
Family
ID=8557801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001563488A Pending JP2003525274A (ja) | 2000-03-01 | 2001-02-28 | α２−アンタゴニストとしてのキノリン誘導体 |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1263733A2 (fr) |
| JP (1) | JP2003525274A (fr) |
| KR (1) | KR20020089372A (fr) |
| CN (1) | CN1468224A (fr) |
| AR (1) | AR034249A1 (fr) |
| AU (1) | AU2001239331A1 (fr) |
| BR (1) | BR0108816A (fr) |
| CA (1) | CA2400657A1 (fr) |
| CZ (1) | CZ20022880A3 (fr) |
| EE (1) | EE200200490A (fr) |
| FI (1) | FI20000480A0 (fr) |
| HU (1) | HUP0204458A3 (fr) |
| IL (1) | IL151093A0 (fr) |
| MX (1) | MXPA02008402A (fr) |
| NO (1) | NO20024159D0 (fr) |
| PE (1) | PE20011084A1 (fr) |
| PL (1) | PL357874A1 (fr) |
| RU (1) | RU2002125944A (fr) |
| SK (1) | SK12332002A3 (fr) |
| WO (1) | WO2001064645A2 (fr) |
| ZA (1) | ZA200206956B (fr) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1628109A (zh) * | 2002-02-05 | 2005-06-15 | 诺沃挪第克公司 | 新颖的芳基－与杂芳基－哌嗪 |
| ATE374773T1 (de) | 2002-04-03 | 2007-10-15 | Orion Corp | Polycyclische verbindungen als potenten alpha2- adrenoceptor antagonisten |
| WO2003082825A1 (fr) * | 2002-04-03 | 2003-10-09 | Orion Corporation | Utilisation de l'antagoniste d'un alfa2-adrenocepteur en cas de maladies du snc |
| AU2003224482A1 (en) * | 2002-04-30 | 2003-11-17 | Korea Research Institute Of Chemical Technology | Quinoline derivatives as caspase-3 inhibitor, preparation for producing the same and pharmaceutical composition comprising the same |
| WO2004067513A1 (fr) * | 2003-01-27 | 2004-08-12 | Oy Juvantia Pharma Ltd | Antagonistes pour recepteurs alpha-2 adrenergiques |
| CA2614116A1 (fr) | 2005-07-04 | 2007-01-11 | Novo Nordisk A/S | Medicaments |
| US8183239B2 (en) | 2005-10-31 | 2012-05-22 | Janssen Pharmaceutica Nv | Substituted piperazines and piperidines as modulators of the neuropeptide Y2 receptor |
| EP1968961A2 (fr) | 2005-12-21 | 2008-09-17 | Decode Genetics EHF | Inhibiteurs de biaryl-azote-heterocycle de lta4h pour traiter l'inflammation |
| RU2008150485A (ru) * | 2006-05-22 | 2010-06-27 | Янссен Фармацевтика Н.В. (Be) | Замещенные производные пиразинона для применения в качестве лекарственного средства |
| US8318927B2 (en) | 2006-05-23 | 2012-11-27 | High Point Pharmaceuticals, Llc | 6-(4-cyclopropylpiperazin-1-yl)-2′-methyl-[3, 4′]-bipyridine and its uses as a medicament |
| CN102295606A (zh) | 2006-05-29 | 2011-12-28 | 高点制药有限责任公司 | 合成3-（1，3-苯并间二氧杂环戊烯-5-基）-6-（4-环丙基哌嗪-1-基）-哒嗪的方法及其适用的中间体 |
| EP2014656A3 (fr) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | Nouveaux antagonistes d'hétéocycliques h3 |
| TWI457122B (zh) | 2007-07-20 | 2014-10-21 | Orion Corp | 作為用於治療周邊和中央神經系統疾病之alpha2C拮抗劑的2,3－二氫苯並[1,4]戴奧辛－2－基甲基衍生物 |
| US8324213B2 (en) | 2008-10-07 | 2012-12-04 | Merck Sharp & Dohme Corp. | Biaryl-spiroaminooxazoline analogues as alpha 2C adrenergic receptor modulators |
| TW201024282A (en) | 2008-11-20 | 2010-07-01 | Orion Corp | New pharmaceutical compounds |
| MX2012006580A (es) * | 2009-12-11 | 2012-09-28 | Genecode As | Metodo para facilitar la sobrevivencia de celulas neurales usando mimeticos de ligandos (gfl) de la familia gdnf o activadores de la ruta de señalizacion de ret. |
| CN103524413B (zh) * | 2012-07-04 | 2016-04-20 | 江苏先声药物研究有限公司 | 氢化吖啶衍生物及其应用 |
| JOP20200052A1 (ar) * | 2013-12-19 | 2017-06-16 | Bayer Pharma AG | بيبريدينيل تتراهيدرو كوينولينات مستبدلة واستخدامها كمعضدات مستقبل أدريني ألفا- 2c |
| WO2015153535A1 (fr) | 2014-03-31 | 2015-10-08 | MiRx Pharmaceuticals, LLC | Nouveaux inhibiteurs hdmx et leur utilisation dans le traitement du cancer |
| WO2016135137A1 (fr) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Dérivés de 4-(phénylamino)quinoléine substitués en tant qu'inhibiteurs de mth1 pour la thérapie du cancer |
| WO2016135140A1 (fr) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Dérivés de 4-aminoquinazoline en tant qu'inhibiteurs de mth1 pour la thérapie du cancer |
| WO2016135139A1 (fr) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Dérivés de 2,3-dihydrocyclopenta[b]quinoléine en tant qu'inhibiteurs de mth1 pour la thérapie du cancer |
| WO2016135138A1 (fr) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Dérivés d'oxoquinoléine en tant qu'inhibiteurs de mth1 pour la thérapie du cancer |
| CN107337641B (zh) * | 2017-07-01 | 2020-04-28 | 广东医科大学 | 一种4-柔性胺基-2-芳乙烯基喹啉类衍生物及其制备方法和应用 |
| JP2024536926A (ja) * | 2021-09-07 | 2024-10-08 | ギズモ セラピューティクス インコーポレイテッド | グリコサミノグリカンとのアミロイドペプチド相互作用の阻害剤を含む化合物及び医薬組成物、治療の方法、並びにその使用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
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2000
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2001
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- 2001-02-28 PL PL01357874A patent/PL357874A1/xx not_active Application Discontinuation
- 2001-02-28 AU AU2001239331A patent/AU2001239331A1/en not_active Abandoned
- 2001-02-28 SK SK1233-2002A patent/SK12332002A3/sk unknown
- 2001-02-28 JP JP2001563488A patent/JP2003525274A/ja active Pending
- 2001-02-28 CZ CZ20022880A patent/CZ20022880A3/cs unknown
- 2001-02-28 CN CNA018059236A patent/CN1468224A/zh active Pending
- 2001-02-28 EP EP01913918A patent/EP1263733A2/fr not_active Withdrawn
- 2001-02-28 WO PCT/FI2001/000203 patent/WO2001064645A2/fr not_active Application Discontinuation
- 2001-02-28 RU RU2002125944/04A patent/RU2002125944A/ru not_active Application Discontinuation
- 2001-02-28 CA CA002400657A patent/CA2400657A1/fr not_active Abandoned
- 2001-02-28 EE EEP200200490A patent/EE200200490A/xx unknown
- 2001-02-28 HU HU0204458A patent/HUP0204458A3/hu unknown
- 2001-02-28 BR BR0108816-5A patent/BR0108816A/pt not_active Application Discontinuation
- 2001-02-28 KR KR1020027011453A patent/KR20020089372A/ko not_active Application Discontinuation
- 2001-02-28 IL IL15109301A patent/IL151093A0/xx unknown
- 2001-03-01 AR ARP010100993A patent/AR034249A1/es unknown
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2002
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- 2002-08-30 NO NO20024159A patent/NO20024159D0/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20024159L (no) | 2002-08-30 |
| ZA200206956B (en) | 2003-12-01 |
| CA2400657A1 (fr) | 2001-09-07 |
| AU2001239331A1 (en) | 2001-09-12 |
| IL151093A0 (en) | 2003-04-10 |
| HUP0204458A3 (en) | 2004-07-28 |
| FI20000480A0 (fi) | 2000-03-01 |
| CZ20022880A3 (cs) | 2003-06-18 |
| KR20020089372A (ko) | 2002-11-29 |
| CN1468224A (zh) | 2004-01-14 |
| PL357874A1 (en) | 2004-07-26 |
| NO20024159D0 (no) | 2002-08-30 |
| AR034249A1 (es) | 2004-02-18 |
| PE20011084A1 (es) | 2001-10-25 |
| WO2001064645A3 (fr) | 2001-12-27 |
| EE200200490A (et) | 2003-12-15 |
| HUP0204458A2 (hu) | 2003-04-28 |
| MXPA02008402A (es) | 2003-10-14 |
| SK12332002A3 (sk) | 2003-07-01 |
| RU2002125944A (ru) | 2004-02-27 |
| WO2001064645A2 (fr) | 2001-09-07 |
| BR0108816A (pt) | 2002-12-10 |
| EP1263733A2 (fr) | 2002-12-11 |
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