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
- 108060003345 Adrenergic Receptor Proteins 0.000 description 2
- 102000017910 Adrenergic receptor Human genes 0.000 description 2
- 108050002822 Alpha 2A adrenoceptor Proteins 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 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
- 208000016285 Movement disease Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 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
- 229940079593 drug Drugs 0.000 description 2
- 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
- 238000010438 heat treatment Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000003137 locomotive effect Effects 0.000 description 2
- 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
- 108090000623 proteins and genes Proteins 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-N 0.000 description 1
- KKFDJZZADQONDE-UHFFFAOYSA-N (hydridonitrato)hydroxidocarbon(.) Chemical compound O[C]=N KKFDJZZADQONDE-UHFFFAOYSA-N 0.000 description 1
- CVEXTAUZJWYDJX-UHFFFAOYSA-N 1,3,4,10-Tetrahydro-9(2H)-acridinone Chemical group N1C2=CC=CC=C2C(=O)C2=C1CCCC2 CVEXTAUZJWYDJX-UHFFFAOYSA-N 0.000 description 1
- SGPLAXFUDTWHRS-UHFFFAOYSA-N 1-(4-nitrophenyl)piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCCCC1 SGPLAXFUDTWHRS-UHFFFAOYSA-N 0.000 description 1
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- YAPCYKZPQAMZQI-UHFFFAOYSA-N 2,3-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(C)C(C)=NC2=CC=CC=C12 YAPCYKZPQAMZQI-UHFFFAOYSA-N 0.000 description 1
- SFGWSUNUVDPPJG-UHFFFAOYSA-N 2,5-diethoxy-4-morpholin-4-ylaniline;dihydrochloride Chemical compound Cl.Cl.C1=C(N)C(OCC)=CC(N2CCOCC2)=C1OCC SFGWSUNUVDPPJG-UHFFFAOYSA-N 0.000 description 1
- JFDDHSGQVDAQEA-UHFFFAOYSA-N 2-[4-(4-aminophenyl)piperazin-1-yl]ethyl acetate Chemical compound NC1=CC=C(C=C1)N1CCN(CC1)CCOC(C)=O JFDDHSGQVDAQEA-UHFFFAOYSA-N 0.000 description 1
- HWAGUHCTQULPHH-UHFFFAOYSA-N 2-acetyl-3-methylbutanoic acid Chemical compound CC(C)C(C(C)=O)C(O)=O HWAGUHCTQULPHH-UHFFFAOYSA-N 0.000 description 1
- AJDNYHSBEVKAHY-UHFFFAOYSA-N 2-methyl-3-propan-2-yl-1h-quinolin-4-one Chemical compound C1=CC=CC2=C(O)C(C(C)C)=C(C)N=C21 AJDNYHSBEVKAHY-UHFFFAOYSA-N 0.000 description 1
- UZQJQJNKYMSTCP-UHFFFAOYSA-N 4-(4-methylpiperidin-1-yl)aniline Chemical compound C1CC(C)CCN1C1=CC=C(N)C=C1 UZQJQJNKYMSTCP-UHFFFAOYSA-N 0.000 description 1
- RAYQAAGRRCPNBD-UHFFFAOYSA-N 4-chloro-3-ethyl-1,6-dimethyl-2h-quinoline Chemical group CC1=CC=C2N(C)CC(CC)=C(Cl)C2=C1 RAYQAAGRRCPNBD-UHFFFAOYSA-N 0.000 description 1
- SXSVJLZUHFLSOJ-UHFFFAOYSA-N 4-chloro-3-ethyl-2,8-dimethylquinoline Chemical group CC1=CC=CC2=C(Cl)C(CC)=C(C)N=C21 SXSVJLZUHFLSOJ-UHFFFAOYSA-N 0.000 description 1
- MYOOCUSHJBZEBU-UHFFFAOYSA-N 4-chloro-3-ethyl-2-methylquinoline Chemical compound C1=CC=CC2=C(Cl)C(CC)=C(C)N=C21 MYOOCUSHJBZEBU-UHFFFAOYSA-N 0.000 description 1
- ZJYLCUAZZANAFR-UHFFFAOYSA-N 4-chloro-3-ethyl-6-methoxy-2-methylquinoline Chemical compound C1=CC(OC)=CC2=C(Cl)C(CC)=C(C)N=C21 ZJYLCUAZZANAFR-UHFFFAOYSA-N 0.000 description 1
- HCXMIOZRXOIQHX-UHFFFAOYSA-N 4-chloroquinoline-3-carbonitrile Chemical compound C1=CC=C2C(Cl)=C(C#N)C=NC2=C1 HCXMIOZRXOIQHX-UHFFFAOYSA-N 0.000 description 1
- ZYEVJRPVZZGDRM-UHFFFAOYSA-N 4-methoxy-10h-acridin-9-one Chemical group N1C2=CC=CC=C2C(=O)C2=C1C(OC)=CC=C2 ZYEVJRPVZZGDRM-UHFFFAOYSA-N 0.000 description 1
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical group CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
- RBNLMAXLHADNEU-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carbonitrile Chemical compound C1=CC=C2C(=O)C(C#N)=CNC2=C1 RBNLMAXLHADNEU-UHFFFAOYSA-N 0.000 description 1
- VAVOYRCCWLRTMS-UHFFFAOYSA-N 4-piperazin-1-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCNCC1 VAVOYRCCWLRTMS-UHFFFAOYSA-N 0.000 description 1
- 101710083129 50S ribosomal protein L10, chloroplastic Proteins 0.000 description 1
- UCDBLYHPJMMFMY-UHFFFAOYSA-N 8-bromoquinoline-4-carbonitrile Chemical compound C1=CN=C2C(Br)=CC=CC2=C1C#N UCDBLYHPJMMFMY-UHFFFAOYSA-N 0.000 description 1
- RPFLKSTVNSAYJV-UHFFFAOYSA-N 9-chloro-1,1,3,3-tetramethyl-2,4-dihydroacridine Chemical compound C1=CC=C2C(Cl)=C(C(C)(C)CC(C)(C)C3)C3=NC2=C1 RPFLKSTVNSAYJV-UHFFFAOYSA-N 0.000 description 1
- IYPJWKLHPNECFJ-UHFFFAOYSA-N 9-chloro-1,2,3,4-tetrahydroacridine Chemical compound C1=CC=C2C(Cl)=C(CCCC3)C3=NC2=C1 IYPJWKLHPNECFJ-UHFFFAOYSA-N 0.000 description 1
- SIKRJWKBUMHLLS-UHFFFAOYSA-N 9-chloro-2-methyl-1,2,3,4-tetrahydroacridine Chemical compound C1=CC=C2C(Cl)=C(CC(C)CC3)C3=NC2=C1 SIKRJWKBUMHLLS-UHFFFAOYSA-N 0.000 description 1
- MMLKZYVOSAHXFR-UHFFFAOYSA-N 9-chloro-4-methoxyacridine Chemical compound C1=CC=C2N=C3C(OC)=CC=CC3=C(Cl)C2=C1 MMLKZYVOSAHXFR-UHFFFAOYSA-N 0.000 description 1
- GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- JBZVWABPSHNPIK-UHFFFAOYSA-N Ethyl-2-amino-1-cyclohexene-1-carboxylate Chemical compound CCOC(=O)C1=C(N)CCCC1 JBZVWABPSHNPIK-UHFFFAOYSA-N 0.000 description 1
- 239000001653 FEMA 3120 Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000013200 Stress disease Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101150104365 Tomt gene Proteins 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- 241001532059 Yucca Species 0.000 description 1
- 235000004552 Yucca aloifolia Nutrition 0.000 description 1
- 235000012044 Yucca brevifolia Nutrition 0.000 description 1
- 235000017049 Yucca glauca Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- 239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000000338 anxiogenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- ZCILODAAHLISPY-UHFFFAOYSA-N biphenyl ether Natural products C1=C(CC=C)C(O)=CC(OC=2C(=CC(CC=C)=CC=2)O)=C1 ZCILODAAHLISPY-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000004965 chloroalkyl group Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000037411 cognitive enhancing Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Chemical group 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical group O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-N 0.000 description 1
- DMIFFKCVURTPTG-UHFFFAOYSA-N ethyl 2-acetyl-3-methylbutanoate Chemical group CCOC(=O)C(C(C)C)C(C)=O DMIFFKCVURTPTG-UHFFFAOYSA-N 0.000 description 1
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 description 1
- SSKRAIDJMJSRJD-UHFFFAOYSA-N ethyl 3-anilino-2-cyanoprop-2-enoate Chemical compound CCOC(=O)C(C#N)=CNC1=CC=CC=C1 SSKRAIDJMJSRJD-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005188 flotation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical group OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/47—Quinolines; Isoquinolines
-
- 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
- A61K31/47—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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/22—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
- A61P25/28—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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- 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)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic 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 (en) | 2000-03-01 | 2001-02-28 | Derivatives of quinoline as alpha-2 antagonists |
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 (sk) |
| JP (1) | JP2003525274A (sk) |
| KR (1) | KR20020089372A (sk) |
| CN (1) | CN1468224A (sk) |
| AR (1) | AR034249A1 (sk) |
| AU (1) | AU2001239331A1 (sk) |
| BR (1) | BR0108816A (sk) |
| CA (1) | CA2400657A1 (sk) |
| CZ (1) | CZ20022880A3 (sk) |
| EE (1) | EE200200490A (sk) |
| FI (1) | FI20000480A0 (sk) |
| HU (1) | HUP0204458A3 (sk) |
| IL (1) | IL151093A0 (sk) |
| MX (1) | MXPA02008402A (sk) |
| NO (1) | NO20024159L (sk) |
| PE (1) | PE20011084A1 (sk) |
| PL (1) | PL357874A1 (sk) |
| RU (1) | RU2002125944A (sk) |
| SK (1) | SK12332002A3 (sk) |
| WO (1) | WO2001064645A2 (sk) |
| ZA (1) | ZA200206956B (sk) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL372390A1 (en) * | 2002-02-05 | 2005-07-25 | Novo Nordisk A/S | Novel aryl- and heteroarylpiperazines |
| CA2480266C (en) * | 2002-04-03 | 2011-07-12 | Orion Corporation | Use of an alpha2-adrenoreceptor antagonist for cns-related diseases |
| EP1490361B1 (en) | 2002-04-03 | 2007-10-03 | Orion Corporation | Polycyclic compounds as potent alpha2-adrenoceptor antagonists |
| CN1304374C (zh) * | 2002-04-30 | 2007-03-14 | 永进药品工业株式会社 | 可用做caspase－3抑制剂的喹啉衍生物及其制备方法和药用组合物 |
| WO2004067513A1 (en) * | 2003-01-27 | 2004-08-12 | Oy Juvantia Pharma Ltd | Antagonists for alpha-2 adrenoceptors |
| BRPI0613564A2 (pt) | 2005-07-04 | 2011-01-18 | Novo Nordisk As | compostos, seus usos na preparação de composições farmacêuticas e composições farmacêuticas compreendendo os mesmos |
| EP1948629A1 (en) | 2005-10-31 | 2008-07-30 | Janssen Pharmaceutica N.V. | Substituted piperazines and piperidines as modulators of the neuropeptide y2 receptor |
| WO2007078335A2 (en) * | 2005-12-21 | 2007-07-12 | Decode Genetics, Ehf. | Biaryl nitrogen heterocycle inhibitors of lta4h for treating inflammation |
| WO2007135131A1 (en) * | 2006-05-22 | 2007-11-29 | Janssen Pharmaceutica N.V. | Substituted pyrazinone derivatives for use as a medicine |
| 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 |
| SG163547A1 (en) | 2006-05-29 | 2010-08-30 | High Point Pharmaceuticals Llc | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| 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 |
| AR073628A1 (es) | 2008-10-07 | 2010-11-17 | Schering Corp | Analogos de biaril espiroaminooxazolina y espiroaminodiazolina moduladores de receptores adrenergicos alfa2c, composiciones farmaceuticas que los comprenden y uso de los mismos en rinitis alergica,trastornos cardiacos y otras enfermedades |
| TW201024282A (en) | 2008-11-20 | 2010-07-01 | Orion Corp | New pharmaceutical compounds |
| US8901129B2 (en) | 2009-12-11 | 2014-12-02 | Genecode As | Methods of facilitating neural cell survival using GDNF family ligand (GFL) mimetics or RET signaling pathway activators |
| 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 |
| US10183912B2 (en) | 2014-03-31 | 2019-01-22 | MiRx Pharmaceuticals, LLC | HDMX inhibitors and their use for cancer treatment |
| WO2016135140A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | 4-aminoquinazoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135138A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Oxoquinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135137A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Substituted 4-(phenylamino)quinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135139A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | 2,3-dihydrocyclopenta[b]quinoline derivatives as mth1 inhibitors for the therapy of 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 |
| EP4398902A1 (en) * | 2021-09-07 | 2024-07-17 | Gismo Therapeutics, Inc. | Compounds and pharmaceutical compositions comprising inhibitors of amyloid peptide interactions with glycosaminoglycans, methods of treatment, and use thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
-
2000
- 2000-03-01 FI FI20000480A patent/FI20000480A0/fi unknown
-
2001
- 2001-02-28 CZ CZ20022880A patent/CZ20022880A3/cs unknown
- 2001-02-28 IL IL15109301A patent/IL151093A0/xx unknown
- 2001-02-28 BR BR0108816-5A patent/BR0108816A/pt not_active Application Discontinuation
- 2001-02-28 PL PL01357874A patent/PL357874A1/xx not_active Application Discontinuation
- 2001-02-28 HU HU0204458A patent/HUP0204458A3/hu unknown
- 2001-02-28 KR KR1020027011453A patent/KR20020089372A/ko not_active Application Discontinuation
- 2001-02-28 AU AU2001239331A patent/AU2001239331A1/en not_active Abandoned
- 2001-02-28 CA CA002400657A patent/CA2400657A1/en not_active Abandoned
- 2001-02-28 EE EEP200200490A patent/EE200200490A/xx unknown
- 2001-02-28 JP JP2001563488A patent/JP2003525274A/ja active Pending
- 2001-02-28 EP EP01913918A patent/EP1263733A2/en not_active Withdrawn
- 2001-02-28 RU RU2002125944/04A patent/RU2002125944A/ru not_active Application Discontinuation
- 2001-02-28 SK SK1233-2002A patent/SK12332002A3/sk unknown
- 2001-02-28 WO PCT/FI2001/000203 patent/WO2001064645A2/en not_active Application Discontinuation
- 2001-02-28 CN CNA018059236A patent/CN1468224A/zh active Pending
- 2001-02-28 MX MXPA02008402A patent/MXPA02008402A/es unknown
- 2001-03-01 AR ARP010100993A patent/AR034249A1/es unknown
- 2001-03-01 PE PE2001000208A patent/PE20011084A1/es not_active Application Discontinuation
-
2002
- 2002-08-29 ZA ZA200206956A patent/ZA200206956B/en unknown
- 2002-08-30 NO NO20024159A patent/NO20024159L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0204458A2 (hu) | 2003-04-28 |
| RU2002125944A (ru) | 2004-02-27 |
| PE20011084A1 (es) | 2001-10-25 |
| CZ20022880A3 (cs) | 2003-06-18 |
| NO20024159D0 (no) | 2002-08-30 |
| SK12332002A3 (sk) | 2003-07-01 |
| AR034249A1 (es) | 2004-02-18 |
| BR0108816A (pt) | 2002-12-10 |
| HUP0204458A3 (en) | 2004-07-28 |
| KR20020089372A (ko) | 2002-11-29 |
| WO2001064645A3 (en) | 2001-12-27 |
| AU2001239331A1 (en) | 2001-09-12 |
| FI20000480A0 (fi) | 2000-03-01 |
| PL357874A1 (en) | 2004-07-26 |
| NO20024159L (no) | 2002-08-30 |
| WO2001064645A2 (en) | 2001-09-07 |
| CA2400657A1 (en) | 2001-09-07 |
| CN1468224A (zh) | 2004-01-14 |
| ZA200206956B (en) | 2003-12-01 |
| IL151093A0 (en) | 2003-04-10 |
| EE200200490A (et) | 2003-12-15 |
| MXPA02008402A (es) | 2003-10-14 |
| EP1263733A2 (en) | 2002-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2003525274A (ja) | α２−アンタゴニストとしてのキノリン誘導体 | |
| NL1029596C2 (nl) | Nieuwe piperidylderivaten van chinazoline en isochinoline. | |
| US9783499B2 (en) | Quinoline derivatives and their applications | |
| EP2609082B1 (de) | Imidazo[4,5-c]chinoline als dna-pk-inhibitoren | |
| US20120258975A1 (en) | Potent Small Molecule Inhibitors of Autophagy, and Methods of Use Thereof | |
| US20070197509A1 (en) | Compositions and methods for modulating gated ion channels | |
| EP2833886B1 (en) | Substituted quinolines as bruton's tyrosine kinase inhibitors | |
| JPH1171380A (ja) | ５Ｈ−チアゾロ（３，２−ａ）ピリミジン誘導体 | |
| JP5856086B2 (ja) | 薬物製造のためのイソキノロン類の使用、新規なイソキノロン類およびそれらの合成方法 | |
| EP0100200A1 (en) | 2-Substituted 4-amino-6,7-dimethoxyquinolines | |
| EP2799437A1 (en) | Quinoline and cinnoline compounds and use thereof | |
| US11851427B2 (en) | Phosphodiesterase inhibitors and uses thereof | |
| TW201737943A (zh) | 使用fasn抑制劑之方法 | |
| ES2254095T3 (es) | Derivados de quinolin-4-ilo y su empleo como bloqueantes de suptipos receptores del nmda. | |
| JPWO2002036577A1 (ja) | キナゾリン誘導体及び医薬 | |
| JP2004512364A (ja) | 中枢神経系疾患の治療のためのスルホンアミド | |
| US6593324B2 (en) | Dervatives of quinoline as alpha-2 antagonists | |
| NZ247302A (en) | 1-oxo-4-phenylisoquinolin-3-yl substituted urea derivatives and pharmaceutical compositions | |
| US10626113B2 (en) | Phosphodiesterase inhibitors and uses thereof | |
| AU2011271480A1 (en) | Riminophenazines with 2-(heteroaryl)amino substituents and their anti-microbial activity | |
| EP2588109A1 (en) | Use of kynurenic acid amide derivatives for the treatment of huntington's disease | |
| JP2003513097A (ja) | Ｃｎｓ障害治療用のイソキノリンおよびキナゾリン誘導体 | |
| US20040259881A1 (en) | Nitrogenous heterocyclic compounds | |
| EP2199284A1 (en) | Pharmaceutical composition for inhibiting accumulation of amyloid- beta protein | |
| CZ2000433A3 (cs) | Deriváty 1,3-dioxolo(4,5-H)(2,3)benzodiazepinu, farmaceutické kompozice je obsahující a způsob přípravy účinné složky |