CA2400657A1 - Derivatives of quinoline as alpha-2 antagonists - Google Patents
Derivatives of quinoline as alpha-2 antagonists Download PDFInfo
- Publication number
- CA2400657A1 CA2400657A1 CA002400657A CA2400657A CA2400657A1 CA 2400657 A1 CA2400657 A1 CA 2400657A1 CA 002400657 A CA002400657 A CA 002400657A CA 2400657 A CA2400657 A CA 2400657A CA 2400657 A1 CA2400657 A1 CA 2400657A1
- Authority
- CA
- Canada
- 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.)
- Abandoned
Links
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 title abstract description 13
- 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 137
- 150000002148 esters Chemical class 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 122
- 229910052736 halogen Inorganic materials 0.000 claims description 66
- 150000002367 halogens Chemical class 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 41
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 30
- -1 1-imidazolyl Chemical group 0.000 claims description 29
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 239000005557 antagonist Substances 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000002837 carbocyclic group Chemical group 0.000 claims description 15
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
- 210000003169 central nervous system Anatomy 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 9
- 108060003345 Adrenergic Receptor Proteins 0.000 claims description 9
- 102000017910 Adrenergic receptor Human genes 0.000 claims description 9
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
- 125000005842 heteroatom Chemical group 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 3
- FXCDZMFOKWHQFP-UHFFFAOYSA-N 1,1,3,3-tetramethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-2,4-dihydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C2C(C)(C)CC(C)(C)CC2=NC2=CC=CC=C12 FXCDZMFOKWHQFP-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- VHXSDKWBFNFFHS-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C=12CC(C)CCC2=NC2=CC=CC=C2C=1NC(C=C1)=CC=C1N1CCN(C)CC1 VHXSDKWBFNFFHS-UHFFFAOYSA-N 0.000 claims description 3
- CEAASZYIQFCQJH-UHFFFAOYSA-N 3-ethyl-2,6-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC(C)=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 CEAASZYIQFCQJH-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- NAUGYWORANWRRP-UHFFFAOYSA-N 3-ethyl-6-methoxy-2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC(OC)=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 NAUGYWORANWRRP-UHFFFAOYSA-N 0.000 claims description 3
- MAUXHXJBQAWVSI-UHFFFAOYSA-N 3-ethyl-n,2-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C=CC=CC2=C1N(C)C(C=C1)=CC=C1N1CCN(C)CC1 MAUXHXJBQAWVSI-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- QSUPSFCOOLCORC-UHFFFAOYSA-N 4-methoxy-n-[4-(4-methylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C12=CC=CC=C2N=C2C(OC)=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 QSUPSFCOOLCORC-UHFFFAOYSA-N 0.000 claims description 3
- WWLIQWZZBMOLAS-UHFFFAOYSA-N 8-fluoro-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC(F)=C12 WWLIQWZZBMOLAS-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- YTMDIHJFKUKUBO-UHFFFAOYSA-N n-(2,5-diethoxy-4-morpholin-4-ylphenyl)acridin-9-amine Chemical compound CCOC=1C=C(NC=2C3=CC=CC=C3N=C3C=CC=CC3=2)C(OCC)=CC=1N1CCOCC1 YTMDIHJFKUKUBO-UHFFFAOYSA-N 0.000 claims description 3
- QBWOIBYDCCMTKF-UHFFFAOYSA-N n-(4-piperidin-1-ylphenyl)acridin-9-amine Chemical compound C1CCCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 QBWOIBYDCCMTKF-UHFFFAOYSA-N 0.000 claims description 3
- KJQWJHXJHKKTTD-UHFFFAOYSA-N n-[4-(4-benzylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CN(C=2C=CC(NC=3C4=CC=CC=C4N=C4C=CC=CC4=3)=CC=2)CCN1CC1=CC=CC=C1 KJQWJHXJHKKTTD-UHFFFAOYSA-N 0.000 claims description 3
- ZHMTVZXBRVBKJJ-UHFFFAOYSA-N n-[4-(4-cyclopropylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CC1N1CCN(C=2C=CC(NC=3C4=CC=CC=C4N=C4C=CC=CC4=3)=CC=2)CC1 ZHMTVZXBRVBKJJ-UHFFFAOYSA-N 0.000 claims description 3
- CPXJYPKLTDRTNF-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4,5,6,7,8-octahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=C1CCCC2 CPXJYPKLTDRTNF-UHFFFAOYSA-N 0.000 claims description 3
- ASJSNRRPCZXGRL-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCC2)C2=NC2=CC=CC=C12 ASJSNRRPCZXGRL-UHFFFAOYSA-N 0.000 claims description 3
- LDFIRHZOIKFLQJ-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]-7,8,9,10-tetrahydro-6h-cyclohepta[b]quinolin-11-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=C(CCCCC2)C2=NC2=CC=CC=C12 LDFIRHZOIKFLQJ-UHFFFAOYSA-N 0.000 claims description 3
- SKJFMEQTIWVLCD-UHFFFAOYSA-N n-[4-(4-methylpiperidin-1-yl)phenyl]acridin-9-amine Chemical compound C1CC(C)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 SKJFMEQTIWVLCD-UHFFFAOYSA-N 0.000 claims description 3
- LVWWUTHVDJHKIR-UHFFFAOYSA-N n-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 LVWWUTHVDJHKIR-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- QYNDZEYXHRVXBK-UHFFFAOYSA-N 2,7-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]-1,2,3,4-tetrahydroacridin-9-amine Chemical compound C=12CC(C)CCC2=NC2=CC=C(C)C=C2C=1NC(C=C1)=CC=C1N1CCN(C)CC1 QYNDZEYXHRVXBK-UHFFFAOYSA-N 0.000 claims description 2
- 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
- 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 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
- MKIZKMFJTXEUHC-UHFFFAOYSA-N 2-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=CC(C)=NC2=CC=CC=C12 MKIZKMFJTXEUHC-UHFFFAOYSA-N 0.000 claims description 2
- GZBPAEYFMVRUNB-UHFFFAOYSA-N 3-ethyl-2,8-dimethyl-n-[4-(4-methylpiperazin-1-yl)phenyl]quinolin-4-amine Chemical compound CCC1=C(C)N=C2C(C)=CC=CC2=C1NC(C=C1)=CC=C1N1CCN(C)CC1 GZBPAEYFMVRUNB-UHFFFAOYSA-N 0.000 claims description 2
- DUYKGBPLYMVLEY-UHFFFAOYSA-N 4-[4-[(6-chloro-2-methoxyacridin-9-yl)amino]phenyl]-n,n-diethylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(CC)CC)CCN1C(C=C1)=CC=C1NC1=C(C=CC(Cl)=C2)C2=NC2=CC=C(OC)C=C12 DUYKGBPLYMVLEY-UHFFFAOYSA-N 0.000 claims description 2
- XMXAKWQIZRUKOE-UHFFFAOYSA-N 4-[4-[(7-chloro-2-methylquinolin-4-yl)amino]phenyl]-n,n-diethylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(CC)CC)CCN1C(C=C1)=CC=C1NC1=CC(C)=NC2=CC(Cl)=CC=C12 XMXAKWQIZRUKOE-UHFFFAOYSA-N 0.000 claims description 2
- 150000001555 benzenes Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- NOJDKJGJUVAORM-UHFFFAOYSA-N n-(4-pyrrolidin-1-ylphenyl)acridin-9-amine Chemical compound C1CCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 NOJDKJGJUVAORM-UHFFFAOYSA-N 0.000 claims description 2
- SSSIZHIHVRNNHH-UHFFFAOYSA-N n-methyl-n-[4-(4-methylpiperazin-1-yl)phenyl]acridin-9-amine Chemical compound C=12C=CC=CC2=NC2=CC=CC=C2C=1N(C)C(C=C1)=CC=C1N1CCN(C)CC1 SSSIZHIHVRNNHH-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 17
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 5
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 description 78
- 238000000034 method Methods 0.000 description 50
- 125000003545 alkoxy group Chemical group 0.000 description 31
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 125000003282 alkyl amino group Chemical group 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 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
- 230000000694 effects Effects 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 15
- 229940125904 compound 1 Drugs 0.000 description 12
- 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 11
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 10
- KGIGZIBMXZQUSF-UHFFFAOYSA-N n-(4-piperazin-1-ylphenyl)acridin-9-amine Chemical compound C1CNCCN1C(C=C1)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 KGIGZIBMXZQUSF-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 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
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 230000008485 antagonism Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229960004253 dexmedetomidine Drugs 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 102000012305 Alpha 2A adrenoceptor Human genes 0.000 description 4
- 108050002822 Alpha 2A adrenoceptor Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 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
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000012528 membrane Substances 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
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- 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
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- 239000003826 tablet Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 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
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- 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
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Classifications
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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
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
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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
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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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- 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
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- 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
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- 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 (en) | 2000-03-01 | 2001-02-28 | Derivatives of quinoline as alpha-2 antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2400657A1 true CA2400657A1 (en) | 2001-09-07 |
Family
ID=8557801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002400657A Abandoned CA2400657A1 (en) | 2000-03-01 | 2001-02-28 | Derivatives of quinoline as alpha-2 antagonists |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1263733A2 (no) |
| JP (1) | JP2003525274A (no) |
| KR (1) | KR20020089372A (no) |
| CN (1) | CN1468224A (no) |
| AR (1) | AR034249A1 (no) |
| AU (1) | AU2001239331A1 (no) |
| BR (1) | BR0108816A (no) |
| CA (1) | CA2400657A1 (no) |
| CZ (1) | CZ20022880A3 (no) |
| EE (1) | EE200200490A (no) |
| FI (1) | FI20000480A0 (no) |
| HU (1) | HUP0204458A3 (no) |
| IL (1) | IL151093A0 (no) |
| MX (1) | MXPA02008402A (no) |
| NO (1) | NO20024159D0 (no) |
| PE (1) | PE20011084A1 (no) |
| PL (1) | PL357874A1 (no) |
| RU (1) | RU2002125944A (no) |
| SK (1) | SK12332002A3 (no) |
| WO (1) | WO2001064645A2 (no) |
| ZA (1) | ZA200206956B (no) |
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 (en) * | 2002-04-03 | 2003-10-09 | Orion Corporation | Use of an alfa2-adrenoreceptor antagonist for cns-related diseases |
| 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 (en) * | 2003-01-27 | 2004-08-12 | Oy Juvantia Pharma Ltd | Antagonists for alpha-2 adrenoceptors |
| CA2614116A1 (en) | 2005-07-04 | 2007-01-11 | Novo Nordisk A/S | Novel medicaments |
| US8183239B2 (en) | 2005-10-31 | 2012-05-22 | Janssen Pharmaceutica Nv | Substituted piperazines and piperidines as modulators of the neuropeptide Y2 receptor |
| EP1968961A2 (en) | 2005-12-21 | 2008-09-17 | Decode Genetics EHF | Biaryl nitrogen heterocycle inhibitors of lta4h for treating 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 (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 |
| 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 (en) | 2014-03-31 | 2015-10-08 | MiRx Pharmaceuticals, LLC | Novel hdmx inhibitors and their use for cancer treatment |
| 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 |
| 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 |
| 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 |
| WO2016135138A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Oxoquinoline 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 |
| 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 |
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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
- 2001-02-28 MX MXPA02008402A patent/MXPA02008402A/es unknown
- 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/en not_active Withdrawn
- 2001-02-28 WO PCT/FI2001/000203 patent/WO2001064645A2/en not_active Application Discontinuation
- 2001-02-28 RU RU2002125944/04A patent/RU2002125944A/ru not_active Application Discontinuation
- 2001-02-28 CA CA002400657A patent/CA2400657A1/en 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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| NO20024159L (no) | 2002-08-30 |
| ZA200206956B (en) | 2003-12-01 |
| 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 (en) | 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 (en) | 2001-09-07 |
| BR0108816A (pt) | 2002-12-10 |
| EP1263733A2 (en) | 2002-12-11 |
| JP2003525274A (ja) | 2003-08-26 |
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