ZA200205801B - Novel use of phenylheteroalkylamine derivatives. - Google Patents
Novel use of phenylheteroalkylamine derivatives. Download PDFInfo
- Publication number
- ZA200205801B ZA200205801B ZA200205801A ZA200205801A ZA200205801B ZA 200205801 B ZA200205801 B ZA 200205801B ZA 200205801 A ZA200205801 A ZA 200205801A ZA 200205801 A ZA200205801 A ZA 200205801A ZA 200205801 B ZA200205801 B ZA 200205801B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- compound
- alkyl
- pharmaceutically acceptable
- racemate
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 85
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 18
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 18
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 14
- 238000011321 prophylaxis Methods 0.000 claims abstract description 14
- 230000009286 beneficial effect Effects 0.000 claims abstract description 12
- 230000000694 effects Effects 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- -1 NR°R’ Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 102000001708 Protein Isoforms Human genes 0.000 claims description 6
- 108010029485 Protein Isoforms Proteins 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229940111134 coxibs Drugs 0.000 claims description 5
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- OLZXHHOEVBLJLQ-OAHLLOKOSA-N 2-[(1r)-3-amino-1-phenylpropyl]sulfanyl-4-chlorobenzonitrile Chemical compound S([C@H](CCN)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N OLZXHHOEVBLJLQ-OAHLLOKOSA-N 0.000 claims description 2
- OYZNFNQMOVSAAW-OAHLLOKOSA-N 2-[[(1r)-3-amino-1-phenylpropyl]amino]-4-chloro-5-fluorobenzonitrile Chemical compound N([C@H](CCN)C=1C=CC=CC=1)C1=CC(Cl)=C(F)C=C1C#N OYZNFNQMOVSAAW-OAHLLOKOSA-N 0.000 claims description 2
- XFCPDHXTMYHGOX-UHFFFAOYSA-N 4-bromo-2-[3-(methylamino)-1-phenylpropyl]sulfanylbenzonitrile Chemical compound C=1C=CC=CC=1C(CCNC)SC1=CC(Br)=CC=C1C#N XFCPDHXTMYHGOX-UHFFFAOYSA-N 0.000 claims description 2
- YOHGBLUSMJJZIO-UHFFFAOYSA-N 4-chloro-2-[3-(methylamino)-1-phenylpropyl]sulfanylbenzonitrile Chemical compound C=1C=CC=CC=1C(CCNC)SC1=CC(Cl)=CC=C1C#N YOHGBLUSMJJZIO-UHFFFAOYSA-N 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 18
- 125000005843 halogen group Chemical group 0.000 claims 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 3
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims 3
- 201000008482 osteoarthritis Diseases 0.000 claims 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 3
- 238000009472 formulation Methods 0.000 claims 2
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 claims 1
- 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 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 4
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 4
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 4
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RCIVUMDLBQZEHP-UHFFFAOYSA-N (2-methylpropan-2-yl)oxycarbamic acid Chemical class CC(C)(C)ONC(O)=O RCIVUMDLBQZEHP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NUCXQAXKICUYCE-OAHLLOKOSA-N 2-[(1r)-3-amino-1-phenylpropyl]sulfanyl-4-(trifluoromethyl)benzonitrile Chemical compound S([C@H](CCN)C=1C=CC=CC=1)C1=CC(C(F)(F)F)=CC=C1C#N NUCXQAXKICUYCE-OAHLLOKOSA-N 0.000 description 2
- LPFUTOIWAPQWNU-UHFFFAOYSA-N 2-[[3-(dimethylamino)-1-phenylpropyl]amino]-4-(trifluoromethyl)benzonitrile Chemical compound C=1C=CC=CC=1C(CCN(C)C)NC1=CC(C(F)(F)F)=CC=C1C#N LPFUTOIWAPQWNU-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 150000003003 phosphines Chemical class 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- ODWWDPLNYSDJRL-UHFFFAOYSA-N 3-[3-(2,5-dichlorophenyl)sulfanylphenyl]-n-methylpropan-1-amine Chemical compound CNCCCC1=CC=CC(SC=2C(=CC=C(Cl)C=2)Cl)=C1 ODWWDPLNYSDJRL-UHFFFAOYSA-N 0.000 description 1
- SVCZJVTZIOTEMW-UHFFFAOYSA-N 3-[3-(2,5-dichlorophenyl)sulfonylphenyl]-n-methylpropan-1-amine Chemical compound CNCCCC1=CC=CC(S(=O)(=O)C=2C(=CC=C(Cl)C=2)Cl)=C1 SVCZJVTZIOTEMW-UHFFFAOYSA-N 0.000 description 1
- RCRGHHSVZNIRSC-MRXNPFEDSA-N 4-chloro-5-fluoro-2-[[(1r)-3-(methylamino)-1-phenylpropyl]amino]benzonitrile Chemical compound N([C@H](CCNC)C=1C=CC=CC=1)C1=CC(Cl)=C(F)C=C1C#N RCRGHHSVZNIRSC-MRXNPFEDSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 101100080274 Mus musculus Nos3 gene Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 239000003446 ligand Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 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
- 230000001537 neural effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000012154 norepinephrine uptake Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
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EP (1) | EP1263718B1 (ru) |
JP (1) | JP2003523995A (ru) |
KR (1) | KR100721087B1 (ru) |
CN (1) | CN1210270C (ru) |
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AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
EP1401821A4 (en) * | 2001-06-12 | 2006-05-31 | Sk Corp | NEW PHENYL ALKYL DIAMINE ANDAMIDANALOGA |
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US466910A (en) * | 1892-01-12 | Machine for covering wire | ||
GB765849A (en) | 1953-09-21 | 1957-01-16 | Univ Leeds | Improvements in or relating to new aminoalkyl phenyl ethers |
GB922600A (en) | 1960-05-06 | 1963-04-03 | Crookes Lab Ltd | Ortho-tertiary-butyl phenolethers |
US3205136A (en) | 1962-12-24 | 1965-09-07 | Smith Kline French Lab | Antidepressant phenyloxyalkylamines |
JPS5144934B1 (ru) * | 1969-12-09 | 1976-12-01 | ||
JPS52941B1 (ru) * | 1969-12-09 | 1977-01-11 | ||
US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
JPS52941A (en) | 1975-06-24 | 1977-01-06 | Hitachi Chem Co Ltd | Polyurethane insulating coating composition |
FR2432500A1 (fr) | 1978-02-24 | 1980-02-29 | Roussel Uclaf | Nouveaux derives de la benzene propanamine et leurs sels, procede de preparation et application a titre de medicaments |
GB2060620B (en) | 1979-09-14 | 1983-05-25 | Wyeth John & Brother Ltd | 3-aryl-3-aryloxypropylamines |
GB2060621A (en) | 1979-09-14 | 1981-05-07 | Wyeth John & Brother Ltd | 3-Aryl-3-aryloxypropylamines |
GB2060622B (en) | 1979-09-14 | 1983-05-25 | Wyeth John & Brother Ltd | 3-aryl-3-aryloxyalkylamines |
DE3138550A1 (de) | 1981-09-28 | 1983-04-07 | Boehringer Ingelheim KG, 6507 Ingelheim | Substituierte 2-phenyl-2-(pyridyloxy)-ethylamine und isostere verbindungen, verfahren zu ihrer herstellung und verwendung |
KR880007433A (ko) | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
DK630987D0 (da) | 1987-12-01 | 1987-12-01 | Ferrosan As | Aryloxyphenylpropylaminer, deres fremstilling og anvendelse |
US4902710A (en) | 1988-12-14 | 1990-02-20 | Eli Lilly And Company | Serotonin and norepinephrine uptake inhibitors |
DK258389D0 (da) | 1989-05-26 | 1989-05-26 | Ferrosan As | Aryloxyphenylpropylaminer, deres fremstilling og anvendelse |
US5320825A (en) * | 1991-05-01 | 1994-06-14 | Trustees Of The University Of Pennsylvania | Serotonin reuptake inhibitors for S.P.E.C.T. imaging |
FR2676054B1 (fr) | 1991-05-03 | 1993-09-03 | Sanofi Elf | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
EP0571685A1 (en) | 1992-05-27 | 1993-12-01 | Novo Nordisk A/S | Aryloxyheteroarylpropylamines, their preparation and use |
EP0576766A1 (en) * | 1992-06-29 | 1994-01-05 | Novo Nordisk A/S | Propanolamine derivatives, their preparation and use |
EP0661266A1 (en) | 1993-12-27 | 1995-07-05 | Toa Eiyo Ltd. | Substituted cyclic amine compounds as 5HT2 antagonists |
SI0707007T1 (en) | 1994-10-14 | 2002-04-30 | Merck Patent Gmbh | (R)-(-)-2-(5-(4-fluorophenyl)-3-pyridylmethylaminomethyl)chromane as CNS active agent |
HN1998000118A (es) | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
HN1998000125A (es) * | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
EP1052992A1 (en) | 1998-02-02 | 2000-11-22 | Merck & Co., Inc. | Cyclic amine modulators of chemokine receptor activity |
AU765851B2 (en) | 1998-06-03 | 2003-10-02 | Pfizer Products Inc. | 2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors |
SE9803773D0 (sv) | 1998-11-05 | 1998-11-05 | Astra Pharma Prod | Compounds |
PL350904A1 (en) | 1999-03-26 | 2003-02-10 | Astrazeneca Ab | Novel compounds |
GB0004149D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
GB0021670D0 (en) | 2000-09-04 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
WO2002030899A1 (en) | 2000-10-09 | 2002-04-18 | Novartis Ag | N-(4-aryloxypiperidin-1-ylalkyl) cinnamic amides as ccr3 receptor antagonists |
CN100469784C (zh) * | 2001-11-21 | 2009-03-18 | 奥尔胡斯大学 | 甘油一酯和甘油二酯糖苷作为抗炎药物的用途 |
-
2000
- 2000-02-23 GB GBGB0004151.7A patent/GB0004151D0/en not_active Ceased
-
2001
- 2001-02-20 IL IL15064001A patent/IL150640A0/xx not_active IP Right Cessation
- 2001-02-20 CO CO01013435A patent/CO5660084A1/es not_active Application Discontinuation
- 2001-02-20 US US10/204,808 patent/US6953797B2/en not_active Expired - Fee Related
- 2001-02-20 WO PCT/SE2001/000371 patent/WO2001062721A1/en active IP Right Grant
- 2001-02-20 AT AT01904777T patent/ATE265428T1/de not_active IP Right Cessation
- 2001-02-20 CN CNB018054560A patent/CN1210270C/zh not_active Expired - Fee Related
- 2001-02-20 AU AU32601/01A patent/AU780781B2/en not_active Ceased
- 2001-02-20 DE DE60103035T patent/DE60103035T2/de not_active Expired - Fee Related
- 2001-02-20 CA CA002396960A patent/CA2396960A1/en not_active Abandoned
- 2001-02-20 MX MXPA02008204A patent/MXPA02008204A/es active IP Right Grant
- 2001-02-20 BR BR0108539-5A patent/BR0108539A/pt not_active IP Right Cessation
- 2001-02-20 KR KR1020027010954A patent/KR100721087B1/ko not_active IP Right Cessation
- 2001-02-20 JP JP2001561730A patent/JP2003523995A/ja not_active Withdrawn
- 2001-02-20 EP EP01904777A patent/EP1263718B1/en not_active Expired - Lifetime
-
2002
- 2002-07-19 ZA ZA200205801A patent/ZA200205801B/en unknown
- 2002-08-22 NO NO20024013A patent/NO20024013L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
WO2001062721A1 (en) | 2001-08-30 |
NO20024013L (no) | 2002-09-06 |
EP1263718A1 (en) | 2002-12-11 |
CO5660084A1 (es) | 2006-07-31 |
CN1210270C (zh) | 2005-07-13 |
AU780781B2 (en) | 2005-04-14 |
CN1404468A (zh) | 2003-03-19 |
NO20024013D0 (no) | 2002-08-22 |
EP1263718B1 (en) | 2004-04-28 |
KR20020091096A (ko) | 2002-12-05 |
MXPA02008204A (es) | 2002-11-29 |
US6953797B2 (en) | 2005-10-11 |
JP2003523995A (ja) | 2003-08-12 |
GB0004151D0 (en) | 2000-04-12 |
ATE265428T1 (de) | 2004-05-15 |
CA2396960A1 (en) | 2001-08-30 |
KR100721087B1 (ko) | 2007-05-23 |
BR0108539A (pt) | 2002-10-22 |
US20030073685A1 (en) | 2003-04-17 |
DE60103035D1 (de) | 2004-06-03 |
DE60103035T2 (de) | 2005-03-24 |
AU3260101A (en) | 2001-09-03 |
IL150640A0 (en) | 2003-02-12 |
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