PL193802B1 - Zastosowanie pochodnych arylo (lub heteroarylo) azolilokarbinoli do wytwarzania leku do leczenia zaburzeń wywoływanych nadmiarem substancji P - Google Patents
Zastosowanie pochodnych arylo (lub heteroarylo) azolilokarbinoli do wytwarzania leku do leczenia zaburzeń wywoływanych nadmiarem substancji PInfo
- Publication number
- PL193802B1 PL193802B1 PL99346221A PL34622199A PL193802B1 PL 193802 B1 PL193802 B1 PL 193802B1 PL 99346221 A PL99346221 A PL 99346221A PL 34622199 A PL34622199 A PL 34622199A PL 193802 B1 PL193802 B1 PL 193802B1
- Authority
- PL
- Poland
- Prior art keywords
- methyl
- imidazole
- dimethylamino
- pyrazole
- chloro
- Prior art date
Links
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 5
- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 5
- 239000003814 drug Substances 0.000 title claims description 7
- 230000001404 mediated effect Effects 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 title description 4
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 title 1
- -1 N-methylpiperidyl group Chemical group 0.000 claims abstract description 65
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
- 230000036506 anxiety Effects 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 6
- 206010013663 drug dependence Diseases 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 6
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 6
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 4
- 241000124008 Mammalia Species 0.000 claims abstract description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 99
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 21
- 102100024304 Protachykinin-1 Human genes 0.000 claims description 21
- 101800003906 Substance P Proteins 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000003254 radicals Chemical class 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 208000028698 Cognitive impairment Diseases 0.000 claims description 4
- 201000003152 motion sickness Diseases 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- KORIJXKQGMTQTO-UHFFFAOYSA-N 1h-pyrrol-2-ylmethanol Chemical class OCC1=CC=CN1 KORIJXKQGMTQTO-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 82
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 72
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 55
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 32
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 8
- DZDYNIMYBBETIC-UHFFFAOYSA-N (1-butylimidazol-2-yl)-(4-chlorophenyl)methanol Chemical compound CCCCN1C=CN=C1C(O)C1=CC=C(Cl)C=C1 DZDYNIMYBBETIC-UHFFFAOYSA-N 0.000 claims 2
- DOEYYTQISIVAMY-UHFFFAOYSA-N 1-(1-methylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]pentan-1-ol Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(O)(CCCC)C1=NC=CN1C DOEYYTQISIVAMY-UHFFFAOYSA-N 0.000 claims 2
- POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 claims 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 125000006178 methyl benzyl group Chemical group 0.000 claims 2
- 229940095064 tartrate Drugs 0.000 claims 2
- GKFJUJCWQUQWCK-UHFFFAOYSA-N (1-butylimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanol Chemical compound CCCCN1C=CN=C1C(O)C1=CC(OC)=C(OC)C(OC)=C1 GKFJUJCWQUQWCK-UHFFFAOYSA-N 0.000 claims 1
- ADWWKGSHHTZDGW-UHFFFAOYSA-N (1-butylimidazol-2-yl)-(3,4-dichlorophenyl)methanol Chemical compound CCCCN1C=CN=C1C(O)C1=CC=C(Cl)C(Cl)=C1 ADWWKGSHHTZDGW-UHFFFAOYSA-N 0.000 claims 1
- PLTSXNZBXQRFSL-UHFFFAOYSA-N (1-butylimidazol-2-yl)-(4-chlorophenyl)-(1-methylpiperidin-4-yl)methanol Chemical compound CCCCN1C=CN=C1C(O)(C=1C=CC(Cl)=CC=1)C1CCN(C)CC1 PLTSXNZBXQRFSL-UHFFFAOYSA-N 0.000 claims 1
- IMFOYQOQIODGQW-UHFFFAOYSA-N (1-butylimidazol-2-yl)-[4-(trifluoromethyl)phenyl]methanol Chemical compound CCCCN1C=CN=C1C(O)C1=CC=C(C(F)(F)F)C=C1 IMFOYQOQIODGQW-UHFFFAOYSA-N 0.000 claims 1
- DVHHTIGJNVCFDE-UHFFFAOYSA-N (1-dodecylimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanol Chemical compound CCCCCCCCCCCCN1C=CN=C1C(O)C1=CC(OC)=C(OC)C(OC)=C1 DVHHTIGJNVCFDE-UHFFFAOYSA-N 0.000 claims 1
- YJQRNWFHOPZNKJ-UHFFFAOYSA-N (1-methylimidazol-2-yl)-(3,4,5-trimethoxyphenyl)methanol Chemical compound COC1=C(OC)C(OC)=CC(C(O)C=2N(C=CN=2)C)=C1 YJQRNWFHOPZNKJ-UHFFFAOYSA-N 0.000 claims 1
- IVWSNLPIJWOKEL-UHFFFAOYSA-N (1-methylimidazol-2-yl)-[3-(trifluoromethyl)phenyl]methanol Chemical compound CN1C=CN=C1C(O)C1=CC=CC(C(F)(F)F)=C1 IVWSNLPIJWOKEL-UHFFFAOYSA-N 0.000 claims 1
- DGBUCHZPKPTBTF-UHFFFAOYSA-N (1-methylimidazol-2-yl)-[4-(trifluoromethyl)phenyl]methanol Chemical compound CN1C=CN=C1C(O)C1=CC=C(C(F)(F)F)C=C1 DGBUCHZPKPTBTF-UHFFFAOYSA-N 0.000 claims 1
- GOVKUSQTCDGAMA-UHFFFAOYSA-N (2-butylpyrazol-3-yl)-(3,4,5-trimethoxyphenyl)methanol Chemical compound CCCCN1N=CC=C1C(O)C1=CC(OC)=C(OC)C(OC)=C1 GOVKUSQTCDGAMA-UHFFFAOYSA-N 0.000 claims 1
- VRNGWCCYQAXTAY-UHFFFAOYSA-N (2-butylpyrazol-3-yl)-phenylmethanol Chemical compound CCCCN1N=CC=C1C(O)C1=CC=CC=C1 VRNGWCCYQAXTAY-UHFFFAOYSA-N 0.000 claims 1
- ASSGWIAWMIEYER-UHFFFAOYSA-N (2-methylphenyl)-(2-methylpyrazol-3-yl)methanol Chemical compound CC1=CC=CC=C1C(O)C1=CC=NN1C ASSGWIAWMIEYER-UHFFFAOYSA-N 0.000 claims 1
- BMASPICGFTWBED-UHFFFAOYSA-N (3,4-dichlorophenyl)-(1-methylimidazol-2-yl)methanol Chemical compound CN1C=CN=C1C(O)C1=CC=C(Cl)C(Cl)=C1 BMASPICGFTWBED-UHFFFAOYSA-N 0.000 claims 1
- FIOLCQAELMTXNL-UHFFFAOYSA-N (3-chlorophenyl)-(1-methylimidazol-2-yl)methanol Chemical compound CN1C=CN=C1C(O)C1=CC=CC(Cl)=C1 FIOLCQAELMTXNL-UHFFFAOYSA-N 0.000 claims 1
- QIWSOABYAGHUCV-UHFFFAOYSA-N (3-chlorophenyl)-(2-methylpyrazol-3-yl)methanol Chemical compound CN1N=CC=C1C(O)C1=CC=CC(Cl)=C1 QIWSOABYAGHUCV-UHFFFAOYSA-N 0.000 claims 1
- CEJLGKWTVRUHIP-UHFFFAOYSA-N (4-chloro-2-methylpyrazol-3-yl)-phenylmethanol Chemical compound CN1N=CC(Cl)=C1C(O)C1=CC=CC=C1 CEJLGKWTVRUHIP-UHFFFAOYSA-N 0.000 claims 1
- PHHMEHHGCXZGHE-UHFFFAOYSA-N (4-chlorophenyl)-(1-methylimidazol-2-yl)-(1-methylpiperidin-4-yl)methanol Chemical compound C1CN(C)CCC1C(O)(C=1C=CC(Cl)=CC=1)C1=NC=CN1C PHHMEHHGCXZGHE-UHFFFAOYSA-N 0.000 claims 1
- RTEQGPTVSNWJNT-UHFFFAOYSA-N (4-chlorophenyl)-(1-methylimidazol-2-yl)methanol Chemical compound CN1C=CN=C1C(O)C1=CC=C(Cl)C=C1 RTEQGPTVSNWJNT-UHFFFAOYSA-N 0.000 claims 1
- CWJSTOWNJMEMTI-UHFFFAOYSA-N (4-chlorophenyl)-(1h-imidazol-2-yl)methanol Chemical compound C=1C=C(Cl)C=CC=1C(O)C1=NC=CN1 CWJSTOWNJMEMTI-UHFFFAOYSA-N 0.000 claims 1
- YWKOHYISRRIRSS-UHFFFAOYSA-N (4-chlorophenyl)-(2-methylpyrazol-3-yl)-phenylmethanol Chemical compound CN1N=CC=C1C(O)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YWKOHYISRRIRSS-UHFFFAOYSA-N 0.000 claims 1
- IZDDUTJSMOSXTR-UHFFFAOYSA-N (4-chlorophenyl)-(2-methylpyrazol-3-yl)methanol Chemical compound CN1N=CC=C1C(O)C1=CC=C(Cl)C=C1 IZDDUTJSMOSXTR-UHFFFAOYSA-N 0.000 claims 1
- PNIZZSHYLPCPHI-UHFFFAOYSA-N (4-chlorophenyl)-cyclohexyl-(1-methylimidazol-2-yl)methanol Chemical compound CN1C=CN=C1C(O)(C=1C=CC(Cl)=CC=1)C1CCCCC1 PNIZZSHYLPCPHI-UHFFFAOYSA-N 0.000 claims 1
- VBOGEAZGCIWJME-UHFFFAOYSA-N (4-methylphenyl)-(2-methylpyrazol-3-yl)methanol Chemical compound C1=CC(C)=CC=C1C(O)C1=CC=NN1C VBOGEAZGCIWJME-UHFFFAOYSA-N 0.000 claims 1
- ZLZQNQQAZJYKCM-UHFFFAOYSA-N 1-(1-benzylimidazol-2-yl)-1-(4-chlorophenyl)ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)(C)C1=NC=CN1CC1=CC=CC=C1 ZLZQNQQAZJYKCM-UHFFFAOYSA-N 0.000 claims 1
- RZEZKKLIJRPJST-UHFFFAOYSA-N 1-(1-benzylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]pentan-1-ol Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(O)(CCCC)C1=NC=CN1CC1=CC=CC=C1 RZEZKKLIJRPJST-UHFFFAOYSA-N 0.000 claims 1
- GQCLQIPBAOEHDS-UHFFFAOYSA-N 1-(1-butylimidazol-2-yl)-1-(2,4-dichlorophenyl)pentan-1-ol Chemical compound CCCCN1C=CN=C1C(O)(CCCC)C1=CC=C(Cl)C=C1Cl GQCLQIPBAOEHDS-UHFFFAOYSA-N 0.000 claims 1
- KETRWBCPIUBRDE-UHFFFAOYSA-N 1-(1-butylimidazol-2-yl)-1-(2-chlorophenyl)pentan-1-ol Chemical compound CCCCN1C=CN=C1C(O)(CCCC)C1=CC=CC=C1Cl KETRWBCPIUBRDE-UHFFFAOYSA-N 0.000 claims 1
- CGBHLJFEXGOGFF-UHFFFAOYSA-N 1-(1-butylimidazol-2-yl)-1-(3,4,5-trimethoxyphenyl)pentan-1-ol Chemical compound CCCCN1C=CN=C1C(O)(CCCC)C1=CC(OC)=C(OC)C(OC)=C1 CGBHLJFEXGOGFF-UHFFFAOYSA-N 0.000 claims 1
- QFLHAYYEBGPZRS-UHFFFAOYSA-N 1-(1-butylimidazol-2-yl)-1-(4-chlorophenyl)ethanol Chemical compound CCCCN1C=CN=C1C(C)(O)C1=CC=C(Cl)C=C1 QFLHAYYEBGPZRS-UHFFFAOYSA-N 0.000 claims 1
- ZFCYGAOBCOKRSM-UHFFFAOYSA-N 1-(1-butylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]propan-1-ol Chemical compound CCCCN1C=CN=C1C(O)(CC)C1=CC=CC(C(F)(F)F)=C1 ZFCYGAOBCOKRSM-UHFFFAOYSA-N 0.000 claims 1
- NYQSCMIJHPKRSK-UHFFFAOYSA-N 1-(1-dodecylimidazol-2-yl)-1-(3,4,5-trimethoxyphenyl)pentan-1-ol Chemical compound CCCCCCCCCCCCN1C=CN=C1C(O)(CCCC)C1=CC(OC)=C(OC)C(OC)=C1 NYQSCMIJHPKRSK-UHFFFAOYSA-N 0.000 claims 1
- HJWSQRCHXSOMQM-UHFFFAOYSA-N 1-(1-methylimidazol-2-yl)-1-(3,4,5-trimethoxyphenyl)ethanol Chemical compound COC1=C(OC)C(OC)=CC(C(C)(O)C=2N(C=CN=2)C)=C1 HJWSQRCHXSOMQM-UHFFFAOYSA-N 0.000 claims 1
- KIGIKUKKDCUOII-UHFFFAOYSA-N 1-(1-methylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=CC(C(F)(F)F)=C1 KIGIKUKKDCUOII-UHFFFAOYSA-N 0.000 claims 1
- XHAZUBPMLWQYNT-UHFFFAOYSA-N 1-(1-methylimidazol-2-yl)-1-[4-(trifluoromethyl)phenyl]ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=C(C(F)(F)F)C=C1 XHAZUBPMLWQYNT-UHFFFAOYSA-N 0.000 claims 1
- QOWMVHIJROGYGR-UHFFFAOYSA-N 1-(2,5-dimethylpyrazol-3-yl)-1-phenylethanol Chemical compound CN1N=C(C)C=C1C(C)(O)C1=CC=CC=C1 QOWMVHIJROGYGR-UHFFFAOYSA-N 0.000 claims 1
- MLLHMGAXTPMXJX-UHFFFAOYSA-N 1-(2-butylpyrazol-3-yl)-1-(4-chlorophenyl)ethanol Chemical compound CCCCN1N=CC=C1C(C)(O)C1=CC=C(Cl)C=C1 MLLHMGAXTPMXJX-UHFFFAOYSA-N 0.000 claims 1
- WVRVNOMMWKEQED-UHFFFAOYSA-N 1-(2-chlorophenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=CC=C1Cl WVRVNOMMWKEQED-UHFFFAOYSA-N 0.000 claims 1
- XPXNVYSLUHGWHD-UHFFFAOYSA-N 1-(2-chlorophenyl)-1-(1-methylimidazol-2-yl)pentan-1-ol Chemical compound C=1C=CC=C(Cl)C=1C(O)(CCCC)C1=NC=CN1C XPXNVYSLUHGWHD-UHFFFAOYSA-N 0.000 claims 1
- PJVPJYXENRKSMH-UHFFFAOYSA-N 1-(2-methylpyrazol-3-yl)-1-(3,4,5-trimethoxyphenyl)ethanol Chemical compound COC1=C(OC)C(OC)=CC(C(C)(O)C=2N(N=CC=2)C)=C1 PJVPJYXENRKSMH-UHFFFAOYSA-N 0.000 claims 1
- MFPQHUMVIGZVPG-UHFFFAOYSA-N 1-(2-methylpyrazol-3-yl)-1-phenylethanol Chemical compound CN1N=CC=C1C(C)(O)C1=CC=CC=C1 MFPQHUMVIGZVPG-UHFFFAOYSA-N 0.000 claims 1
- XEBCHPNMVGYZCJ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=C(Cl)C(Cl)=C1 XEBCHPNMVGYZCJ-UHFFFAOYSA-N 0.000 claims 1
- XMPXFKVLHVGEFZ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-1-(1-methylimidazol-2-yl)pentan-1-ol Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(O)(CCCC)C1=NC=CN1C XMPXFKVLHVGEFZ-UHFFFAOYSA-N 0.000 claims 1
- DWDVLGPIYRLKRH-UHFFFAOYSA-N 1-(3-chlorophenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=CC(Cl)=C1 DWDVLGPIYRLKRH-UHFFFAOYSA-N 0.000 claims 1
- SFHYMEZVPKTHKV-UHFFFAOYSA-N 1-(3-chlorophenyl)-1-(1-methylimidazol-2-yl)pentan-1-ol Chemical compound C=1C=CC(Cl)=CC=1C(O)(CCCC)C1=NC=CN1C SFHYMEZVPKTHKV-UHFFFAOYSA-N 0.000 claims 1
- KTHPEZGAKABABA-UHFFFAOYSA-N 1-(4-chlorophenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=C(Cl)C=C1 KTHPEZGAKABABA-UHFFFAOYSA-N 0.000 claims 1
- ZQQAEIBJOGBKHF-UHFFFAOYSA-N 1-(4-chlorophenyl)-1-(1-methylimidazol-2-yl)propan-1-ol Chemical compound C=1C=C(Cl)C=CC=1C(O)(CC)C1=NC=CN1C ZQQAEIBJOGBKHF-UHFFFAOYSA-N 0.000 claims 1
- XSWMNDDYGZVTNX-UHFFFAOYSA-N 1-(4-chlorophenyl)-1-[1-(2-piperidin-1-ylethyl)imidazol-2-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)(C)C1=NC=CN1CCN1CCCCC1 XSWMNDDYGZVTNX-UHFFFAOYSA-N 0.000 claims 1
- BLIIGCBWMDJXSY-UHFFFAOYSA-N 1-(4-chlorophenyl)-1-[1-[3-(dimethylamino)propyl]imidazol-2-yl]ethanol Chemical compound CN(C)CCCN1C=CN=C1C(C)(O)C1=CC=C(Cl)C=C1 BLIIGCBWMDJXSY-UHFFFAOYSA-N 0.000 claims 1
- BQWWWOBZYLAWTJ-UHFFFAOYSA-N 1-(4-fluorophenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound CN1C=CN=C1C(C)(O)C1=CC=C(F)C=C1 BQWWWOBZYLAWTJ-UHFFFAOYSA-N 0.000 claims 1
- STUAYPBVIKRCLW-UHFFFAOYSA-N 1-(4-methoxyphenyl)-1-(1-methylimidazol-2-yl)ethanol Chemical compound C1=CC(OC)=CC=C1C(C)(O)C1=NC=CN1C STUAYPBVIKRCLW-UHFFFAOYSA-N 0.000 claims 1
- PGZIXIJCMBPHCS-UHFFFAOYSA-N 1-[2-[1-(1-methylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]ethoxy]ethyl]piperidine Chemical compound CN1C=CN=C1C(C)(C=1C=C(C=CC=1)C(F)(F)F)OCCN1CCCCC1 PGZIXIJCMBPHCS-UHFFFAOYSA-N 0.000 claims 1
- APKDHLMIBHYURQ-UHFFFAOYSA-N 1h-imidazol-2-yl(phenyl)methanol Chemical compound C=1C=CC=CC=1C(O)C1=NC=CN1 APKDHLMIBHYURQ-UHFFFAOYSA-N 0.000 claims 1
- IUHGHUIFWRTGTR-UHFFFAOYSA-N 2-[(2,5-dimethylpyrazol-3-yl)-phenylmethoxy]-n,n-dimethylethanamine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC(C)=NN1C IUHGHUIFWRTGTR-UHFFFAOYSA-N 0.000 claims 1
- YDSOLFXBVMACID-UHFFFAOYSA-N 2-[1-(2,5-dimethylpyrazol-3-yl)-1-phenylethoxy]-n,n-dimethylethanamine Chemical compound C=1C=CC=CC=1C(C)(OCCN(C)C)C1=CC(C)=NN1C YDSOLFXBVMACID-UHFFFAOYSA-N 0.000 claims 1
- YUURMFIDDXWWMJ-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)-1-(2-pyrrolidin-1-ylethoxy)ethyl]-1-methylimidazole Chemical compound CN1C=CN=C1C(C)(C=1C=C(Cl)C=CC=1)OCCN1CCCC1 YUURMFIDDXWWMJ-UHFFFAOYSA-N 0.000 claims 1
- RODCVPCSMMTJFX-UHFFFAOYSA-N 2-[cyclohexyl-(3,4-dichlorophenyl)-(1-methylimidazol-2-yl)methoxy]-n,n-dimethylethanamine Chemical compound N=1C=CN(C)C=1C(C=1C=C(Cl)C(Cl)=CC=1)(OCCN(C)C)C1CCCCC1 RODCVPCSMMTJFX-UHFFFAOYSA-N 0.000 claims 1
- CQKPZFVNMOPDKR-UHFFFAOYSA-N 3-[(1-butylimidazol-2-yl)-[4-(trifluoromethyl)phenyl]methoxy]-n,n-dimethylpropan-1-amine Chemical compound CCCCN1C=CN=C1C(OCCCN(C)C)C1=CC=C(C(F)(F)F)C=C1 CQKPZFVNMOPDKR-UHFFFAOYSA-N 0.000 claims 1
- PXTODOBTOILXNZ-UHFFFAOYSA-N 3-[(3,4-dichlorophenyl)-(1-methylimidazol-2-yl)methoxy]-n,n-dimethylpropan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(OCCCN(C)C)C1=NC=CN1C PXTODOBTOILXNZ-UHFFFAOYSA-N 0.000 claims 1
- LCTSRXWBCXUBJO-UHFFFAOYSA-N 3-[(4-chlorophenyl)-cyclohexyl-(1-methylimidazol-2-yl)methoxy]-n,n-dimethylpropan-1-amine Chemical compound N=1C=CN(C)C=1C(C=1C=CC(Cl)=CC=1)(OCCCN(C)C)C1CCCCC1 LCTSRXWBCXUBJO-UHFFFAOYSA-N 0.000 claims 1
- OMUCRIUSLKRQQO-UHFFFAOYSA-N 3-[(4-methoxyphenyl)-(1-methylimidazol-2-yl)methoxy]-n,n-dimethylpropan-1-amine Chemical compound C1=CC(OC)=CC=C1C(OCCCN(C)C)C1=NC=CN1C OMUCRIUSLKRQQO-UHFFFAOYSA-N 0.000 claims 1
- ADRWDPJGYRTLGB-UHFFFAOYSA-N 3-[1-(1-butylimidazol-2-yl)-1-(2,4-dichlorophenyl)pentoxy]-n,n-dimethylpropan-1-amine Chemical compound CCCCN1C=CN=C1C(CCCC)(OCCCN(C)C)C1=CC=C(Cl)C=C1Cl ADRWDPJGYRTLGB-UHFFFAOYSA-N 0.000 claims 1
- QFRRSSNCWWLXBD-UHFFFAOYSA-N 3-[1-(1-butylimidazol-2-yl)-1-(2-chlorophenyl)pentoxy]-n,n-dimethylpropan-1-amine Chemical compound CCCCN1C=CN=C1C(CCCC)(OCCCN(C)C)C1=CC=CC=C1Cl QFRRSSNCWWLXBD-UHFFFAOYSA-N 0.000 claims 1
- HGUZXMYZWIVVTL-UHFFFAOYSA-N 3-[1-(1-butylimidazol-2-yl)-1-(3,4,5-trimethoxyphenyl)pentoxy]-n,n-dimethylpropan-1-amine Chemical compound CCCCN1C=CN=C1C(CCCC)(OCCCN(C)C)C1=CC(OC)=C(OC)C(OC)=C1 HGUZXMYZWIVVTL-UHFFFAOYSA-N 0.000 claims 1
- ZPOXGAUHNNPHHP-UHFFFAOYSA-N 3-[1-(3,4-dichlorophenyl)-1-(1-methylimidazol-2-yl)ethoxy]-n,n-dimethylpropan-1-amine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C)(OCCCN(C)C)C1=NC=CN1C ZPOXGAUHNNPHHP-UHFFFAOYSA-N 0.000 claims 1
- BOAQHYBGDBXNQO-UHFFFAOYSA-N 3-[1-(4-chlorophenyl)-1-[1-(2-piperidin-1-ylpropyl)imidazol-2-yl]ethoxy]-n,n-dimethylpropan-1-amine Chemical compound C1CCCCN1C(C)CN1C=CN=C1C(C)(OCCCN(C)C)C1=CC=C(Cl)C=C1 BOAQHYBGDBXNQO-UHFFFAOYSA-N 0.000 claims 1
- QTGBQHNTGMWLCP-UHFFFAOYSA-N 3-[1-(4-fluorophenyl)-1-(1-methylimidazol-2-yl)ethoxy]-n,n-dimethylpropan-1-amine Chemical compound C=1C=C(F)C=CC=1C(C)(OCCCN(C)C)C1=NC=CN1C QTGBQHNTGMWLCP-UHFFFAOYSA-N 0.000 claims 1
- IUFQWWLCBPEUAH-UHFFFAOYSA-N 3-[1-(4-methoxyphenyl)-1-(1-methylimidazol-2-yl)ethoxy]-n,n-dimethylpropan-1-amine Chemical compound C1=CC(OC)=CC=C1C(C)(OCCCN(C)C)C1=NC=CN1C IUFQWWLCBPEUAH-UHFFFAOYSA-N 0.000 claims 1
- ODLNHYJTUCBYMC-UHFFFAOYSA-N 3-[2-[(3,4-dichlorophenyl)-hydroxymethyl]imidazol-1-yl]propan-1-ol Chemical compound OCCCN1C=CN=C1C(O)C1=CC=C(Cl)C(Cl)=C1 ODLNHYJTUCBYMC-UHFFFAOYSA-N 0.000 claims 1
- ZYZYSYJGWFMBEU-UHFFFAOYSA-N 3-[2-[(3-chlorophenyl)-hydroxymethyl]imidazol-1-yl]propanoic acid Chemical compound C=1C=CC(Cl)=CC=1C(O)C1=NC=CN1CCC(O)=O ZYZYSYJGWFMBEU-UHFFFAOYSA-N 0.000 claims 1
- VHBFGAIGLBITIQ-UHFFFAOYSA-N 3-[2-[(4-chlorophenyl)-hydroxymethyl]imidazol-1-yl]propanenitrile Chemical compound C=1C=C(Cl)C=CC=1C(O)C1=NC=CN1CCC#N VHBFGAIGLBITIQ-UHFFFAOYSA-N 0.000 claims 1
- GCMHNPWUDCICKI-UHFFFAOYSA-N 3-[2-[hydroxy(phenyl)methyl]imidazol-1-yl]propan-1-ol Chemical compound OCCCN1C=CN=C1C(O)C1=CC=CC=C1 GCMHNPWUDCICKI-UHFFFAOYSA-N 0.000 claims 1
- VOSXHOBMKDGQPI-UHFFFAOYSA-N 3-[2-[hydroxy-(4-methoxyphenyl)methyl]imidazol-1-yl]propan-1-ol Chemical compound C1=CC(OC)=CC=C1C(O)C1=NC=CN1CCCO VOSXHOBMKDGQPI-UHFFFAOYSA-N 0.000 claims 1
- IFKSDZMUAAHWAT-UHFFFAOYSA-N 3-[2-[hydroxy-(4-methylphenyl)methyl]imidazol-1-yl]propan-1-ol Chemical compound C1=CC(C)=CC=C1C(O)C1=NC=CN1CCCO IFKSDZMUAAHWAT-UHFFFAOYSA-N 0.000 claims 1
- AFWCGACIIQRYSI-UHFFFAOYSA-N 4-[2-[(4-chlorophenyl)-hydroxymethyl]imidazol-1-yl]butan-1-ol Chemical compound OCCCCN1C=CN=C1C(O)C1=CC=C(Cl)C=C1 AFWCGACIIQRYSI-UHFFFAOYSA-N 0.000 claims 1
- JVHPPQUTVOXZRQ-UHFFFAOYSA-N 4-[2-[(4-chlorophenyl)-hydroxymethyl]imidazol-1-yl]butanenitrile Chemical compound C=1C=C(Cl)C=CC=1C(O)C1=NC=CN1CCCC#N JVHPPQUTVOXZRQ-UHFFFAOYSA-N 0.000 claims 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims 1
- MDSUTZZMOHJZRK-UHFFFAOYSA-N [1-(3-aminopropyl)imidazol-2-yl]-(4-chlorophenyl)methanol Chemical compound NCCCN1C=CN=C1C(O)C1=CC=C(Cl)C=C1 MDSUTZZMOHJZRK-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- FQCRGDMJUPSKIY-UHFFFAOYSA-N cyclohexyl-(1-methylimidazol-2-yl)-[3-(trifluoromethyl)phenyl]methanol Chemical compound CN1C=CN=C1C(O)(C=1C=C(C=CC=1)C(F)(F)F)C1CCCCC1 FQCRGDMJUPSKIY-UHFFFAOYSA-N 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- GWRBROJJJXZXJO-UHFFFAOYSA-N n,n-dimethyl-2-[(2-methylphenyl)-(2-methylpyrazol-3-yl)methoxy]ethanamine Chemical compound C=1C=CC=C(C)C=1C(OCCN(C)C)C1=CC=NN1C GWRBROJJJXZXJO-UHFFFAOYSA-N 0.000 claims 1
- NSLDMDYZZZQFQK-UHFFFAOYSA-N n,n-dimethyl-3-[1-(1-methylimidazol-2-yl)-1-[3-(trifluoromethyl)phenyl]pentoxy]propan-1-amine Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(OCCCN(C)C)(CCCC)C1=NC=CN1C NSLDMDYZZZQFQK-UHFFFAOYSA-N 0.000 claims 1
- RCPBRMSVUJLAEM-UHFFFAOYSA-N n,n-dimethyl-3-[1-(1-methylimidazol-2-yl)-1-[4-(trifluoromethyl)phenyl]ethoxy]propan-1-amine Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C)(OCCCN(C)C)C1=NC=CN1C RCPBRMSVUJLAEM-UHFFFAOYSA-N 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 abstract description 7
- 210000003169 central nervous system Anatomy 0.000 abstract description 5
- 241000282414 Homo sapiens Species 0.000 abstract description 3
- 230000033001 locomotion Effects 0.000 abstract description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 abstract description 2
- 208000028017 Psychotic disease Diseases 0.000 abstract 1
- 230000001149 cognitive effect Effects 0.000 abstract 1
- 125000001544 thienyl group Chemical group 0.000 abstract 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 84
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 42
- 230000000694 effects Effects 0.000 description 21
- 238000012360 testing method Methods 0.000 description 15
- JLKUMSHHQYQLSG-UHFFFAOYSA-N 3-carboxy-3,5-dihydroxy-5-oxopentanoate;dimethyl-[2-[(2-methylpyrazol-3-yl)-phenylmethoxy]ethyl]azanium Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=NN1C JLKUMSHHQYQLSG-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 230000001430 anti-depressive effect Effects 0.000 description 7
- 239000000935 antidepressant agent Substances 0.000 description 7
- 229940005513 antidepressants Drugs 0.000 description 7
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 description 6
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 5
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 5
- 229960003147 reserpine Drugs 0.000 description 5
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 5
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 4
- 206010015995 Eyelid ptosis Diseases 0.000 description 4
- 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 4
- 101100029763 Rattus norvegicus Inpp5j gene Proteins 0.000 description 4
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000007913 intrathecal administration Methods 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 201000003004 ptosis Diseases 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 210000003523 substantia nigra Anatomy 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- IUQJDHJVPLLKFL-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetate;dimethylazanium Chemical compound CNC.OC(=O)COC1=CC=C(Cl)C=C1Cl IUQJDHJVPLLKFL-UHFFFAOYSA-N 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
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 description 2
- 125000006202 diisopropylaminoethyl group Chemical group [H]C([H])([H])C([H])(N(C([H])([H])C([H])([H])*)C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000001153 interneuron Anatomy 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- DCMJBKFKXGPPMT-UHFFFAOYSA-N n,n-dimethyl-2-[(2-methylpyrazol-3-yl)-phenylmethoxy]ethanamine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=NN1C DCMJBKFKXGPPMT-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 1
- FZIPCQLKPTZZIM-UHFFFAOYSA-N 2-oxidanylpropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FZIPCQLKPTZZIM-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 230000000338 anxiogenic effect Effects 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 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
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000002536 noncholinergic effect Effects 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 230000003997 social interaction Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 108060008037 tachykinin Proteins 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
- 210000001519 tissue Anatomy 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES009801708A ES2150378B1 (es) | 1998-08-07 | 1998-08-07 | Empleo de derivados de aril(o heteroaril)azolilcarbinoles en la elaboracion de un medicamento para el tratamiento de los trastornos mediados por un exceso de substancia p. |
| PCT/ES1999/000255 WO2000007542A2 (es) | 1998-08-07 | 1999-08-05 | Empleo de derivados de aril(o heteroaril)azolilcarbinoles en la elaboracion de un medicamento para el tratamiento de los trastornos mediados por un exceso de substancia p |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL346221A1 PL346221A1 (en) | 2002-01-28 |
| PL193802B1 true PL193802B1 (pl) | 2007-03-30 |
Family
ID=8304839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL99346221A PL193802B1 (pl) | 1998-08-07 | 1999-08-05 | Zastosowanie pochodnych arylo (lub heteroarylo) azolilokarbinoli do wytwarzania leku do leczenia zaburzeń wywoływanych nadmiarem substancji P |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6518295B1 (https=) |
| EP (1) | EP1103243B1 (https=) |
| JP (1) | JP2002522359A (https=) |
| KR (1) | KR100558506B1 (https=) |
| CN (1) | CN1151789C (https=) |
| AR (1) | AR019999A1 (https=) |
| AT (1) | ATE257379T1 (https=) |
| AU (1) | AU754124B2 (https=) |
| BR (1) | BR9912807A (https=) |
| CA (1) | CA2339661C (https=) |
| CO (1) | CO5080747A1 (https=) |
| CZ (1) | CZ292065B6 (https=) |
| DE (1) | DE69914085T8 (https=) |
| DK (1) | DK1103243T3 (https=) |
| ES (2) | ES2150378B1 (https=) |
| HU (1) | HUP0105428A3 (https=) |
| IL (1) | IL141295A0 (https=) |
| NO (1) | NO20010634L (https=) |
| NZ (1) | NZ509645A (https=) |
| PL (1) | PL193802B1 (https=) |
| PT (1) | PT1103243E (https=) |
| RU (1) | RU2223116C2 (https=) |
| TR (1) | TR200100378T2 (https=) |
| TW (1) | TW445259B (https=) |
| WO (1) | WO2000007542A2 (https=) |
| ZA (1) | ZA200100867B (https=) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2174756B2 (es) * | 2001-04-06 | 2003-11-16 | Esteve Labor Dr | Derivados de aril (o heteroaril) azolilcarbinoles para el tratamiento de enfermedades respiratorias. |
| US20040142929A1 (en) * | 2001-07-06 | 2004-07-22 | Ramon Merce-Vidal | Derivatives of aryl (or heteroaryl) azolylcarbinoles for the treatment of urinary incontinence |
| ES2180449B1 (es) * | 2001-07-06 | 2004-01-16 | Esteve Labor Dr | Derivados de aril (o heteroaril) azolilcarbinoles para el tratamiento de la incontinencia urinaria. |
| DE10335566A1 (de) * | 2003-07-31 | 2005-02-24 | Grünenthal GmbH | Arzneimittel enthaltend Derivate von Aryl( oder Heteroaryl)azolylcarbinolen |
| EP1584335A3 (en) * | 2004-04-05 | 2006-02-22 | Laboratorios Del Dr. Esteve, S.A. | Active substance combination comprising a carbinol composition and an opioid |
| ES2244326B1 (es) * | 2004-04-05 | 2007-02-16 | Laboratorios Del Dr. Esteve, S.A. | Combinacion de substancias activas. |
| EP1784178A1 (en) * | 2004-07-30 | 2007-05-16 | Laboratorios Del Dr. Esteve, S.A. | Aryl (or heteroaryl) azolylcarbinols |
| CA2580694A1 (en) * | 2004-09-23 | 2006-03-30 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| US20080045610A1 (en) * | 2004-09-23 | 2008-02-21 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| EP1690537A1 (en) * | 2005-02-15 | 2006-08-16 | Laboratorios Del Dr. Esteve, S.A. | Derivatives of aryl(or heteroaryl) azolycarbinols for the treatment of fibromyalgia |
| ES2286920B1 (es) * | 2005-02-15 | 2008-08-16 | Laboratorios Del Dr. Esteve, S.A. | Derivados de aril (o heteroaril)azolilcarbinoles para el tratamiento de la fibromialgia. |
| EP1695704A1 (en) * | 2005-02-28 | 2006-08-30 | Laboratorios Del Dr. Esteve, S.A. | Derivatives of aryl (or heteroaryl) azolylcarbinols for the treatment of fibromyalgia |
| WO2006087147A2 (en) * | 2005-02-15 | 2006-08-24 | Laboratorios Del Dr. Esteve, S.A. | Derivatives of aryl (or heteroaryl) azolylcarbinols for the treatment of fibromyalgia |
| AU2007209381A1 (en) * | 2006-01-27 | 2007-08-02 | F. Hoffmann-La Roche Ag | Use of substituted 2-imidazole of imidazoline derivatives |
| EP1820502A1 (en) * | 2006-02-10 | 2007-08-22 | Laboratorios Del Dr. Esteve, S.A. | Active substance combination comprising azolylcarbinol compounds |
| AU2007312390B2 (en) | 2006-10-19 | 2013-03-28 | F. Hoffmann-La Roche Ag | Aminomethyl-4-imidazoles |
| CA2668454A1 (en) | 2006-11-02 | 2008-05-08 | F. Hoffmann-La Roche Ag | Substituted 2-imidazoles |
| WO2008058867A2 (en) | 2006-11-16 | 2008-05-22 | F. Hoffmann-La Roche Ag | Substituted 4-imidazoles |
| CN101190330A (zh) | 2006-11-30 | 2008-06-04 | 深圳市鼎兴生物医药技术开发有限公司 | 胆碱酯酶在拮抗速激肽药物中的应用 |
| ES2364701T3 (es) | 2006-12-13 | 2011-09-12 | F. Hoffmann-La Roche Ag | Nuevos 2-imidazoles como ligandos para receptores asociados a aminas trazas. |
| EP2114906B1 (en) | 2007-02-02 | 2014-08-06 | F. Hoffmann-La Roche AG | 2-aminooxazolines as taar1 ligands for cns disorders |
| CA2676944C (en) | 2007-02-15 | 2016-01-19 | F. Hoffmann-La Roche Ag | 2-aminooxazolines as taar1 ligands |
| WO2009003868A2 (en) | 2007-07-02 | 2009-01-08 | F. Hoffmann-La Roche Ag | 2 -imidazolines having a good affinity to the trace amine associated receptors (taars) |
| AU2008270444A1 (en) | 2007-07-03 | 2009-01-08 | F. Hoffmann-La Roche Ag | 4-imidazolines and their use as antidepressants |
| CA2694362A1 (en) | 2007-07-27 | 2009-02-05 | F. Hoffmann-La Roche Ag | 2-azetidinemethaneamines and 2-pyrrolidinemethaneamines as taar-ligands |
| AU2008285795A1 (en) | 2007-08-03 | 2009-02-12 | F. Hoffmann-La Roche Ag | Pyridinecarboxamide and benzamide derivatives as TAAR1 ligands |
| US8242153B2 (en) | 2008-07-24 | 2012-08-14 | Hoffmann-La Roche Inc. | 4,5-dihydro-oxazol-2YL derivatives |
| WO2010123999A2 (en) * | 2009-04-21 | 2010-10-28 | Auspex Pharmaceuticals, Inc. | 1-methylpyrazole modulators of substance p, calcitonin gene-related peptide, adrenergic receptor, and/or 5-ht receptor |
| US8354441B2 (en) | 2009-11-11 | 2013-01-15 | Hoffmann-La Roche Inc. | Oxazoline derivatives |
| US9452980B2 (en) | 2009-12-22 | 2016-09-27 | Hoffmann-La Roche Inc. | Substituted benzamides |
| WO2017157873A1 (en) | 2016-03-17 | 2017-09-21 | F. Hoffmann-La Roche Ag | 5-ethyl-4-methyl-pyrazole-3-carboxamide derivative having activity as agonist of taar |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2613720B1 (fr) * | 1987-04-10 | 1990-01-19 | Esteve Labor Dr | Derives d'aryl-heteroaryl carbinols avec activite analgesique |
| FR2681322B1 (fr) * | 1991-09-12 | 1993-12-17 | Laboratorios Dr Esteve Sa | Derives d'aryl-heteroaryl-{n-[2-(3,4-dimethoxyphenyl)-ethyl]-n-methyl-3-aminopropoxy}-methane leur preparation et leur application en tant que medicaments . |
| CA2154116A1 (en) * | 1994-07-22 | 1996-01-23 | Philip Arthur Hipskind | 1-aryl-2-acetamidopentanone derivatives for use as tachykinin receptor antagonists |
| FR2742147B1 (fr) * | 1995-12-06 | 1998-02-27 | Esteve Labor Dr | Procede de separation de carbinols |
| CA2273807A1 (en) * | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating schizophrenic disorders |
| CA2273853A1 (en) * | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating cognitive disorders |
| EP0942734A1 (en) * | 1996-12-02 | 1999-09-22 | MERCK SHARP & DOHME LTD. | Use of nk-1 receptor antagonists for treating severe anxiety disorders |
| DE69732133T2 (de) * | 1996-12-02 | 2005-12-22 | Merck Sharp & Dohme Ltd., Hoddesdon | Verwendung von NK-1 Rezeptorantagonisten zur Behandlung von schweren Depressionen |
| ES2150353B1 (es) * | 1998-04-15 | 2001-07-01 | Esteve Labor Dr | Tienilazolilalcoxietanaminas, su preparacion y su aplicacion como medicamentos. |
-
1998
- 1998-08-07 ES ES009801708A patent/ES2150378B1/es not_active Expired - Fee Related
-
1999
- 1999-08-04 AR ARP990103870A patent/AR019999A1/es unknown
- 1999-08-04 CO CO99049291A patent/CO5080747A1/es unknown
- 1999-08-05 TW TW088113353A patent/TW445259B/zh not_active IP Right Cessation
- 1999-08-05 NZ NZ509645A patent/NZ509645A/xx unknown
- 1999-08-05 US US09/762,079 patent/US6518295B1/en not_active Expired - Fee Related
- 1999-08-05 HU HU0105428A patent/HUP0105428A3/hu unknown
- 1999-08-05 BR BR9912807-1A patent/BR9912807A/pt not_active Application Discontinuation
- 1999-08-05 AT AT99940199T patent/ATE257379T1/de not_active IP Right Cessation
- 1999-08-05 TR TR2001/00378T patent/TR200100378T2/xx unknown
- 1999-08-05 CA CA002339661A patent/CA2339661C/en not_active Expired - Fee Related
- 1999-08-05 ES ES99940199T patent/ES2213380T3/es not_active Expired - Lifetime
- 1999-08-05 DE DE69914085T patent/DE69914085T8/de not_active Expired - Fee Related
- 1999-08-05 PT PT99940199T patent/PT1103243E/pt unknown
- 1999-08-05 KR KR1020017001560A patent/KR100558506B1/ko not_active Expired - Fee Related
- 1999-08-05 AU AU54229/99A patent/AU754124B2/en not_active Ceased
- 1999-08-05 RU RU2001106644/15A patent/RU2223116C2/ru not_active IP Right Cessation
- 1999-08-05 DK DK99940199T patent/DK1103243T3/da active
- 1999-08-05 WO PCT/ES1999/000255 patent/WO2000007542A2/es not_active Ceased
- 1999-08-05 JP JP2000563228A patent/JP2002522359A/ja active Pending
- 1999-08-05 CN CNB998109150A patent/CN1151789C/zh not_active Expired - Fee Related
- 1999-08-05 PL PL99346221A patent/PL193802B1/pl not_active IP Right Cessation
- 1999-08-05 CZ CZ2001412A patent/CZ292065B6/cs not_active IP Right Cessation
- 1999-08-05 EP EP99940199A patent/EP1103243B1/en not_active Expired - Lifetime
-
2001
- 2001-01-31 ZA ZA200100867A patent/ZA200100867B/en unknown
- 2001-02-06 NO NO20010634A patent/NO20010634L/no not_active Application Discontinuation
- 2001-02-07 IL IL14129501A patent/IL141295A0/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PL193802B1 (pl) | Zastosowanie pochodnych arylo (lub heteroarylo) azolilokarbinoli do wytwarzania leku do leczenia zaburzeń wywoływanych nadmiarem substancji P | |
| JP5966014B2 (ja) | 新規トリフルオロメチル−オキサジアゾール誘導体および疾患の処置におけるその使用 | |
| JP6114355B2 (ja) | アルツハイマー病を処置するための組成物および方法 | |
| RU2001106644A (ru) | Применение производных арил (или гетероарил) азолилкарбинолов в приготовлении лекарственного средства для лечения нарушений, опосредованных избытком вещества p | |
| KR101855358B1 (ko) | 골암통증에서의 시그마 리간드의 용도 | |
| HUP0202399A2 (hu) | Dopamin D3 receptor ligandumok alkalmazása veseelégtelenség kezelésére szolgáló gyógyszerek előállítására | |
| JP2002522359A5 (https=) | ||
| RU2012139828A (ru) | Производные пиразолопиперидина в качестве ингибиторов nadph-оксидазы | |
| JP2017014224A (ja) | 帯状疱疹関連痛の急性期疼痛の予防又は治療剤 | |
| AU2006321907A1 (en) | Use of a CB1 antagonist for treating negative symptoms of schizophrenia | |
| AU716665B2 (en) | Medicament intended to the treatment of obsessive compulsive troubles, sleep apnoea, sexual dysfunctions, emesa and transport sickness | |
| JP2006503025A (ja) | ｐ３８ＭＡＰキナーゼの抑制による疼痛治療 | |
| CA2587026A1 (en) | Use of dipyridamole in combination with antithrombotics for treatment and prevention of thromboembolic diseases | |
| ZA200609058B (en) | Use of dipyridamole for treatment of resistance to platelet inhibitors | |
| JP2012505226A5 (https=) | ||
| WO2016096125A1 (en) | Use of sigma receptor ligands in osteoarthritis | |
| WO2019181854A1 (ja) | てんかん治療剤 | |
| CN101137373A (zh) | 含有大麻素受体拮抗化合物与防治精神病剂组合的药物组合物 | |
| MXPA01001438A (en) | Utilization of aryl(or heteroaryl)azolylcarbinol derivatives in the preparation of a medicament for the treatment of troubles mediated by an excess of substance p | |
| KR20100022955A (ko) | (티오) -카르바모일-시클로헥산 유도체 및 정신분열 치료 방법 | |
| Matta | 17 CB1 Receptor Antagonists in Obesity Treatment: Current Advances and Perspectives | |
| KR20140038219A (ko) | 게스트리논을 포함하는 류마티스 관절염의 예방 또는 치료용 약학 조성물 | |
| RU97115227A (ru) | Лекарство для лечения расстройств, связанных с навязчивым желанием совершить действие, апноэ во сне, сексуальных дисфункций, эмеза и укачивания в транспорте |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Decisions on the lapse of the protection rights |
Effective date: 20070805 |