BRPI0610681A2 - derivados de oxadiazol, composição farmacêutica que os compreende e seu uso - Google Patents

Info

Publication number

BRPI0610681A2

BRPI0610681A2 BRPI0610681-1A BRPI0610681A BRPI0610681A2 BR PI0610681 A2 BRPI0610681 A2 BR PI0610681A2 BR PI0610681 A BRPI0610681 A BR PI0610681A BR PI0610681 A2 BRPI0610681 A2 BR PI0610681A2

Authority

BR

Brazil

Prior art keywords

piperidin

oxadiazol

methanone

phenyl

fluorophenyl

Prior art date

2005-05-18

Links

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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
• 150000004866 oxadiazoles Chemical class 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 217
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 12
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical class C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims abstract description 6
• 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract 3
• 238000000034 method Methods 0.000 claims description 267
• -1 hydroxy, amino Chemical group 0.000 claims description 187
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 149
• 125000000217 alkyl group Chemical group 0.000 claims description 86
• 125000003118 aryl group Chemical group 0.000 claims description 57
• 125000001072 heteroaryl group Chemical group 0.000 claims description 49
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 38
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 33
• 238000004519 manufacturing process Methods 0.000 claims description 29
• 239000000203 mixture Substances 0.000 claims description 26
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 24
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 21
• 230000003281 allosteric effect Effects 0.000 claims description 20
• 239000001257 hydrogen Substances 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 150000002367 halogens Chemical class 0.000 claims description 19
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 13
• 201000000980 schizophrenia Diseases 0.000 claims description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 229940025084 amphetamine Drugs 0.000 claims description 12
• 230000002265 prevention Effects 0.000 claims description 12
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 11
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims description 10
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims description 10
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 208000028017 Psychotic disease Diseases 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 6
• 150000001204 N-oxides Chemical class 0.000 claims description 6
• 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 6
• 150000004677 hydrates Chemical class 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 208000019901 Anxiety disease Diseases 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 210000003169 central nervous system Anatomy 0.000 claims description 5
• 208000010877 cognitive disease Diseases 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 238000003384 imaging method Methods 0.000 claims description 4
• 230000003227 neuromodulating effect Effects 0.000 claims description 4
• JSVZRUOSIODDMU-AWEZNQCLSA-N (4-fluoro-2-methylphenyl)-[(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2)F)CCC1 JSVZRUOSIODDMU-AWEZNQCLSA-N 0.000 claims description 3
• BDWLILFPLXVQLM-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2SC=CC=2)CCC1 BDWLILFPLXVQLM-ZDUSSCGKSA-N 0.000 claims description 3
• QCEZQFAPIXPJNK-AWEZNQCLSA-N (4-fluorophenyl)-[(3s)-3-[3-(5-methylfuran-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound O1C(C)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 QCEZQFAPIXPJNK-AWEZNQCLSA-N 0.000 claims description 3
• NHOFNYNXSRPXCX-ZDUSSCGKSA-N (4-fluorophenyl)-[(3s)-3-[3-(furan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2OC=CC=2)CCC1 NHOFNYNXSRPXCX-ZDUSSCGKSA-N 0.000 claims description 3
• WWPISKFGYAYDHO-ZDUSSCGKSA-N (5-ethyl-1,2-oxazol-4-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1CC WWPISKFGYAYDHO-ZDUSSCGKSA-N 0.000 claims description 3
• JWGJNZULNIBAFQ-LBPRGKRZSA-N [(3s)-3-[3-(2-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C(=CC=CC=2)F)=C1C JWGJNZULNIBAFQ-LBPRGKRZSA-N 0.000 claims description 3
• 230000003287 optical effect Effects 0.000 claims description 3
• XNUMYFLOQVCEKO-AWEZNQCLSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 XNUMYFLOQVCEKO-AWEZNQCLSA-N 0.000 claims description 2
• HKDCESZSMXPUKC-HNNXBMFYSA-N (4-fluoro-3-methoxyphenyl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=C(F)C(OC)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1 HKDCESZSMXPUKC-HNNXBMFYSA-N 0.000 claims description 2
• VXQCCZHCFBHTTD-OAHLLOKOSA-N (4-fluorophenyl)-[(3r)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 VXQCCZHCFBHTTD-OAHLLOKOSA-N 0.000 claims description 2
• YZGSXHUWEYBUCB-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CN=CC=2)CCC1 YZGSXHUWEYBUCB-HNNXBMFYSA-N 0.000 claims description 2
• PKOCQAVNDBHVSN-LBPRGKRZSA-N (4-fluorophenyl)-[(3s)-3-[3-(1,3-thiazol-4-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2N=CSC=2)CCC1 PKOCQAVNDBHVSN-LBPRGKRZSA-N 0.000 claims description 2
• WCXPJZVEABSGRX-AWEZNQCLSA-N (4-fluorophenyl)-[(3s)-3-[3-(1-methylpyrrol-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CN1C=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 WCXPJZVEABSGRX-AWEZNQCLSA-N 0.000 claims description 2
• XTALYXOQCLWHAX-INIZCTEOSA-N (4-fluorophenyl)-[(3s)-3-[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 XTALYXOQCLWHAX-INIZCTEOSA-N 0.000 claims description 2
• YKSCFSZDWWZLEF-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[3-(3-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CN=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 YKSCFSZDWWZLEF-HNNXBMFYSA-N 0.000 claims description 2
• OFYMSNJTOQIZRF-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 OFYMSNJTOQIZRF-HNNXBMFYSA-N 0.000 claims description 2
• RWFCKJHNXMCJDE-HNNXBMFYSA-N (4-fluorophenyl)-[(3s)-3-[3-(6-methylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CC1=CC=CC(C=2N=C(ON=2)[C@@H]2CN(CCC2)C(=O)C=2C=CC(F)=CC=2)=N1 RWFCKJHNXMCJDE-HNNXBMFYSA-N 0.000 claims description 2
• ZAMRYTAWPYUCCA-UHFFFAOYSA-N (4-fluorophenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-4-methylpiperazin-1-yl]methanone Chemical compound CN1CCN(C(=O)C=2C=CC(F)=CC=2)CC1C(ON=1)=NC=1C1=CC=C(F)C=C1 ZAMRYTAWPYUCCA-UHFFFAOYSA-N 0.000 claims description 2
• LGMVMAZHYUIXOA-DJZRFWRSSA-N (5-fluoro-2,3-dihydro-1h-inden-1-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2C3=CC=C(F)C=C3CC2)=N1 LGMVMAZHYUIXOA-DJZRFWRSSA-N 0.000 claims description 2
• OWHVTMNWZKUIPA-NSHDSACASA-N (5-methyl-1,2-oxazol-4-yl)-[(3s)-3-(3-thiophen-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C2=CSC=C2)=C1C OWHVTMNWZKUIPA-NSHDSACASA-N 0.000 claims description 2
• 125000006718 (C3-C7) heterocycloalkenyl group Chemical group 0.000 claims description 2
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
• OMWQVSXCNLOTNT-HNNXBMFYSA-N 2,3-dihydro-1,4-benzodioxin-5-yl-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=3OCCOC=3C=CC=2)=N1 OMWQVSXCNLOTNT-HNNXBMFYSA-N 0.000 claims description 2
• 208000030814 Eating disease Diseases 0.000 claims description 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
• 208000019022 Mood disease Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• FRJRBJINBTUKIV-ZDUSSCGKSA-N [(3s)-3-[3-(2,6-difluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C(=CC=CC=2F)F)CCC1 FRJRBJINBTUKIV-ZDUSSCGKSA-N 0.000 claims description 2
• VEHWGLRNTHIQQL-LBPRGKRZSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(1,3-thiazol-2-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2SC=CN=2)=N1 VEHWGLRNTHIQQL-LBPRGKRZSA-N 0.000 claims description 2
• FGSKISOVLNNQFO-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-methylfuran-3-yl)methanone Chemical compound O1C=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C FGSKISOVLNNQFO-AWEZNQCLSA-N 0.000 claims description 2
• LYBJGCCRCPRHOY-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(2-methylpyridin-3-yl)methanone Chemical compound CC1=NC=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 LYBJGCCRCPRHOY-HNNXBMFYSA-N 0.000 claims description 2
• SXGLZFNQHQDZSH-SFHVURJKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-imidazol-1-ylphenyl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(=CC=2)N2C=NC=C2)=N1 SXGLZFNQHQDZSH-SFHVURJKSA-N 0.000 claims description 2
• YGNFIZHFAPPOIR-LBPRGKRZSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methylthiadiazol-5-yl)methanone Chemical compound N1=NSC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C YGNFIZHFAPPOIR-LBPRGKRZSA-N 0.000 claims description 2
• WPXAVYSKTIOGKI-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(furan-3-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2=COC=C2)=N1 WPXAVYSKTIOGKI-ZDUSSCGKSA-N 0.000 claims description 2
• IKHYAWIWACYCNL-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(thian-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C2CCSCC2)=N1 IKHYAWIWACYCNL-HNNXBMFYSA-N 0.000 claims description 2
• GDHFGNLBOPKOGV-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[2-(methylamino)phenyl]methanone Chemical compound CNC1=CC=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 GDHFGNLBOPKOGV-HNNXBMFYSA-N 0.000 claims description 2
• XWLNRGMVWCNKGC-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=CC(OC(F)(F)F)=CC=2)=N1 XWLNRGMVWCNKGC-HNNXBMFYSA-N 0.000 claims description 2
• UOLHJLVCCDQPQT-ZDUSSCGKSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-[5-(methoxymethyl)-1,2-oxazol-4-yl]methanone Chemical compound O1N=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1COC UOLHJLVCCDQPQT-ZDUSSCGKSA-N 0.000 claims description 2
• QFADMZQACXNHLE-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-quinoxalin-6-ylmethanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C3N=CC=NC3=CC=2)=N1 QFADMZQACXNHLE-INIZCTEOSA-N 0.000 claims description 2
• WKZGPTRKMXRGDT-AWEZNQCLSA-N [4-fluoro-2-(methylamino)phenyl]-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CNC1=CC(F)=CC=C1C(=O)N1C[C@@H](C=2ON=C(N=2)C=2C=CC(F)=CC=2)CCC1 WKZGPTRKMXRGDT-AWEZNQCLSA-N 0.000 claims description 2
• 230000006735 deficit Effects 0.000 claims description 2
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• 239000003937 drug carrier Substances 0.000 claims description 2
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• 206010012289 Dementia Diseases 0.000 claims 5
• 150000002431 hydrogen Chemical class 0.000 claims 3
• XDFWUDHCDXZYMV-LBPRGKRZSA-N (6-fluoropyridin-3-yl)-[(3s)-3-[3-(2-methyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound S1C(C)=NC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=NC(F)=CC=2)=N1 XDFWUDHCDXZYMV-LBPRGKRZSA-N 0.000 claims 2
• JUVULXADAWDDQO-UHFFFAOYSA-N 3-(4-fluorophenyl)benzamide Chemical compound NC(=O)C1=CC=CC(C=2C=CC(F)=CC=2)=C1 JUVULXADAWDDQO-UHFFFAOYSA-N 0.000 claims 2
• 208000007848 Alcoholism Diseases 0.000 claims 2
• 206010012218 Delirium Diseases 0.000 claims 2
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• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 2
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• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims 2
• 208000029364 generalized anxiety disease Diseases 0.000 claims 2
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• 230000002085 persistent effect Effects 0.000 claims 2
• 208000028173 post-traumatic stress disease Diseases 0.000 claims 2
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims 1
• PLMYBEXDLFAAJL-HNNXBMFYSA-N (2,5-dimethylfuran-3-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound O1C(C)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C PLMYBEXDLFAAJL-HNNXBMFYSA-N 0.000 claims 1
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