NZ519032A

NZ519032A - Combination treatment for alcoholism and alcohol dependence

Combination treatment for alcoholism and alcohol dependence

Info

Publication number: NZ519032A
Authority: NZ; New Zealand
Prior art keywords: dichlorophenoxy; methylamine; formula; ring; independently
Prior art date: 2001-05-23

Application number

NZ519032A

Other languages

English (en)

Inventor

Harry Ralph Howard

Original Assignee

Pfizer Prod Inc

Priority date

2001-05-23

Filing date

2002-05-17

Publication date

2003-10-31

2002-05-17 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2003-10-31 Publication of NZ519032A publication Critical patent/NZ519032A/en

Links

208000007848 Alcoholism Diseases 0.000 title claims abstract description 88
201000007930 alcohol dependence Diseases 0.000 title claims abstract description 87
238000011284 combination treatment Methods 0.000 title claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 62
-1 biaryl ether derivative Chemical class 0.000 claims abstract description 47
239000003401 opiate antagonist Substances 0.000 claims abstract description 35
238000011282 treatment Methods 0.000 claims abstract description 32
241000124008 Mammalia Species 0.000 claims abstract description 18
239000003937 drug carrier Substances 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 168
150000003839 salts Chemical class 0.000 claims description 80
229910052739 hydrogen Inorganic materials 0.000 claims description 55
239000001257 hydrogen Substances 0.000 claims description 55
238000000034 method Methods 0.000 claims description 53
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
239000000203 mixture Substances 0.000 claims description 44
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 28
125000001624 naphthyl group Chemical group 0.000 claims description 27
125000005842 heteroatom Chemical group 0.000 claims description 25
229910052799 carbon Inorganic materials 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 23
125000001153 fluoro group Chemical group F* 0.000 claims description 22
239000003814 drug Substances 0.000 claims description 20
230000027455 binding Effects 0.000 claims description 18
238000009739 binding Methods 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 18
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
229940126403 monoamine reuptake inhibitor Drugs 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
150000002431 hydrogen Chemical group 0.000 claims description 15
239000001301 oxygen Substances 0.000 claims description 15
125000001424 substituent group Chemical group 0.000 claims description 15
125000004432 carbon atom Chemical group C* 0.000 claims description 14
229910052717 sulfur Inorganic materials 0.000 claims description 12
229920006395 saturated elastomer Polymers 0.000 claims description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
239000013543 active substance Substances 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
238000012360 testing method Methods 0.000 claims description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 claims description 8
238000003556 assay Methods 0.000 claims description 8
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 8
125000001072 heteroaryl group Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
239000007983 Tris buffer Substances 0.000 claims description 6
239000000556 agonist Substances 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 claims description 4
OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
LLVVRQNZUNMHJV-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-(furan-2-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(C=2OC=CC=2)C=C1OC1=CC=C(Cl)C(Cl)=C1 LLVVRQNZUNMHJV-UHFFFAOYSA-N 0.000 claims description 3
JERYDYFQMRCTFJ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-pyridin-4-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2C=CN=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 JERYDYFQMRCTFJ-UHFFFAOYSA-N 0.000 claims description 3
GKVABNNXZNUTSR-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-thiophen-3-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C2=CSC=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 GKVABNNXZNUTSR-UHFFFAOYSA-N 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
NPJYROQKHDJYRQ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4,5-dimethylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C)=C(C)C=C1OC1=CC=C(Cl)C(Cl)=C1 NPJYROQKHDJYRQ-UHFFFAOYSA-N 0.000 claims description 2
DKXDRPCDKRMICS-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-methoxyphenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(OC)C=C1OC1=CC=C(Cl)C(Cl)=C1 DKXDRPCDKRMICS-UHFFFAOYSA-N 0.000 claims description 2
APMXCCUBPMTTLK-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(1,3-thiazol-2-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2SC=CN=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 APMXCCUBPMTTLK-UHFFFAOYSA-N 0.000 claims description 2
YTEXZARZLHLRJB-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(furan-3-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C2=COC=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 YTEXZARZLHLRJB-UHFFFAOYSA-N 0.000 claims description 2
HYLYTRKKGFVHIE-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-fluorophenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC(F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 HYLYTRKKGFVHIE-UHFFFAOYSA-N 0.000 claims description 2
JPBFWBNMQFVEEC-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-pyridin-3-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2C=NC=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 JPBFWBNMQFVEEC-UHFFFAOYSA-N 0.000 claims description 2
FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 claims description 2
XQFSLGJDGVQPGP-UHFFFAOYSA-N 2-[2-(3,4-dichlorophenoxy)-5-fluorophenyl]pyrrolidine Chemical compound C1CCNC1C1=CC(F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 XQFSLGJDGVQPGP-UHFFFAOYSA-N 0.000 claims description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 2
ZPJJDPPFWWSPPB-UHFFFAOYSA-N 4-(3,4-dichlorophenoxy)-3-(methylaminomethyl)benzonitrile Chemical compound CNCC1=CC(C#N)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 ZPJJDPPFWWSPPB-UHFFFAOYSA-N 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
239000007995 HEPES buffer Substances 0.000 claims description 2
239000012131 assay buffer Substances 0.000 claims description 2
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 2
239000008121 dextrose Substances 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 2
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims 2
SOCXCXJYEMOKAM-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-(1,2,4-triazol-1-yl)phenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC=C(N2N=CN=C2)C=C1OC1=CC=C(Cl)C(Cl)=C1 SOCXCXJYEMOKAM-UHFFFAOYSA-N 0.000 claims 1
BWBOBCUPLKYBOV-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-methoxyphenyl]-n,n-dimethylmethanamine Chemical compound COC1=CC=C(CN(C)C)C(OC=2C=C(Cl)C(Cl)=CC=2)=C1 BWBOBCUPLKYBOV-UHFFFAOYSA-N 0.000 claims 1
KBGXEJXXNBUUKO-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-phenylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(C=2C=CC=CC=2)C=C1OC1=CC=C(Cl)C(Cl)=C1 KBGXEJXXNBUUKO-UHFFFAOYSA-N 0.000 claims 1
MRHLSXLWXQUUIW-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(4-methylphenyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2C=CC(C)=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 MRHLSXLWXQUUIW-UHFFFAOYSA-N 0.000 claims 1
JMPDXZXUFVZHHI-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(furan-2-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2OC=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 JMPDXZXUFVZHHI-UHFFFAOYSA-N 0.000 claims 1
FQEBOQLYHASAOY-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-fluorophenyl]-n-methylmethanamine Chemical compound CNCC1=CC(F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 FQEBOQLYHASAOY-UHFFFAOYSA-N 0.000 claims 1
HJIWIMXZBPSSTO-UHFFFAOYSA-N 1-[2-(3-chloro-4-fluorophenoxy)-5-fluorophenyl]-n-methylmethanamine Chemical compound CNCC1=CC(F)=CC=C1OC1=CC=C(F)C(Cl)=C1 HJIWIMXZBPSSTO-UHFFFAOYSA-N 0.000 claims 1
FZCQKTZYKUFNAJ-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenoxy)-3-(methylaminomethyl)phenyl]pyrazol-3-amine Chemical compound CNCC1=CC(N2N=C(N)C=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 FZCQKTZYKUFNAJ-UHFFFAOYSA-N 0.000 claims 1
XKFGLVWDKDNTGI-UHFFFAOYSA-N 1-[5-bromo-2-(3,4-dichlorophenoxy)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(Br)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 XKFGLVWDKDNTGI-UHFFFAOYSA-N 0.000 claims 1
QFWNAKAETMKRTM-UHFFFAOYSA-N 3-(3,4-dichlorophenoxy)-4-(methylaminomethyl)benzonitrile Chemical compound CNCC1=CC=C(C#N)C=C1OC1=CC=C(Cl)C(Cl)=C1 QFWNAKAETMKRTM-UHFFFAOYSA-N 0.000 claims 1
KZLLRXARLPOUMH-UHFFFAOYSA-N n-[4-(3,4-dichlorophenoxy)-3-[(dimethylamino)methyl]phenyl]acetamide Chemical compound CN(C)CC1=CC(NC(C)=O)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 KZLLRXARLPOUMH-UHFFFAOYSA-N 0.000 claims 1
239000003643 water by type Substances 0.000 claims 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 34
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229940076279 serotonin Drugs 0.000 abstract description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 31
238000003786 synthesis reaction Methods 0.000 description 29
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
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