CA2386740A1

CA2386740A1 - Combination treatment for alcoholism and alcohol dependence

Combination treatment for alcoholism and alcohol dependence Download PDF

Info

Publication number: CA2386740A1
Authority: CA; Canada
Prior art keywords: dichlorophenoxy; methylamine; alkyl; independently; ring
Prior art date: 2001-05-23
Legal status : Abandoned

Application number

CA002386740A

Other languages

English (en)

French (fr)

Inventor

Harry Ralph Howard Jr.

Current Assignee

Individual

Original Assignee

Pfizer Products Inc

Priority date

2001-05-23

Filing date

2002-05-17

Publication date

2002-11-23

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

2002-11-23 Publication of CA2386740A1 publication Critical patent/CA2386740A1/en

Status Abandoned legal-status Critical Current

Links

208000007848 Alcoholism Diseases 0.000 title claims abstract description 146
201000007930 alcohol dependence Diseases 0.000 title claims abstract description 145
238000011284 combination treatment Methods 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 106
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 67
239000003401 opiate antagonist Substances 0.000 claims abstract description 43
241000124008 Mammalia Species 0.000 claims abstract description 29
239000003937 drug carrier Substances 0.000 claims abstract description 15
150000001875 compounds Chemical class 0.000 claims description 183
150000003839 salts Chemical class 0.000 claims description 102
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 72
229910052739 hydrogen Inorganic materials 0.000 claims description 66
239000001257 hydrogen Substances 0.000 claims description 64
-1 cyano, nitro, amino, hydroxy, carbonyl Chemical group 0.000 claims description 48
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 42
239000000203 mixture Substances 0.000 claims description 41
229910052757 nitrogen Inorganic materials 0.000 claims description 40
229910052799 carbon Inorganic materials 0.000 claims description 34
125000005842 heteroatom Chemical group 0.000 claims description 33
125000001153 fluoro group Chemical group F* 0.000 claims description 32
238000011282 treatment Methods 0.000 claims description 32
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
125000001624 naphthyl group Chemical group 0.000 claims description 26
230000027455 binding Effects 0.000 claims description 24
238000009739 binding Methods 0.000 claims description 24
125000005843 halogen group Chemical group 0.000 claims description 22
229910052760 oxygen Inorganic materials 0.000 claims description 22
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 21
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
239000001301 oxygen Substances 0.000 claims description 19
150000002431 hydrogen Chemical group 0.000 claims description 18
239000013543 active substance Substances 0.000 claims description 17
229910052717 sulfur Inorganic materials 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
229920006395 saturated elastomer Polymers 0.000 claims description 13
239000011593 sulfur Substances 0.000 claims description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
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 9
125000003282 alkyl amino group Chemical group 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
239000002552 dosage form Substances 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
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 6
125000002837 carbocyclic group Chemical group 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
125000004434 sulfur atom Chemical group 0.000 claims description 6
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
XNKUKCFVELTTTO-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4,5-dimethoxyphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(OC)=C(OC)C=C1OC1=CC=C(Cl)C(Cl)=C1 XNKUKCFVELTTTO-UHFFFAOYSA-N 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 3
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 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
AAQZZAVVFRIEOD-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-(trifluoromethyl)phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=C(C(F)(F)F)C=C1OC1=CC=C(Cl)C(Cl)=C1 AAQZZAVVFRIEOD-UHFFFAOYSA-N 0.000 claims description 3
ONXYECUKUIZIBT-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-(trifluoromethyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(C(F)(F)F)C=C1OC1=CC=C(Cl)C(Cl)=C1 ONXYECUKUIZIBT-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
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 3
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 description 3
YMZHLLFBCASHHB-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-thiophen-2-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(C=2SC=CC=2)C=C1OC1=CC=C(Cl)C(Cl)=C1 YMZHLLFBCASHHB-UHFFFAOYSA-N 0.000 claims description 3
SFTJBUCEUIKDJD-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-4-thiophen-3-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(C2=CSC=C2)C=C1OC1=CC=C(Cl)C(Cl)=C1 SFTJBUCEUIKDJD-UHFFFAOYSA-N 0.000 claims description 3
IQGWBOYXUSLCFT-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(1,2,4-triazol-4-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(N2C=NN=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 IQGWBOYXUSLCFT-UHFFFAOYSA-N 0.000 claims description 3
QLTUAGOAYVRRPQ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(1,3-thiazol-2-yl)phenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC(C=2SC=CN=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 QLTUAGOAYVRRPQ-UHFFFAOYSA-N 0.000 claims description 3
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 3
LYRAGSVEZOIZJQ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(2h-tetrazol-5-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2NN=NN=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 LYRAGSVEZOIZJQ-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
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 description 3
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 3
WDOHSBCURHURPV-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(triazol-1-yl)phenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC(N2N=NC=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 WDOHSBCURHURPV-UHFFFAOYSA-N 0.000 claims description 3
MNAHJPYGOSWSBX-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(triazol-1-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(N2N=NC=C2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 MNAHJPYGOSWSBX-UHFFFAOYSA-N 0.000 claims description 3
ULJOCBVUVYUVEY-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(triazol-2-yl)phenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC(N2N=CC=N2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 ULJOCBVUVYUVEY-UHFFFAOYSA-N 0.000 claims description 3
MGHGKQQYNNPDLG-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(triazol-2-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(N2N=CC=N2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 MGHGKQQYNNPDLG-UHFFFAOYSA-N 0.000 claims description 3
YJHCOYWCYPKAQN-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(trifluoromethyl)phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC(C(F)(F)F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 YJHCOYWCYPKAQN-UHFFFAOYSA-N 0.000 claims description 3
VXVOMNFSZSXTSE-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(trifluoromethyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C(F)(F)F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 VXVOMNFSZSXTSE-UHFFFAOYSA-N 0.000 claims description 3
MCCUQEYBDREHCZ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-fluorophenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC(F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 MCCUQEYBDREHCZ-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
ARYNSJMHZVVGNH-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-methylphenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC(C)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 ARYNSJMHZVVGNH-UHFFFAOYSA-N 0.000 claims description 3
KCRBGCHPNCBUCW-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-phenylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2C=CC=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 KCRBGCHPNCBUCW-UHFFFAOYSA-N 0.000 claims description 3
NLTGIMKNKKMQPE-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-pyridin-2-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2N=CC=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 NLTGIMKNKKMQPE-UHFFFAOYSA-N 0.000 claims description 3
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 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
MFVLUIJGQADSJH-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-thiophen-2-ylphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2SC=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 MFVLUIJGQADSJH-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
QFDTVBGMNGXZGK-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)phenyl]-n,n-dimethylethanamine Chemical compound CN(C)C(C)C1=CC=CC=C1OC1=CC=C(Cl)C(Cl)=C1 QFDTVBGMNGXZGK-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
QLVUBIIDSKNVLZ-UHFFFAOYSA-N 1-[2-(4-chloro-3-fluorophenoxy)-5-fluorophenyl]-n-methylmethanamine Chemical compound CNCC1=CC(F)=CC=C1OC1=CC=C(Cl)C(F)=C1 QLVUBIIDSKNVLZ-UHFFFAOYSA-N 0.000 claims description 3
WJHPAIHCWWZGFM-UHFFFAOYSA-N 1-[2-(4-chlorophenoxy)-5-fluorophenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC(F)=CC=C1OC1=CC=C(Cl)C=C1 WJHPAIHCWWZGFM-UHFFFAOYSA-N 0.000 claims description 3
PMXOUAJLQYBUOO-UHFFFAOYSA-N 1-[2-(4-chlorophenoxy)-5-fluorophenyl]-n-methylmethanamine Chemical compound CNCC1=CC(F)=CC=C1OC1=CC=C(Cl)C=C1 PMXOUAJLQYBUOO-UHFFFAOYSA-N 0.000 claims description 3
MNHWUSSFFCLNEP-UHFFFAOYSA-N 1-[2-(4-chlorophenoxy)phenyl]-n-methylethanamine Chemical compound CNC(C)C1=CC=CC=C1OC1=CC=C(Cl)C=C1 MNHWUSSFFCLNEP-UHFFFAOYSA-N 0.000 claims description 3
CBFOMONXEQWNRB-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenoxy)-3-(methylaminomethyl)phenyl]piperidin-2-one Chemical compound CNCC1=CC(N2C(CCCC2)=O)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 CBFOMONXEQWNRB-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
WJYRLEWZANLZLM-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenoxy)-3-(methylaminomethyl)phenyl]pyrrolidin-2-one Chemical compound CNCC1=CC(N2C(CCC2)=O)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 WJYRLEWZANLZLM-UHFFFAOYSA-N 0.000 claims description 3
QGLOKMBXFYKGID-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenoxy)-3-[1-(methylamino)ethyl]phenyl]pyrrolidin-2-one Chemical compound CNC(C)C1=CC(N2C(CCC2)=O)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 QGLOKMBXFYKGID-UHFFFAOYSA-N 0.000 claims description 3
WJQHBBMQIFJYHD-UHFFFAOYSA-N 1-[4-bromo-2-(3,4-dichlorophenoxy)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(Br)C=C1OC1=CC=C(Cl)C(Cl)=C1 WJQHBBMQIFJYHD-UHFFFAOYSA-N 0.000 claims description 3
KGEKHVCIFGADFG-UHFFFAOYSA-N 1-[4-chloro-2-(3,4-dichlorophenoxy)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC=C(Cl)C=C1OC1=CC=C(Cl)C(Cl)=C1 KGEKHVCIFGADFG-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
TYLANFGUNBMRFO-UHFFFAOYSA-N 2-[2-(3,4-dichlorophenoxy)-5-fluorophenyl]-1-methylpyrrolidine Chemical compound CN1CCCC1C1=CC(F)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 TYLANFGUNBMRFO-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
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 3
GQNWCHJJMVQERW-UHFFFAOYSA-N n-[3-[4-(3,4-dichlorophenoxy)-3-(methylaminomethyl)phenyl]phenyl]acetamide Chemical compound CNCC1=CC(C=2C=C(NC(C)=O)C=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 GQNWCHJJMVQERW-UHFFFAOYSA-N 0.000 claims description 3
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 description 3
WKOZOESISFTQMB-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(5-methylthiophen-2-yl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2SC(C)=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 WKOZOESISFTQMB-UHFFFAOYSA-N 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 30
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 4
SHXLCIMINLRWNL-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-methoxyphenyl]-n-methylmethanamine Chemical compound CNCC1=CC(OC)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 SHXLCIMINLRWNL-UHFFFAOYSA-N 0.000 claims 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
229940126403 monoamine reuptake inhibitor Drugs 0.000 abstract description 17
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 32
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
238000003786 synthesis reaction Methods 0.000 description 29
230000000694 effects Effects 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
230000015572 biosynthetic process Effects 0.000 description 19
239000000543 intermediate Substances 0.000 description 19
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 18
239000003814 drug Substances 0.000 description 18
230000000407 monoamine reuptake Effects 0.000 description 18
208000035475 disorder Diseases 0.000 description 16
239000003112 inhibitor Substances 0.000 description 16
239000002253 acid Substances 0.000 description 14
210000004027 cell Anatomy 0.000 description 14
201000010099 disease Diseases 0.000 description 14
229940124597 therapeutic agent Drugs 0.000 description 14
239000002585 base Substances 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000003887 narcotic antagonist Substances 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
239000000126 substance Substances 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
239000000872 buffer Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
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