HUP0201722A2

HUP0201722A2 - Gyógyászati készítmények alkoholizmus és alkoholfüggőség kezelésére

Gyógyászati készítmények alkoholizmus és alkoholfüggőség kezelésére Download PDF

Info

Publication number: HUP0201722A2
Authority: HU; Hungary
Prior art keywords: dichlorophenoxy; methylamine; alkyl; formula; ring
Prior art date: 2001-05-23

Application number

HU0201722A

Other languages

English (en)

Hungarian (hu)

Inventor

Harry Ralph Howard

Original Assignee

Pfizer Products Inc.

Priority date

2001-05-23

Filing date

2002-05-22

Publication date

2003-07-28

2002-05-22 Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.

2002-07-29 Publication of HU0201722D0 publication Critical patent/HU0201722D0/hu

2003-07-28 Publication of HUP0201722A2 publication Critical patent/HUP0201722A2/hu

Links

208000007848 Alcoholism Diseases 0.000 title claims abstract description 148
201000007930 alcohol dependence Diseases 0.000 title claims abstract description 147
239000008194 pharmaceutical composition Substances 0.000 title claims description 65
150000001875 compounds Chemical class 0.000 claims abstract description 239
150000003839 salts Chemical class 0.000 claims abstract description 102
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 51
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 46
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
239000003401 opiate antagonist Substances 0.000 claims abstract description 38
125000005842 heteroatom Chemical group 0.000 claims abstract description 35
229910052799 carbon Inorganic materials 0.000 claims abstract description 31
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 30
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
125000001624 naphthyl group Chemical group 0.000 claims abstract description 29
125000001424 substituent group Chemical group 0.000 claims abstract description 29
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 26
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 17
229920006395 saturated elastomer Polymers 0.000 claims abstract description 15
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 13
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 11
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 9
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 9
125000002837 carbocyclic group Chemical group 0.000 claims abstract description 7
125000005843 halogen group Chemical group 0.000 claims abstract description 5
-1 cyano, nitro, amino, hydroxyl Chemical group 0.000 claims description 145
238000000034 method Methods 0.000 claims description 72
238000011282 treatment Methods 0.000 claims description 67
229910052739 hydrogen Inorganic materials 0.000 claims description 58
239000001257 hydrogen Substances 0.000 claims description 57
239000004480 active ingredient Substances 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
150000002431 hydrogen Chemical class 0.000 claims description 27
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
241000124008 Mammalia Species 0.000 claims description 26
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 25
229910052731 fluorine Inorganic materials 0.000 claims description 25
239000011737 fluorine Substances 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical group 0.000 claims description 19
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 17
BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
239000003937 drug carrier Substances 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
239000011593 sulfur Substances 0.000 claims description 13
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
125000003282 alkyl amino group Chemical group 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
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 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000004434 sulfur atom Chemical group 0.000 claims description 6
239000002552 dosage form Substances 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
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
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
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
VTOCPMQDJCNXJC-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenoxy)-5-(4-fluorophenyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C=2C=CC(F)=CC=2)=CC=C1OC1=CC=C(Cl)C(Cl)=C1 VTOCPMQDJCNXJC-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
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
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
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
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
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
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
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 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
ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-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 2
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 2
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 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
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 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 2
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 2
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 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
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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 1
238000002360 preparation method Methods 0.000 abstract description 33
125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 31
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239000000243 solution Substances 0.000 description 23
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125000004435 hydrogen atom Chemical group [H]* 0.000 description 12
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239000002585 base Substances 0.000 description 10
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WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 description 9
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229910052801 chlorine Inorganic materials 0.000 description 9
229960003638 dopamine Drugs 0.000 description 9
150000001299 aldehydes Chemical group 0.000 description 8
239000007853 buffer solution Substances 0.000 description 8
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ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
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101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 6
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