CA2539763A1

CA2539763A1 - Phenylpiperazine cycloalkanol derivatives and methods of their use

Phenylpiperazine cycloalkanol derivatives and methods of their use Download PDF

Info

Publication number: CA2539763A1
Authority: CA; Canada
Prior art keywords: piperazin; ylethyl; chlorophenyl; subject; bromophenyl
Prior art date: 2003-10-14
Legal status : Abandoned

Application number

CA002539763A

Other languages

English (en)

French (fr)

Inventor

Paige Erin Mahaney

Eugene John Trybulski

Lori Krim Gavrin

An Thien Vu

Current Assignee

Wyeth LLC

Original Assignee

Individual

Priority date

2003-10-14

Filing date

2004-10-13

Publication date

2005-04-28

2004-10-13 Application filed by Individual filed Critical Individual

2005-04-28 Publication of CA2539763A1 publication Critical patent/CA2539763A1/en

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 61
YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 title abstract description 6
208000002193 Pain Diseases 0.000 claims abstract description 55
230000036407 pain Effects 0.000 claims abstract description 50
208000024891 symptom Diseases 0.000 claims abstract description 39
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
230000001457 vasomotor Effects 0.000 claims abstract description 29
208000035475 disorder Diseases 0.000 claims abstract description 28
239000000203 mixture Substances 0.000 claims abstract description 27
201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 16
231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 16
206010066218 Stress Urinary Incontinence Diseases 0.000 claims abstract description 11
208000011580 syndromic disease Diseases 0.000 claims abstract description 11
208000000921 Urge Urinary Incontinence Diseases 0.000 claims abstract description 10
230000001668 ameliorated effect Effects 0.000 claims abstract description 10
230000002496 gastric effect Effects 0.000 claims abstract description 10
230000000407 monoamine reuptake Effects 0.000 claims abstract description 10
206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims abstract description 9
208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 9
208000012902 Nervous system disease Diseases 0.000 claims abstract description 9
208000024714 major depressive disease Diseases 0.000 claims abstract description 9
208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims abstract description 9
150000001875 compounds Chemical class 0.000 claims description 115
-1 methylenedioxy Chemical group 0.000 claims description 46
150000003839 salts Chemical class 0.000 claims description 41
125000004432 carbon atom Chemical group C* 0.000 claims description 28
206010060800 Hot flush Diseases 0.000 claims description 23
125000000217 alkyl group Chemical group 0.000 claims description 19
125000000623 heterocyclic group Chemical group 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
208000001640 Fibromyalgia Diseases 0.000 claims description 8
150000001721 carbon Chemical group 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
PZQVDLYPNAADGQ-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCC1 PZQVDLYPNAADGQ-UHFFFAOYSA-N 0.000 claims description 5
REBCRUZAHKPPJG-UHFFFAOYSA-N 1-[1-(4-bromophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(Br)=CC=1)C1(O)CCC1 REBCRUZAHKPPJG-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
208000022170 stress incontinence Diseases 0.000 claims description 4
BLTKKNKJEHRTJP-UHFFFAOYSA-N 1-[1-(2-fluorophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C(=CC=CC=1)F)C1(O)CCC1 BLTKKNKJEHRTJP-UHFFFAOYSA-N 0.000 claims description 3
IAXITOGKMSXBJM-UHFFFAOYSA-N 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]cyclooctan-1-ol Chemical compound C1=C(Br)C(OC)=CC=C1C(C1(O)CCCCCCC1)CN1CCNCC1 IAXITOGKMSXBJM-UHFFFAOYSA-N 0.000 claims description 3
CZRBZQHNTQGFDV-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]cyclooctan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCCCCC1 CZRBZQHNTQGFDV-UHFFFAOYSA-N 0.000 claims description 3
RMNOTTSKUONNGC-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCC1 RMNOTTSKUONNGC-UHFFFAOYSA-N 0.000 claims description 3
DIMZLFDDDJZTNC-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclooctan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCCCC1 DIMZLFDDDJZTNC-UHFFFAOYSA-N 0.000 claims description 3
QWUVCZDEMPCCJX-UHFFFAOYSA-N 1-[1-(3-fluorophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(F)C=CC=1)C1(O)CCC1 QWUVCZDEMPCCJX-UHFFFAOYSA-N 0.000 claims description 3
HPBLUEOXHZOXFX-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(Cl)=CC=1)C1(O)CCC1 HPBLUEOXHZOXFX-UHFFFAOYSA-N 0.000 claims description 3
IQHHTOSZORUSLE-UHFFFAOYSA-N 1-[1-(4-fluorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(F)=CC=1)C1(O)CCCCC1 IQHHTOSZORUSLE-UHFFFAOYSA-N 0.000 claims description 3
KZMYISUBTLBMKL-UHFFFAOYSA-N 1-[2-(4-methylpiperazin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl]cyclobutan-1-ol Chemical compound C1CN(C)CCN1CC(C1(O)CCC1)C1=CC=CC(C(F)(F)F)=C1 KZMYISUBTLBMKL-UHFFFAOYSA-N 0.000 claims description 3
MCGGADLCNVOIBI-UHFFFAOYSA-N 1-[2-piperazin-1-yl-1-[3-(trifluoromethyl)phenyl]ethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(C=CC=1)C(F)(F)F)C1(O)CCC1 MCGGADLCNVOIBI-UHFFFAOYSA-N 0.000 claims description 3
206010041250 Social phobia Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
208000019116 sleep disease Diseases 0.000 claims description 3
PZQVDLYPNAADGQ-QGZVFWFLSA-N 1-[(1s)-1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound OC1([C@H](CN2CCNCC2)C=2C=C(Cl)C=CC=2)CCCCC1 PZQVDLYPNAADGQ-QGZVFWFLSA-N 0.000 claims description 2
QFIJRJZGJBEPSZ-UHFFFAOYSA-N 1-[1-(2-bromophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C(=CC=CC=1)Br)C1(O)CCCCC1 QFIJRJZGJBEPSZ-UHFFFAOYSA-N 0.000 claims description 2
LBHZTGKCTKOYTN-UHFFFAOYSA-N 1-[1-(2-fluorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C(=CC=CC=1)F)C1(O)CCCCC1 LBHZTGKCTKOYTN-UHFFFAOYSA-N 0.000 claims description 2
OPAKGKQKMQGOGL-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C(Cl)=CC=1)C1(O)CCCCC1 OPAKGKQKMQGOGL-UHFFFAOYSA-N 0.000 claims description 2
DGBKDBRUKWAZBY-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclooctan-1-ol Chemical compound C1CN(C)CCN1CC(C1(O)CCCCCCC1)C1=CC=CC(Br)=C1 DGBKDBRUKWAZBY-UHFFFAOYSA-N 0.000 claims description 2
OBYMFFTYBMFUTN-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCC1 OBYMFFTYBMFUTN-UHFFFAOYSA-N 0.000 claims description 2
HHRVKAJJFQQGMY-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]cycloheptan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCCCC1 HHRVKAJJFQQGMY-UHFFFAOYSA-N 0.000 claims description 2
QIEWQGGMPRNSTF-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCCC1 QIEWQGGMPRNSTF-UHFFFAOYSA-N 0.000 claims description 2
DHGBPKXIJTZIQH-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-piperazin-1-ylethyl]cyclopentan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCC1 DHGBPKXIJTZIQH-UHFFFAOYSA-N 0.000 claims description 2
SIMGTBMOANUZIG-NNJIEVJOSA-N 1-[1-(3-chlorophenyl)-2-[(3r)-3-methylpiperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C1CN[C@H](C)CN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 SIMGTBMOANUZIG-NNJIEVJOSA-N 0.000 claims description 2
SBXWKBLGYGJAMJ-MCPYQZEQSA-N 1-[1-(3-chlorophenyl)-2-[(3r,5s)-3,5-dimethylpiperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C1[C@@H](C)N[C@@H](C)CN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 SBXWKBLGYGJAMJ-MCPYQZEQSA-N 0.000 claims description 2
SIMGTBMOANUZIG-BUSXIPJBSA-N 1-[1-(3-chlorophenyl)-2-[(3s)-3-methylpiperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C1CN[C@@H](C)CN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 SIMGTBMOANUZIG-BUSXIPJBSA-N 0.000 claims description 2
GNFBWBLHLHVEHI-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cycloheptan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCCC1 GNFBWBLHLHVEHI-UHFFFAOYSA-N 0.000 claims description 2
BDZIOTCFFYFCSB-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclopentan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCC1 BDZIOTCFFYFCSB-UHFFFAOYSA-N 0.000 claims description 2
PIBZTCVMCNNFRR-UHFFFAOYSA-N 1-[1-(3-fluorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=C(F)C=CC=1)C1(O)CCCCC1 PIBZTCVMCNNFRR-UHFFFAOYSA-N 0.000 claims description 2
ZNOWPRXCOCARHQ-UHFFFAOYSA-N 1-[1-(4-bromophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclobutan-1-ol Chemical compound C1CN(C)CCN1CC(C1(O)CCC1)C1=CC=C(Br)C=C1 ZNOWPRXCOCARHQ-UHFFFAOYSA-N 0.000 claims description 2
WZKIGEMCGDZHTR-UHFFFAOYSA-N 1-[1-(4-bromophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(Br)=CC=1)C1(O)CCCCC1 WZKIGEMCGDZHTR-UHFFFAOYSA-N 0.000 claims description 2
KHWNQEDSMGUKSX-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(Cl)=CC=1)C1(O)CCCCC1 KHWNQEDSMGUKSX-UHFFFAOYSA-N 0.000 claims description 2
JMKKGNSMJRPWLW-UHFFFAOYSA-N 1-[1-(4-fluorophenyl)-2-piperazin-1-ylethyl]cyclobutan-1-ol Chemical compound C1CNCCN1CC(C=1C=CC(F)=CC=1)C1(O)CCC1 JMKKGNSMJRPWLW-UHFFFAOYSA-N 0.000 claims description 2
208000019901 Anxiety disease Diseases 0.000 claims description 2
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PZQVDLYPNAADGQ-KRWDZBQOSA-N 1-[(1r)-1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexan-1-ol Chemical compound OC1([C@@H](CN2CCNCC2)C=2C=C(Cl)C=CC=2)CCCCC1 PZQVDLYPNAADGQ-KRWDZBQOSA-N 0.000 claims 1
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BSNFRMQEINNSIJ-UHFFFAOYSA-N 1-[1-(3-bromo-4-methoxyphenyl)-2-piperazin-1-ylethyl]cyclopentan-1-ol Chemical compound C1=C(Br)C(OC)=CC=C1C(C1(O)CCCC1)CN1CCNCC1 BSNFRMQEINNSIJ-UHFFFAOYSA-N 0.000 claims 1
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APZLULIMMIJDAY-UHFFFAOYSA-N 1-[1-(3-fluorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclobutan-1-ol Chemical compound C1CN(C)CCN1CC(C1(O)CCC1)C1=CC=CC(F)=C1 APZLULIMMIJDAY-UHFFFAOYSA-N 0.000 claims 1
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UZVBARIHCIAPAS-UHFFFAOYSA-N 1-[1-(4-fluorophenyl)-2-(4-methylpiperazin-1-yl)ethyl]cyclobutan-1-ol Chemical compound C1CN(C)CCN1CC(C1(O)CCC1)C1=CC=C(F)C=C1 UZVBARIHCIAPAS-UHFFFAOYSA-N 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 21
230000002265 prevention Effects 0.000 abstract description 8
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 23
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