JP2007508395A - 血管運動症状を治療するためのモノアミン再取り込み調節剤としての置換n−ピペリジン誘導体 - Google Patents
血管運動症状を治療するためのモノアミン再取り込み調節剤としての置換n−ピペリジン誘導体 Download PDFInfo
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- JP2007508395A JP2007508395A JP2006535619A JP2006535619A JP2007508395A JP 2007508395 A JP2007508395 A JP 2007508395A JP 2006535619 A JP2006535619 A JP 2006535619A JP 2006535619 A JP2006535619 A JP 2006535619A JP 2007508395 A JP2007508395 A JP 2007508395A
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- Prior art keywords
- ethyl
- cyclohexanol
- dihydrochloride
- phenyl
- chlorophenyl
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- 208000024891 symptom Diseases 0.000 title claims abstract description 66
- 230000001457 vasomotor Effects 0.000 title claims abstract description 31
- 230000000407 monoamine reuptake Effects 0.000 title claims abstract description 13
- 238000011282 treatment Methods 0.000 title abstract description 23
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 23
- 238000000034 method Methods 0.000 claims abstract description 124
- 208000002193 Pain Diseases 0.000 claims abstract description 56
- 230000036407 pain Effects 0.000 claims abstract description 49
- 239000000203 mixture Substances 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 208000035475 disorder Diseases 0.000 claims abstract description 29
- 208000001640 Fibromyalgia Diseases 0.000 claims abstract description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 19
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 17
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 17
- 206010066218 Stress Urinary Incontinence Diseases 0.000 claims abstract description 13
- 208000000921 Urge Urinary Incontinence Diseases 0.000 claims abstract description 12
- 230000002496 gastric effect Effects 0.000 claims abstract description 12
- 230000001668 ameliorated effect Effects 0.000 claims abstract description 11
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims abstract description 10
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 10
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 10
- 208000024714 major depressive disease Diseases 0.000 claims abstract description 10
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims abstract description 10
- 206010046494 urge incontinence Diseases 0.000 claims abstract description 9
- 208000022170 stress incontinence Diseases 0.000 claims abstract description 8
- -1 methylenedioxy, benzyloxy Chemical group 0.000 claims description 525
- 150000001875 compounds Chemical class 0.000 claims description 160
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 95
- 150000003839 salts Chemical class 0.000 claims description 83
- 125000004432 carbon atom Chemical group C* 0.000 claims description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 47
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 43
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 43
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- WVSAVJBOUPZGJG-UHFFFAOYSA-N cyclohexanol;dihydrochloride Chemical compound Cl.Cl.OC1CCCCC1 WVSAVJBOUPZGJG-UHFFFAOYSA-N 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 230000009245 menopause Effects 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 150000001721 carbon Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 9
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 9
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 150000003462 sulfoxides Chemical class 0.000 claims description 9
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 8
- 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 claims description 8
- 229940124530 sulfonamide Drugs 0.000 claims description 8
- 150000003456 sulfonamides Chemical class 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- OUOMBEXRGSKOSY-UHFFFAOYSA-N 1-[1-(3-chloro-4-phenylmethoxyphenyl)-2-(4-methoxypiperidin-1-yl)ethyl]cyclohexan-1-ol;hydrochloride Chemical compound Cl.C1CC(OC)CCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 OUOMBEXRGSKOSY-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- SRZVCJDLOUJRQP-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCC2)CCN1CC(C=1C=C(Cl)C(Cl)=CC=1)C1(O)CCCCC1 SRZVCJDLOUJRQP-UHFFFAOYSA-N 0.000 claims description 4
- MFWGKFYEILSNQN-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=C(Cl)C(Cl)=C1 MFWGKFYEILSNQN-UHFFFAOYSA-N 0.000 claims description 4
- PPVIWCCBXKMCER-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C1(O)CCCCC1)C1=CC=C(Cl)C(Cl)=C1 PPVIWCCBXKMCER-UHFFFAOYSA-N 0.000 claims description 4
- BVCSLVPUUKBSRR-UHFFFAOYSA-N 1-[1-(3-bromo-4-methoxyphenyl)-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1=C(Br)C(OC)=CC=C1C(C1(O)CCCCC1)CN1CCC(N2CCCCC2)CC1 BVCSLVPUUKBSRR-UHFFFAOYSA-N 0.000 claims description 4
- TZKIWCHJJIEHRF-UHFFFAOYSA-N 1-[1-(3-bromo-4-methoxyphenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1=C(Br)C(OC)=CC=C1C(C1(O)CCCCC1)CN1CCC(N(C)C)CC1 TZKIWCHJJIEHRF-UHFFFAOYSA-N 0.000 claims description 4
- JZGJRBJPBPBLPD-UHFFFAOYSA-N 1-[1-(3-bromo-4-methoxyphenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C1(O)CCCCC1)C1=CC=C(OC)C(Br)=C1 JZGJRBJPBPBLPD-UHFFFAOYSA-N 0.000 claims description 4
- GYOPETZBXPUTFN-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCCC2)CCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCCC1 GYOPETZBXPUTFN-UHFFFAOYSA-N 0.000 claims description 4
- QQMFGZVXHOYHFF-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCC2)CCN1CC(C=1C=C(Br)C=CC=1)C1(O)CCCCC1 QQMFGZVXHOYHFF-UHFFFAOYSA-N 0.000 claims description 4
- VZIJXZCJZQJVIJ-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Br)=C1 VZIJXZCJZQJVIJ-UHFFFAOYSA-N 0.000 claims description 4
- BVHSFKQXXOILDZ-UHFFFAOYSA-N 1-[1-(3-bromophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Br)=C1 BVHSFKQXXOILDZ-UHFFFAOYSA-N 0.000 claims description 4
- XANIWQSKECPOAC-VZBZPWRVSA-N 1-[1-(3-chloro-4-phenylmethoxyphenyl)-2-[(3s)-3-(methylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](NC)CCCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 XANIWQSKECPOAC-VZBZPWRVSA-N 0.000 claims description 4
- KORRHYJQPWWYEA-DRYXINTFSA-N 1-[1-(3-chloro-4-phenylmethoxyphenyl)-2-[(3s)-3-(methylamino)pyrrolidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](NC)CCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 KORRHYJQPWWYEA-DRYXINTFSA-N 0.000 claims description 4
- ZPBKQBHZQNKRIU-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCCC2)CCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCC1 ZPBKQBHZQNKRIU-UHFFFAOYSA-N 0.000 claims description 4
- NFENJUSJENXBEO-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCC2)CCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCC1 NFENJUSJENXBEO-UHFFFAOYSA-N 0.000 claims description 4
- CWIPOWUTMHBBMH-HQDRINPVSA-N 1-[1-(3-chlorophenyl)-2-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@H](N(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 CWIPOWUTMHBBMH-HQDRINPVSA-N 0.000 claims description 4
- IHVWEKYKMLMEDS-FFDAWYENSA-N 1-[1-(3-chlorophenyl)-2-[(3r)-3-(methylamino)pyrrolidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@H](NC)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 IHVWEKYKMLMEDS-FFDAWYENSA-N 0.000 claims description 4
- CWIPOWUTMHBBMH-XMWICJOTSA-N 1-[1-(3-chlorophenyl)-2-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 CWIPOWUTMHBBMH-XMWICJOTSA-N 0.000 claims description 4
- XKOCQKZDILHUDH-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-[4-(dimethylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 XKOCQKZDILHUDH-UHFFFAOYSA-N 0.000 claims description 4
- DYNDQFJHGGEBFZ-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 DYNDQFJHGGEBFZ-UHFFFAOYSA-N 0.000 claims description 4
- GZXOGSFTBFMIER-UHFFFAOYSA-N 1-[1-(3-phenoxyphenyl)-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCC2)CCN1CC(C=1C=C(OC=2C=CC=CC=2)C=CC=1)C1(O)CCCCC1 GZXOGSFTBFMIER-UHFFFAOYSA-N 0.000 claims description 4
- CWDDOYNJPSEQHR-UHFFFAOYSA-N 1-[1-naphthalen-2-yl-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCCC2)CCN1CC(C=1C=C2C=CC=CC2=CC=1)C1(O)CCCCC1 CWDDOYNJPSEQHR-UHFFFAOYSA-N 0.000 claims description 4
- MGSUTQBUGDWZKK-UHFFFAOYSA-N 1-[1-naphthalen-2-yl-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCC2)CCN1CC(C=1C=C2C=CC=CC2=CC=1)C1(O)CCCCC1 MGSUTQBUGDWZKK-UHFFFAOYSA-N 0.000 claims description 4
- DJPZSDRVVABZMY-UHFFFAOYSA-N 1-[2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]ethyl]piperidin-4-ol;hydrochloride Chemical compound Cl.C1CC(O)CCN1CC(C1(O)CCCCC1)C1=CC=CC(OC(F)(F)F)=C1 DJPZSDRVVABZMY-UHFFFAOYSA-N 0.000 claims description 4
- INDZFJNPDMNGBX-UHFFFAOYSA-N 1-[2-(3-chloro-4-phenylmethoxyphenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-ol;hydrochloride Chemical compound Cl.C1CC(O)CCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 INDZFJNPDMNGBX-UHFFFAOYSA-N 0.000 claims description 4
- BLCWDRHQNANBLZ-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]-n,n-dimethylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCCCC1 BLCWDRHQNANBLZ-UHFFFAOYSA-N 0.000 claims description 4
- KYGOYSZJECEPMA-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cycloheptylethyl]-n-methylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCCCC1 KYGOYSZJECEPMA-UHFFFAOYSA-N 0.000 claims description 4
- OQTNFUIQBHMILJ-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-n,n-dimethylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCCC1 OQTNFUIQBHMILJ-UHFFFAOYSA-N 0.000 claims description 4
- DVHITDBRGKLHMG-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cyclohexylethyl]-n-methylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCCC1 DVHITDBRGKLHMG-UHFFFAOYSA-N 0.000 claims description 4
- YNBXOMCBZWSFAZ-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-n,n-dimethylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)C)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCC1 YNBXOMCBZWSFAZ-UHFFFAOYSA-N 0.000 claims description 4
- OFUWCTAPSJQHPU-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)-2-cyclopentylethyl]-n-methylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(NC)CCN1CC(C=1C=C(Cl)C=CC=1)C1CCCC1 OFUWCTAPSJQHPU-UHFFFAOYSA-N 0.000 claims description 4
- RVYNLWCURWSQHX-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3,4-dichlorophenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=C(Cl)C(Cl)=C1 RVYNLWCURWSQHX-UHFFFAOYSA-N 0.000 claims description 4
- HVQWIUXGTPPNJI-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromo-4-methoxyphenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1=C(Br)C(OC)=CC=C1C(C1(O)CCCCC1)CN1CCC(N)CC1 HVQWIUXGTPPNJI-UHFFFAOYSA-N 0.000 claims description 4
- UWYYRZMKEQAYMC-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3-bromophenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Br)=C1 UWYYRZMKEQAYMC-UHFFFAOYSA-N 0.000 claims description 4
- CAODEKOFILDNTI-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]-4-methylcyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(C)CCC1(O)C(C=1C=C(Cl)C=CC=1)CN1CCC(N)CC1 CAODEKOFILDNTI-UHFFFAOYSA-N 0.000 claims description 4
- RRFKJAVCBRGKSM-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 RRFKJAVCBRGKSM-UHFFFAOYSA-N 0.000 claims description 4
- LTGDKKXOMQJMIU-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(5-methoxy-1-benzothiophen-3-yl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C12=CC(OC)=CC=C2SC=C1C(C1(O)CCCCC1)CN1CCC(N)CC1 LTGDKKXOMQJMIU-UHFFFAOYSA-N 0.000 claims description 4
- GEBCWEHNEZYLNG-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(C(F)(F)F)=C1 GEBCWEHNEZYLNG-UHFFFAOYSA-N 0.000 claims description 4
- AIGZXOUFYPSSKG-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-[4-(trifluoromethoxy)phenyl]ethyl]cyclobutan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCC1)C1=CC=C(OC(F)(F)F)C=C1 AIGZXOUFYPSSKG-UHFFFAOYSA-N 0.000 claims description 4
- SFOWKBVDHIQPIY-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-[4-(trifluoromethoxy)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=C(OC(F)(F)F)C=C1 SFOWKBVDHIQPIY-UHFFFAOYSA-N 0.000 claims description 4
- VEALBBNLMSGRDL-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-naphthalen-1-ylethyl]cyclobutan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCC1)C1=CC=CC2=CC=CC=C12 VEALBBNLMSGRDL-UHFFFAOYSA-N 0.000 claims description 4
- XDXQQZIFDMNDQQ-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-naphthalen-2-ylethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CCCCC1)C1=CC=C(C=CC=C2)C2=C1 XDXQQZIFDMNDQQ-UHFFFAOYSA-N 0.000 claims description 4
- AANYYRCJLCRSAF-UHFFFAOYSA-N 1-[2-(4-piperidin-1-ylpiperidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCCC2)CCN1CC(C=1C=C(C=CC=1)C(F)(F)F)C1(O)CCCCC1 AANYYRCJLCRSAF-UHFFFAOYSA-N 0.000 claims description 4
- OVDUXQXVMKDHRB-UHFFFAOYSA-N 1-[2-(4-piperidin-1-ylpiperidin-1-yl)-1-[4-(trifluoromethoxy)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N2CCCCC2)CCN1CC(C=1C=CC(OC(F)(F)F)=CC=1)C1(O)CCCCC1 OVDUXQXVMKDHRB-UHFFFAOYSA-N 0.000 claims description 4
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- 230000002152 alkylating effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 4
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- DVHUSLPVEFQUIF-VEEDUFMYSA-N 1-[2-[(3s)-3-aminopyrrolidin-1-yl]-1-(3-chlorophenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 DVHUSLPVEFQUIF-VEEDUFMYSA-N 0.000 claims description 3
- FNWBBOBGVZJBDF-CTAXNUCUSA-N 1-[2-[(3s)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethoxy)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(OC(F)(F)F)=C1 FNWBBOBGVZJBDF-CTAXNUCUSA-N 0.000 claims description 3
- CGRAUPGXOYQYDQ-VEEDUFMYSA-N 1-[2-[(3s)-3-aminopyrrolidin-1-yl]-1-[3-(trifluoromethyl)phenyl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N)CCN1CC(C1(O)CCCCC1)C1=CC=CC(C(F)(F)F)=C1 CGRAUPGXOYQYDQ-VEEDUFMYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
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Classifications
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| US7517899B2 (en) * | 2004-03-30 | 2009-04-14 | Wyeth | Phenylaminopropanol derivatives and methods of their use |
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| US7994190B2 (en) | 2006-11-01 | 2011-08-09 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| UY32858A (es) | 2009-08-31 | 2011-03-31 | Abbott Healthcare Products Bv | Derivados de (tio)morfolina como moduladores de sip |
| JP5752691B2 (ja) | 2009-09-29 | 2015-07-22 | グラクソ グループ リミテッドGlaxo Group Limited | 新規化合物 |
| JP6209720B2 (ja) | 2010-02-02 | 2017-10-11 | エージェンシー フォー サイエンス,テクノロジー アンド リサーチ | 官能化された防汚化合物及びその使用 |
| TW201206893A (en) * | 2010-07-09 | 2012-02-16 | Abbott Healthcare Products Bv | Bisaryl (thio) morpholine derivatives as S1P modulators |
| TWI522361B (zh) | 2010-07-09 | 2016-02-21 | 艾伯維公司 | 作為s1p調節劑的稠合雜環衍生物 |
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| BR112022008113A2 (pt) | 2019-10-31 | 2022-07-19 | Escape Bio Inc | Formas sólidas de um modulador de receptor s1p |
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| WO2002079156A1 (en) * | 2001-03-30 | 2002-10-10 | Astrazeneca Ab | Novel piperidine derivatives as modulators of chemokine receptor |
| WO2003042205A1 (en) * | 2001-11-15 | 2003-05-22 | Astrazeneca Ab | Piperidine derivatives and their use as modulators of chemokine receptor activity (especially ccr5) |
| WO2003066004A2 (en) * | 2002-02-08 | 2003-08-14 | President And Fellows Of Harvard College | Therapeutic compounds |
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| US4310524A (en) * | 1980-04-11 | 1982-01-12 | Richardson-Merrell, Inc. | TCA Composition and method for rapid onset antidepressant therapy |
| PH18686A (en) | 1981-05-26 | 1985-08-29 | Merck & Co Inc | 1-(3 halo-2-pyridinyl) piperazine |
| US4535186A (en) * | 1983-04-19 | 1985-08-13 | American Home Products Corporation | 2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives |
| ZA864772B (en) | 1985-07-02 | 1987-02-25 | Merrell Dow Pharma | Novel chemical compounds |
| CA1327795C (en) | 1987-08-14 | 1994-03-15 | Jules Freedman | Antidepressants which are aryloxy inadanamines |
| US4826844A (en) * | 1987-09-30 | 1989-05-02 | American Home Products Corporation | Substituted 1-(aralkyl-piperazinoalkyl) cycloalkanols |
| ATE114467T1 (de) | 1990-06-01 | 1994-12-15 | Merrell Dow Pharma | (+)-alpha-(2,3 dimethoxyphenyl)-1-(2- (fluorophenyl)ethyl>-4-piperidinmethanol. |
| US5502047A (en) * | 1993-03-22 | 1996-03-26 | Kavey; Neil B. | Treatment for insomnia |
| CZ296263B6 (cs) | 1996-03-25 | 2006-02-15 | Eli Lilly And Company | Farmaceutická kompozice pro lécení bolesti a jejípouzití |
| KR20010015918A (ko) | 1998-03-02 | 2001-02-26 | 피터 지. 스트링거 | 안면홍조를 감소시키기 위한 플루옥세틴 히드로클로라이드 |
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- 2004-10-13 KR KR1020067007312A patent/KR20070026326A/ko not_active Withdrawn
- 2004-10-13 WO PCT/US2004/033732 patent/WO2005037279A1/en not_active Ceased
- 2004-10-13 CA CA002540191A patent/CA2540191A1/en not_active Abandoned
- 2004-10-13 AT AT04794958T patent/ATE400273T1/de not_active IP Right Cessation
- 2004-10-13 EP EP04794958A patent/EP1673084B1/en not_active Expired - Lifetime
- 2004-10-13 MX MXPA06003880A patent/MXPA06003880A/es active IP Right Grant
- 2004-10-13 JP JP2006535619A patent/JP2007508395A/ja active Pending
- 2004-10-13 DE DE602004014955T patent/DE602004014955D1/de not_active Expired - Fee Related
- 2004-10-13 TW TW093131002A patent/TW200526619A/zh unknown
- 2004-10-13 BR BRPI0415294-8A patent/BRPI0415294A/pt not_active IP Right Cessation
- 2004-10-13 AU AU2004281746A patent/AU2004281746A1/en not_active Withdrawn
- 2004-10-14 PA PA20048615001A patent/PA8615001A1/es unknown
- 2004-10-14 AR ARP040103715A patent/AR046283A1/es unknown
- 2004-10-14 PE PE2004000995A patent/PE20050440A1/es not_active Application Discontinuation
-
2006
- 2006-03-21 IL IL174472A patent/IL174472A0/en unknown
- 2006-04-12 EC EC2006006506A patent/ECSP066506A/es unknown
-
2009
- 2009-05-18 US US12/467,594 patent/US20090227585A1/en not_active Abandoned
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| WO2002079156A1 (en) * | 2001-03-30 | 2002-10-10 | Astrazeneca Ab | Novel piperidine derivatives as modulators of chemokine receptor |
| WO2003042205A1 (en) * | 2001-11-15 | 2003-05-22 | Astrazeneca Ab | Piperidine derivatives and their use as modulators of chemokine receptor activity (especially ccr5) |
| WO2003066004A2 (en) * | 2002-02-08 | 2003-08-14 | President And Fellows Of Harvard College | Therapeutic compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| IL174472A0 (en) | 2006-08-01 |
| KR20070026326A (ko) | 2007-03-08 |
| ECSP066506A (es) | 2006-10-10 |
| US20050187251A1 (en) | 2005-08-25 |
| TW200526619A (en) | 2005-08-16 |
| PA8615001A1 (es) | 2005-08-10 |
| PE20050440A1 (es) | 2005-07-25 |
| WO2005037279A1 (en) | 2005-04-28 |
| AU2004281746A1 (en) | 2005-04-28 |
| DE602004014955D1 (de) | 2008-08-21 |
| BRPI0415294A (pt) | 2006-12-19 |
| US7550485B2 (en) | 2009-06-23 |
| ATE400273T1 (de) | 2008-07-15 |
| AR046283A1 (es) | 2005-11-30 |
| MXPA06003880A (es) | 2006-07-03 |
| CA2540191A1 (en) | 2005-04-28 |
| EP1673084A1 (en) | 2006-06-28 |
| EP1673084B1 (en) | 2008-07-09 |
| US20090227585A1 (en) | 2009-09-10 |
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