TW200526619A - Substituted N-heterocycle derivatives and methods of their use - Google Patents
Substituted N-heterocycle derivatives and methods of their use Download PDFInfo
- Publication number
- TW200526619A TW200526619A TW093131002A TW93131002A TW200526619A TW 200526619 A TW200526619 A TW 200526619A TW 093131002 A TW093131002 A TW 093131002A TW 93131002 A TW93131002 A TW 93131002A TW 200526619 A TW200526619 A TW 200526619A
- Authority
- TW
- Taiwan
- Prior art keywords
- ethyl
- cyclohexanol
- dihydrochloride
- phenyl
- chlorophenyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 663
- 208000002193 Pain Diseases 0.000 claims abstract description 58
- 230000036407 pain Effects 0.000 claims abstract description 55
- 208000024891 symptom Diseases 0.000 claims abstract description 48
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 230000001457 vasomotor Effects 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 208000001640 Fibromyalgia Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 16
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 16
- 230000002496 gastric effect Effects 0.000 claims abstract description 12
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims abstract description 11
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims abstract description 11
- 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 9
- 230000002265 prevention Effects 0.000 claims abstract description 5
- -1 methylenedioxy, benzyloxy Chemical group 0.000 claims description 717
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 506
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 208
- WVSAVJBOUPZGJG-UHFFFAOYSA-N cyclohexanol;dihydrochloride Chemical compound Cl.Cl.OC1CCCCC1 WVSAVJBOUPZGJG-UHFFFAOYSA-N 0.000 claims description 197
- 150000001875 compounds Chemical class 0.000 claims description 163
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 140
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 107
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 98
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 78
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 75
- 125000004432 carbon atom Chemical group C* 0.000 claims description 71
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 68
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 48
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 44
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 41
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 24
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 21
- 125000001624 naphthyl group Chemical group 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 206010060800 Hot flush Diseases 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 230000009245 menopause Effects 0.000 claims description 18
- 230000009103 reabsorption Effects 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
- SLOVAXRWKHCZHG-UHFFFAOYSA-N Cl.Cl.CCCCCCO Chemical compound Cl.Cl.CCCCCCO SLOVAXRWKHCZHG-UHFFFAOYSA-N 0.000 claims description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 10
- 208000025609 Urogenital disease Diseases 0.000 claims description 10
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 206010021639 Incontinence Diseases 0.000 claims description 9
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 208000025966 Neurological disease Diseases 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 7
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 claims description 7
- 150000002825 nitriles Chemical class 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000007983 Tris buffer Substances 0.000 claims description 5
- 206010016256 fatigue Diseases 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 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 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 206010046543 Urinary incontinence Diseases 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 208000019116 sleep disease Diseases 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 3
- 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 3
- 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 3
- 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 3
- 208000000112 Myalgia Diseases 0.000 claims description 3
- 241000009298 Trigla lyra Species 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000001568 sexual effect Effects 0.000 claims description 3
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 3
- NGZYRKGJWYJGRS-YFKPBYRVSA-N (3s)-n-methylpyrrolidin-3-amine Chemical compound CN[C@H]1CCNC1 NGZYRKGJWYJGRS-YFKPBYRVSA-N 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- RWDZGCQTWDMBHW-UHFFFAOYSA-N 1-[1-[4-[2-(4-methoxyphenyl)ethoxy]phenyl]-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol Chemical compound C1=CC(OC)=CC=C1CCOC1=CC=C(C(CN2CCC(CC2)N2CCCCC2)C2(O)CCCCC2)C=C1 RWDZGCQTWDMBHW-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- WXTDXCCEOAQFOA-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(6-methoxynaphthalen-2-yl)ethyl]cyclohexan-1-ol Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C(C1(O)CCCCC1)CN1CCC(N)CC1 WXTDXCCEOAQFOA-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- ITRDPYOXHPOVBA-UHFFFAOYSA-N 1-[2-(4-morpholin-4-ylpiperidin-1-yl)-1-[3-(trifluoromethoxy)phenyl]ethyl]cyclohexan-1-ol Chemical compound C1CC(N2CCOCC2)CCN1CC(C=1C=C(OC(F)(F)F)C=CC=1)C1(O)CCCCC1 ITRDPYOXHPOVBA-UHFFFAOYSA-N 0.000 claims description 2
- MNJYBOCMFOUNIW-QTTLMUINSA-N 1-[2-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-1-(4-phenylmethoxyphenyl)ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N(C)C)CCN1CC(C1(O)CCCCC1)C(C=C1)=CC=C1OCC1=CC=CC=C1 MNJYBOCMFOUNIW-QTTLMUINSA-N 0.000 claims description 2
- DMVLYQQWORENHP-SANRYGKWSA-N 1-[2-[(3s)-3-aminopyrrolidin-1-yl]-1-naphthalen-1-ylethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N)CCN1CC(C1(O)CCCCC1)C1=CC=CC2=CC=CC=C12 DMVLYQQWORENHP-SANRYGKWSA-N 0.000 claims description 2
- OVDYNHQMVJQLRT-UHFFFAOYSA-N 2-[2-(4-aminopiperidin-1-yl)-1-(3-chlorophenyl)ethyl]-3,4,4a,5,6,7,8,8a-octahydro-1h-naphthalen-2-ol;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1CC(C1(O)CC2CCCCC2CC1)C1=CC=CC(Cl)=C1 OVDYNHQMVJQLRT-UHFFFAOYSA-N 0.000 claims description 2
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 229910052770 Uranium Inorganic materials 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 125000000732 arylene group Chemical group 0.000 claims description 2
- 150000007514 bases Chemical class 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000005567 fluorenylene group Chemical group 0.000 claims description 2
- 208000013465 muscle pain Diseases 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 230000035946 sexual desire Effects 0.000 claims description 2
- 208000022925 sleep disturbance Diseases 0.000 claims description 2
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 210000002700 urine Anatomy 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 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 1
- 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 1
- AWBKQEAFRBCNRO-UHFFFAOYSA-N 1-[1-(3-chloro-4-methoxyphenyl)-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol Chemical compound C1=C(Cl)C(OC)=CC=C1C(C1(O)CCCCC1)CN1CCC(N2CCCCC2)CC1 AWBKQEAFRBCNRO-UHFFFAOYSA-N 0.000 claims 1
- FSKRAXWGFULMLI-UHFFFAOYSA-N 1-[1-(3-chloro-4-phenylmethoxyphenyl)-2-(4-methoxypiperidin-1-yl)ethyl]cyclohexan-1-ol Chemical compound C1CC(OC)CCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 FSKRAXWGFULMLI-UHFFFAOYSA-N 0.000 claims 1
- ZGJKAFRMONTUAK-ALSOZGBCSA-N 1-[1-(3-chloro-4-phenylmethoxyphenyl)-2-[(3s)-3-(dimethylamino)piperidin-1-yl]ethyl]cyclohexan-1-ol;dihydrochloride Chemical compound Cl.Cl.C1[C@@H](N(C)C)CCCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 ZGJKAFRMONTUAK-ALSOZGBCSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- IAWXIOLZWOAIRG-UHFFFAOYSA-N 1-[1-(6-methoxynaphthalen-2-yl)-2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]cyclohexan-1-ol Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C(C1(O)CCCCC1)CN(CC1)CCC1N1CCCCC1 IAWXIOLZWOAIRG-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- KAGXSGIXHYOZNL-UHFFFAOYSA-N 1-[2-(4-aminopiperidin-1-yl)-1-(3-chloro-4-phenylmethoxyphenyl)ethyl]cyclohexan-1-ol Chemical compound C1CC(N)CCN1CC(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 KAGXSGIXHYOZNL-UHFFFAOYSA-N 0.000 claims 1
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- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| US51104203P | 2003-10-14 | 2003-10-14 | |
| US56144804P | 2004-04-12 | 2004-04-12 | |
| US57002604P | 2004-05-11 | 2004-05-11 | |
| US10/962,971 US7550485B2 (en) | 2003-10-14 | 2004-10-12 | Substituted N-heterocycle derivatives and methods of their use |
Publications (1)
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|---|---|
| TW200526619A true TW200526619A (en) | 2005-08-16 |
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|---|---|---|---|
| TW093131002A TW200526619A (en) | 2003-10-14 | 2004-10-13 | Substituted N-heterocycle derivatives and methods of their use |
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| BR (1) | BRPI0415294A (enExample) |
| CA (1) | CA2540191A1 (enExample) |
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| IL (1) | IL174472A0 (enExample) |
| MX (1) | MXPA06003880A (enExample) |
| PA (1) | PA8615001A1 (enExample) |
| PE (1) | PE20050440A1 (enExample) |
| TW (1) | TW200526619A (enExample) |
| WO (1) | WO2005037279A1 (enExample) |
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| US7414052B2 (en) * | 2004-03-30 | 2008-08-19 | Wyeth | Phenylaminopropanol derivatives and methods of their use |
| US7517899B2 (en) * | 2004-03-30 | 2009-04-14 | Wyeth | Phenylaminopropanol derivatives and methods of their use |
| ATE484509T1 (de) | 2004-08-02 | 2010-10-15 | Glaxo Group Ltd | Antibakterielle mittel |
| WO2007067575A2 (en) * | 2005-12-05 | 2007-06-14 | Wyeth | Process for preparing substituted aryl cycloalkanol derivatives |
| 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 |
| TWI543984B (zh) | 2010-07-09 | 2016-08-01 | 艾伯維公司 | 作為s1p調節劑的螺-哌啶衍生物 |
| BR112022008113A2 (pt) | 2019-10-31 | 2022-07-19 | Escape Bio Inc | Formas sólidas de um modulador de receptor s1p |
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| US1963458A (en) * | 1930-01-22 | 1934-06-19 | George M Holley | Carburetor |
| US1962880A (en) * | 1931-06-20 | 1934-06-12 | Schwab Max | Electric drive for household sewing machines |
| US1962897A (en) * | 1931-11-03 | 1934-06-12 | Edward J Duffy | Printing press |
| US1963111A (en) * | 1932-01-08 | 1934-06-19 | Backes Henry | Dispensing attachment for liquid cement containers |
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| US1962881A (en) * | 1932-11-04 | 1934-06-12 | Connor B Shanley | Manhole cover and anchoring means therefor |
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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 |
| ES2305606T3 (es) | 1999-04-06 | 2008-11-01 | Sepracor Inc. | Succinato de o-desmetilvenlafaxina. |
| TW564247B (en) * | 1999-04-08 | 2003-12-01 | Akzo Nobel Nv | Bicyclic heteraromatic compound |
| JP2003503450A (ja) * | 1999-07-01 | 2003-01-28 | ファルマシア・アンド・アップジョン・カンパニー | 高選択的ノルエピネフリン再取込みインヒビターおよびその使用方法 |
| AU6640800A (en) * | 1999-08-11 | 2001-03-05 | Vermeer Manufacturing Company | Automated lubricant dispensing system and method for a horizontal directional drilling machine |
| AU2001279294A1 (en) * | 2000-07-06 | 2002-01-21 | Neurogen Corporation | Melanin concentrating hormone receptor ligands |
| DE60119047D1 (de) | 2000-08-31 | 2006-06-01 | Pfizer | Phenoxyphenylheterozyklen als Serotonin-Wiederaufnahmehemmer |
| DE60122015T2 (de) | 2000-10-13 | 2006-11-23 | Neurosearch A/S | Behandlung affektiver störungen durch kombinierte wirkung eines nikotinischen rezeptoragonisten und einer monoaminergischen substanz |
| ATE369330T1 (de) | 2001-02-12 | 2007-08-15 | Wyeth Corp | O-desmethyl-venlafaxine succinat salz |
| US6557831B2 (en) * | 2001-03-05 | 2003-05-06 | Erwin Industries, Inc. | Fence bracket |
| EP1383495A1 (en) | 2001-03-29 | 2004-01-28 | Eli Lilly And Company | Duloxetine for treatment of hot flashes |
| GB0108046D0 (en) | 2001-03-30 | 2001-05-23 | Astrazeneca Ab | Chemical compounds |
| EP1266659A1 (en) | 2001-06-11 | 2002-12-18 | Pantarhei Bioscience B.V. | Pyridoxal in combination with serotonin re-uptake inhibitor for the treatment of hot flushes |
| US20040259850A1 (en) | 2001-10-31 | 2004-12-23 | Alves Stephen E. | Method for treating or preventing symptoms of hormonal variation including hot flashes |
| US6602911B2 (en) | 2001-11-05 | 2003-08-05 | Cypress Bioscience, Inc. | Methods of treating fibromyalgia |
| SE0103818D0 (sv) * | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| CA2476218A1 (en) | 2002-02-08 | 2003-08-14 | President And Fellows Of Harvard College | Therapeutic compounds |
| PL223471B1 (pl) | 2002-03-15 | 2016-10-31 | Cypress Bioscience Inc | Kompozycja farmaceutyczna zawierająca milnacypran do stosowania w leczeniu zespołu nadwrażliwości jelita grubego |
| TW200402289A (en) * | 2002-05-17 | 2004-02-16 | Wyeth Corp | Methods of treating gastrointestinary and genitourinary pain disorders |
| CA2495452A1 (en) | 2002-08-14 | 2004-02-26 | Pharmacia & Upjohn Company Llc | Use of reboxetine for the treatment of hot flashes |
| US20040180879A1 (en) * | 2002-10-15 | 2004-09-16 | Deecher Darlene Coleman | Novel method of treating vasomotor symptoms |
| US20040152710A1 (en) * | 2002-10-15 | 2004-08-05 | Deecher Darlene Coleman | Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms |
| US7345096B2 (en) * | 2002-10-15 | 2008-03-18 | Wyeth | Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms |
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2004
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- 2004-10-13 KR KR1020067007312A patent/KR20070026326A/ko not_active Withdrawn
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- 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
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- 2004-10-13 AU AU2004281746A patent/AU2004281746A1/en not_active Withdrawn
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- 2004-10-14 PE PE2004000995A patent/PE20050440A1/es not_active Application Discontinuation
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2006
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2009
- 2009-05-18 US US12/467,594 patent/US20090227585A1/en not_active Abandoned
Also Published As
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| JP2007508395A (ja) | 2007-04-05 |
| IL174472A0 (en) | 2006-08-01 |
| KR20070026326A (ko) | 2007-03-08 |
| ECSP066506A (es) | 2006-10-10 |
| US20050187251A1 (en) | 2005-08-25 |
| 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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