MXPA06003881A - Derivados de arilalquily cicloalquilalquil-piperazina y metodos de su uso. - Google Patents
Derivados de arilalquily cicloalquilalquil-piperazina y metodos de su uso.Info
- Publication number
- MXPA06003881A MXPA06003881A MXPA06003881A MXPA06003881A MXPA06003881A MX PA06003881 A MXPA06003881 A MX PA06003881A MX PA06003881 A MXPA06003881 A MX PA06003881A MX PA06003881 A MXPA06003881 A MX PA06003881A MX PA06003881 A MXPA06003881 A MX PA06003881A
- Authority
- MX
- Mexico
- Prior art keywords
- ethyl
- esi
- cyclohexanol
- dichlorohydrate
- prepared
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 66
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title abstract description 5
- 208000002193 Pain Diseases 0.000 claims abstract description 58
- 230000036407 pain Effects 0.000 claims abstract description 50
- 208000024891 symptom Diseases 0.000 claims abstract description 41
- 230000001457 vasomotor Effects 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 208000035475 disorder Diseases 0.000 claims abstract description 29
- 208000001640 Fibromyalgia Diseases 0.000 claims abstract description 21
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 17
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 17
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims abstract description 12
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims abstract description 12
- 230000002496 gastric effect Effects 0.000 claims abstract description 11
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 10
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 9
- 208000024714 major depressive disease Diseases 0.000 claims abstract description 9
- 206010066218 Stress Urinary Incontinence Diseases 0.000 claims abstract description 5
- -1 methylenedioxy Chemical group 0.000 claims description 1188
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 350
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 208
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 145
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 127
- 150000001875 compounds Chemical class 0.000 claims description 115
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 97
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 92
- AQAFFYMEIWJBCK-UHFFFAOYSA-N chloro hypochlorite cyclohexanol Chemical compound O(Cl)Cl.C1(CCCCC1)O AQAFFYMEIWJBCK-UHFFFAOYSA-N 0.000 claims description 74
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000004432 carbon atom Chemical group C* 0.000 claims description 42
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000009103 reabsorption Effects 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 206010046543 Urinary incontinence Diseases 0.000 claims description 7
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 7
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 206010021639 Incontinence Diseases 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- MFHXCOHNVRVIHA-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-[4-(pyridin-3-ylmethyl)piperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C1CN(CC=2C=NC=CC=2)CCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCC1 MFHXCOHNVRVIHA-UHFFFAOYSA-N 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- XKGSUIZTLBVSMC-UHFFFAOYSA-N ClOCl.O1C(CCCC1)O Chemical compound ClOCl.O1C(CCCC1)O XKGSUIZTLBVSMC-UHFFFAOYSA-N 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- UJUMNMYEMMYYEG-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-[4-(2-phenylpropyl)piperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCN1CC(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 UJUMNMYEMMYYEG-UHFFFAOYSA-N 0.000 claims description 2
- LVBACBXYFYURCN-UHFFFAOYSA-N 1-[1-(3-chlorophenyl)-2-[4-(cyclohex-3-en-1-ylmethyl)piperazin-1-yl]ethyl]cyclohexan-1-ol Chemical compound C1CN(CC2CC=CCC2)CCN1CC(C=1C=C(Cl)C=CC=1)C1(O)CCCCC1 LVBACBXYFYURCN-UHFFFAOYSA-N 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 208000022925 sleep disturbance Diseases 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 5
- 208000020401 Depressive disease Diseases 0.000 claims 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 230000005284 excitation Effects 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 38
- 238000011282 treatment Methods 0.000 abstract description 30
- 230000002265 prevention Effects 0.000 abstract description 16
- 230000001668 ameliorated effect Effects 0.000 abstract description 6
- 208000000921 Urge Urinary Incontinence Diseases 0.000 abstract description 2
- 208000011580 syndromic disease Diseases 0.000 abstract description 2
- 230000000407 monoamine reuptake Effects 0.000 abstract 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 203
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 125
- 239000002253 acid Substances 0.000 description 112
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 111
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 104
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 102
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 92
- 239000000243 solution Substances 0.000 description 91
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 86
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 81
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 80
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 76
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 76
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 73
- 235000019439 ethyl acetate Nutrition 0.000 description 55
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 43
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 40
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 29
- HYEPAONYVPIVMR-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=CC(OC(F)(F)F)=C1 HYEPAONYVPIVMR-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- 238000004808 supercritical fluid chromatography Methods 0.000 description 28
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 28
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 27
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 26
- 229960002748 norepinephrine Drugs 0.000 description 26
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 239000000460 chlorine Substances 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 24
- 239000007864 aqueous solution Substances 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 21
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 20
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 20
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 20
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 20
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 18
- 206010060800 Hot flush Diseases 0.000 description 18
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 18
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 17
- UQXFLQAZOOTXEZ-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-[4-(trifluoromethoxy)phenyl]acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=C(OC(F)(F)F)C=C1 UQXFLQAZOOTXEZ-UHFFFAOYSA-N 0.000 description 16
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 16
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 15
- QJIBYGWDEICULP-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-naphthalen-2-ylacetic acid Chemical compound C=1C=C2C=CC=CC2=CC=1C(C(=O)O)C1(O)CCCCC1 QJIBYGWDEICULP-UHFFFAOYSA-N 0.000 description 15
- OANNCEVIYONFOC-UHFFFAOYSA-N 2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl)acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=CC(Cl)=C1 OANNCEVIYONFOC-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000000377 silicon dioxide Substances 0.000 description 15
- 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 description 14
- WFPMUFXQDKMVCO-UHFFFAOYSA-N 2-(3-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1 WFPMUFXQDKMVCO-UHFFFAOYSA-N 0.000 description 14
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 208000033830 Hot Flashes Diseases 0.000 description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
- AGUXIBJEWUEHLS-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=CC(C(F)(F)F)=C1 AGUXIBJEWUEHLS-UHFFFAOYSA-N 0.000 description 12
- RNAFFCDDPQAGDR-UHFFFAOYSA-N 2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=CC(Br)=C1 RNAFFCDDPQAGDR-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000000262 estrogen Substances 0.000 description 12
- 229940011871 estrogen Drugs 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 12
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 11
- KYZJWANBOFKFGX-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-naphthalen-1-ylacetic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C(C(=O)O)C1(O)CCCCC1 KYZJWANBOFKFGX-UHFFFAOYSA-N 0.000 description 11
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- HYEPAONYVPIVMR-LBPRGKRZSA-N (2r)-2-(1-hydroxycyclohexyl)-2-[3-(trifluoromethoxy)phenyl]acetic acid Chemical compound C1([C@@H](C(=O)O)C2(O)CCCCC2)=CC=CC(OC(F)(F)F)=C1 HYEPAONYVPIVMR-LBPRGKRZSA-N 0.000 description 10
- SKARCIAFKUSVEF-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C1=CC=C(Cl)C(Cl)=C1 SKARCIAFKUSVEF-UHFFFAOYSA-N 0.000 description 10
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 230000001331 thermoregulatory effect Effects 0.000 description 10
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 9
- 239000005971 1-naphthylacetic acid Substances 0.000 description 9
- ZFUAOMZGERUFJP-UHFFFAOYSA-N 2-(1-hydroxycyclohexyl)-2-(4-phenylmethoxyphenyl)acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C(C=C1)=CC=C1OCC1=CC=CC=C1 ZFUAOMZGERUFJP-UHFFFAOYSA-N 0.000 description 9
- KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 9
- UPFWHRIMKFAUDL-UHFFFAOYSA-N 2-(3-chloro-4-phenylmethoxyphenyl)-2-(1-hydroxycyclohexyl)acetic acid Chemical compound C1CCCCC1(O)C(C(=O)O)C(C=C1Cl)=CC=C1OCC1=CC=CC=C1 UPFWHRIMKFAUDL-UHFFFAOYSA-N 0.000 description 9
- 210000003169 central nervous system Anatomy 0.000 description 9
- HFNCOTSLOKKPHU-UHFFFAOYSA-N cyclohexanol;hydrochloride Chemical compound Cl.OC1CCCCC1 HFNCOTSLOKKPHU-UHFFFAOYSA-N 0.000 description 9
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- KPHFFCRRYZHCBA-UHFFFAOYSA-N tert-butyl 4-[2-[1-[tert-butyl(dimethyl)silyl]indol-3-yl]-2-(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)C(C1(O)CCCCC1)C1=CN([Si](C)(C)C(C)(C)C)C2=CC=CC=C12 KPHFFCRRYZHCBA-UHFFFAOYSA-N 0.000 description 1
- IEBCVOVCYWPMPS-UHFFFAOYSA-N tert-butyl 4-[2-[3-(3,4-dichlorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(C=2C=C(Cl)C(Cl)=CC=2)=C1 IEBCVOVCYWPMPS-UHFFFAOYSA-N 0.000 description 1
- ZRKANOGZSZGSBX-UHFFFAOYSA-N tert-butyl 4-[2-[3-(3-chlorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(C=2C=C(Cl)C=CC=2)=C1 ZRKANOGZSZGSBX-UHFFFAOYSA-N 0.000 description 1
- OSUUXLGMFJMNLE-UHFFFAOYSA-N tert-butyl 4-[2-[3-(4-chlorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=CC(C=2C=CC(Cl)=CC=2)=C1 OSUUXLGMFJMNLE-UHFFFAOYSA-N 0.000 description 1
- DUCLDRCUUDRWSO-UHFFFAOYSA-N tert-butyl 4-[2-[3-chloro-4-(2-phenylethoxy)phenyl]-2-(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)C(C1(O)CCCCC1)C(C=C1Cl)=CC=C1OCCC1=CC=CC=C1 DUCLDRCUUDRWSO-UHFFFAOYSA-N 0.000 description 1
- MDKIVNTUPRYVEV-UHFFFAOYSA-N tert-butyl 4-[2-[4-(2-chlorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=C(C=2C(=CC=CC=2)Cl)C=C1 MDKIVNTUPRYVEV-UHFFFAOYSA-N 0.000 description 1
- HRSXHKPUMHJEAI-UHFFFAOYSA-N tert-butyl 4-[2-[4-(3,4-dichlorophenyl)phenyl]-2-(1-hydroxycyclobutyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCC1)C1=CC=C(C=2C=C(Cl)C(Cl)=CC=2)C=C1 HRSXHKPUMHJEAI-UHFFFAOYSA-N 0.000 description 1
- HHUXIDJJHIRZBQ-UHFFFAOYSA-N tert-butyl 4-[2-[4-(3-cyanophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=C(C=2C=C(C=CC=2)C#N)C=C1 HHUXIDJJHIRZBQ-UHFFFAOYSA-N 0.000 description 1
- SILWAVHPFUZFGT-UHFFFAOYSA-N tert-butyl 4-[2-[4-(3-fluorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=C(C=2C=C(F)C=CC=2)C=C1 SILWAVHPFUZFGT-UHFFFAOYSA-N 0.000 description 1
- RSDIUKSNXMZMGC-UHFFFAOYSA-N tert-butyl 4-[2-[4-(4-chlorophenyl)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC(C1(O)CCCCC1)C1=CC=C(C=2C=CC(Cl)=CC=2)C=C1 RSDIUKSNXMZMGC-UHFFFAOYSA-N 0.000 description 1
- ZPYLADGUWFOTGJ-UHFFFAOYSA-N tert-butyl 4-[2-[4-ethoxy-3-(trifluoromethoxy)phenyl]-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate Chemical compound C1=C(OC(F)(F)F)C(OCC)=CC=C1C(C1(O)CCCCC1)CN1CCN(C(=O)OC(C)(C)C)CC1 ZPYLADGUWFOTGJ-UHFFFAOYSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- IMSRZOXPJUYDHX-MRTLOADZSA-N tert-butyl n-[(3r)-1-[2-(3-chlorophenyl)-2-(1-hydroxycyclohexyl)acetyl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CCN1C(=O)C(C1(O)CCCCC1)C1=CC=CC(Cl)=C1 IMSRZOXPJUYDHX-MRTLOADZSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 208000012720 thalamic disease Diseases 0.000 description 1
- 230000000542 thalamic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- JGOIIPRSFZFFHG-UHFFFAOYSA-N trimethyl(2-tributylstannylethynyl)silane Chemical compound CCCC[Sn](CCCC)(CCCC)C#C[Si](C)(C)C JGOIIPRSFZFFHG-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- 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
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- 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
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- 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
- C07D333/06—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Pyridine Compounds (AREA)
- Pyrane Compounds (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51100203P | 2003-10-14 | 2003-10-14 | |
| US56145304P | 2004-04-12 | 2004-04-12 | |
| US57004304P | 2004-05-11 | 2004-05-11 | |
| US10/962,881 US7524846B2 (en) | 2003-10-14 | 2004-10-12 | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
| PCT/US2004/033670 WO2005037807A1 (en) | 2003-10-14 | 2004-10-13 | Arylalkyl- and cycloalkylalkyl-piperazine derivatives and methods of their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06003881A true MXPA06003881A (es) | 2006-07-03 |
Family
ID=34468488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06003881A MXPA06003881A (es) | 2003-10-14 | 2004-10-13 | Derivados de arilalquily cicloalquilalquil-piperazina y metodos de su uso. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7524846B2 (enExample) |
| EP (1) | EP1678154A1 (enExample) |
| JP (1) | JP2007508392A (enExample) |
| AU (1) | AU2004282164A1 (enExample) |
| BR (1) | BRPI0415410A (enExample) |
| CA (1) | CA2539761A1 (enExample) |
| MX (1) | MXPA06003881A (enExample) |
| WO (1) | WO2005037807A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7491723B2 (en) * | 2003-10-14 | 2009-02-17 | Wyeth | Alkanol and cycloalkanol-amine derivatives and methods of their use |
| US7531543B2 (en) * | 2003-10-14 | 2009-05-12 | Wyeth | Phenylpiperazine cycloalkanol derivatives and methods of their use |
| 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 |
| JP2008512417A (ja) * | 2004-09-10 | 2008-04-24 | ユセベ ファルマ ソシエテ アノニム | シグマ受容体リガンド |
| US20070021488A1 (en) * | 2005-07-21 | 2007-01-25 | Wyeth | Method for treating nervous system disorders and conditions |
| WO2007067575A2 (en) * | 2005-12-05 | 2007-06-14 | Wyeth | Process for preparing substituted aryl cycloalkanol derivatives |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2636032A (en) * | 1949-04-12 | 1953-04-21 | Abbott Lab | N, n'-disubstituted piperazines and process of preparing same |
| US2971955A (en) * | 1958-12-29 | 1961-02-14 | Abbott Lab | Cyclohexylcarbinol derivatives of piperazine |
| US3454554A (en) * | 1960-10-14 | 1969-07-08 | Colgate Palmolive Co | Aminoalkyliminodibenzyl compounds |
| FR2035785A6 (enExample) | 1969-03-28 | 1970-12-24 | Delalande Sa | |
| CS175831B1 (enExample) | 1974-12-17 | 1977-05-31 | ||
| IL56369A (en) * | 1978-01-20 | 1984-05-31 | Erba Farmitalia | Alpha-phenoxybenzyl propanolamine derivatives,their preparation and pharmaceutical compositions comprising them |
| 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 |
| US6387897B1 (en) * | 1998-06-30 | 2002-05-14 | Neuromed Technologies, Inc. | Preferentially substituted calcium channel blockers |
| ES2305606T3 (es) | 1999-04-06 | 2008-11-01 | Sepracor Inc. | Succinato de o-desmetilvenlafaxina. |
| 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 |
| ATE369330T1 (de) | 2001-02-12 | 2007-08-15 | Wyeth Corp | O-desmethyl-venlafaxine succinat salz |
| EP1383495A1 (en) | 2001-03-29 | 2004-01-28 | Eli Lilly And Company | Duloxetine for treatment of hot flashes |
| 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 |
| EP1468990A4 (en) | 2001-12-21 | 2006-01-04 | Taisho Pharmaceutical Co Ltd | PIPERAZINE DERIVATIVE |
| 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 |
| US20040152710A1 (en) | 2002-10-15 | 2004-08-05 | Deecher Darlene Coleman | Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms |
| US20040180879A1 (en) * | 2002-10-15 | 2004-09-16 | Deecher Darlene Coleman | Novel method of treating vasomotor symptoms |
| US7345096B2 (en) | 2002-10-15 | 2008-03-18 | Wyeth | Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms |
| US7491723B2 (en) * | 2003-10-14 | 2009-02-17 | Wyeth | Alkanol and cycloalkanol-amine derivatives and methods of their use |
| US7531543B2 (en) * | 2003-10-14 | 2009-05-12 | Wyeth | Phenylpiperazine cycloalkanol derivatives and methods of their use |
-
2004
- 2004-10-12 US US10/962,881 patent/US7524846B2/en not_active Expired - Fee Related
- 2004-10-13 AU AU2004282164A patent/AU2004282164A1/en not_active Abandoned
- 2004-10-13 EP EP04794904A patent/EP1678154A1/en not_active Withdrawn
- 2004-10-13 WO PCT/US2004/033670 patent/WO2005037807A1/en not_active Ceased
- 2004-10-13 JP JP2006535598A patent/JP2007508392A/ja active Pending
- 2004-10-13 BR BRPI0415410-0A patent/BRPI0415410A/pt not_active IP Right Cessation
- 2004-10-13 MX MXPA06003881A patent/MXPA06003881A/es unknown
- 2004-10-13 CA CA002539761A patent/CA2539761A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2539761A1 (en) | 2005-04-28 |
| EP1678154A1 (en) | 2006-07-12 |
| BRPI0415410A (pt) | 2006-12-05 |
| US20050148595A1 (en) | 2005-07-07 |
| US7524846B2 (en) | 2009-04-28 |
| JP2007508392A (ja) | 2007-04-05 |
| AU2004282164A1 (en) | 2005-04-28 |
| WO2005037807A1 (en) | 2005-04-28 |
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