KR20050026702A - 신규한 화합물 및 이의 용도 - Google Patents
신규한 화합물 및 이의 용도 Download PDFInfo
- Publication number
- KR20050026702A KR20050026702A KR1020047018539A KR20047018539A KR20050026702A KR 20050026702 A KR20050026702 A KR 20050026702A KR 1020047018539 A KR1020047018539 A KR 1020047018539A KR 20047018539 A KR20047018539 A KR 20047018539A KR 20050026702 A KR20050026702 A KR 20050026702A
- Authority
- KR
- South Korea
- Prior art keywords
- trifluoromethyl
- pyridin
- piperazine
- acetate
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 103
- 238000000034 method Methods 0.000 claims abstract description 45
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 158
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 101
- -1 2-tetrahydrofuryl Chemical group 0.000 claims description 87
- 102000005962 receptors Human genes 0.000 claims description 45
- 108020003175 receptors Proteins 0.000 claims description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 229940076279 serotonin Drugs 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 208000024891 symptom Diseases 0.000 claims description 14
- 208000019901 Anxiety disease Diseases 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 208000008589 Obesity Diseases 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 206010013654 Drug abuse Diseases 0.000 claims description 7
- 208000033830 Hot Flashes Diseases 0.000 claims description 7
- 206010060800 Hot flush Diseases 0.000 claims description 7
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 7
- 206010046543 Urinary incontinence Diseases 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 7
- 208000011117 substance-related disease Diseases 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 6
- 208000030814 Eating disease Diseases 0.000 claims description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 6
- 208000019022 Mood disease Diseases 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 208000014679 binge eating disease Diseases 0.000 claims description 6
- 235000014632 disordered eating Nutrition 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 235000003642 hunger Nutrition 0.000 claims description 6
- 230000009245 menopause Effects 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 230000004584 weight gain Effects 0.000 claims description 6
- 235000019786 weight gain Nutrition 0.000 claims description 6
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 229940124811 psychiatric drug Drugs 0.000 claims description 5
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 150000003573 thiols Chemical class 0.000 claims description 5
- OLQYIWBVVISDKZ-SSDOTTSWSA-N (2r)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1C1=CC=C(C(F)(F)F)C(Cl)=N1 OLQYIWBVVISDKZ-SSDOTTSWSA-N 0.000 claims description 4
- OLQYIWBVVISDKZ-ZETCQYMHSA-N (2s)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(Cl)=N1 OLQYIWBVVISDKZ-ZETCQYMHSA-N 0.000 claims description 4
- SGLNIXKCLOPOJJ-ZETCQYMHSA-N (3s)-1-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(Cl)=N1 SGLNIXKCLOPOJJ-ZETCQYMHSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- XJXIZRHEURHPLD-LBPRGKRZSA-N (2s)-1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]-2-methylpiperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(SCC=2C(=CC=CC=2)Cl)=N1 XJXIZRHEURHPLD-LBPRGKRZSA-N 0.000 claims description 3
- SZSVGTFMHBWDFK-ZDUSSCGKSA-N (2s)-2-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C[C@H]1CNCCN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 SZSVGTFMHBWDFK-ZDUSSCGKSA-N 0.000 claims description 3
- NWBUKSZRBSOPDH-LBPRGKRZSA-N (3s)-1-[6-[(2-chlorophenyl)methylsulfanyl]-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(SCC=2C(=CC=CC=2)Cl)=N1 NWBUKSZRBSOPDH-LBPRGKRZSA-N 0.000 claims description 3
- NTUXZOOPCXJLMQ-VIFPVBQESA-N (3s)-1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]-3-methylpiperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2C[C@H](C)NCC2)=C1 NTUXZOOPCXJLMQ-VIFPVBQESA-N 0.000 claims description 3
- MGNJRCXEEAHGRW-ZDUSSCGKSA-N (3s)-3-methyl-1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1CN[C@@H](C)CN1C1=CC=C(C(F)(F)F)C(OCC=2C=CC=CC=2)=N1 MGNJRCXEEAHGRW-ZDUSSCGKSA-N 0.000 claims description 3
- JDBDRBLDOHFQGQ-UHFFFAOYSA-N 1-[6-(1-phenylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C=1C=CC=CC=1C(C)OC(C(=CC=1)C(F)(F)F)=NC=1N1CCNCC1 JDBDRBLDOHFQGQ-UHFFFAOYSA-N 0.000 claims description 3
- PNJPYOVAPXMJKI-UHFFFAOYSA-N 1-[6-(2,3-dihydro-1,4-benzodioxin-6-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound N1=C(OCC=2C=C3OCCOC3=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 PNJPYOVAPXMJKI-UHFFFAOYSA-N 0.000 claims description 3
- BRXXSRUTEAWYSZ-UHFFFAOYSA-N 1-[6-(2-cyclohexylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCC1CCCCC1 BRXXSRUTEAWYSZ-UHFFFAOYSA-N 0.000 claims description 3
- ISXKGCKVAMMYCG-UHFFFAOYSA-N 1-[6-(2-cyclopentylethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCC1CCCC1 ISXKGCKVAMMYCG-UHFFFAOYSA-N 0.000 claims description 3
- LGUCZURKPZRUKT-UHFFFAOYSA-N 1-[6-(2-naphthalen-2-yloxyethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound N1=C(OCCOC=2C=C3C=CC=CC3=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 LGUCZURKPZRUKT-UHFFFAOYSA-N 0.000 claims description 3
- CWMFJKDGYIOIEP-UHFFFAOYSA-N 1-[6-(2-phenoxyethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCOC1=CC=CC=C1 CWMFJKDGYIOIEP-UHFFFAOYSA-N 0.000 claims description 3
- GJZATGDNYDSWNH-UHFFFAOYSA-N 1-[6-(3-pyridin-3-ylpropoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCCCC1=CC=CN=C1 GJZATGDNYDSWNH-UHFFFAOYSA-N 0.000 claims description 3
- GGMIYHLTSHVBCU-UHFFFAOYSA-N 1-[6-(furan-2-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CO1 GGMIYHLTSHVBCU-UHFFFAOYSA-N 0.000 claims description 3
- ZTWDVAVUSQVHNU-UHFFFAOYSA-N 1-[6-(thiophen-3-ylmethoxy)-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC=1C=CSC=1 ZTWDVAVUSQVHNU-UHFFFAOYSA-N 0.000 claims description 3
- YYSRVJMCMWYNLJ-UHFFFAOYSA-N 1-[6-[(2,3-difluorophenyl)methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC1=CC=CC(COC=2C(=CC=C(N=2)N2CCNCC2)C(F)(F)F)=C1F YYSRVJMCMWYNLJ-UHFFFAOYSA-N 0.000 claims description 3
- IEFCYRREPDRTBO-UHFFFAOYSA-N 1-[6-[(2,6-difluorophenyl)methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC1=CC=CC(F)=C1COC1=NC(N2CCNCC2)=CC=C1C(F)(F)F IEFCYRREPDRTBO-UHFFFAOYSA-N 0.000 claims description 3
- OBLMRDRFYUMUQH-UHFFFAOYSA-N 1-[6-[2-(2,6-difluorophenoxy)ethoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC1=CC=CC(F)=C1OCCOC1=NC(N2CCNCC2)=CC=C1C(F)(F)F OBLMRDRFYUMUQH-UHFFFAOYSA-N 0.000 claims description 3
- VLTFROJFPRTUBA-UHFFFAOYSA-N 1-[6-[[2-(phenoxymethyl)phenyl]methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC=C1COC1=CC=CC=C1 VLTFROJFPRTUBA-UHFFFAOYSA-N 0.000 claims description 3
- LADXOCROYYAJEV-UHFFFAOYSA-N 1-[6-cyclopentyloxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OC1CCCC1 LADXOCROYYAJEV-UHFFFAOYSA-N 0.000 claims description 3
- GGIPYRBPIJCYSD-UHFFFAOYSA-N 1-[6-ethylsulfanyl-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(SCC)=NC(N2CCNCC2)=C1 GGIPYRBPIJCYSD-UHFFFAOYSA-N 0.000 claims description 3
- JEVYYEYMKYNXTN-UHFFFAOYSA-N 1-[6-methoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(OC)=NC(N2CCNCC2)=C1 JEVYYEYMKYNXTN-UHFFFAOYSA-N 0.000 claims description 3
- OCEZFJULIYXWAR-UHFFFAOYSA-N 1-[6-phenylmethoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC=C1 OCEZFJULIYXWAR-UHFFFAOYSA-N 0.000 claims description 3
- VRGJESCGGWQCRP-UHFFFAOYSA-N 1-[6-propoxy-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1=C(C(F)(F)F)C(OCCC)=NC(N2CCNCC2)=C1 VRGJESCGGWQCRP-UHFFFAOYSA-N 0.000 claims description 3
- VREOKOJKZOOCSM-UHFFFAOYSA-N 3-[[6-piperazin-1-yl-3-(trifluoromethyl)pyridin-2-yl]oxymethyl]benzonitrile Chemical compound FC(F)(F)C1=CC=C(N2CCNCC2)N=C1OCC1=CC=CC(C#N)=C1 VREOKOJKZOOCSM-UHFFFAOYSA-N 0.000 claims description 3
- BMBLRVKOLIKNPO-UHFFFAOYSA-N 8-[2-[6-piperazin-1-yl-3-(trifluoromethyl)pyridin-2-yl]oxyethoxy]quinoline Chemical compound N1=C(OCCOC=2C3=NC=CC=C3C=CC=2)C(C(F)(F)F)=CC=C1N1CCNCC1 BMBLRVKOLIKNPO-UHFFFAOYSA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims 2
- JUYFEDCVVGHNAT-UHFFFAOYSA-N acetic acid;1-[6-[(5-fluoro-2-methoxyphenyl)methoxy]-5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound CC(O)=O.COC1=CC=C(F)C=C1COC1=NC(N2CCNCC2)=CC=C1C(F)(F)F JUYFEDCVVGHNAT-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 20
- 238000002360 preparation method Methods 0.000 abstract description 12
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- 239000007858 starting material Substances 0.000 description 35
- 238000004458 analytical method Methods 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
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- 239000000018 receptor agonist Substances 0.000 description 10
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- 239000002253 acid Substances 0.000 description 9
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- 239000003446 ligand Substances 0.000 description 8
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- 238000003786 synthesis reaction Methods 0.000 description 7
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- 239000013078 crystal Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000862 serotonergic effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 208000026139 Memory disease Diseases 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- 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
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- C07D409/12—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 chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Biomedical Technology (AREA)
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- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Liquid Crystal Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| SE0201544-4 | 2002-05-17 | ||
| SE0201544A SE0201544D0 (sv) | 2002-05-17 | 2002-05-17 | Novel compounds and thier use |
| US41003802P | 2002-09-12 | 2002-09-12 | |
| US60/410,038 | 2002-09-12 |
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| KR20050026702A true KR20050026702A (ko) | 2005-03-15 |
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| MX (1) | MXPA04011437A (https=) |
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| NZ (1) | NZ536409A (https=) |
| PT (1) | PT1506185E (https=) |
| RS (1) | RS99804A (https=) |
| SE (1) | SE0201544D0 (https=) |
| SI (1) | SI1506185T1 (https=) |
| WO (1) | WO2003097636A1 (https=) |
| ZA (1) | ZA200408975B (https=) |
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| US20030236259A1 (en) * | 2002-02-05 | 2003-12-25 | Rolf Hohlweg | Novel aryl- and heteroarylpiperazines |
| EP2248524A3 (en) | 2004-08-25 | 2011-03-09 | Takeda Pharmaceutical Company Limited | Preventives/remedies for stress urinary incontinence and method of screening the same |
| GT200500317A (es) * | 2004-11-05 | 2006-10-27 | Proceso para preparar compuestos de quinolina y productos obtenidos de los mismos | |
| RU2499795C2 (ru) | 2005-07-04 | 2013-11-27 | Хай Пойнт Фармасьютикалс, ЛЛС | Антагонисты гистаминовых н3-рецепторов |
| AR054849A1 (es) * | 2005-07-26 | 2007-07-18 | Wyeth Corp | Diazepinoquinolinas, sintesis de las mismas, e intermediarios para obtenerlas |
| JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
| TW200734334A (en) * | 2006-01-13 | 2007-09-16 | Wyeth Corp | Treatment of substance abuse |
| KR20080110759A (ko) * | 2006-03-24 | 2008-12-19 | 와이어쓰 | 통증 치료 |
| KR20080105104A (ko) * | 2006-03-24 | 2008-12-03 | 와이어쓰 | 우울증 치료를 위한 신규한 치료학적 병용제 |
| EP2742936A1 (en) | 2006-05-16 | 2014-06-18 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound and use thereof |
| SG163547A1 (en) * | 2006-05-29 | 2010-08-30 | High Point Pharmaceuticals Llc | 3- (1, 3-benz0di0x0l-5-yl) -6- (4-cyclopropylpiperazin-1-yl) -pyridazine, its salts and solvates and its use as histamine h3 receptor antagonist |
| US20070293475A1 (en) * | 2006-06-20 | 2007-12-20 | Alcon Manufacturing Ltd. | Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma |
| TW200823187A (en) * | 2006-10-24 | 2008-06-01 | Wyeth Corp | Benzodioxane derivatives and uses thereof |
| JO2642B1 (en) | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| KR20100016620A (ko) | 2007-04-23 | 2010-02-12 | 얀센 파마슈티카 엔.브이. | 속해리성 도파민 2 수용체 길항제로서의 4-알콕시피리다진 유도체 |
| AU2008240729B2 (en) | 2007-04-23 | 2012-08-23 | Janssen Pharmaceutica N.V. | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
| EP2014656A3 (en) * | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| CL2008002777A1 (es) * | 2007-09-21 | 2010-01-22 | Wyeth Corp | Metodo de preparacion de compuestos diazepinoquinolinicos quirales por recristalizacion en un sistema de solvente ternario. |
| EP2789338A3 (en) | 2007-11-15 | 2015-01-14 | Takeda Pharmaceutical Company Limited | Condensed pyridine derivate and use thereof |
| RU2502734C2 (ru) | 2008-07-03 | 2013-12-27 | Янссен Фармацевтика Нв | Замещенные 6-(1-пиперазинил)-пиридазины в качестве антагонистов 5-нт6 рецептора |
| CA2730774C (en) | 2008-07-31 | 2016-09-13 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
| MX2011013081A (es) | 2009-06-15 | 2012-01-20 | Takeda Pharmaceutical | Derivados de pirazinooxazepina. |
| JPWO2011071136A1 (ja) | 2009-12-11 | 2013-04-22 | アステラス製薬株式会社 | 線維筋痛症治療剤 |
| US20130267500A1 (en) | 2010-09-01 | 2013-10-10 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists in the treatment of disorders ameliorated by reduction of norepinephrine level |
| TWI589576B (zh) | 2011-07-15 | 2017-07-01 | 諾華公司 | 氮雜－雙環二芳基醚之鹽類及製造彼等或其前驅物之方法 |
| WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC AGENT FOR URINARY INCONTINENCE OF STRESS AND FECAL INCONTINENCE |
| TW202504600A (zh) * | 2023-07-04 | 2025-02-01 | 大陸商杭州中美華東製藥有限公司 | Glp1r激動劑及其中間體的製備方法 |
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| US4078063A (en) * | 1976-09-24 | 1978-03-07 | Merck & Co., Inc. | Piperazinylpyridines |
| DE68912282T2 (de) * | 1988-11-24 | 1994-04-28 | Akzo Nv | 1-[Mono- oder bis(trifluormethyl)-2-pyridinyl]piperazine enthaltende pharmazeutische Zusammensetzungen. |
| JPH0665203A (ja) * | 1992-06-25 | 1994-03-08 | Elf Sanofi | ピペラジンのヘテロ環誘導体 |
| EP0580465A1 (fr) * | 1992-06-25 | 1994-01-26 | Sanofi | Nouvelle utilisation thérapeutique d'hétérocyclyl-pipérazines comme 5-HT3 agonistes et nouveaux dérivés |
| SE9202265D0 (sv) * | 1992-07-31 | 1992-07-31 | Kabi Pharmacia Ab | Novel- pyridyl and pyrimidylpiperazine derivatives |
| JPH0797370A (ja) * | 1993-09-29 | 1995-04-11 | Asahi Chem Ind Co Ltd | ２−アルコキシピラジン誘導体およびその用途 |
| WO1998033504A1 (en) * | 1997-02-03 | 1998-08-06 | Akzo Nobel N.V. | Treatment of urinary incontinence |
| JP3989102B2 (ja) * | 1997-10-02 | 2007-10-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 縮合ピリジン誘導体 |
| UA77650C2 (en) * | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| BR0115400A (pt) * | 2000-11-20 | 2003-09-30 | Biovitrum Ab | Compostos de piperazinilpirazina atuando como agonistas ou antagonistas do receptor 5ht-2 de serotonina |
| EP1213017A3 (en) | 2000-12-05 | 2003-11-12 | Akzo Nobel N.V. | Use of a 5-HT2C receptor agonist for the treatment of hot flushes |
| US6498184B2 (en) * | 2000-12-05 | 2002-12-24 | Akzo Nobel N.V. | Serotonergic compound for a method of treatment of hot flushes in post-menopausal women |
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Also Published As
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|---|---|
| SE0201544D0 (sv) | 2002-05-17 |
| US7229997B2 (en) | 2007-06-12 |
| ES2263971T3 (es) | 2006-12-16 |
| RS99804A (sr) | 2006-12-15 |
| CY1105162T1 (el) | 2010-03-03 |
| WO2003097636A1 (en) | 2003-11-27 |
| EA200401526A1 (ru) | 2005-04-28 |
| NO20045486L (no) | 2005-02-02 |
| AU2003228196A1 (en) | 2003-12-02 |
| DE60305484T2 (de) | 2006-11-09 |
| CN1701068A (zh) | 2005-11-23 |
| IL164974A0 (en) | 2005-12-18 |
| DE60305484D1 (de) | 2006-06-29 |
| JP2005529926A (ja) | 2005-10-06 |
| EA007543B1 (ru) | 2006-10-27 |
| CN1329389C (zh) | 2007-08-01 |
| CA2483619A1 (en) | 2003-11-27 |
| ATE327229T1 (de) | 2006-06-15 |
| US20030232814A1 (en) | 2003-12-18 |
| AU2003228196B2 (en) | 2009-12-17 |
| PT1506185E (pt) | 2006-10-31 |
| DK1506185T3 (da) | 2006-10-02 |
| HK1084941A1 (en) | 2006-08-11 |
| SI1506185T1 (sl) | 2006-10-31 |
| ZA200408975B (en) | 2005-11-14 |
| JP4865221B2 (ja) | 2012-02-01 |
| EP1506185A1 (en) | 2005-02-16 |
| BR0310077A (pt) | 2005-02-22 |
| EP1506185B1 (en) | 2006-05-24 |
| MXPA04011437A (es) | 2005-02-17 |
| NZ536409A (en) | 2007-11-30 |
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