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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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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
- C07D405/02—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 containing two hetero rings
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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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- 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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- Veterinary Medicine (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Liquid Crystal Substances (AREA)
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| SE0201544-4 | 2002-05-17 | ||
| US41003802P | 2002-09-12 | 2002-09-12 | |
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| US20030236259A1 (en) * | 2002-02-05 | 2003-12-25 | Rolf Hohlweg | Novel aryl- and heteroarylpiperazines |
| EP1792629A4 (en) | 2004-08-25 | 2010-08-25 | Takeda Pharmaceutical | MEANS FOR THE PREVENTION / TREATMENT OF STRESS-RELATED HARNINE INCONTINENCE AND PRECAUTIONARY METHOD FOR THIS |
| GT200500317A (es) * | 2004-11-05 | 2006-10-27 | Proceso para preparar compuestos de quinolina y productos obtenidos de los mismos | |
| EP2233470B1 (en) * | 2005-07-04 | 2011-12-07 | High Point Pharmaceuticals, LLC | Histamine H3 receptor antagonists |
| 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 |
| AU2007231011A1 (en) * | 2006-03-24 | 2007-10-04 | Wyeth | New therapeutic combinations for the treatment of depression |
| JP2009531434A (ja) * | 2006-03-24 | 2009-09-03 | ワイス | 痛みの治療 |
| EP2727585A1 (en) | 2006-05-16 | 2014-05-07 | Takeda Pharmaceutical Company Limited | In-vivo screening method |
| WO2007137968A1 (en) * | 2006-05-29 | 2007-12-06 | 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 |
| WO2007149728A2 (en) * | 2006-06-20 | 2007-12-27 | Alcon Research, Ltd. | Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma |
| CL2007003065A1 (es) * | 2006-10-24 | 2008-01-25 | Wyeth Corp | Compuestos derivados de benzodioxano, agonista 5ht2c, composicion farmaceutica que lois comprende; y sus uso en el tratamiento de un trastorno psicotico, ansiedad, depresion, trastorno bipolar, sindrome premenstrual, entre otros |
| 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 |
| JP5431306B2 (ja) | 2007-04-23 | 2014-03-05 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 高速解離性ドパミン２受容体アンタゴニストとしてのチア（ジア）ゾール |
| WO2008128995A1 (en) | 2007-04-23 | 2008-10-30 | Janssen Pharmaceutica N.V. | 4-alkoxypyridazine derivatives 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. |
| US20100266504A1 (en) | 2007-11-15 | 2010-10-21 | Takahiro Matsumoto | Condensed pyridine derivative and use thereof |
| CN102159554B (zh) | 2008-07-03 | 2014-09-24 | 詹森药业有限公司 | 作为5-ht6受体拮抗剂的取代的6-(1-哌嗪基)-哒嗪 |
| CA2730774C (en) * | 2008-07-31 | 2016-09-13 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
| HRP20140589T1 (hr) | 2009-06-15 | 2014-08-01 | Takeda Pharmaceutical Company Limited | Derivati pirazinooksazepina |
| US20120253036A1 (en) | 2009-12-11 | 2012-10-04 | Yukinori Nagakura | Agent for treating fibromyalgia |
| 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 |
| JP6263469B2 (ja) | 2011-07-15 | 2018-01-17 | ノバルティス アーゲー | アザ二環式ジ−アリールエーテルの塩およびその製造方法またはその前駆体の製造方法 |
| WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| US20210052600A1 (en) | 2017-12-27 | 2021-02-25 | Takeda Pharmaceutical Company Limited | Therapeutic agents for stress urinary incontinence and incotinence of feces |
| 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 |
| ES2061953T3 (es) * | 1988-11-24 | 1994-12-16 | Akzo Nv | Un procedimiento para preparar una composicion farmaceutica. |
| EP0580465A1 (fr) * | 1992-06-25 | 1994-01-26 | Sanofi | Nouvelle utilisation thérapeutique d'hétérocyclyl-pipérazines comme 5-HT3 agonistes et nouveaux dérivés |
| JPH0665203A (ja) * | 1992-06-25 | 1994-03-08 | Elf Sanofi | ピペラジンのヘテロ環誘導体 |
| 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 |
| EP1335907B1 (en) * | 2000-11-20 | 2010-06-09 | Biovitrum AB (publ) | Piperazinylpyrazine compounds as agonist or antagonist of serotonin 5ht-2 receptor |
| 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 |
| 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 |
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| US7229997B2 (en) | 2007-06-12 |
| AU2003228196A1 (en) | 2003-12-02 |
| AU2003228196B2 (en) | 2009-12-17 |
| HK1084941A1 (en) | 2006-08-11 |
| JP4865221B2 (ja) | 2012-02-01 |
| ATE327229T1 (de) | 2006-06-15 |
| ES2263971T3 (es) | 2006-12-16 |
| IL164974A0 (en) | 2005-12-18 |
| SI1506185T1 (sl) | 2006-10-31 |
| EP1506185A1 (en) | 2005-02-16 |
| DE60305484T2 (de) | 2006-11-09 |
| CY1105162T1 (el) | 2010-03-03 |
| MXPA04011437A (es) | 2005-02-17 |
| EA200401526A1 (ru) | 2005-04-28 |
| CN1329389C (zh) | 2007-08-01 |
| CN1701068A (zh) | 2005-11-23 |
| SE0201544D0 (sv) | 2002-05-17 |
| DE60305484D1 (de) | 2006-06-29 |
| US20030232814A1 (en) | 2003-12-18 |
| RS99804A (sr) | 2006-12-15 |
| NO20045486L (no) | 2005-02-02 |
| NZ536409A (en) | 2007-11-30 |
| BR0310077A (pt) | 2005-02-22 |
| PT1506185E (pt) | 2006-10-31 |
| JP2005529926A (ja) | 2005-10-06 |
| WO2003097636A1 (en) | 2003-11-27 |
| DK1506185T3 (da) | 2006-10-02 |
| CA2483619A1 (en) | 2003-11-27 |
| ZA200408975B (en) | 2005-11-14 |
| EA007543B1 (ru) | 2006-10-27 |
| EP1506185B1 (en) | 2006-05-24 |
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