BG107864A - Производни на заместени пиразинохиноксалини като агонисти и антагонисти на серотонинов рецептор - Google Patents

Производни на заместени пиразинохиноксалини като агонисти и антагонисти на серотонинов рецептор Download PDF

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Publication number: BG107864A
Authority: BG; Bulgaria
Prior art keywords: phenyl; substituted; alkyl; independently selected; alkenyl
Prior art date: 2000-12-20

Application number

BG107864A

Other languages

Bulgarian (bg)

English (en)

Inventor

Albert Robichaud

Ian S. Mitchell

Taekyu Lee

Wenting Chen

Original Assignee

Bristol-Myers Squibb Pharma Company

Priority date (The priority date 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 date listed.)

2000-12-20

Filing date

2003-05-30

Publication date

2004-03-31

2003-05-30 Application filed by Bristol-Myers Squibb Pharma Company filed Critical Bristol-Myers Squibb Pharma Company

2004-03-31 Publication of BG107864A publication Critical patent/BG107864A/bg

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239000003420 antiserotonin agent Substances 0.000 title abstract description 8
239000000952 serotonin receptor agonist Substances 0.000 title abstract description 7
CVSGFMWKZVZOJD-UHFFFAOYSA-N pyrazino[2,3-f]quinoxaline Chemical class C1=CN=C2C3=NC=CN=C3C=CC2=N1 CVSGFMWKZVZOJD-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 144
238000011282 treatment Methods 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 37
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
201000000980 schizophrenia Diseases 0.000 claims abstract description 13
208000008589 Obesity Diseases 0.000 claims abstract description 10
235000020824 obesity Nutrition 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
-1 ethylenedioxy Chemical group 0.000 claims description 426
125000000217 alkyl group Chemical group 0.000 claims description 336
229910052739 hydrogen Inorganic materials 0.000 claims description 187
VEAUDLLZYJVHRI-UHFFFAOYSA-N Trichlormethine Chemical compound Cl.ClCCN(CCCl)CCCl VEAUDLLZYJVHRI-UHFFFAOYSA-N 0.000 claims description 148
125000003342 alkenyl group Chemical group 0.000 claims description 147
125000000304 alkynyl group Chemical group 0.000 claims description 143
125000003118 aryl group Chemical group 0.000 claims description 133
125000005842 heteroatom Chemical group 0.000 claims description 127
125000000623 heterocyclic group Chemical group 0.000 claims description 127
229910052799 carbon Inorganic materials 0.000 claims description 124
229910052717 sulfur Inorganic materials 0.000 claims description 122
229910052760 oxygen Inorganic materials 0.000 claims description 119
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 118
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 116
125000005843 halogen group Chemical group 0.000 claims description 107
125000003545 alkoxy group Chemical group 0.000 claims description 102
239000013256 coordination polymer Substances 0.000 claims description 100
125000001188 haloalkyl group Chemical group 0.000 claims description 81
125000004093 cyano group Chemical group *C#N 0.000 claims description 70
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 68
125000002837 carbocyclic group Chemical group 0.000 claims description 67
229910052757 nitrogen Inorganic materials 0.000 claims description 65
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 65
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 60
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 46
125000001153 fluoro group Chemical group F* 0.000 claims description 45
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 44
229910052801 chlorine Inorganic materials 0.000 claims description 43
229910052731 fluorine Inorganic materials 0.000 claims description 43
125000000753 cycloalkyl group Chemical group 0.000 claims description 42
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 37
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 35
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 33
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 32
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
125000001309 chloro group Chemical group Cl* 0.000 claims description 28
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 25
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 21
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 20
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 20
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 17
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 17
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
102000006902 5-HT2C Serotonin Receptor Human genes 0.000 claims description 15
125000004414 alkyl thio group Chemical group 0.000 claims description 15
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 15
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 14
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 14
102000049773 5-HT2A Serotonin Receptor Human genes 0.000 claims description 14
101150065749 Churc1 gene Proteins 0.000 claims description 14
102100038239 Protein Churchill Human genes 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 14
125000004438 haloalkoxy group Chemical group 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
229920006395 saturated elastomer Polymers 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 13
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 12
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
235000010290 biphenyl Nutrition 0.000 claims description 10
125000000000 cycloalkoxy group Chemical group 0.000 claims description 10
125000001041 indolyl group Chemical group 0.000 claims description 9
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 8
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000002619 bicyclic group Chemical group 0.000 claims description 8
125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 8
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 8
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 8
125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 7
FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 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 7
125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 7
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
125000000168 pyrrolyl group Chemical group 0.000 claims description 7
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
125000005002 aryl methyl group Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
230000001225 therapeutic effect Effects 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims description 5
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 5
125000005916 2-methylpentyl group Chemical group 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 5
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
125000005917 3-methylpentyl group Chemical group 0.000 claims description 5
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 5
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 5
125000002757 morpholinyl group Chemical group 0.000 claims description 5
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 5
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 4
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 4
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
108010072564 5-HT2A Serotonin Receptor Proteins 0.000 claims description 4
125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 4
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 4
239000002400 serotonin 2A antagonist Substances 0.000 claims description 4
239000002485 serotonin 2C agonist Substances 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 3
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
RMAINTGPKFNBDP-UHFFFAOYSA-N 2-methylphenol Chemical group [CH2]C1=CC=CC=C1O RMAINTGPKFNBDP-UHFFFAOYSA-N 0.000 claims description 3
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 3
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
108010072553 5-HT2C Serotonin Receptor Proteins 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
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000004125 inden-2-yl group Chemical group [H]C1=C(*)C([H])([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 3
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 1
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
208000020401 Depressive disease Diseases 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 19
208000035475 disorder Diseases 0.000 abstract description 16
239000004480 active ingredient Substances 0.000 abstract description 14
208000019901 Anxiety disease Diseases 0.000 abstract description 13
230000036506 anxiety Effects 0.000 abstract description 13
208000019695 Migraine disease Diseases 0.000 abstract description 8
208000028017 Psychotic disease Diseases 0.000 abstract description 8
208000018522 Gastrointestinal disease Diseases 0.000 abstract description 7
230000004064 dysfunction Effects 0.000 abstract description 6
208000012201 sexual and gender identity disease Diseases 0.000 abstract description 6
208000015891 sexual disease Diseases 0.000 abstract description 6
208000019116 sleep disease Diseases 0.000 abstract description 6
208000015114 central nervous system disease Diseases 0.000 abstract description 5
238000009472 formulation Methods 0.000 abstract description 4
206010027599 migraine Diseases 0.000 abstract description 4
208000002193 Pain Diseases 0.000 abstract description 3
230000007958 sleep Effects 0.000 abstract description 3
210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
230000004899 motility Effects 0.000 abstract description 2
230000002265 prevention Effects 0.000 abstract description 2
206010041250 Social phobia Diseases 0.000 abstract 1
238000000034 method Methods 0.000 description 42
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 23
239000000243 solution Substances 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
238000002360 preparation method Methods 0.000 description 21
102000005962 receptors Human genes 0.000 description 18
108020003175 receptors Proteins 0.000 description 18
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
230000000694 effects Effects 0.000 description 16
102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 15
108091005479 5-HT2 receptors Proteins 0.000 description 15
238000005481 NMR spectroscopy Methods 0.000 description 15
210000004027 cell Anatomy 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 14
150000001412 amines Chemical class 0.000 description 13
235000019439 ethyl acetate Nutrition 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
150000003951 lactams Chemical class 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
101150104779 HTR2A gene Proteins 0.000 description 10
101150013372 Htr2c gene Proteins 0.000 description 10
241000700159 Rattus Species 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
238000001727 in vivo Methods 0.000 description 10
239000000651 prodrug Substances 0.000 description 10
229940002612 prodrug Drugs 0.000 description 10
239000007787 solid Substances 0.000 description 10
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
230000027455 binding Effects 0.000 description 9
210000003169 central nervous system Anatomy 0.000 description 9
239000013058 crude material Substances 0.000 description 9
102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 8
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239000004006 olive oil Substances 0.000 description 1
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239000001301 oxygen Substances 0.000 description 1
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230000001766 physiological effect Effects 0.000 description 1
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WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
238000010257 thawing Methods 0.000 description 1
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125000004306 triazinyl group Chemical group 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
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 1
125000004950 trifluoroalkyl group Chemical group 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
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125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Obesity (AREA)
Hematology (AREA)
Diabetes (AREA)
Child & Adolescent Psychology (AREA)
Anesthesiology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Saccharide Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG107864A 2000-12-20 2003-05-30 Производни на заместени пиразинохиноксалини като агонисти и антагонисти на серотонинов рецептор BG107864A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25676500P	2000-12-20	2000-12-20
PCT/US2001/049374 WO2002059127A2 (en)	2000-12-20	2001-12-19	Pyrazinoquinoxaline derivatives as serotonin agonists and antagonists

Publications (1)

Publication Number	Publication Date
BG107864A true BG107864A (bg)	2004-03-31

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Country Status (23)

Country	Link
US (1)	US6638934B2 (de)
EP (1)	EP1345942B9 (de)
JP (2)	JP4346307B2 (de)
KR (1)	KR20030069192A (de)
CN (1)	CN1505631A (de)
AT (1)	ATE318819T1 (de)
AU (1)	AU2002248216B2 (de)
BG (1)	BG107864A (de)
BR (1)	BR0116347A (de)
CA (1)	CA2431970A1 (de)
DE (1)	DE60117617T2 (de)
EE (1)	EE200300301A (de)
ES (1)	ES2260335T3 (de)
HU (1)	HUP0303513A3 (de)
IL (1)	IL156201A0 (de)
IS (1)	IS6850A (de)
MX (1)	MXPA03005437A (de)
NO (1)	NO20032795L (de)
PL (1)	PL366060A1 (de)
RU (1)	RU2003121406A (de)
SK (1)	SK7022003A3 (de)
WO (1)	WO2002059127A2 (de)
ZA (1)	ZA200304303B (de)

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PL366060A1 (en) *	2000-12-20	2005-01-24	Bristol-Myers Squibb Pharma Company	Substituted pyrazinoquinoxaline derivatives as serotonin receptor agonists and antagonists
US7244843B2 (en)	2003-10-07	2007-07-17	Bristol-Myers Squibb Company	Modulators of serotonin receptors
GB0417558D0 (en) *	2004-08-06	2004-09-08	Merck Sharp & Dohme	Novel combination therapy
JP5173190B2 (ja)	2004-08-25	2013-03-27	武田薬品工業株式会社	腹圧性尿失禁の予防・治療剤及びそのスクリーニング方法
EP2727585A1 (de)	2006-05-16	2014-05-07	Takeda Pharmaceutical Company Limited	In-vivo Screening-Methode
EP2789338A3 (de)	2007-11-15	2015-01-14	Takeda Pharmaceutical Company Limited	Kondensiertes Pyridinderivat und seine Verwendung
EP2510949A4 (de)	2009-12-11	2013-11-13	Astellas Pharma Inc	Therapeutikum für fibromyalgie
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
US20140206667A1 (en)	2012-11-14	2014-07-24	Michela Gallagher	Methods and compositions for treating schizophrenia
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

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US4183936A (en)	1972-06-19	1980-01-15	Endo Laboratories, Inc.	Pyridopyrrolobenzheterocycles
US4238607A (en)	1972-06-19	1980-12-09	Endo Laboratories Inc.	Pyridopyrrolo benzheterocycles
US3914421A (en)	1972-06-19	1975-10-21	Endo Lab	Pyridopyrrolobenzheterocycles for combatting depression
US4115577A (en)	1972-06-19	1978-09-19	Endo Laboratories, Inc.	Pyridopyrrolobenzheterocycles
US4013652A (en)	1972-06-19	1977-03-22	Endo Laboratories, Inc.	Pyridopyrrolobenzoxazine
US4219550A (en)	1978-11-09	1980-08-26	E. I. Du Pont De Nemours And Company	Cis- and trans- octahydropyridopyrrolobenzheterocycles
HUT61548A (en) *	1990-08-27	1993-01-28	Sandoz Ag	Process for producing indolonaphthyridine derivatives and pharmaceutical compositions comprising such compounds
NZ512765A (en) *	1998-12-17	2003-10-31	Wyeth Corp	2,3,4,4A-tetrahydro-1H-pyrazino(1,2-A)quinoxalin- 5(6H)one derivatives being 5HT2C agonists
PL366060A1 (en) *	2000-12-20	2005-01-24	Bristol-Myers Squibb Pharma Company	Substituted pyrazinoquinoxaline derivatives as serotonin receptor agonists and antagonists

2001
- 2001-12-19 PL PL01366060A patent/PL366060A1/xx not_active Application Discontinuation
- 2001-12-19 DE DE60117617T patent/DE60117617T2/de not_active Expired - Lifetime
- 2001-12-19 KR KR10-2003-7008273A patent/KR20030069192A/ko not_active Withdrawn
- 2001-12-19 JP JP2002559429A patent/JP4346307B2/ja not_active Expired - Fee Related
- 2001-12-19 BR BR0116347-7A patent/BR0116347A/pt not_active Application Discontinuation
- 2001-12-19 AT AT01997097T patent/ATE318819T1/de active
- 2001-12-19 WO PCT/US2001/049374 patent/WO2002059127A2/en not_active Ceased
- 2001-12-19 EE EEP200300301A patent/EE200300301A/xx unknown
- 2001-12-19 EP EP01997097A patent/EP1345942B9/de not_active Expired - Lifetime
- 2001-12-19 RU RU2003121406/04A patent/RU2003121406A/ru not_active Application Discontinuation
- 2001-12-19 ES ES01997097T patent/ES2260335T3/es not_active Expired - Lifetime
- 2001-12-19 HU HU0303513A patent/HUP0303513A3/hu not_active Application Discontinuation
- 2001-12-19 SK SK702-2003A patent/SK7022003A3/sk unknown
- 2001-12-19 AU AU2002248216A patent/AU2002248216B2/en not_active Ceased
- 2001-12-19 CA CA002431970A patent/CA2431970A1/en not_active Abandoned
- 2001-12-19 IL IL15620101A patent/IL156201A0/xx unknown
- 2001-12-19 CN CNA01822704XA patent/CN1505631A/zh active Pending
- 2001-12-19 US US10/026,404 patent/US6638934B2/en not_active Expired - Lifetime
- 2001-12-19 MX MXPA03005437A patent/MXPA03005437A/es unknown
2003
- 2003-05-30 BG BG107864A patent/BG107864A/bg unknown
- 2003-06-02 ZA ZA200304303A patent/ZA200304303B/en unknown
- 2003-06-18 IS IS6850A patent/IS6850A/is unknown
- 2003-06-19 NO NO20032795A patent/NO20032795L/no not_active Application Discontinuation
2009
- 2009-05-11 JP JP2009114360A patent/JP5117440B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CN1505631A (zh)	2004-06-16
RU2003121406A (ru)	2004-12-27
EP1345942B9 (de)	2006-11-15
US20020177596A1 (en)	2002-11-28
JP4346307B2 (ja)	2009-10-21
NO20032795L (no)	2003-08-04
US6638934B2 (en)	2003-10-28
JP2009215304A (ja)	2009-09-24
DE60117617T2 (de)	2007-01-25
PL366060A1 (en)	2005-01-24
CA2431970A1 (en)	2002-08-01
DE60117617D1 (de)	2006-04-27
ATE318819T1 (de)	2006-03-15
JP2004524298A (ja)	2004-08-12
BR0116347A (pt)	2004-07-06
KR20030069192A (ko)	2003-08-25
ES2260335T3 (es)	2006-11-01
EE200300301A (et)	2003-10-15
WO2002059127A2 (en)	2002-08-01
IL156201A0 (en)	2003-12-23
EP1345942A2 (de)	2003-09-24
JP5117440B2 (ja)	2013-01-16
WO2002059127A3 (en)	2002-10-03
MXPA03005437A (es)	2003-09-10
HUP0303513A3 (en)	2005-12-28
AU2002248216B2 (en)	2007-03-01
IS6850A (is)	2003-06-18
SK7022003A3 (en)	2004-08-03
NO20032795D0 (no)	2003-06-19
HUP0303513A2 (hu)	2004-01-28
EP1345942B1 (de)	2006-03-01
ZA200304303B (en)	2004-09-02

Publication	Publication Date	Title
EP1189905B1 (de)	2004-09-29	Substituierte heterocyclylkondensierte gamma carboline
JP5117440B2 (ja)	2013-01-16	セロトニン受容体アゴニストおよびアンタゴニストとしての置換されたピラジノキノキサリン誘導体
AU2002246726B2 (en)	2007-03-01	Substituted pyrroloquinolines and pyridoquinolines as serotonin agonists and antagonists
KR20030070073A (ko)	2003-08-27	세로토닌 효능제 및 길항제로서의 치환된 피리도인돌
AU2002248216A1 (en)	2003-02-06	Pyrazinoquinoxaline derivatives as serotonin agonists and antagonists
US6780862B2 (en)	2004-08-24	Aryl and aminoaryl substituted serotonin receptor agonist and antagonist ligands
AU2002246725A1 (en)	2002-08-06	Aryl and aminoaryl substituted serotonin receptor agonist and antagonist ligands