RU2531274C2 - Феноксиметильные гетероциклические соединения - Google Patents

Феноксиметильные гетероциклические соединения Download PDF

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Publication number: RU2531274C2
Authority: RU; Russia
Prior art keywords: cyclopropyl; mmol; imidazo; alkyl; phenyl
Prior art date: 2009-05-07

Application number

RU2011149637/04A

Other languages

English (en)

Russian (ru)

Other versions

RU2011149637A (ru

Inventor

Гидеон ШАПИРО

Эми Рипка

Ричард ЧЕСУОРТ

Original Assignee

Энвиво Фармасьютикалз, Инк.

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.)

2009-05-07

Filing date

2009-12-18

Publication date

2014-10-20

2009-12-18 Application filed by Энвиво Фармасьютикалз, Инк. filed Critical Энвиво Фармасьютикалз, Инк.

2013-06-20 Publication of RU2011149637A publication Critical patent/RU2011149637A/ru

2014-10-20 Application granted granted Critical

2014-10-20 Publication of RU2531274C2 publication Critical patent/RU2531274C2/ru

Links

-1 Phenoxymethyl heterocyclic compounds Chemical class 0.000 title claims abstract description 171
150000001875 compounds Chemical class 0.000 claims abstract description 81
125000005843 halogen group Chemical group 0.000 claims abstract description 27
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
238000000034 method Methods 0.000 claims abstract description 23
150000003839 salts Chemical class 0.000 claims abstract description 17
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 14
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 12
125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
208000015114 central nervous system disease Diseases 0.000 claims abstract 2
230000002401 inhibitory effect Effects 0.000 claims abstract 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 81
125000001424 substituent group Chemical group 0.000 claims description 26
201000000980 schizophrenia Diseases 0.000 claims description 16
208000008589 Obesity Diseases 0.000 claims description 8
235000020824 obesity Nutrition 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
208000023105 Huntington disease Diseases 0.000 claims description 7
208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
206010043118 Tardive Dyskinesia Diseases 0.000 claims description 4
208000030814 Eating disease Diseases 0.000 claims description 3
208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
206010034158 Pathological gambling Diseases 0.000 claims description 3
235000014632 disordered eating Nutrition 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
230000000632 dystonic effect Effects 0.000 claims description 3
201000003631 narcolepsy Diseases 0.000 claims description 3
208000012201 sexual and gender identity disease Diseases 0.000 claims description 3
208000015891 sexual disease Diseases 0.000 claims description 3
208000019116 sleep disease Diseases 0.000 claims description 3
230000005586 smoking cessation Effects 0.000 claims description 3
208000019022 Mood disease Diseases 0.000 claims description 2
206010012601 diabetes mellitus Diseases 0.000 claims description 2
ZGGFWJNIADZKOR-UHFFFAOYSA-N 4-[4-(imidazo[1,2-b]pyridazin-2-ylmethoxy)phenyl]-2,2-dimethyl-5-pyridin-4-ylfuran-3-one Chemical compound C=1C=C(OCC=2N=C3C=CC=NN3C=2)C=CC=1C=1C(=O)C(C)(C)OC=1C1=CC=NC=C1 ZGGFWJNIADZKOR-UHFFFAOYSA-N 0.000 claims 1
208000020925 Bipolar disease Diseases 0.000 claims 1
125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims 1
239000003814 drug Substances 0.000 abstract description 27
230000000694 effects Effects 0.000 abstract description 13
239000000126 substance Substances 0.000 abstract description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
239000000243 solution Substances 0.000 description 117
239000000203 mixture Substances 0.000 description 89
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
239000011541 reaction mixture Substances 0.000 description 86
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 72
239000007787 solid Substances 0.000 description 72
235000019439 ethyl acetate Nutrition 0.000 description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
238000006243 chemical reaction Methods 0.000 description 52
238000005481 NMR spectroscopy Methods 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
125000000217 alkyl group Chemical group 0.000 description 36
238000001819 mass spectrum Methods 0.000 description 35
239000000284 extract Substances 0.000 description 34
239000012299 nitrogen atmosphere Substances 0.000 description 34
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
238000004128 high performance liquid chromatography Methods 0.000 description 32
239000000741 silica gel Substances 0.000 description 31
229910002027 silica gel Inorganic materials 0.000 description 31
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 30
238000003818 flash chromatography Methods 0.000 description 30
229910052938 sodium sulfate Inorganic materials 0.000 description 30
235000011152 sodium sulphate Nutrition 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 25
125000001072 heteroaryl group Chemical group 0.000 description 24
238000003756 stirring Methods 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
238000012360 testing method Methods 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
125000000753 cycloalkyl group Chemical group 0.000 description 21
229940079593 drug Drugs 0.000 description 21
239000012267 brine Substances 0.000 description 19
239000011734 sodium Substances 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
125000004429 atom Chemical group 0.000 description 18
125000003118 aryl group Chemical group 0.000 description 17
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
125000000592 heterocycloalkyl group Chemical group 0.000 description 16
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
125000004183 alkoxy alkyl group Chemical group 0.000 description 14
125000004390 alkyl sulfonyl group Chemical group 0.000 description 14
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
238000002347 injection Methods 0.000 description 14
239000007924 injection Substances 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 14
239000012044 organic layer Substances 0.000 description 14
229910000024 caesium carbonate Inorganic materials 0.000 description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
235000002639 sodium chloride Nutrition 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
LMXYGAVAHBJETI-UHFFFAOYSA-N 4-(4-hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3-one Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(O)=CC=2)C(=O)C(C)(C)O1 LMXYGAVAHBJETI-UHFFFAOYSA-N 0.000 description 12
125000003545 alkoxy group Chemical group 0.000 description 12
239000012298 atmosphere Substances 0.000 description 12
229940098779 methanesulfonic acid Drugs 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
239000000164 antipsychotic agent Substances 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
208000035475 disorder Diseases 0.000 description 10
239000000725 suspension Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
239000003826 tablet Substances 0.000 description 9
SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 8
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
125000003282 alkyl amino group Chemical group 0.000 description 8
125000005605 benzo group Chemical group 0.000 description 8
210000004556 brain Anatomy 0.000 description 8
125000005112 cycloalkylalkoxy group Chemical group 0.000 description 8
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 8
239000007788 liquid Substances 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
239000002904 solvent Substances 0.000 description 8
208000024891 symptom Diseases 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
CHLICZRVGGXEOD-UHFFFAOYSA-N Cc(cc1)ccc1OC Chemical compound Cc(cc1)ccc1OC CHLICZRVGGXEOD-UHFFFAOYSA-N 0.000 description 7
125000003710 aryl alkyl group Chemical group 0.000 description 7
210000003169 central nervous system Anatomy 0.000 description 7
239000012043 crude product Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
125000005412 pyrazyl group Chemical group 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
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 description 7
229910052717 sulfur Inorganic materials 0.000 description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 6
MHHSOUOHZKOJSR-UHFFFAOYSA-N 4-[3-(4-hydroxyphenyl)-5,5-dimethyl-4-oxofuran-2-yl]benzonitrile Chemical compound O=C1C(C)(C)OC(C=2C=CC(=CC=2)C#N)=C1C1=CC=C(O)C=C1 MHHSOUOHZKOJSR-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
208000028017 Psychotic disease Diseases 0.000 description 6
125000005083 alkoxyalkoxy group Chemical group 0.000 description 6
239000007900 aqueous suspension Substances 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
125000004663 dialkyl amino group Chemical group 0.000 description 6
239000002552 dosage form Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
238000009472 formulation Methods 0.000 description 6
125000004446 heteroarylalkyl group Chemical group 0.000 description 6
229910052739 hydrogen Inorganic materials 0.000 description 6
239000012071 phase Substances 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
LBCREEUWXFNSAC-UHFFFAOYSA-N 2-(chloromethyl)imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC(CCl)=CN21 LBCREEUWXFNSAC-UHFFFAOYSA-N 0.000 description 5
FEUFGVKXORXZCI-UHFFFAOYSA-N 4-(5,5-dimethyl-4-oxofuran-2-yl)benzonitrile Chemical compound O=C1C(C)(C)OC(C=2C=CC(=CC=2)C#N)=C1 FEUFGVKXORXZCI-UHFFFAOYSA-N 0.000 description 5
GPFTVIIACHNMNI-UHFFFAOYSA-N 4-[4-(imidazo[1,2-a]pyridin-2-ylmethoxy)phenyl]-5-(4-methoxyphenyl)-2,2-dimethylfuran-3-one Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(OCC=3N=C4C=CC=CN4C=3)=CC=2)C(=O)C(C)(C)O1 GPFTVIIACHNMNI-UHFFFAOYSA-N 0.000 description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
IFZRTIRNCMQNFZ-UHFFFAOYSA-N 5-(4-methoxyphenyl)-2,2-dimethyl-4-[4-[(5-methylpyridin-2-yl)methoxy]phenyl]furan-3-one Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(OCC=3N=CC(C)=CC=3)=CC=2)C(=O)C(C)(C)O1 IFZRTIRNCMQNFZ-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
239000000443 aerosol Substances 0.000 description 5
125000003368 amide group Chemical group 0.000 description 5
125000004104 aryloxy group Chemical group 0.000 description 5
239000003693 atypical antipsychotic agent Substances 0.000 description 5
229940127236 atypical antipsychotics Drugs 0.000 description 5
239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
125000000000 cycloalkoxy group Chemical group 0.000 description 5
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
235000014113 dietary fatty acids Nutrition 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000000194 fatty acid Substances 0.000 description 5
229930195729 fatty acid Natural products 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
239000000499 gel Substances 0.000 description 5
125000005553 heteroaryloxy group Chemical group 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
238000001990 intravenous administration Methods 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000003755 preservative agent Substances 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
125000004001 thioalkyl group Chemical group 0.000 description 5
238000005406 washing Methods 0.000 description 5
239000000080 wetting agent Substances 0.000 description 5
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
KNBUWUONENIUDS-UHFFFAOYSA-N 2-(chloromethyl)-3,5-dimethylpyridine Chemical compound CC1=CN=C(CCl)C(C)=C1 KNBUWUONENIUDS-UHFFFAOYSA-N 0.000 description 4
MXOPKPMEGUYUCV-UHFFFAOYSA-N 2-(chloromethyl)-5-methylpyridine Chemical compound CC1=CC=C(CCl)N=C1 MXOPKPMEGUYUCV-UHFFFAOYSA-N 0.000 description 4
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
VZEFBYIBQRLFAX-UHFFFAOYSA-N 4-[3-[4-(imidazo[1,2-a]pyridin-2-ylmethoxy)phenyl]-5,5-dimethyl-4-oxofuran-2-yl]benzonitrile Chemical compound C=1C=C(OCC=2N=C3C=CC=CN3C=2)C=CC=1C=1C(=O)C(C)(C)OC=1C1=CC=C(C#N)C=C1 VZEFBYIBQRLFAX-UHFFFAOYSA-N 0.000 description 4
SQSONOMEPOTDLQ-UHFFFAOYSA-N 4-[4-(imidazo[1,2-b]pyridazin-2-ylmethoxy)phenyl]-5-(4-methoxyphenyl)-2,2-dimethylfuran-3-one Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC(OCC=3N=C4C=CC=NN4C=3)=CC=2)C(=O)C(C)(C)O1 SQSONOMEPOTDLQ-UHFFFAOYSA-N 0.000 description 4
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ZCEFMSGNAOIBOU-UHFFFAOYSA-N n-methoxy-n-methylpyridine-4-carboxamide Chemical compound CON(C)C(=O)C1=CC=NC=C1 ZCEFMSGNAOIBOU-UHFFFAOYSA-N 0.000 description 1
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URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
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GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 description 1
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WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
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150000003536 tetrazoles Chemical class 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
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239000010409 thin film Substances 0.000 description 1
HBDDRESWUAFAHY-UHFFFAOYSA-N thiomorpholin-3-one Chemical compound O=C1CSCCN1 HBDDRESWUAFAHY-UHFFFAOYSA-N 0.000 description 1
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210000000211 third ventricle Anatomy 0.000 description 1
238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
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239000004408 titanium dioxide Substances 0.000 description 1
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208000018724 torsion dystonia Diseases 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
150000003628 tricarboxylic acids Chemical class 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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150000003751 zinc Chemical class 0.000 description 1
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MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

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

RU2011149637/04A 2009-05-07 2009-12-18 Феноксиметильные гетероциклические соединения RU2531274C2 (ru)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US17641309P	2009-05-07	2009-05-07
US61/176,413		2009-05-07
PCT/US2009/068644 WO2010128995A1 (en)	2009-05-07	2009-12-18	Phenoxymethyl heterocyclic compounds

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RU2531274C2 true RU2531274C2 (ru)	2014-10-20

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US (3)	US8343973B2 (2)
EP (3)	EP2617420B1 (2)
JP (2)	JP5628902B2 (2)
KR (1)	KR101662699B1 (2)
CN (2)	CN105125547A (2)
AU (1)	AU2009345802B2 (2)
BR (1)	BRPI0924617A8 (2)
CA (1)	CA2761032A1 (2)
CL (1)	CL2011002792A1 (2)
CO (1)	CO6460744A2 (2)
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RU2011149637A (ru)	2013-06-20
IL216149A0 (en)	2012-01-31
RS52838B (sr)	2013-10-31
PH12013501321B1 (en)	2014-08-27
HRP20130482T1 (en)	2013-08-31
PH12013501321A1 (en)	2014-08-27
NZ596753A (en)	2013-09-27
ME02375B (me)	2016-06-20
AU2009345802B2 (en)	2016-05-26
EP3020716A1 (en)	2016-05-18
MY183910A (en)	2021-03-17
IL244059A0 (en)	2016-04-21
SMT201300070B (it)	2013-09-06
SMT201600031B (it)	2016-02-25
PT2617420E (pt)	2015-12-18
CR20110648A (es)	2012-03-28
CL2011002792A1 (es)	2012-06-01
ECSP11011479A (es)	2011-12-30
EP2427454B1 (en)	2013-03-20
JP2012526107A (ja)	2012-10-25
PT2427454E (pt)	2013-06-20
US20130143888A1 (en)	2013-06-06
KR101662699B1 (ko)	2016-10-05
AU2009345802A1 (en)	2011-12-15
RS54529B1 (sr)	2016-06-30
PL2617420T3 (pl)	2016-04-29
MX2011011755A (es)	2012-03-16
DK2617420T3 (da)	2015-12-07
HK1186981A1 (en)	2014-03-28
HRP20151273T1 (hr)	2016-01-29
ES2409404T3 (es)	2013-06-26
EP2617420B1 (en)	2015-09-23
CN102459242B (zh)	2015-08-26
CA2761032A1 (en)	2010-11-11
SG175900A1 (en)	2011-12-29
HUE026238T2 (en)	2016-06-28
ES2554788T3 (es)	2015-12-23
PE20120900A1 (es)	2012-08-14
WO2010128995A1 (en)	2010-11-11
BRPI0924617A2 (2)	2017-07-11
HK1167402A1 (en)	2012-11-30
US20150322069A1 (en)	2015-11-12
US20100292238A1 (en)	2010-11-18
EP2427454A1 (en)	2012-03-14
JP5943053B2 (ja)	2016-06-29
CO6460744A2 (es)	2012-06-15
ZA201108920B (en)	2012-08-29
PL2427454T3 (pl)	2013-09-30
US8343973B2 (en)	2013-01-01
IL216149A (en)	2016-02-29
BRPI0924617A8 (pt)	2017-10-03
SI2427454T1 (sl)	2013-08-30
US8946222B2 (en)	2015-02-03
JP2015038112A (ja)	2015-02-26
JP5628902B2 (ja)	2014-11-19
EP2617420A1 (en)	2013-07-24
SI2617420T1 (sl)	2016-02-29
KR20120027268A (ko)	2012-03-21
CN102459242A (zh)	2012-05-16
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Publication	Publication Date	Title
JP5820921B2 (ja)	2015-11-24	１，２−二置換複素環式化合物
EP2427454B1 (en)	2013-03-20	Phenoxymethyl heterocyclic compounds
HK1167402B (en)	2013-12-13	Phenoxymethyl heterocyclic compounds
HK1186981B (en)	2016-05-20	Phenoxymethyl heterocyclic compounds