TWI236471B - Substituted piperazine compounds - Google Patents

Substituted piperazine compounds Download PDF

Info

Publication number: TWI236471B
Authority: TW; Taiwan
Prior art keywords: group; hydrogen; scope; alkyl; patent application
Prior art date: 2000-02-22

Application number

TW090104080A

Other languages

English (en)

Chinese (zh)

Inventor

Jeff Zablocki

Elfatih Elzein

Grigory Nudelman

Tim Marquart

Vaibhav Varkhedkar

Original Assignee

Cv Therapeutics Inc

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.)

2000-02-22

Filing date

2001-04-13

Publication date

2005-07-21

2001-04-13 Application filed by Cv Therapeutics Inc filed Critical Cv Therapeutics Inc

2005-07-21 Application granted granted Critical

2005-07-21 Publication of TWI236471B publication Critical patent/TWI236471B/zh

Links

150000004885 piperazines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 140
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 20
201000010099 disease Diseases 0.000 claims abstract description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
210000002027 skeletal muscle Anatomy 0.000 claims abstract description 12
208000010125 myocardial infarction Diseases 0.000 claims abstract description 11
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 9
210000001519 tissue Anatomy 0.000 claims abstract description 8
208000014674 injury Diseases 0.000 claims abstract description 7
210000000056 organ Anatomy 0.000 claims abstract description 7
208000007718 Stable Angina Diseases 0.000 claims abstract description 6
206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 6
230000009885 systemic effect Effects 0.000 claims abstract description 6
210000003205 muscle Anatomy 0.000 claims abstract description 5
230000001746 atrial effect Effects 0.000 claims abstract description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims abstract description 3
230000008733 trauma Effects 0.000 claims abstract description 3
125000000217 alkyl group Chemical group 0.000 claims description 187
229910052739 hydrogen Inorganic materials 0.000 claims description 157
239000001257 hydrogen Substances 0.000 claims description 156
-1 picolin compound Chemical class 0.000 claims description 148
125000003118 aryl group Chemical group 0.000 claims description 119
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 89
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 63
125000001072 heteroaryl group Chemical group 0.000 claims description 61
150000002431 hydrogen Chemical class 0.000 claims description 60
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 52
125000005843 halogen group Chemical group 0.000 claims description 50
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
125000000753 cycloalkyl group Chemical group 0.000 claims description 43
WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 claims description 41
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
125000001424 substituent group Chemical group 0.000 claims description 41
125000004432 carbon atom Chemical group C* 0.000 claims description 38
125000000623 heterocyclic group Chemical group 0.000 claims description 33
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 30
101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 claims description 29
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 23
239000000203 mixture Substances 0.000 claims description 23
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 21
125000004076 pyridyl group Chemical group 0.000 claims description 21
QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 19
229910052799 carbon Inorganic materials 0.000 claims description 18
150000001412 amines Chemical class 0.000 claims description 17
125000004122 cyclic group Chemical group 0.000 claims description 13
239000008194 pharmaceutical composition Substances 0.000 claims description 13
125000000304 alkynyl group Chemical group 0.000 claims description 11
OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 10
NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
150000003254 radicals Chemical class 0.000 claims description 7
206010040560 shock Diseases 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
238000002054 transplantation Methods 0.000 claims description 5
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
229910052786 argon Inorganic materials 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 3
239000002775 capsule Substances 0.000 claims description 3
230000004927 fusion Effects 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000006384 methylpyridyl group Chemical group 0.000 claims description 3
OAPVPGPVBZRARK-UHFFFAOYSA-N n-ethyl-2,6-dimethylaniline Chemical compound CCNC1=C(C)C=CC=C1C OAPVPGPVBZRARK-UHFFFAOYSA-N 0.000 claims description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
230000000747 cardiac effect Effects 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims 3
241000282376 Panthera tigris Species 0.000 claims 2
UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 claims 2
150000002220 fluorenes Chemical group 0.000 claims 2
UOKINRKWPYVMSZ-LADGPHEKSA-N (5r,11as)-2-benzyl-5-(3-hydroxyphenyl)-6h-1,2,3,5,11,11a-hexahydro-imidazo[1,5-b]-β-carboline-1,3-dione Chemical compound OC1=CC=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@@H]3N2C(N(CC=2C=CC=CC=2)C3=O)=O)=C1 UOKINRKWPYVMSZ-LADGPHEKSA-N 0.000 claims 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
BGXRAGCQZCSMOT-UHFFFAOYSA-N 1,3-dimethyl-2-phenylbenzene Chemical compound CC1=CC=CC(C)=C1C1=CC=CC=C1 BGXRAGCQZCSMOT-UHFFFAOYSA-N 0.000 claims 1
ZEMLYWMOSZRCQL-UWSZBUKDSA-N 2-[(3r,5r,6s)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2s)-1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]-2-oxopiperidin-3-yl]acetic acid Chemical compound C1([C@@H]2[C@H](N(C([C@@H](CC(O)=O)C2)=O)[C@@H](CC)C(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)=CC=CC(Cl)=C1 ZEMLYWMOSZRCQL-UWSZBUKDSA-N 0.000 claims 1
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
241001498622 Cixius wagneri Species 0.000 claims 1
POECHIXSIXBYKI-UHFFFAOYSA-N N-fluorenylacetamide Chemical compound C1C2=CC=CC=C2C2=C1C(NC(=O)C)=CC=C2 POECHIXSIXBYKI-UHFFFAOYSA-N 0.000 claims 1
241000700159 Rattus Species 0.000 claims 1
101100264226 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) XRN1 gene Proteins 0.000 claims 1
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
210000000988 bone and bone Anatomy 0.000 claims 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 1
OFPZFTWBJUGNGE-UHFFFAOYSA-N cyclopenta-1,3-dien-1-ylbenzene Chemical compound C1C=CC=C1C1=CC=CC=C1 OFPZFTWBJUGNGE-UHFFFAOYSA-N 0.000 claims 1
210000004513 dentition Anatomy 0.000 claims 1
238000009313 farming Methods 0.000 claims 1
NRPTXWYBRKRZES-UHFFFAOYSA-N n-(2,6-dimethylphenyl)acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1C NRPTXWYBRKRZES-UHFFFAOYSA-N 0.000 claims 1
GVRKNSAEOVXHOS-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)acetamide Chemical compound CC(=O)NC1=CC=C(Cl)C=C1F GVRKNSAEOVXHOS-UHFFFAOYSA-N 0.000 claims 1
FLKGOWKSFPYGAX-UHFFFAOYSA-N n-(4-chloro-2-methoxy-5-methylphenyl)acetamide Chemical compound COC1=CC(Cl)=C(C)C=C1NC(C)=O FLKGOWKSFPYGAX-UHFFFAOYSA-N 0.000 claims 1
FWCIAVMWCOEWGF-UHFFFAOYSA-N n-(4-morpholin-4-ylphenyl)acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1N1CCOCC1 FWCIAVMWCOEWGF-UHFFFAOYSA-N 0.000 claims 1
KNVQTRVKSOEHPU-UHFFFAOYSA-N o-Chloroacetanilide Chemical compound CC(=O)NC1=CC=CC=C1Cl KNVQTRVKSOEHPU-UHFFFAOYSA-N 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
230000036346 tooth eruption Effects 0.000 claims 1
125000004360 trifluorophenyl group Chemical group 0.000 claims 1
206010007559 Cardiac failure congestive Diseases 0.000 abstract description 5
230000006378 damage Effects 0.000 abstract description 5
239000002253 acid Substances 0.000 abstract description 4
150000003839 salts Chemical class 0.000 abstract description 4
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238000011049 filling Methods 0.000 description 47
230000002079 cooperative effect Effects 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
229910052757 nitrogen Inorganic materials 0.000 description 18
NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
125000004104 aryloxy group Chemical group 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
125000003545 alkoxy group Chemical group 0.000 description 11
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
125000004414 alkyl thio group Chemical group 0.000 description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
238000006467 substitution reaction Methods 0.000 description 10
CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 8
125000003396 thiol group Chemical class [H]S* 0.000 description 8
230000000694 effects Effects 0.000 description 7
239000002904 solvent Substances 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
239000004202 carbamide Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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150000001448 anilines Chemical class 0.000 description 4
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
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125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 4
RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 4
125000005553 heteroaryloxy group Chemical group 0.000 description 4
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231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 4
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LFQREKVEOMIWQF-UHFFFAOYSA-N ericifolin Natural products COC1=CC(CC=C)=CC(OC2C(C(O)C(O)C(COC(=O)C=3C=C(O)C(O)=C(O)C=3)O2)O)=C1O LFQREKVEOMIWQF-UHFFFAOYSA-N 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
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VXAWCKIQYKXJMD-UHFFFAOYSA-N ethynamine Chemical compound NC#C VXAWCKIQYKXJMD-UHFFFAOYSA-N 0.000 description 1
235000013861 fat-free Nutrition 0.000 description 1
GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
238000003682 fluorination reaction Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000005224 heteroarylcarbonylamino group Chemical group 0.000 description 1
125000005226 heteroaryloxycarbonyl group Chemical group 0.000 description 1
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 description 1
150000007857 hydrazones Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
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125000001041 indolyl group Chemical group 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000009434 installation Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
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230000007803 itching Effects 0.000 description 1
238000011068 loading method Methods 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
230000003387 muscular Effects 0.000 description 1
150000002829 nitrogen Chemical class 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
238000003359 percent control normalization Methods 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
150000003220 pyrenes Chemical class 0.000 description 1
125000001725 pyrenyl group Chemical group 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229960000213 ranolazine Drugs 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
DCQXTYAFFMSNNH-UHFFFAOYSA-M sodium;2-[bis(2-hydroxyethyl)amino]ethanol;acetate Chemical compound [Na+].CC([O-])=O.OCCN(CCO)CCO DCQXTYAFFMSNNH-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
235000021286 stilbenes Nutrition 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
238000005533 tritiation Methods 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P39/06—Free radical scavengers or antioxidants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Neurology (AREA)
Epidemiology (AREA)
Toxicology (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Biochemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicinal Preparation (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
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TW090104080A 2000-02-22 2001-04-13 Substituted piperazine compounds TWI236471B (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date
US18430600P	2000-02-22	2000-02-22
US18445700P	2000-02-22	2000-02-22
US18418200P	2000-02-22	2000-02-22
US20639600P	2000-05-23	2000-05-23
US20926200P	2000-06-05	2000-06-05

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TWI236471B true TWI236471B (en)	2005-07-21

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TW090104080A TWI236471B (en)	2000-02-22	2001-04-13	Substituted piperazine compounds

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EP (1)	EP1259493A2 (es)
JP (2)	JP3980885B2 (es)
KR (1)	KR100595942B1 (es)
CN (1)	CN1404471A (es)
AR (1)	AR029229A1 (es)
AU (2)	AU3862301A (es)
BR (1)	BR0108592A (es)
CA (2)	CA2657986A1 (es)
IL (1)	IL151178A0 (es)
MX (1)	MXPA02008213A (es)
NO (1)	NO324837B1 (es)
NZ (1)	NZ520782A (es)
TW (1)	TWI236471B (es)
WO (1)	WO2001062744A2 (es)

Families Citing this family (11)

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Publication number	Priority date	Publication date	Assignee	Title
HK1048250A1 (zh) *	2000-02-18	2003-03-28	Cv Therapeutics, Inc.	在治疗充血性心力衰竭中使用的部分脂肪酸氧化抑制剂
DK1406898T3 (da)	2001-07-19	2005-05-30	Cv Therapeutics Inc	Substituerede piperazinforbindelser og anvendelse af disse som fedtsyreoxidationsinhibitorer
US7001909B2 (en)	2001-07-19	2006-02-21	Cv Therapeutics, Inc.	Substituted heterocyclic compounds
JP2006510670A (ja) *	2002-12-05	2006-03-30	シーブイ・セラピューティクス・インコーポレイテッド	置換ヘテロ環化合物
EP1806346B1 (en) *	2002-12-05	2009-07-22	Cv Therapeutics, Inc.	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
NZ541069A (en) *	2003-01-03	2008-09-26	Cv Therapeutics Inc	Piperazine derivatives as fatty acid oxidation inhibitors
NZ544449A (en) *	2003-06-23	2008-10-31	Cv Therapeutics Inc	Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors
WO2005061470A1 (en) *	2003-12-18	2005-07-07	Cv Therapeutics, Inc.	1-akan-2-ol substituted piperazine and piperidine compounds
AU2005282492A1 (en) *	2004-09-08	2006-03-16	Gilead Palo Alto, Inc.	Substituted piperazine compounds and their use as fatty acid oxidation inhibitors
CN102875490A (zh) *	2012-10-19	2013-01-16	四川大学	一种用于制备雷诺嗪的合成方法
CN107043361B (zh) *	2017-05-25	2019-07-02	合肥医工医药股份有限公司	治疗心绞痛的化合物、制备方法及用途

Family Cites Families (8)

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Publication number	Priority date	Publication date	Assignee	Title
JPS584774A (ja) *	1981-06-23	1983-01-11	ジヤンセン・フア−マシユ−チカ・ナ−ムロ−ゼ・フエンノ−トシヤツプ	Ｎ−アリ−ル−ピペラジンアルカンアミド類
US4766125A (en) *	1981-06-23	1988-08-23	Janssen Pharmaceutica N.V.	N-aryl-piperazinealkanamides useful for protecting hearts from myocardial injury caused by ischaemia, anoxia or hypoxia
US4567264A (en) *	1983-05-18	1986-01-28	Syntex (U.S.A.) Inc.	Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry
US4558129A (en) *	1983-05-18	1985-12-10	Syntex (U.S.A.) Inc.	Benzodioxanyl-hydroxyethylene-piperazinyl acetanilides which effect calcium entry and β-blockade
FR2552083B1 (fr) *	1983-09-15	1986-05-09	Cerm Cent Europ Rech Mauvernay	Derives de (alkynyloxy-3 hydroxy-2-propyl)-4 piperazinyl-1 n-phenyl acetamide, leur preparation et leur application en therapeutique
EP0714660B1 (en) *	1989-06-23	2002-09-04	Syntex (U.S.A.) LLC	Ranolazine and related piperazines for protecting skeletal muscles
JPH03141258A (ja) *	1989-10-25	1991-06-17	Kowa Co	新規なピペラジン誘導体
HU209723B (en) *	1990-10-31	1994-10-28	Richter Gedeon Vegyeszet	Process for producing of piperazine derivatives

2001
- 2001-02-22 NZ NZ520782A patent/NZ520782A/en unknown
- 2001-02-22 KR KR1020027011014A patent/KR100595942B1/ko not_active Expired - Fee Related
- 2001-02-22 EP EP01911085A patent/EP1259493A2/en not_active Withdrawn
- 2001-02-22 MX MXPA02008213A patent/MXPA02008213A/es active IP Right Grant
- 2001-02-22 CA CA002657986A patent/CA2657986A1/en not_active Abandoned
- 2001-02-22 WO PCT/US2001/005606 patent/WO2001062744A2/en not_active Ceased
- 2001-02-22 JP JP2001562526A patent/JP3980885B2/ja not_active Expired - Lifetime
- 2001-02-22 AU AU3862301A patent/AU3862301A/xx active Pending
- 2001-02-22 CA CA002400176A patent/CA2400176C/en not_active Expired - Fee Related
- 2001-02-22 AU AU2001238623A patent/AU2001238623B2/en not_active Ceased
- 2001-02-22 BR BR0108592-1A patent/BR0108592A/pt not_active Application Discontinuation
- 2001-02-22 IL IL15117801A patent/IL151178A0/xx unknown
- 2001-02-22 AR ARP010100804A patent/AR029229A1/es unknown
- 2001-02-22 CN CN01805442A patent/CN1404471A/zh active Pending
- 2001-04-13 TW TW090104080A patent/TWI236471B/zh not_active IP Right Cessation
2002
- 2002-08-20 NO NO20023954A patent/NO324837B1/no not_active IP Right Cessation
2007
- 2007-01-15 JP JP2007005347A patent/JP2007211009A/ja active Pending

Also Published As

Publication number	Publication date
WO2001062744A3 (en)	2002-02-07
BR0108592A (pt)	2004-06-29
CA2400176A1 (en)	2001-08-30
IL151178A0 (en)	2003-04-10
EP1259493A2 (en)	2002-11-27
JP3980885B2 (ja)	2007-09-26
WO2001062744A2 (en)	2001-08-30
KR20020079893A (ko)	2002-10-19
CA2657986A1 (en)	2001-08-30
KR100595942B1 (ko)	2006-07-03
CA2400176C (en)	2009-04-28
JP2007211009A (ja)	2007-08-23
AR029229A1 (es)	2003-06-18
AU3862301A (en)	2001-09-03
CN1404471A (zh)	2003-03-19
NO324837B1 (no)	2007-12-17
JP2003531116A (ja)	2003-10-21
AU2001238623B2 (en)	2004-09-23
MXPA02008213A (es)	2004-04-05
NO20023954L (no)	2002-09-30
NO20023954D0 (no)	2002-08-20
NZ520782A (en)	2004-03-26

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2011-04-21	MM4A	Annulment or lapse of patent due to non-payment of fees