ZA200410057B - 1-Ä(Indol-3-yl) carbonylÜpiperazine derivatives. - Google Patents

1-Ä(Indol-3-yl) carbonylÜpiperazine derivatives. Download PDF

Info

Publication number: ZA200410057B
Authority: ZA; South Africa
Prior art keywords: indol; carbonyl; formula; alkyl; methoxy
Prior art date: 2002-06-21

Application number

ZA200410057A

Other languages

English (en)

Inventor

Phillip Martin Cowley

Jason Tierney

Julia Adam-Worrall

Wilson Caulfield

James Cairns

Mark York

Original Assignee

Akzo Nobel Nv

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.)

2002-06-21

Filing date

2004-12-13

Publication date

2005-10-20

2004-12-13 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2005-10-20 Publication of ZA200410057B publication Critical patent/ZA200410057B/en

Links

125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 title claims description 13
150000001875 compounds Chemical class 0.000 claims description 59
239000000203 mixture Substances 0.000 claims description 29
238000000034 method Methods 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 19
208000002193 Pain Diseases 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 16
FBXWDVALKBNEJV-UHFFFAOYSA-N 1h-indol-3-yl(piperazin-1-yl)methanone Chemical class C=1NC2=CC=CC=C2C=1C(=O)N1CCNCC1 FBXWDVALKBNEJV-UHFFFAOYSA-N 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
238000002360 preparation method Methods 0.000 claims description 2
239000000126 substance Substances 0.000 claims 5
125000005843 halogen group Chemical group 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
238000002451 electron ionisation mass spectrometry Methods 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
210000004027 cell Anatomy 0.000 description 14
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
-1 INDOL-3-YL Chemical class 0.000 description 11
239000003557 cannabinoid Substances 0.000 description 11
229930003827 cannabinoid Natural products 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000000556 agonist Substances 0.000 description 8
230000027455 binding Effects 0.000 description 7
230000014509 gene expression Effects 0.000 description 7
108020004414 DNA Proteins 0.000 description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
FSOPPXYMWZOKRM-UHFFFAOYSA-N 7-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1NC=C2 FSOPPXYMWZOKRM-UHFFFAOYSA-N 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 5
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
239000012458 free base Substances 0.000 description 5
230000004044 response Effects 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000011976 maleic acid Substances 0.000 description 4
238000012986 modification Methods 0.000 description 4
230000004048 modification Effects 0.000 description 4
229940005483 opioid analgesics Drugs 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
102000018208 Cannabinoid Receptor Human genes 0.000 description 3
108050007331 Cannabinoid receptor Proteins 0.000 description 3
102100033868 Cannabinoid receptor 1 Human genes 0.000 description 3
101710187010 Cannabinoid receptor 1 Proteins 0.000 description 3
102100036214 Cannabinoid receptor 2 Human genes 0.000 description 3
101710187022 Cannabinoid receptor 2 Proteins 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
208000008238 Muscle Spasticity Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
108700008625 Reporter Genes Proteins 0.000 description 3
239000013543 active substance Substances 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
238000003556 assay Methods 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
VROBVTOKXNHTBI-UHFFFAOYSA-N cyclopentylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCCC1 VROBVTOKXNHTBI-UHFFFAOYSA-N 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
150000004820 halides Chemical group 0.000 description 3
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
201000006417 multiple sclerosis Diseases 0.000 description 3
208000004296 neuralgia Diseases 0.000 description 3
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229910052757 nitrogen Inorganic materials 0.000 description 3
239000003921 oil Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
208000023504 respiratory system disease Diseases 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
208000018198 spasticity Diseases 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
IBCZLOMXNJRQBF-UHFFFAOYSA-N 1-(1-cyclohexylethylsulfonyl)-4-methylbenzene Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)C(C)C1CCCCC1 IBCZLOMXNJRQBF-UHFFFAOYSA-N 0.000 description 2
NRUJFIWNKXQLBY-UHFFFAOYSA-N 1-(cyclohexylmethyl)-5-fluoroindole Chemical compound C1=CC2=CC(F)=CC=C2N1CC1CCCCC1 NRUJFIWNKXQLBY-UHFFFAOYSA-N 0.000 description 2
LEXVLCRGSBTKBD-UHFFFAOYSA-N 1-(cyclohexylmethyl)-7-methoxyindole-3-carboxylic acid Chemical compound C1=2C(OC)=CC=CC=2C(C(O)=O)=CN1CC1CCCCC1 LEXVLCRGSBTKBD-UHFFFAOYSA-N 0.000 description 2
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 2
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241000282412 Homo Species 0.000 description 2
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
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DXGTUUQHTDOFFQ-UHFFFAOYSA-N [N].C1=CC=C2NC=CC2=C1 Chemical group [N].C1=CC=C2NC=CC2=C1 DXGTUUQHTDOFFQ-UHFFFAOYSA-N 0.000 description 2
230000010933 acylation Effects 0.000 description 2
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239000008346 aqueous phase Substances 0.000 description 2
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UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 2
239000003520 cannabinoid receptor affecting agent Substances 0.000 description 2
239000003537 cannabinoid receptor agonist Substances 0.000 description 2
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210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
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230000005494 condensation Effects 0.000 description 2
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239000003480 eluent Substances 0.000 description 2
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- C07—ORGANIC CHEMISTRY
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Engineering & Computer Science (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Rheumatology (AREA)
Ophthalmology & Optometry (AREA)
Pulmonology (AREA)
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Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Anesthesiology (AREA)
Immunology (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
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Indole Compounds (AREA)

ZA200410057A 2002-06-21 2004-12-13 1-Ä(Indol-3-yl) carbonylÜpiperazine derivatives. ZA200410057B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP02077505		2002-06-21

Publications (1)

Publication Number	Publication Date
ZA200410057B true ZA200410057B (en)	2005-10-20

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ID=29797228

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200410057A ZA200410057B (en)	2002-06-21	2004-12-13	1-Ä(Indol-3-yl) carbonylÜpiperazine derivatives.

Country Status (32)

Country	Link
US (1)	US7304064B2 (de)
EP (1)	EP1549637B1 (de)
JP (1)	JP4408804B2 (de)
KR (1)	KR20050009755A (de)
CN (1)	CN1298716C (de)
AR (1)	AR040274A1 (de)
AT (1)	ATE361290T1 (de)
AU (1)	AU2003250245B2 (de)
BR (1)	BR0311960A (de)
CA (1)	CA2490141C (de)
CO (1)	CO5680419A2 (de)
CY (1)	CY1107677T1 (de)
DE (1)	DE60313640T2 (de)
DK (1)	DK1549637T3 (de)
EC (1)	ECSP045503A (de)
ES (1)	ES2285183T3 (de)
HR (1)	HRP20041186A2 (de)
IL (1)	IL165572A0 (de)
IS (1)	IS2443B (de)
MX (1)	MXPA04012856A (de)
NO (1)	NO20045351L (de)
NZ (1)	NZ537143A (de)
PE (1)	PE20040578A1 (de)
PL (1)	PL375152A1 (de)
PT (1)	PT1549637E (de)
RS (1)	RS111104A (de)
RU (1)	RU2318821C2 (de)
SI (1)	SI1549637T1 (de)
TW (1)	TW200402417A (de)
UA (1)	UA78317C2 (de)
WO (1)	WO2004000832A1 (de)
ZA (1)	ZA200410057B (de)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TWI242015B (en)	1999-11-29	2005-10-21	Akzo Nobel Nv	6-mercapto-cyclodextrin derivatives: reversal agents for drug-induced neuromuscular block
ATE375349T1 (de)	2002-08-02	2007-10-15	Merck & Co Inc	Substituierte furo(2,3-b)pyridin derivate
DE10253426B4 (de)	2002-11-15	2005-09-22	Elbion Ag	Neue Hydroxyindole, deren Verwendung als Inhibitoren der Phosphodiesterase 4 und Verfahren zu deren Herstellung
DE602004005893T2 (de)	2003-12-17	2007-09-06	N.V. Organon	Trizyklische 1-((3-indol-3-yl)-carbonyl)-piperazin-derivate als cannabinoid-cb1-rezeptoragonisten
TWI330635B (en) *	2004-03-05	2010-09-21	Organon Nv	(indol-3-yl)-heterocycle derivatives
US20090029984A1 (en) *	2005-07-11	2009-01-29	N.V. Organon	Synergistic combination for the treatment of pain (cannabinoid receptor agonist and opioid receptor agonist)
CN102295636A (zh) *	2005-07-29	2011-12-28	弗·哈夫曼-拉罗切有限公司	吲哚-3-基-羰基-哌啶和哌嗪衍生物
TW200745096A (en) *	2005-08-23	2007-12-16	Organon Nv	Indole derivatives
US7763732B2 (en)	2005-08-24	2010-07-27	N.V. Organon	Indole derivatives
CA2623525A1 (en) *	2005-09-23	2007-04-05	Janssen Pharmaceutica N.V.	Tetrahydro-indazolyl cannabinoid modulators
TW200848417A (en)	2007-02-22	2008-12-16	Organon Nv	Indole derivatives
RU2387642C2 (ru)	2007-10-31	2010-04-27	Общество С Ограниченной Ответственностью "Бинатех"	Производные 5-замещенных индол-3-карбоновой кислоты, обладающие противовирусной активностью, способ их получения и применение
GB201106817D0 (en) *	2011-04-21	2011-06-01	Astex Therapeutics Ltd	New compound
CN115368356B (zh)	2013-12-20	2025-05-09	阿斯特克斯治疗有限公司	双环杂环化合物及其治疗用途
EP3737680A1 (de)	2018-01-08	2020-11-18	F. Hoffmann-La Roche AG	Octahydropyrido[1,2-alpha]pyrazine als magl-inhibitoren
CN108752342A (zh) *	2018-08-17	2018-11-06	西安瑞联新材料股份有限公司	1-H-吡啶并[1,2-a]-6-氢吡嗪-1,4-二酮的制备方法
CN111100063B (zh) *	2018-10-25	2022-05-17	南京药石科技股份有限公司	一种合成2-氟甲基取代的吡咯烷、哌啶以及哌嗪衍生物的制备方法
CN114072405A (zh)	2019-07-03	2022-02-18	豪夫迈·罗氏有限公司	杂环单酰基甘油脂肪酶(magl)抑制剂
KR20220034104A (ko)	2019-07-09	2022-03-17	에프. 호프만-라 로슈 아게	신규 헤테로고리 화합물

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9203454A (es) *	1989-12-28	1992-08-01	Upjohn Co	Compuestos anti sida diaromaticos substituidos.
WO1998006715A1 (en)	1996-08-09	1998-02-19	Smithkline Beecham Corporation	Novel piperazine containing compounds
AU1887401A (en) *	1999-12-14	2001-06-25	Nippon Shinyaku Co. Ltd.	Medicinal composition
JP2004502642A (ja) *	2000-02-11	2004-01-29	ブリストル−マイヤーズ　スクイブ　カンパニー	カンナビノイドレセプターモジュレーター、それらの製造方法、および呼吸系および非呼吸系疾患の処置のためのカンナビノイドレセプターモジュレーターの使用

2003
- 2003-06-11 TW TW092115888A patent/TW200402417A/zh unknown
- 2003-06-13 RS YUP-1111/04A patent/RS111104A/sr unknown
- 2003-06-13 DK DK03760704T patent/DK1549637T3/da active
- 2003-06-13 AT AT03760704T patent/ATE361290T1/de active
- 2003-06-13 DE DE60313640T patent/DE60313640T2/de not_active Expired - Lifetime
- 2003-06-13 PT PT03760704T patent/PT1549637E/pt unknown
- 2003-06-13 RU RU2005101349/04A patent/RU2318821C2/ru not_active IP Right Cessation
- 2003-06-13 HR HR20041186A patent/HRP20041186A2/xx not_active Application Discontinuation
- 2003-06-13 US US10/518,279 patent/US7304064B2/en not_active Expired - Fee Related
- 2003-06-13 AU AU2003250245A patent/AU2003250245B2/en not_active Ceased
- 2003-06-13 WO PCT/EP2003/050226 patent/WO2004000832A1/en not_active Ceased
- 2003-06-13 BR BR0311960-2A patent/BR0311960A/pt not_active IP Right Cessation
- 2003-06-13 NZ NZ537143A patent/NZ537143A/en unknown
- 2003-06-13 CN CNB038170906A patent/CN1298716C/zh not_active Expired - Fee Related
- 2003-06-13 JP JP2004514874A patent/JP4408804B2/ja not_active Expired - Fee Related
- 2003-06-13 KR KR10-2004-7020734A patent/KR20050009755A/ko not_active Ceased
- 2003-06-13 UA UA20041210112A patent/UA78317C2/uk unknown
- 2003-06-13 EP EP03760704A patent/EP1549637B1/de not_active Expired - Lifetime
- 2003-06-13 SI SI200330855T patent/SI1549637T1/sl unknown
- 2003-06-13 CA CA2490141A patent/CA2490141C/en not_active Expired - Fee Related
- 2003-06-13 PL PL03375152A patent/PL375152A1/xx not_active Application Discontinuation
- 2003-06-13 MX MXPA04012856A patent/MXPA04012856A/es active IP Right Grant
- 2003-06-13 ES ES03760704T patent/ES2285183T3/es not_active Expired - Lifetime
- 2003-06-18 PE PE2003000614A patent/PE20040578A1/es not_active Application Discontinuation
- 2003-06-19 AR ARP030102174A patent/AR040274A1/es unknown
2004
- 2004-12-06 IL IL16557204A patent/IL165572A0/xx unknown
- 2004-12-07 NO NO20045351A patent/NO20045351L/no not_active Application Discontinuation
- 2004-12-09 IS IS7590A patent/IS2443B/is unknown
- 2004-12-13 ZA ZA200410057A patent/ZA200410057B/en unknown
- 2004-12-21 EC EC2004005503A patent/ECSP045503A/es unknown
2005
- 2005-01-20 CO CO05004561A patent/CO5680419A2/es not_active Application Discontinuation
2007
- 2007-06-18 CY CY20071100804T patent/CY1107677T1/el unknown

Also Published As

Publication number	Publication date
IS7590A (is)	2004-12-09
BR0311960A (pt)	2005-03-22
AR040274A1 (es)	2005-03-23
IS2443B (is)	2008-11-15
AU2003250245B2 (en)	2008-07-03
PT1549637E (pt)	2007-05-31
DK1549637T3 (da)	2007-07-16
PE20040578A1 (es)	2004-09-15
WO2004000832A1 (en)	2003-12-31
SI1549637T1 (sl)	2007-10-31
CN1298716C (zh)	2007-02-07
CO5680419A2 (es)	2006-09-29
DE60313640T2 (de)	2007-12-27
US20050250760A1 (en)	2005-11-10
JP4408804B2 (ja)	2010-02-03
RU2005101349A (ru)	2005-06-27
AU2003250245A1 (en)	2004-01-06
JP2005533801A (ja)	2005-11-10
RU2318821C2 (ru)	2008-03-10
CN1668611A (zh)	2005-09-14
DE60313640D1 (de)	2007-06-14
US7304064B2 (en)	2007-12-04
RS111104A (sr)	2007-02-05
KR20050009755A (ko)	2005-01-25
CA2490141C (en)	2011-01-25
HRP20041186A2 (en)	2005-06-30
ES2285183T3 (es)	2007-11-16
ATE361290T1 (de)	2007-05-15
PL375152A1 (en)	2005-11-28
CA2490141A1 (en)	2003-12-31
IL165572A0 (en)	2006-01-15
MXPA04012856A (es)	2005-03-31
HK1076630A1 (en)	2006-01-20
TW200402417A (en)	2004-02-16
NZ537143A (en)	2005-05-27
ECSP045503A (es)	2005-03-10
EP1549637B1 (de)	2007-05-02
NO20045351L (no)	2005-01-20
EP1549637A1 (de)	2005-07-06
CY1107677T1 (el)	2013-04-18
UA78317C2 (en)	2007-03-15

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JP2978566B2 (ja)	1999-11-15	ノイロキニンレセプター拮抗薬としての５−アザビシクロ［３．１．０］ヘキシルアルキル−２−ピペリドンおよび−グルタルイミド
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US5661169A (en)	1997-08-26	1-benzyl-1,3-dihydro-2H-benzimidazol-2-one derivatives, their preparation and the pharmaceutical compositions containing them
KR20070083843A (ko)	2007-08-24	아자인돌 카르복사미드
EP2588458B1 (de)	2014-06-04	Neuartige tetrahydrochinolinderivate
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JP2005531561A (ja)	2005-10-20	イミダゾール化合物およびα−２−アドレナリン作動性受容体としてのその使用