ZA200504725B - Sipirocyclic cyclohexane derivatives - Google Patents

Sipirocyclic cyclohexane derivatives Download PDF

Info

Publication number: ZA200504725B
Authority: ZA; South Africa
Prior art keywords: unsubstituted; mono; polysubstituted; dimethylamino; alkyl
Prior art date: 2002-11-11

Application number

ZA200504725A

Other languages

English (en)

Inventor

Claudia Hinze

Berned Sundermann

Elmar Friderichs

Babette-Yvonne Koegel

Hans Schick

Birgitta Henkel

Michael Lipkin

Otto Aulenbacher

Stefan Oberboersch

Werner Englberger

Klaus Linz

Helmut Sonnenschein

Valerie S Rose

Original Assignee

Gruenenthal Gmbh

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.)

2002-11-11

Filing date

2005-06-09

Publication date

2006-08-30

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=32185555&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ZA200504725(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2005-06-09 Application filed by Gruenenthal Gmbh filed Critical Gruenenthal Gmbh

2006-08-30 Publication of ZA200504725B publication Critical patent/ZA200504725B/en

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125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 title claims description 24
-1 2-cyanophenyl Chemical group 0.000 claims description 87
125000003118 aryl group Chemical group 0.000 claims description 42
150000001875 compounds Chemical class 0.000 claims description 42
229920006395 saturated elastomer Polymers 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 38
125000001072 heteroaryl group Chemical group 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 30
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 29
239000003814 drug Substances 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
238000000034 method Methods 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 21
238000002360 preparation method Methods 0.000 claims description 18
208000002193 Pain Diseases 0.000 claims description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
125000006239 protecting group Chemical group 0.000 claims description 15
239000000126 substance Substances 0.000 claims description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
150000007513 acids Chemical class 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 12
150000001768 cations Chemical class 0.000 claims description 12
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 12
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 claims description 11
125000005418 aryl aryl group Chemical group 0.000 claims description 11
230000008569 process Effects 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
230000001771 impaired effect Effects 0.000 claims description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 8
230000036407 pain Effects 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 7
230000003444 anaesthetic effect Effects 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
239000002904 solvent Substances 0.000 claims description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
208000024827 Alzheimer disease Diseases 0.000 claims description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
229910006069 SO3H Inorganic materials 0.000 claims description 6
229940005483 opioid analgesics Drugs 0.000 claims description 6
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
208000000094 Chronic Pain Diseases 0.000 claims description 5
208000004296 neuralgia Diseases 0.000 claims description 5
208000021722 neuropathic pain Diseases 0.000 claims description 5
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 5
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
206010012335 Dependence Diseases 0.000 claims description 4
206010012735 Diarrhoea Diseases 0.000 claims description 4
208000004880 Polyuria Diseases 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
206010046543 Urinary incontinence Diseases 0.000 claims description 4
230000001154 acute effect Effects 0.000 claims description 4
208000005298 acute pain Diseases 0.000 claims description 4
238000011260 co-administration Methods 0.000 claims description 4
230000035619 diuresis Effects 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
230000037406 food intake Effects 0.000 claims description 4
235000012631 food intake Nutrition 0.000 claims description 4
229940098779 methanesulfonic acid Drugs 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
230000037023 motor activity Effects 0.000 claims description 4
230000004770 neurodegeneration Effects 0.000 claims description 4
208000015122 neurodegenerative disease Diseases 0.000 claims description 4
230000002981 neuropathic effect Effects 0.000 claims description 4
239000002858 neurotransmitter agent Substances 0.000 claims description 4
230000001777 nootropic effect Effects 0.000 claims description 4
230000028327 secretion Effects 0.000 claims description 4
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
208000019901 Anxiety disease Diseases 0.000 claims description 3
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208000003251 Pruritus Diseases 0.000 claims description 3
206010039966 Senile dementia Diseases 0.000 claims description 3
239000000654 additive Substances 0.000 claims description 3
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
208000022531 anorexia Diseases 0.000 claims description 3
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206010061428 decreased appetite Diseases 0.000 claims description 3
230000002950 deficient Effects 0.000 claims description 3
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RERZNCLIYCABFS-UHFFFAOYSA-N harmaline Chemical compound C1CN=C(C)C2=C1C1=CC=C(OC)C=C1N2 RERZNCLIYCABFS-UHFFFAOYSA-N 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
230000036543 hypotension Effects 0.000 claims description 3
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206010027599 migraine Diseases 0.000 claims description 3
239000003158 myorelaxant agent Substances 0.000 claims description 3
235000020824 obesity Nutrition 0.000 claims description 3
239000000014 opioid analgesic Substances 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
PCEJCVJVVLFKTJ-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;1h-indole Chemical compound C1=CC=C2NC=CC2=C1.OC(=O)CC(O)(C(O)=O)CC(O)=O PCEJCVJVVLFKTJ-UHFFFAOYSA-N 0.000 claims description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
SRCYHILUJAGLAP-UHFFFAOYSA-N C1=CC=CC=2C3=CC=CC=C3CC12.C(CC(O)(C(=O)O)CC(=O)O)(=O)O Chemical compound C1=CC=CC=2C3=CC=CC=C3CC12.C(CC(O)(C(=O)O)CC(=O)O)(=O)O SRCYHILUJAGLAP-UHFFFAOYSA-N 0.000 claims description 2
201000001880 Sexual dysfunction Diseases 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
150000008064 anhydrides 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
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 2
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
239000007800 oxidant agent Substances 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 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
231100000872 sexual dysfunction Toxicity 0.000 claims description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 4
150000004677 hydrates Chemical class 0.000 claims 3
239000012453 solvate Substances 0.000 claims 3
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FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 claims 1
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150000001934 cyclohexanes Chemical class 0.000 description 26
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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Classifications

- 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
- C07D471/10—Spiro-condensed systems
- A—HUMAN NECESSITIES
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ZA200504725A 2002-11-11 2005-06-09 Sipirocyclic cyclohexane derivatives ZA200504725B (en)

Applications Claiming Priority (1)

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DE2002152667 DE10252667A1 (de)	2002-11-11	2002-11-11	Spirocyclische Cyclohexan-Derivate

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EP (4)	EP2233487B1 (pl)
JP (4)	JP4728645B2 (pl)
KR (2)	KR101075810B1 (pl)
CN (2)	CN100577664C (pl)
AR (2)	AR041932A1 (pl)
AT (1)	ATE441650T1 (pl)
AU (2)	AU2003296563B2 (pl)
BR (2)	BRPI0315296B8 (pl)
CA (1)	CA2505555C (pl)
CO (1)	CO5580765A2 (pl)
CY (2)	CY1110558T1 (pl)
DE (2)	DE10252667A1 (pl)
DK (2)	DK2062898T3 (pl)
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ES (4)	ES2438269T3 (pl)
HK (3)	HK1080478A1 (pl)
IL (2)	IL168473A (pl)
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NZ (1)	NZ540575A (pl)
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PL (2)	PL217804B1 (pl)
PT (2)	PT2062898E (pl)
RU (1)	RU2354656C2 (pl)
SI (2)	SI1560835T1 (pl)
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ZA (1)	ZA200504725B (pl)

Families Citing this family (101)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7776314B2 (en)	2002-06-17	2010-08-17	Grunenthal Gmbh	Abuse-proofed dosage system
DE10252667A1 (de)	2002-11-11	2004-05-27	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102004020220A1 (de) *	2004-04-22	2005-11-10	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform
PL1842533T3 (pl) *	2003-08-06	2013-08-30	Gruenenthal Gmbh	Postać aplikacyjna zabezpieczona przed nadużyciem
DE102005005446A1 (de) *	2005-02-04	2006-08-10	Grünenthal GmbH	Bruchfeste Darreichungsformen mit retardierter Freisetzung
US8075872B2 (en)	2003-08-06	2011-12-13	Gruenenthal Gmbh	Abuse-proofed dosage form
DE10336400A1 (de) *	2003-08-06	2005-03-24	Grünenthal GmbH	Gegen Missbrauch gesicherte Darreichungsform
DE10361596A1 (de) *	2003-12-24	2005-09-29	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102004032051A1 (de)	2004-07-01	2006-01-19	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform
US20070048228A1 (en)	2003-08-06	2007-03-01	Elisabeth Arkenau-Maric	Abuse-proofed dosage form
DE10360793A1 (de) *	2003-12-23	2005-07-28	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE10360792A1 (de) *	2003-12-23	2005-07-28	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102004032049A1 (de)	2004-07-01	2006-01-19	Grünenthal GmbH	Gegen Missbrauch gesicherte, orale Darreichungsform
DE102004032103A1 (de) *	2004-07-01	2006-01-19	Grünenthal GmbH	Gegen Missbrauch gesicherte, orale Darreichungsform
DE102004039382A1 (de) *	2004-08-13	2006-02-23	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102005005449A1 (de)	2005-02-04	2006-08-10	Grünenthal GmbH	Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform
DE102005016460A1 (de) *	2005-04-11	2006-10-19	Grünenthal GmbH	Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit
WO2007062175A2 (en) *	2005-11-21	2007-05-31	Amgen Inc.	Spiro-substituted tricyclic heterocycles cxcr3 antagonists
DE102006019597A1 (de)	2006-04-27	2007-10-31	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102006033109A1 (de)	2006-07-18	2008-01-31	Grünenthal GmbH	Substituierte Heteroaryl-Derivate
DE102006033114A1 (de) *	2006-07-18	2008-01-24	Grünenthal GmbH	Spirocyclische Azaindol-Derivate
DE102006046745A1 (de) *	2006-09-29	2008-04-03	Grünenthal GmbH	Gemischte ORL1/µ-Agonisten zur Behandlung von Schmerz
DE102007009235A1 (de) *	2007-02-22	2008-09-18	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102007009319A1 (de) *	2007-02-22	2008-08-28	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
DE102007011485A1 (de)	2007-03-07	2008-09-11	Grünenthal GmbH	Darreichungsform mit erschwertem Missbrauch
NZ586792A (en)	2008-01-25	2012-09-28	Gruenenthal Chemie	Tamper resistant controlled release pharmaceutical tablets form having convex and concave surfaces
WO2009118171A1 (de)	2008-03-27	2009-10-01	Grünenthal GmbH	Hydroxymethylcyclohexylamine
KR101615505B1 (ko) *	2008-03-27	2016-04-26	그뤼넨탈 게엠베하	치환된 스피로사이클릭 사이클로헥산 유도체
NZ588779A (en)	2008-03-27	2012-06-29	Gruenenthal Chemie	Substituted 4-aminocyclohexane derivatives
ES2375543T3 (es)	2008-03-27	2012-03-01	Grünenthal GmbH	Derivados de espiro(5.5)undecano.
CL2009000733A1 (es)	2008-03-27	2009-05-15	Gruenenthal Chemie	Compuestos derivados de (hetero) aril-ciclohexano sustituidos, composicion farmaceutica que contiene a dicho compuesto y su uso como moduladores del receptor de opioides µ y el receptor orl-1 para tratar el dolor, ansiedad, depresion, epilepsia, alzheimer, demencia senil, sintomas de abstinencia, abuso de alcohol.
PE20091823A1 (es)	2008-03-27	2009-12-10	Gruenenthal Chemie	Ciclohexildiaminas sustituidas
CN102123701B (zh)	2008-05-09	2013-03-27	格吕伦塔尔有限公司	使用喷雾冻凝步骤制备中间粉末制剂以及最终固体剂型的方法
ES2534908T3 (es)	2009-07-22	2015-04-30	Grünenthal GmbH	Forma de dosificación de liberación controlada extruida por fusión en caliente
PL2456424T3 (pl)	2009-07-22	2013-12-31	Gruenenthal Gmbh	Stabilizowana przed utlenianiem odporna na naruszenie postać dawkowania
NZ767139A (en) *	2009-12-04	2022-08-26	Sunovion Pharmaceuticals Inc	Multicyclic compounds and methods of use thereof
TWI582092B (zh)	2010-07-28	2017-05-11	歌林達股份有限公司	順式－四氫－螺旋（環己烷－１,１’－吡啶［３,４－b］吲哚）－４－胺－衍生物
BR112013002734A2 (pt) *	2010-08-04	2016-06-07	Gruenenthal Gmbh	uso de agente farmacologicamente ativo e forma de dosagem farmacêutica
PL2600846T3 (pl)	2010-08-04	2016-05-31	Gruenenthal Gmbh	Farmaceutyczna postać dawki zawierająca 6'-fluoro-(n-metylo- albo N,N-dimetylo-)-4-fenylo-4',9'-dihydro-3'H-spiro[cykloheksano-1,1'-pirano[3,4,b]indol]-4-aminę
KR101788535B1 (ko) *	2010-08-04	2017-10-20	그뤼넨탈 게엠베하	６’플루오로（Ｎ메틸 또는 Ｎ,Ｎ디메틸）４페닐４’，９’디하이드로３’Ｈ스피로［사이클로헥산１，１’피라노［３，４，ｂ］인돌］４아민을 포함하는 약제학적 투여형
SI2600839T1 (en) *	2010-08-04	2018-04-30	Gruenenthal Gmbh	A pharmaceutical dosage form comprising 6'-fluoro- (N-methyl- or N, N-dimethyl-4-phenyl-4 ', 9'-dihydro-3'H- spiro- (cyclohexane-1,1'- pyrano- (3,4, b) indol) -4-amine
CN103179956A (zh)	2010-09-02	2013-06-26	格吕伦塔尔有限公司	包含阴离子聚合物的抗破碎剂型
NZ608865A (en)	2010-09-02	2015-03-27	Gruenenthal Chemie	Tamper resistant dosage form comprising an anionic polymer
CN103269688A (zh)	2010-09-02	2013-08-28	格吕伦塔尔有限公司	包含无机盐的抗破碎剂型
PT2649044T (pt) *	2010-12-08	2017-12-07	Gruenenthal Gmbh	Método para síntese de derivados de aminociclo-hexanona substituídos
EP2729470B1 (en) *	2011-07-08	2017-06-21	Grünenthal GmbH	Crystalline (1r,4r)-6'-fluoro-n,n-dimethyl-4-phenyl-4',9'-dihydro-3'h-spiro[cyclohexane-1,1'-pyrano[3,4,b]indol]-4-amine
US8614245B2 (en)	2011-07-08	2013-12-24	Gruenenthal Gmbh	Crystalline (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine
WO2013017242A1 (en)	2011-07-29	2013-02-07	Grünenthal GmbH	Tamper-resistant tablet providing immediate drug release
AR087360A1 (es)	2011-07-29	2014-03-19	Gruenenthal Gmbh	Tableta a prueba de manipulacion que proporciona liberacion de farmaco inmediato
CN104159902B (zh)	2011-12-12	2016-05-04	格吕伦塔尔有限公司	制备(1r,4r)-6’-氟-(N,N-二甲基-和N-甲基)-4-苯基-4’,9’-二氢-3’H-螺[环己烷-1,1’-吡喃并[3,4,b]吲哚]-4-胺的方法
AU2012350763B2 (en) *	2011-12-12	2017-03-30	Grunenthal Gmbh	Solid forms of (1r,4r)-6'-fluoro-(N,N-dimethyl)-4-phenyl-4',9'-dihydro-3'H-spiro-[cyclohexane-1,1'-pyrano-[3,4,b]indol]-4-amine and sulfuric acid
EA032462B1 (ru) *	2011-12-12	2019-05-31	Грюненталь Гмбх	ТВЕРДЫЕ ФОРМЫ ГИДРОХЛОРИДА (1r,4r)-6'-ФТОР-(N,N-ДИМЕТИЛ)-4-ФЕНИЛ-4',9'-ДИГИДРО-3'Н-СПИРО-[ЦИКЛОГЕКСАН-1,1'-ПИРАНО-[3,4,b]ИНДОЛ]-4-АМИНА
HUE035312T2 (en) *	2012-01-31	2018-05-02	Gruenenthal Gmbh	Pharmaceutical patch (1R, 4R) -6'-fluoro-N, N-dimethyl-4-phenyl-4 ', 9'-dihydro-3'H-spiro [cyclohexane-1,1'-pyrano [3,4- b] for transdermal administration of indole] -4-amine
CN104168897B (zh) *	2012-02-03	2016-09-28	格吕伦塔尔有限公司	用于治疗纤维肌痛和慢性疲劳综合征的(1r,4r)-6’-氟-(N-甲基-或N,N-二甲基-)-4-苯基-4’,9’-二氢-3’H-螺-[环己烷-1,1’-吡喃并[3,4,b]吲哚]-4-胺
JP6117249B2 (ja)	2012-02-28	2017-04-19	グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング	薬理学的に活性な化合物および陰イオン性ポリマーを含むタンパーレジスタント剤形
WO2013127830A1 (en)	2012-02-28	2013-09-06	Grünenthal GmbH	Tamper-resistant pharmaceutical dosage form comprising nonionic surfactant
SG11201405990PA (en)	2012-03-23	2014-11-27	Codexis Inc	Biocatalysts and methods for synthesizing derivatives of tryptamine and tryptamine analogs
EP2838512B1 (en)	2012-04-18	2018-08-22	Grünenthal GmbH	Tamper resistant and dose-dumping resistant pharmaceutical dosage form
PT2846835T (pt)	2012-05-11	2017-12-15	Gruenenthal Gmbh	Forma farmacêutica termoformada, resistente à adulteração contendo zinco
US10064945B2 (en)	2012-05-11	2018-09-04	Gruenenthal Gmbh	Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc
US9345689B2 (en) *	2012-05-18	2016-05-24	Gruenenthal Gmbh	Pharmaceutical composition comprising (1r,4r)-6′-fluoro-N, N-dimethyl-4-phenyl-4,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and an anticonvulsant
US9855286B2 (en) *	2012-05-18	2018-01-02	Gruenenthal Gmbh	Pharmaceutical composition comprising (1r,4r)-6′-fluoro-N,N-di methyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano-[3,4,b]indol]-4-amine and a salicylic acid component
US9320725B2 (en) *	2012-05-18	2016-04-26	Gruenenthal Gmbh	Pharmaceutical composition comprising (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and a gabapentinoid
US9320729B2 (en)	2012-05-18	2016-04-26	Gruenenthal Gmbh	Pharmaceutical composition comprising (1r,4r)-6′-flouro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano-[3,4,b]indol]-4-amine and a propionic acid derivative
US8912226B2 (en)	2012-05-18	2014-12-16	Gruenenthal Gmbh	Pharmaceutical composition comprising (1r,4r) -6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine and a NSAR
US9308196B2 (en)	2012-05-18	2016-04-12	Gruenenthal Gmbh	Pharmaceutical composition comprising (1 r,4r) -6'-fluoro-N ,N-dimethyl-4-phenyl-4',9'-d ihydro-3'H-spiro[cyclohexane-1,1'-pyrano-[3,4,b]indol]-4-amine and an oxicam
US20130310385A1 (en) *	2012-05-18	2013-11-21	Gruenenthal Gmbh	Pharmaceutical Composition Comprising (1r,4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4,b]indol]-4-amine and Antidepressants
US20130310435A1 (en) *	2012-05-18	2013-11-21	Gruenenthal Gmbh	Pharmaceutical Composition Comprising (1r,4r)-6'-fluoro-N, N-dimethyl-4-phenyl-4,9' -dihydro-3'H-spiro[cyclohexane-1,1' -pyrano[3,4,b]indol]-4-amine and Paracetamol or Propacetamol
EP2970284B1 (en)	2013-03-15	2017-11-01	Grünenthal GmbH	Crystalline cis-(e)-4-(3-fluorophenyl)-2',3',4',9'-tetrahydro-n,n-dimethyl-2'-(1-oxo-3-phenyl-2-propenyl)-spiro[cyclohexane-1,1'[1h]-pyrido[3,4-b]indol]-4-amine
EP3003283A1 (en)	2013-05-29	2016-04-13	Grünenthal GmbH	Tamper resistant dosage form with bimodal release profile
JP6445537B2 (ja)	2013-05-29	2018-12-26	グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング	１個または複数の粒子を含有する改変防止（ｔａｍｐｅｒ−ｒｅｓｉｓｔａｎｔ）剤形
EP3019157A1 (en)	2013-07-12	2016-05-18	Grünenthal GmbH	Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
JP6480936B2 (ja)	2013-11-26	2019-03-13	グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング	クライオミリングによる粉末状医薬組成物の調製
MX2016007848A (es)	2013-12-16	2016-09-07	Gruenenthal Gmbh	Forma de dosificacion resistente a alteraciones con perfil de liberacion bimodal fabricado mediante co-extrusion.
ES2689447T3 (es)	2014-02-27	2018-11-14	Grünenthal GmbH	Procedimiento para la preparación de 5-fluorotriptofol
MX2016014738A (es)	2014-05-12	2017-03-06	Gruenenthal Gmbh	Formulacion en capsula de liberacion inmediata resistente a alteraciones que comprende tapentadol.
EA201692388A1 (ru)	2014-05-26	2017-05-31	Грюненталь Гмбх	Лекарственная форма в виде множества частиц, защищенная от вызываемого этанолом сброса дозы
US10214520B2 (en)	2014-07-15	2019-02-26	Gruenenthal Gmbh	Substituted azaspiro(4.5)decane derivatives
TW201607923A (zh)	2014-07-15	2016-03-01	歌林達有限公司	被取代之氮螺環（４．５）癸烷衍生物
WO2016116280A1 (en) *	2015-01-23	2016-07-28	Grünenthal GmbH	Cebranopadol for treating pain in subjects with impaired hepatic and/or impaired renal function
EP3253374B1 (en)	2015-02-02	2018-11-28	ratiopharm GmbH	Composition comprising cebranopadol in a dissolved form
CA2975653A1 (en)	2015-02-03	2016-08-11	Grunenthal Gmbh	Tamper-resistant dosage form comprising a polyethylene glycol graft copolymer
EP3285745A1 (en)	2015-04-24	2018-02-28	Grünenthal GmbH	Tamper-resistant dosage form with immediate release and resistance against solvent extraction
AU2016319203A1 (en)	2015-09-10	2018-02-22	Grünenthal GmbH	Protecting oral overdose with abuse deterrent immediate release formulations
CN108271369A (zh)	2015-10-23	2018-07-10	法尔玛赞公司	用于制备色胺及其衍生物的新工艺
WO2017121648A1 (en) *	2016-01-13	2017-07-20	Grünenthal GmbH	3-((hetero-)aryl)-alkyl-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
HRP20250176T1 (hr) *	2016-01-13	2025-04-11	Grünenthal GmbH	Derivati 3-((hetero-)aril)-8-amino-2-okso-1,3-diaza-spiro-[4.5]-dekana
ES2821969T3 (es) *	2016-01-13	2021-04-28	Gruenenthal Gmbh	Derivados de 8-amino-2-oxo-1,3-diazaespiro-[4.5]-decano
EP3402783B1 (en) *	2016-01-13	2020-03-04	Grünenthal GmbH	3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
ES2793384T3 (es) *	2016-01-13	2020-11-13	Gruenenthal Gmbh	Derivados de 3-(carboximetil)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decano
BR112018017167A2 (pt)	2016-02-29	2019-01-02	Gruenenthal Gmbh	titulação de cebranopadol
EP3481378A1 (en)	2016-07-06	2019-05-15	Grünenthal GmbH	Reinforced pharmaceutical dosage form
TW201908295A (zh)	2017-07-12	2019-03-01	德商歌林達有限公司	１，３－二氮雜－螺－［３．４］－辛烷衍生物
EP3613747A1 (en)	2018-08-24	2020-02-26	Grünenthal GmbH	Crystalline forms of trans-6'-fluoro-n-methyl-4-phenyl-4',9'-dihydro-3'h-spiro[cyclohexane-1,1'-pyrano[3,4-b]indol]-4-amine
AU2020415511A1 (en)	2019-12-26	2022-07-14	Gilgamesh Pharmaceuticals, Inc.	Arylcyclohexylamine derivatives and their use in the treatment of psychiatric disorders
RS66496B1 (sr)	2020-02-18	2025-03-31	Gilgamesh Pharmaceuticals Inc	Specifični triptamini za upotrebu u lečenju poremećaja raspoloženja
CN112279813B (zh) *	2020-10-29	2023-02-28	上海中医药大学	1-环己基吡唑啉酮类羧酸酯酶1抑制剂、其制备及应用
WO2024129782A1 (en)	2022-12-12	2024-06-20	Park Therapeutics, Inc.	Regimens and compositions useful for alleviating pain
WO2024173714A1 (en)	2023-02-15	2024-08-22	Park Therapeutics, Inc.	Regimens and compositions useful for alleviating pain
US12180158B1 (en)	2023-08-03	2024-12-31	Gilgamesh Pharmaceuticals, Inc.	Crystalline fumarate salts of n-ethyl-2-(5-fluoro-1H-indol-3-yl)-n-methylethan-1-amine
US12129234B1 (en)	2023-08-03	2024-10-29	Gilgamesh Pharmaceuticals, Inc.	Crystalline salts of N-ethyl-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1055203A (en)	1964-09-16	1967-01-18	Ici Ltd	-ß-carboline derivatives, a process for their manufacture, and compositions containing them
US3843681A (en) *	1971-06-01	1974-10-22	American Home Prod	1-carboxamido pyrano(thiopyrano)(3,4-6)indole derivatives
US4021451A (en) *	1972-05-16	1977-05-03	American Home Products Corporation	Process for preparing polycyclic heterocycles having a pyran ring
JPS5638594A (en) *	1979-09-05	1981-04-13	Toshiba Corp	Multistage capability controlling method
US4291039A (en)	1980-08-08	1981-09-22	Miles Laboratories, Inc.	Tetrahydro β-carbolines having anti-hypertensive activity
DE3309596A1 (de)	1982-08-05	1984-04-05	Basf Ag, 6700 Ludwigshafen	2-substituierte 1-(3'-aminoalkyl)-1,2,3,4-tetrahydro-ss-carboline, ihre herstellung und verwendung als arzneimittel
US5328905A (en)	1987-07-20	1994-07-12	Duphar International Research B.V.	8,9-anellated-1,2,3,4-tetrahydro-β-carboline derivatives
FR2663935A1 (fr) *	1990-06-27	1992-01-03	Adir	Nouveaux 1,2,3,4,5,6-hexahydroazepino [4,5-b] indoles et 1,2,3,4-tetrahydrobethacarbolines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
EP0620222A3 (en) *	1993-04-14	1995-04-12	Lilly Co Eli	Tetrahydro-beta-carbolines.
US5631265A (en)	1994-03-11	1997-05-20	Eli Lilly And Company	8-substituted tetrahydro-beta-carbolines
US5861408A (en)	1995-05-19	1999-01-19	Eli Lilly And Company	Tetrahydro-Beta-Carbolines
WO1997035578A1 (en) *	1996-03-25	1997-10-02	Eli Lilly And Company	Tetrahydro-beta-carboline compounds
EP1086101B1 (en) *	1998-06-12	2002-12-18	Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S.	Beta-carboline compounds
US20040038970A1 (en) *	1998-06-12	2004-02-26	Societe De Conseils De Recherches Etd' Application Scientifiques, S.A.S. A Paris, France Corp.	Beta-carboline compounds
WO2000038720A1 (fr) *	1998-12-24	2000-07-06	Meiji Seika Kaisha, Ltd.	Remedes contre la douleur
TWI329111B (en) *	2002-05-24	2010-08-21	X Ceptor Therapeutics Inc	Azepinoindole and pyridoindole derivatives as pharmaceutical agents
US7595311B2 (en) *	2002-05-24	2009-09-29	Exelixis, Inc.	Azepinoindole derivatives as pharmaceutical agents
DE10252667A1 (de)	2002-11-11	2004-05-27	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
WO2004113336A1 (en) *	2003-06-16	2004-12-29	Chroma Therapeutics Limited	Carboline and betacarboline derivatives for use as hdac enzyme inhibitors
TW200526668A (en) *	2003-10-02	2005-08-16	Salmedix Inc	Substituted indole derivatives
DE10360792A1 (de) *	2003-12-23	2005-07-28	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
MX2007006179A (es) *	2004-11-23	2007-06-20	Ptc Therapeutics Inc	Tetrahidrocarbazoles como agentes activos para inhibir la produccion del factor de crecimiento endotelial vascular por control de la traduccion.
DE102005016460A1 (de) *	2005-04-11	2006-10-19	Grünenthal GmbH	Spriocyclische Cyclohexanderivate zur Behandlung von Substanzabhängigkeit
EP1747779A1 (en) *	2005-07-28	2007-01-31	Laboratorios Del Dr. Esteve, S.A.	Tetrahydro-b-carbolin-sulfonamide derivatives as 5-HT6 ligands
WO2007062175A2 (en) *	2005-11-21	2007-05-31	Amgen Inc.	Spiro-substituted tricyclic heterocycles cxcr3 antagonists
DE102006046745A1 (de) *	2006-09-29	2008-04-03	Grünenthal GmbH	Gemischte ORL1/µ-Agonisten zur Behandlung von Schmerz

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- 2010-04-19 US US12/762,719 patent/US7951948B2/en not_active Expired - Lifetime
- 2010-09-06 JP JP2010199045A patent/JP5539821B2/ja not_active Expired - Fee Related
- 2010-09-06 JP JP2010199044A patent/JP5442565B2/ja not_active Expired - Fee Related
- 2010-12-31 HK HK10112311.5A patent/HK1146044A1/zh not_active IP Right Cessation
2011
- 2011-09-02 US US13/225,008 patent/US9120797B2/en not_active Expired - Lifetime
2013
- 2013-11-04 CY CY20131100973T patent/CY1114616T1/el unknown
2015
- 2015-07-21 US US14/804,847 patent/US9862719B2/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
EP1560835A1 (de)	2005-08-10
CN100577664C (zh)	2010-01-06
DE10252667A1 (de)	2004-05-27
JP2010270155A (ja)	2010-12-02
NO20093060L (no)	2005-06-07
BRPI0315296B8 (pt)	2021-05-25
JP5442565B2 (ja)	2014-03-12
CN1735619A (zh)	2006-02-15
EP1560835B1 (de)	2009-09-02
NO331818B1 (no)	2012-04-10
ES2333956T3 (es)	2010-03-03
AR074529A2 (es)	2011-01-26
US7547707B2 (en)	2009-06-16
IL203141A (en)	2012-04-30
CO5580765A2 (es)	2005-11-30
US7799931B2 (en)	2010-09-21
US7951948B2 (en)	2011-05-31
PT1560835E (pt)	2009-12-10
ATE441650T1 (de)	2009-09-15
JP2011016829A (ja)	2011-01-27
ES2587185T3 (es)	2016-10-21
US20090156626A1 (en)	2009-06-18
US20060004034A1 (en)	2006-01-05
JP2010006815A (ja)	2010-01-14
EP2116544A2 (de)	2009-11-11
WO2004043967A1 (de)	2004-05-27
US20100240897A1 (en)	2010-09-23
NO331776B1 (no)	2012-03-26
PL215227B1 (pl)	2013-11-29
PE20040830A1 (es)	2004-11-17
AU2003296563A1 (en)	2004-06-03
CY1110558T1 (el)	2015-04-29
AU2010200219B2 (en)	2012-04-12
NO20052761L (no)	2005-06-07
US20150322080A1 (en)	2015-11-12
PL217804B1 (pl)	2014-08-29
RU2005118403A (ru)	2006-04-27
EP2062898A3 (de)	2010-09-22
JP2006508114A (ja)	2006-03-09
EP2116544B1 (de)	2016-05-18
US9862719B2 (en)	2018-01-09
PT2062898E (pt)	2013-10-22
PL390420A1 (pl)	2010-04-26
HK1146044A1 (zh)	2011-05-13
EP2233487A1 (de)	2010-09-29
SI2062898T1 (sl)	2013-11-29
CA2505555C (en)	2011-01-04
AU2003296563B2 (en)	2010-03-11
EP2116544A3 (de)	2010-09-22
KR20050074579A (ko)	2005-07-18
PL376793A1 (pl)	2006-01-09
AR041932A1 (es)	2005-06-01
DK2062898T3 (da)	2013-10-28
EP2233487B1 (de)	2016-05-18
US20090163716A1 (en)	2009-06-25
CN101693714A (zh)	2010-04-14
JP4728645B2 (ja)	2011-07-20
US20110319440A1 (en)	2011-12-29
EP2062898B1 (de)	2013-10-02
JP5539821B2 (ja)	2014-07-02
MXPA05004959A (es)	2005-08-02
ES2587013T3 (es)	2016-10-20
IL168473A (en)	2012-10-31
DE50311874D1 (en)	2009-10-15
US8053576B2 (en)	2011-11-08
BRPI0318811B1 (pt)	2020-11-03
US9120797B2 (en)	2015-09-01
HK1130491A1 (en)	2009-12-31
BRPI0315296B1 (pt)	2018-10-09
HK1080478A1 (en)	2006-04-28
CN101693714B (zh)	2013-05-29
EP2062898A2 (de)	2009-05-27
ECSP055786A (es)	2005-08-11
CA2505555A1 (en)	2004-05-27
NO20052761D0 (no)	2005-06-07
ES2438269T3 (es)	2014-01-16
NZ540575A (en)	2007-11-30
KR20090129521A (ko)	2009-12-16
KR101075810B1 (ko)	2011-10-25
AU2010200219A1 (en)	2010-02-11
BRPI0318811B8 (pt)	2021-05-25
KR101075817B1 (ko)	2011-10-25
BR0315296A (pt)	2005-08-30
CY1114616T1 (el)	2016-10-05
RU2354656C2 (ru)	2009-05-10
SI1560835T1 (sl)	2010-01-29
DK1560835T3 (da)	2010-01-04

Publication	Publication Date	Title
ZA200504725B (en)	2006-08-30	Sipirocyclic cyclohexane derivatives
RU2470933C2 (ru)	2012-12-27	Спироциклические производные циклогексана
CA2550868C (en)	2012-03-06	Spirocyclic cyclohexane derivatives with affinity for the orl1-receptor
CN101622255A (zh)	2010-01-06	螺环状的环己烷衍生物