OA11590A - 2-Substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists. - Google Patents
2-Substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists. Download PDFInfo
- Publication number
- OA11590A OA11590A OA1200100031A OA1200100031A OA11590A OA 11590 A OA11590 A OA 11590A OA 1200100031 A OA1200100031 A OA 1200100031A OA 1200100031 A OA1200100031 A OA 1200100031A OA 11590 A OA11590 A OA 11590A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- halo
- group
- aromatic
- aryl
- Prior art date
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- -1 2-Substituted-1-piperidyl benzimidazole compounds Chemical class 0.000 title claims description 268
- 108010020615 nociceptin receptor Proteins 0.000 title claims description 7
- 239000000018 receptor agonist Substances 0.000 title description 3
- 229940044601 receptor agonist Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- 125000003118 aryl group Chemical group 0.000 claims abstract description 152
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 239000001257 hydrogen Substances 0.000 claims abstract description 62
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 61
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 43
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 31
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims abstract description 22
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 22
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 18
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 187
- 125000005843 halogen group Chemical group 0.000 claims description 144
- 238000000034 method Methods 0.000 claims description 126
- 150000001412 amines Chemical class 0.000 claims description 89
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 49
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 239000011541 reaction mixture Substances 0.000 claims description 46
- 229910052799 carbon Inorganic materials 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 40
- 125000003386 piperidinyl group Chemical group 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
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- 125000006413 ring segment Chemical group 0.000 claims description 37
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000001624 naphthyl group Chemical group 0.000 claims description 24
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
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- 125000004076 pyridyl group Chemical group 0.000 claims description 13
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 11
- 230000008878 coupling Effects 0.000 claims description 11
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- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 9
- 125000005936 piperidyl group Chemical group 0.000 claims description 9
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
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- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- 229960005196 titanium dioxide Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Neurology (AREA)
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- Neurosurgery (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
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- Rheumatology (AREA)
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- Obesity (AREA)
- Toxicology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
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| IBPCT/IB98/01206 | 1998-08-06 |
Publications (1)
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| OA11590A true OA11590A (en) | 2004-08-18 |
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| OA1200100031A OA11590A (en) | 1998-08-06 | 1999-07-05 | 2-Substituted-1-piperidyl benzimidazole compounds as ORL1-receptor agonists. |
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| US6340681B1 (en) * | 1999-07-16 | 2002-01-22 | Pfizer Inc | 2-benzimidazolylamine compounds as ORL-1-receptor agonists |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| DE60023100T2 (de) | 2000-01-05 | 2006-07-06 | Pfizer Inc. | Benzimidazol-Verbindungen zur Verwendung als ORL1-Rezeptor-Antagonisten |
| GB2359078A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB0005642D0 (en) | 2000-03-10 | 2000-05-03 | Astrazeneca Uk Ltd | Chemical compounds |
| SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| WO2002040019A1 (en) | 2000-11-15 | 2002-05-23 | Banyu Pharmaceutical Co.,Ltd. | Benzimidazole derivatives |
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| GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
| SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| NZ551453A (en) * | 2001-04-18 | 2008-02-29 | Euro Celtique Sa | Nociceptin analogs for the treatment of pain |
| PT1385514E (pt) | 2001-04-18 | 2009-02-04 | Euro Celtique Sa | Compostos espiroindeno e espiroindano |
| KR100855204B1 (ko) | 2001-04-18 | 2008-09-01 | 유로-셀티크 소시에떼 아노뉨 | 노시셉틴 유사체 |
| US6872733B2 (en) | 2001-04-18 | 2005-03-29 | Euro-Celtique S.A. | Benzimidazolone compounds |
| KR100628292B1 (ko) | 2001-04-18 | 2006-09-27 | 유로-셀티크 소시에떼 아노뉨 | 스파이로파이라졸 화합물 |
| EP1406629A1 (en) * | 2001-07-02 | 2004-04-14 | Omeros Corporation | Method for inducing analgesia comprising administration alternatively of an opioid receptor agonist and an opioid receptor like receptor 1 agonist for and an implantable infusion pump |
| US20030040479A1 (en) * | 2001-07-02 | 2003-02-27 | Omeros Corporation | Rotational intrathecal analgesia method and device |
| SE0102716D0 (sv) * | 2001-08-14 | 2001-08-14 | Astrazeneca Ab | Novel compounds |
| SE0103818D0 (sv) * | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| AU2002360561A1 (en) * | 2001-12-11 | 2003-06-23 | Sepracor, Inc. | 4-substituted piperidines, and methods of use thereof |
| JP4056977B2 (ja) | 2002-03-29 | 2008-03-05 | 田辺三菱製薬株式会社 | 睡眠障害治療薬 |
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| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| DE10252666A1 (de) * | 2002-11-11 | 2004-08-05 | Grünenthal GmbH | N-Piperidyl-cyclohexan-Derivate |
| DE10252665A1 (de) * | 2002-11-11 | 2004-06-03 | Grünenthal GmbH | 4-Aminomethyl-1-aryl-cyclohexylamin-Derivate |
| SE0301369D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| GB0315203D0 (en) * | 2003-06-28 | 2003-08-06 | Celltech R&D Ltd | Chemical compounds |
| SA04250305B1 (ar) | 2003-09-25 | 2008-06-02 | سولفاي فارماسوتيكالز بي . في | مشتقات بنزيميدازولون cenzimidazolone وكينازولينون quinazolinone كمساعادات على مستقبلات ORL1 البشرية |
| GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| US20050228023A1 (en) * | 2003-12-19 | 2005-10-13 | Sri International | Agonist and antagonist ligands of the nociceptin receptor |
| WO2006038738A1 (ja) * | 2004-10-08 | 2006-04-13 | Takeda Pharmaceutical Company Limited | 受容体機能調節剤 |
| US7842817B2 (en) | 2005-01-11 | 2010-11-30 | Neurosearch A/S | 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels |
| US20090239880A1 (en) * | 2006-07-03 | 2009-09-24 | Ulrik Svane Sorensen | Combinations of monoamine reuptake inhibitors and potassium channel activators |
| EP2280008B1 (en) | 2007-01-16 | 2013-05-29 | Purdue Pharma L.P. | Heterocyclic-substituted piperidines as orl-1 ligands |
| TW201322983A (zh) | 2007-08-31 | 2013-06-16 | Purdue Pharma Lp | 經取代之喹□啉型哌啶化合物及其用途 |
| US8119661B2 (en) * | 2007-09-11 | 2012-02-21 | Astrazeneca Ab | Piperidine derivatives and their use as muscarinic receptor modulators |
| CN102105465B (zh) | 2008-07-21 | 2015-03-11 | 普渡制药公司 | 取代的喹喔啉型桥连哌啶化合物及其用途 |
| CN103168032A (zh) | 2010-08-05 | 2013-06-19 | 安美基公司 | 抑制间变性淋巴瘤激酶的苯并咪唑和氮杂苯并咪唑化合物 |
| JP6007262B2 (ja) | 2012-01-06 | 2016-10-12 | ノーバス・インターナショナル・インコーポレイテッドＮｏｖｕｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ，Ｉｎｃ． | スルホキシドベース界面活性剤 |
| EP2812313A4 (en) | 2012-02-09 | 2015-09-30 | Novus Int Inc | FUNCTIONALIZED POLYMERIC COMPOSITIONS |
| JO3300B1 (ar) | 2012-06-06 | 2018-09-16 | Novartis Ag | مركبات وتركيبات لتعديل نشاط egfr |
| MX2015000395A (es) | 2012-07-12 | 2015-04-10 | Novus Int Inc | Composiciones de matriz y capa para proteccion de bioactivos. |
| US9085561B2 (en) * | 2012-07-30 | 2015-07-21 | Purdue Pharma L.P. | Cyclic urea- or lactam-substituted quinoxaline-type piperidines as ORL-1 modulators |
| US9090618B2 (en) | 2012-12-27 | 2015-07-28 | Purdue Pharma L.P. | Substituted benzimidazole-type piperidine compounds and uses thereof |
| WO2014153529A1 (en) | 2013-03-22 | 2014-09-25 | The Scripps Research Institute | Substituted benzimidazoles as nociceptin receptor modulators |
| KR102416358B1 (ko) * | 2014-03-20 | 2022-07-07 | 카펠라 테라퓨틱스, 인크. | 암 치료용의 ｅｒｂｂ 티로신 키나제 억제제로서의 벤즈이미다졸 유도체 |
| US10227551B2 (en) | 2015-11-12 | 2019-03-12 | Novus International, Inc. | Sulfur-containing compounds as solvents |
| US10584306B2 (en) | 2017-08-11 | 2020-03-10 | Board Of Regents Of The University Of Oklahoma | Surfactant microemulsions |
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|---|---|---|---|---|
| US3318900A (en) * | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| JPS5297978A (en) * | 1976-06-02 | 1977-08-17 | Yoshitomi Pharmaceut Ind Ltd | Preparation of alicyclic derivatives |
| US5821219A (en) | 1995-08-11 | 1998-10-13 | Oregon Health Sciences University | Opioid antagonists and methods of their use |
| WO1997007208A1 (en) | 1995-08-15 | 1997-02-27 | Universite Libre De Bruxelles | Nucleic acid molecules encoding peptides having pronociceptive properties |
| US5866346A (en) | 1995-09-27 | 1999-02-02 | Indiana Unversity Foundation | Methods of using dynorphins as ligands for XOR1 receptor |
| WO1997040035A1 (en) * | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
| EP0813065A3 (en) | 1996-06-13 | 1998-07-22 | F. Hoffmann-La Roche Ag | Modulation of LC132 (opioid-like) receptor function |
| EP0829481A1 (en) * | 1996-09-16 | 1998-03-18 | Pfizer Inc. | Morphinan hydroxamic acid compounds |
| US5718912A (en) * | 1996-10-28 | 1998-02-17 | Merck & Co., Inc. | Muscarine agonists |
| WO1998054168A1 (en) | 1997-05-30 | 1998-12-03 | Banyu Pharmaceutical Co., Ltd. | 2-oxoimidazole derivatives |
| WO1999003880A1 (en) | 1997-07-15 | 1999-01-28 | Novo Nordisk A/S | Nociceptin analogues |
| US5929035A (en) | 1998-04-14 | 1999-07-27 | Regents Of The University Of Michigan | Methods of treating intestinal disorders |
| ID29137A (id) | 1998-07-27 | 2001-08-02 | Schering Corp | Ligan-ligan afinitas tinggi untuk reseptor nosiseptin orl-1 |
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1999
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