CA2387741A1 - Positive modulators of nicotinic receptor agonists - Google Patents
Positive modulators of nicotinic receptor agonists Download PDFInfo
- Publication number
- CA2387741A1 CA2387741A1 CA002387741A CA2387741A CA2387741A1 CA 2387741 A1 CA2387741 A1 CA 2387741A1 CA 002387741 A CA002387741 A CA 002387741A CA 2387741 A CA2387741 A CA 2387741A CA 2387741 A1 CA2387741 A1 CA 2387741A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- indole
- hydroxy
- disease
- carboxamide
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title claims abstract description 26
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 title claims abstract description 26
- 229940044601 receptor agonist Drugs 0.000 title description 9
- 239000000018 receptor agonist Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 176
- 238000000034 method Methods 0.000 claims abstract description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 58
- 239000001257 hydrogen Substances 0.000 claims abstract description 58
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 50
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000000556 agonist Substances 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 235000001508 sulfur Nutrition 0.000 claims abstract description 7
- 230000005540 biological transmission Effects 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 239000011593 sulfur Substances 0.000 claims abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract 4
- 229940123925 Nicotinic receptor agonist Drugs 0.000 claims description 27
- 239000000181 nicotinic agonist Substances 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 18
- 230000006735 deficit Effects 0.000 claims description 17
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- 125000000217 alkyl group Chemical group 0.000 claims description 13
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
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- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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 10
- CKZLTECAOSGTBC-UHFFFAOYSA-N 4-hydroxy-1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1O CKZLTECAOSGTBC-UHFFFAOYSA-N 0.000 claims description 9
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
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- HGHBXVSSWNDWGV-UHFFFAOYSA-N n-(1-fluoro-3-phenylpropan-2-yl)-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NC(CF)CC1=CC=CC=C1 HGHBXVSSWNDWGV-UHFFFAOYSA-N 0.000 claims description 4
- QTAABPDKPSKCNJ-UHFFFAOYSA-N 4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(N)=O)=CC2=C1O QTAABPDKPSKCNJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- NCFRPTLPGWKEIX-UHFFFAOYSA-N ethyl 4-hydroxy-1-methylindole-2-carboxylate Chemical compound C1=CC=C2N(C)C(C(=O)OCC)=CC2=C1O NCFRPTLPGWKEIX-UHFFFAOYSA-N 0.000 claims description 3
- DISOOVOIBKFPCC-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCC1=CC=C(Cl)C=C1 DISOOVOIBKFPCC-UHFFFAOYSA-N 0.000 claims description 3
- NHZLWLAHJVXVQW-UHFFFAOYSA-N n-benzyl-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCC1=CC=CC=C1 NHZLWLAHJVXVQW-UHFFFAOYSA-N 0.000 claims description 3
- YCZADCRYQVJCLW-UHFFFAOYSA-N (4-hydroxy-1-methylindol-2-yl)-pyrrolidin-1-ylmethanone Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)N1CCCC1 YCZADCRYQVJCLW-UHFFFAOYSA-N 0.000 claims description 2
- HCMUPTQEYTYGHB-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-(2-phenylethyl)indole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCCC1=CC=CC=C1 HCMUPTQEYTYGHB-UHFFFAOYSA-N 0.000 claims description 2
- XMXWFSWWQPUYDJ-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-(3-phenylpropyl)indole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCCCC1=CC=CC=C1 XMXWFSWWQPUYDJ-UHFFFAOYSA-N 0.000 claims description 2
- VNUZXARZRWELJO-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-(4-phenylbutyl)indole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCCCCC1=CC=CC=C1 VNUZXARZRWELJO-UHFFFAOYSA-N 0.000 claims description 2
- FTFBINRINIORBJ-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-phenylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NC1=CC=CC=C1 FTFBINRINIORBJ-UHFFFAOYSA-N 0.000 claims description 2
- VIGGBSWKZAAVBB-AWEZNQCLSA-N 4-hydroxy-n-[(1r)-2-hydroxy-1-phenylethyl]-1-methylindole-2-carboxamide Chemical compound C1([C@H](CO)NC(=O)C=2N(C3=CC=CC(O)=C3C=2)C)=CC=CC=C1 VIGGBSWKZAAVBB-AWEZNQCLSA-N 0.000 claims description 2
- XRGYOXWBAUCLAX-AWEZNQCLSA-N diazonio-[(2s)-2-[(4-hydroxy-1-methylindole-2-carbonyl)amino]-3-phenylpropyl]azanide Chemical compound C([C@@H](CN=[N+]=[N-])NC(=O)C=1N(C2=CC=CC(O)=C2C=1)C)C1=CC=CC=C1 XRGYOXWBAUCLAX-AWEZNQCLSA-N 0.000 claims description 2
- MPKQMEXBCWRJSI-UHFFFAOYSA-N n-(4-chlorophenyl)-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NC1=CC=C(Cl)C=C1 MPKQMEXBCWRJSI-UHFFFAOYSA-N 0.000 claims description 2
- GDXAEGSNSMJISF-UHFFFAOYSA-N n-[[4-(dimethylamino)phenyl]methyl]-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1CNC(=O)C1=CC2=C(O)C=CC=C2N1C GDXAEGSNSMJISF-UHFFFAOYSA-N 0.000 claims description 2
- JQKJBEJXYCWGPM-UHFFFAOYSA-N n-ethyl-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(=O)NCC)=CC2=C1O JQKJBEJXYCWGPM-UHFFFAOYSA-N 0.000 claims description 2
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- 230000009286 beneficial effect Effects 0.000 claims 3
- 230000000391 smoking effect Effects 0.000 claims 3
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- UWEAINNLPOKQDF-UHFFFAOYSA-N n-(2-fluoroethyl)-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(=O)NCCF)=CC2=C1O UWEAINNLPOKQDF-UHFFFAOYSA-N 0.000 claims 1
- VSDMPNPFAOTDRA-CQSZACIVSA-N n-[(2r)-2-fluoro-3-phenylpropyl]-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C([C@@H](F)CNC(=O)C=1N(C2=CC=CC(O)=C2C=1)C)C1=CC=CC=C1 VSDMPNPFAOTDRA-CQSZACIVSA-N 0.000 claims 1
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- 239000002904 solvent Substances 0.000 description 29
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- 102000004169 proteins and genes Human genes 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/16—Anti-Parkinson drugs
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- A61P25/00—Drugs for disorders of the nervous system
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903998-4 | 1999-11-03 | ||
| SE9903998A SE9903998D0 (sv) | 1999-11-03 | 1999-11-03 | New compounds |
| PCT/SE2000/002147 WO2001032622A1 (en) | 1999-11-03 | 2000-11-01 | Positive modulators of nicotinic receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2387741A1 true CA2387741A1 (en) | 2001-05-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002387741A Abandoned CA2387741A1 (en) | 1999-11-03 | 2000-11-01 | Positive modulators of nicotinic receptor agonists |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7064143B1 (enExample) |
| EP (1) | EP1230218A1 (enExample) |
| JP (1) | JP2003513073A (enExample) |
| KR (1) | KR20020063175A (enExample) |
| CN (1) | CN1216864C (enExample) |
| AU (1) | AU783602B2 (enExample) |
| BR (1) | BR0015193A (enExample) |
| CA (1) | CA2387741A1 (enExample) |
| CO (1) | CO5280079A1 (enExample) |
| IL (1) | IL149096A0 (enExample) |
| MX (1) | MXPA02004240A (enExample) |
| NO (1) | NO323077B1 (enExample) |
| NZ (1) | NZ518449A (enExample) |
| SE (1) | SE9903998D0 (enExample) |
| WO (1) | WO2001032622A1 (enExample) |
| ZA (1) | ZA200203181B (enExample) |
Families Citing this family (42)
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| WO2003039540A2 (en) * | 2001-11-09 | 2003-05-15 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| GB0205170D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205166D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205162D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205175D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205176D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205165D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| EP1531820A1 (en) | 2002-08-30 | 2005-05-25 | Memory Pharmaceuticals Corporation | Anabaseine derivatives useful in the treatment of neurodegenerative diseases |
| SK288115B6 (sk) | 2002-09-25 | 2013-09-03 | Memory Pharmaceuticals Corporation | Indazoles, pharmaceutical compositions comprising them and their use |
| GB0222909D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| GB0222912D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| US7405210B2 (en) | 2003-05-21 | 2008-07-29 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase |
| AU2004312530A1 (en) | 2003-12-29 | 2005-07-21 | Sepracor Inc. | Pyrrole and pyrazole DAAO inhibitors |
| DE602005023965D1 (de) | 2004-03-08 | 2010-11-18 | Prosidion Ltd | Pyrrolopyridin-2-carbonsäurehydrazide als inhibitoren von glykogenphosphorylase |
| MXPA06010852A (es) | 2004-03-25 | 2007-01-16 | Memory Pharm Corp | Indazoles, benzotiazoles, benzoisotiazoles, bencisoxazoles y preparacion y usos de los mismos. |
| JP4698671B2 (ja) | 2004-06-01 | 2011-06-08 | エフ．ホフマン−ラ ロシュ アーゲー | モノアミン再取り込み阻害剤としての３−アミノ−１−アリールプロピルインドール |
| AU2005284908B2 (en) | 2004-09-13 | 2011-12-08 | Morningside Venture Investments Limited | Biosynchronous transdermal drug delivery |
| US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
| US7223786B2 (en) | 2004-11-15 | 2007-05-29 | Bristol-Myers Squibb Company | 2-aminonaphthalene derivatives and related glycogen phosphorylase inhibitors |
| US7226942B2 (en) | 2004-11-15 | 2007-06-05 | Bristol-Myers Squibb Company | 2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| WO2006055463A2 (en) | 2004-11-15 | 2006-05-26 | Bristol-Myers Squibb Company | 2-amino-3-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| US7214704B2 (en) | 2004-11-15 | 2007-05-08 | Bristol-Myers Squibb Company | 2-Amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| EP1819332B1 (en) | 2004-12-02 | 2009-03-11 | Prosidion Limited | Pyrrolopyridine-2-carboxylic acid amides |
| FR2888847B1 (fr) | 2005-07-22 | 2007-08-31 | Sanofi Aventis Sa | Derives de n-(heteriaryl)-1-heteorarylalkyl-1h-indole-2- carboxamides, leur preparation et application en therapeutique |
| JP2009517432A (ja) | 2005-11-30 | 2009-04-30 | エフ．ホフマン−ラ ロシュ アーゲー | ３−アミノ−２−アリールプロピルアザインドールおよびその使用 |
| WO2007062994A1 (en) | 2005-11-30 | 2007-06-07 | F. Hoffmann-La Roche Ag | Methods for synthesis of 3-amino-1-arylpropyl indoles |
| RU2008120138A (ru) | 2005-11-30 | 2010-01-10 | Ф. Хоффманн-Ля Рош Аг (Ch) | 3-амино-1-арилпропилиндолы и аза-замещенные индолы |
| US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| KR20090096716A (ko) * | 2007-01-09 | 2009-09-14 | 바이엘 쉐링 파마 악티엔게젤샤프트 | 아지리딘의 플루오르화에 의한 방사성표지 |
| EP1944288A1 (en) * | 2007-01-09 | 2008-07-16 | Bayer Schering Pharma Aktiengesellschaft | Radiolabelling via fluorination of aziridines |
| ES2521494T3 (es) * | 2007-04-02 | 2014-11-12 | Parkinson's Institute | Métodos y composiciones para la reducción de los efectos secundarios de tratamientos terapéuticos |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| PT3029039T (pt) | 2010-05-17 | 2017-11-28 | Forum Pharmaceuticals Inc | Formulações farmacêuticas que compreendem formas cristalinas de cloridrato de (r)-7-cloro-n-(quinuclidin-3-il)benzo(b)tiofeno-2-carboxamida mono-hidratado |
| AR085509A1 (es) | 2011-03-09 | 2013-10-09 | Bayer Cropscience Ag | Indol- y bencimidazolcarboxamidas como insecticidas y acaricidas |
| EP2729148A4 (en) | 2011-07-06 | 2015-04-22 | Parkinson S Inst | COMPOSITIONS AND METHOD FOR THE TREATMENT OF SYMPTOMS IN PATIENTS WITH MORBUS PARKINSON |
| EP2846796A4 (en) | 2012-05-08 | 2015-10-21 | Forum Pharmaceuticals Inc | METHODS OF MAINTAINING, PROCESSING OR ENHANCING COGNITIVE FUNCTION |
| WO2016123406A1 (en) | 2015-01-28 | 2016-08-04 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
| AU2016228779A1 (en) | 2015-03-12 | 2017-09-07 | Chrono Therapeutics Inc. | Craving input and support system |
| CA3049529A1 (en) | 2017-01-06 | 2018-07-12 | Chrono Therapeutics Inc. | Transdermal drug delivery devices and methods |
| CA3101966A1 (en) | 2018-05-29 | 2019-12-05 | Morningside Venture Investments Limited | Drug delivery methods and systems |
| US12397141B2 (en) | 2018-11-16 | 2025-08-26 | Morningside Venture Investments Limited | Thermally regulated transdermal drug delivery system |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE758766A (fr) * | 1969-11-17 | 1971-05-10 | Ici Ltd | Nouveaux derives de la morpholine et de la |
| US4704390A (en) * | 1986-02-13 | 1987-11-03 | Warner-Lambert Company | Phenyl and heterocyclic tetrahydropyridyl alkoxy-benzheterocyclic compounds as antipsychotic agents |
| EP0550507A1 (en) | 1990-09-13 | 1993-07-14 | Beecham Group p.l.c. | Indole ureas as 5 ht receptor antagonist |
| FI942395A7 (fi) * | 1991-11-25 | 1994-05-24 | Pfizer | Indolijohdannaiset |
| WO1993018026A1 (en) * | 1992-03-04 | 1993-09-16 | Beecham Group Plc | Indole ureas as 5-ht1c receptor antogonists |
| US5504101A (en) * | 1994-05-06 | 1996-04-02 | Allelix Biopharmaceuticals, Inc. | 5-HT-1D receptor ligands |
| FR2722686B1 (fr) * | 1994-07-22 | 1996-08-30 | Oreal | Set, procede, dispositif et composition de teinture des fibres keratiniques |
| US5576321A (en) | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| SE9903997D0 (sv) * | 1999-11-03 | 1999-11-03 | Astra Ab | New compounds |
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- 1999-11-03 SE SE9903998A patent/SE9903998D0/xx unknown
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- 2000-11-01 CO CO00083137A patent/CO5280079A1/es not_active Application Discontinuation
- 2000-11-01 IL IL14909600A patent/IL149096A0/xx unknown
- 2000-11-01 MX MXPA02004240A patent/MXPA02004240A/es not_active Application Discontinuation
- 2000-11-01 AU AU14263/01A patent/AU783602B2/en not_active Ceased
- 2000-11-01 CA CA002387741A patent/CA2387741A1/en not_active Abandoned
- 2000-11-01 JP JP2001534774A patent/JP2003513073A/ja not_active Abandoned
- 2000-11-01 US US10/111,029 patent/US7064143B1/en not_active Expired - Fee Related
- 2000-11-01 KR KR1020027005705A patent/KR20020063175A/ko not_active Ceased
- 2000-11-01 EP EP00976499A patent/EP1230218A1/en not_active Withdrawn
- 2000-11-01 BR BR0015193-9A patent/BR0015193A/pt not_active IP Right Cessation
- 2000-11-01 WO PCT/SE2000/002147 patent/WO2001032622A1/en not_active Ceased
- 2000-11-01 NZ NZ518449A patent/NZ518449A/en unknown
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2002
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- 2002-05-02 NO NO20022105A patent/NO323077B1/no unknown
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2005
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| NO20022105L (no) | 2002-07-02 |
| NZ518449A (en) | 2004-07-30 |
| NO20022105D0 (no) | 2002-05-02 |
| MXPA02004240A (es) | 2002-10-17 |
| IL149096A0 (en) | 2002-11-10 |
| WO2001032622A1 (en) | 2001-05-10 |
| US7402604B2 (en) | 2008-07-22 |
| BR0015193A (pt) | 2002-06-18 |
| JP2003513073A (ja) | 2003-04-08 |
| US20050245595A1 (en) | 2005-11-03 |
| NO323077B1 (no) | 2006-12-27 |
| US7064143B1 (en) | 2006-06-20 |
| CO5280079A1 (es) | 2003-05-30 |
| SE9903998D0 (sv) | 1999-11-03 |
| AU783602B2 (en) | 2005-11-10 |
| ZA200203181B (en) | 2003-07-22 |
| EP1230218A1 (en) | 2002-08-14 |
| KR20020063175A (ko) | 2002-08-01 |
| CN1216864C (zh) | 2005-08-31 |
| CN1387513A (zh) | 2002-12-25 |
| AU1426301A (en) | 2001-05-14 |
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| FZDE | Discontinued |