CA2275425C - Aminoindan derivatives - Google Patents
Aminoindan derivatives Download PDFInfo
- Publication number
- CA2275425C CA2275425C CA002275425A CA2275425A CA2275425C CA 2275425 C CA2275425 C CA 2275425C CA 002275425 A CA002275425 A CA 002275425A CA 2275425 A CA2275425 A CA 2275425A CA 2275425 C CA2275425 C CA 2275425C
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- Canada
- Prior art keywords
- compound
- pharmaceutical composition
- therapeutically effective
- effective amount
- methyl
- 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.)
- Expired - Lifetime
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- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical class C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 38
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- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 239000003937 drug carrier Substances 0.000 claims abstract description 16
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 5
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- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 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 9
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- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/56—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- 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
-
- 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
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/44—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/58—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Centrifugal Separators (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL11985396A IL119853A0 (en) | 1996-12-18 | 1996-12-18 | Aminoindan derivatives |
| IL119853 | 1996-12-18 | ||
| IL120510 | 1997-03-24 | ||
| IL12051097A IL120510A0 (en) | 1997-03-24 | 1997-03-24 | Phenylethylamine derivatives |
| PCT/US1997/024155 WO1998027055A1 (en) | 1996-12-18 | 1997-12-18 | Aminoindan derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2275425A1 CA2275425A1 (en) | 1998-06-25 |
| CA2275425C true CA2275425C (en) | 2009-08-04 |
Family
ID=26323338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002275425A Expired - Lifetime CA2275425C (en) | 1996-12-18 | 1997-12-18 | Aminoindan derivatives |
Country Status (13)
| Country | Link |
|---|---|
| US (4) | US6303650B1 (https=) |
| EP (2) | EP1535902B1 (https=) |
| JP (1) | JP4222632B2 (https=) |
| AT (2) | ATE292619T1 (https=) |
| AU (1) | AU5726898A (https=) |
| CA (1) | CA2275425C (https=) |
| DE (2) | DE69738275T2 (https=) |
| DK (1) | DK0966435T3 (https=) |
| ES (1) | ES2241064T3 (https=) |
| HU (1) | HU229507B1 (https=) |
| IL (1) | IL130528A (https=) |
| PT (1) | PT966435E (https=) |
| WO (1) | WO1998027055A1 (https=) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69738275T2 (de) * | 1996-12-18 | 2008-08-28 | Teva Pharmaceutical Industries Ltd. | Aminoindanderivate |
| US6486178B1 (en) * | 1998-06-03 | 2002-11-26 | Nissan Chemical Industries, Ltd. | Indane derivatives |
| IL149308A0 (en) | 1999-10-27 | 2002-11-10 | Teva Pharma | Use of 1-aminoindan derivatives for treatment of manic disorders |
| JP2005523289A (ja) * | 2002-02-27 | 2005-08-04 | テバ ファーマシューティカル インダストリーズ リミティド | 脳選択性ｍａｏ阻害剤としてのプロパルギルアミノインダン誘導体及びプロパルギルアミノテトラリン誘導体 |
| US20040010038A1 (en) * | 2002-02-27 | 2004-01-15 | Eran Blaugrund | Propargylamino indan derivatives and propargylamino tetralin derivatives as brain-selective MAO inhibitors |
| EP1565185A4 (en) * | 2002-11-07 | 2011-01-05 | Technion Res & Dev Foundation | NEUROPROTECTIVE IRON CHELATORS AND PHARMACEUTICAL COMPOSITIONS THEREWITH |
| US8097608B2 (en) | 2003-11-25 | 2012-01-17 | Technion Research And Development Foundation Ltd. | Methods for treatment of cardiovascular disorders and diseases |
| WO2005051371A1 (en) * | 2003-11-25 | 2005-06-09 | Technion Research & Development Foundation Ltd. | Compositions and methods for treatment of cardiovascular disorders and diseases |
| JP2005232148A (ja) * | 2004-02-03 | 2005-09-02 | Technion Research & Development Foundation Ltd | 神経保護剤としてプロパルギルアミンの使用 |
| EP1574498A1 (en) * | 2004-02-19 | 2005-09-14 | PPG-Sipsy | Process for the synthesis of substituted alpha-aminoindan derivatives |
| WO2006014973A2 (en) * | 2004-07-26 | 2006-02-09 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical dosage forms including rasagiline |
| WO2006014968A2 (en) * | 2004-07-27 | 2006-02-09 | Teva Pharmaceutical Industries, Ltd. | Propargyl nitroxydes and indanyl nitroxides and their use for the treatment of neurologic diseases and disorders |
| US7262326B2 (en) | 2004-09-08 | 2007-08-28 | Teva Pharmaceuticals Industries Ltd. | Process for the synthesis of indanylamine or aminotetralin derivatives and novel intermediates |
| WO2006089164A1 (en) * | 2005-02-17 | 2006-08-24 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis |
| EP1851188A1 (en) | 2005-02-22 | 2007-11-07 | Teva Pharmaceutical Industries Limited | Improved process for the synthesis of enantiomeric indanylamine derivatives |
| CA2901244A1 (en) | 2005-02-23 | 2006-08-31 | Teva Pharmaceutical Industries, Ltd. | Rasagiline formulations of improved content uniformity |
| CA2600010A1 (en) * | 2005-02-24 | 2006-08-31 | Teva Pharmaceutical Industries Ltd. | Crystals of ladostigil tartrate, methods of production and pharmaceutical compositions thereof |
| EP1848417A1 (en) * | 2005-02-24 | 2007-10-31 | Teva Pharmaceutical Industries Ltd | Formulations of ladostigil tartrate |
| WO2006130726A2 (en) * | 2005-06-01 | 2006-12-07 | Teva Pharmaceutical Industries, Ltd. | Use of ladostigil for the treatment of multiple sclerosis |
| CN101300006B (zh) * | 2005-06-02 | 2012-07-25 | 叶林发现公司 | 用于治疗肥胖的mao-b抑制剂 |
| US7539261B2 (en) * | 2005-08-22 | 2009-05-26 | Nec Laboratories America, Inc. | Multi-layer coded modulation for non-ergodic block fading channels |
| WO2007038676A2 (en) * | 2005-09-28 | 2007-04-05 | Teva Pharmaceutical Industries Ltd. | Polymorphic forms of ladostigil tartrate |
| US20070093549A1 (en) * | 2005-09-28 | 2007-04-26 | Judith Aronhime | Methods for preparation of ladostigil tartrate crystalline form A1 |
| US8263655B2 (en) * | 2005-10-06 | 2012-09-11 | Technion Research And Development Foundation Ltd | Methods for treatment of renal failure |
| WO2007056403A2 (en) * | 2005-11-04 | 2007-05-18 | Teva Pharmaceutical Industries Ltd. | Asymmetric hydrogenation of acyl enamides |
| US20070238895A1 (en) * | 2005-11-07 | 2007-10-11 | Lee Boulton | N-protected aminoindanes and methods of their preparation |
| EP1954667B1 (en) * | 2005-11-17 | 2017-02-08 | Teva Pharmaceutical Industries Ltd | Methods for isolating propargylated aminoindans |
| US7572834B1 (en) | 2005-12-06 | 2009-08-11 | Teva Pharmaceutical Industries, Ltd. | Rasagiline formulations and processes for their preparation |
| US20070135518A1 (en) * | 2005-12-09 | 2007-06-14 | Marta Weinstock-Rosin | Use of low-dose ladostigil for neuroprotection |
| AU2006326642B2 (en) * | 2005-12-09 | 2012-05-03 | Technion Research And Development Foundation Ltd. | Use of low-dose ladostigil for neuroprotection |
| JP5701485B2 (ja) | 2006-02-21 | 2015-04-15 | テバ ファーマシューティカル インダストリーズ リミティド | 多系統萎縮症の治療のためのラサギリンの使用 |
| TW200744576A (en) | 2006-02-24 | 2007-12-16 | Teva Pharma | Propargylated aminoindans, processes for preparation, and uses thereof |
| WO2007126898A2 (en) * | 2006-03-31 | 2007-11-08 | Teva Pharmaceutical Industries, Ltd. | Use of ladostigil for the treatment of schizophrenia |
| CA2646250A1 (en) * | 2006-04-03 | 2007-10-18 | Teva Pharmaceutical Industries Ltd. | Use of rasagiline for the treatment of restless legs syndrome |
| EP1892233A1 (de) * | 2006-08-18 | 2008-02-27 | Ratiopharm GmbH | Neue Salze des Wirkstoffs Rasagilin |
| ZA200903903B (en) * | 2006-12-14 | 2010-08-25 | Teva Pharma | Crystalline solid rasagiline base |
| JP5356248B2 (ja) | 2006-12-14 | 2013-12-04 | テバ ファーマシューティカル インダストリーズ リミティド | ラサギリンのタンニン酸塩 |
| EP1987816A1 (de) * | 2007-04-30 | 2008-11-05 | Ratiopharm GmbH | Adsorbate eines Rasagilinsalzes mit einem wasserlöslichen Hilfsstoff |
| US8188149B2 (en) * | 2007-09-17 | 2012-05-29 | Teva Pharmaceutical Industries, Ltd. | Use of R(+)-N-propargy1-1-aminoindan to treat or prevent hearing loss |
| US20090181086A1 (en) * | 2008-01-11 | 2009-07-16 | Muhammad Safadi | Rasagiline formulations, their preparation and use |
| WO2009151594A1 (en) * | 2008-06-10 | 2009-12-17 | Teva Pharmaceutical Industries, Ltd. | Rasagiline soft gelatin capsules |
| JP2011522892A (ja) * | 2008-06-13 | 2011-08-04 | テバ ファーマシューティカル インダストリーズ リミティド | パーキンソン病緩和のためのラサギリン |
| MX2010013875A (es) | 2008-06-19 | 2011-01-20 | Teva Pharma | Proceso para preparar y secar base de rasagilina solida. |
| AU2009260733B2 (en) * | 2008-06-19 | 2015-01-29 | Teva Pharmaceutical Industries, Ltd. | Process for purifying rasagiline base |
| US20100189790A1 (en) * | 2009-01-23 | 2010-07-29 | Teva Pharmaceutical Industries, Ltd. | Delayed release rasagiline formulation |
| SI2451771T1 (sl) | 2009-07-09 | 2014-10-30 | Ratiopharm Gmbh | Soli rasagilina in njihovi farmacevtski pripravki |
| RU2607595C2 (ru) | 2010-02-03 | 2017-01-10 | Фарма Ту Б Лтд. | Составы разагилина с пролонгированным высвобождением и их применение |
| CA2806740A1 (en) | 2010-07-27 | 2012-02-02 | Teva Pharmaceutical Industries Ltd. | Use of rasagiline for the treatment of olfactory dysfunction |
| AU2011282716A1 (en) | 2010-07-27 | 2013-03-14 | Teva Pharmaceutical Industries Ltd. | Dispersions of rasagiline citrate |
| WO2013055687A2 (en) | 2011-10-10 | 2013-04-18 | Teva Pharmaceutical Industries Ltd. | R(+)-n-formyl-propargyl-aminoindan |
| JP2014534197A (ja) | 2011-10-10 | 2014-12-18 | テバ ファーマシューティカル インダストリーズ リミティド | Ｒ（＋）−ｎ−メチル−プロパルギルアミノインダン |
| WO2013118126A1 (en) * | 2012-02-12 | 2013-08-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Ladostigil therapy for immunomodulation |
| US9308182B2 (en) | 2012-08-17 | 2016-04-12 | Teva Pharmaceutical Industries, Ltd. | Parenteral formulations of rasagiline |
| EP4692050A1 (en) * | 2023-03-31 | 2026-02-11 | Mitsui Chemicals, Inc. | Carbamate compound |
Family Cites Families (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3201470A (en) | 1965-08-17 | Chsx c cech | ||
| US2916490A (en) | 1959-12-08 | Ocjhs | ||
| US2982783A (en) | 1961-05-02 | Amevoevdanes | ||
| US3123642A (en) | 1964-03-03 | Indanyl and tetrahydronaphthyl | ||
| SE371190B (https=) | 1972-03-24 | 1974-11-11 | Kabi Ab | |
| US2573645A (en) | 1949-05-25 | 1951-10-30 | Smith Kline French Lab | N-hydroxyethyl aminoindanes |
| GB852735A (en) | 1956-04-13 | 1960-11-02 | Schering Ag | Manufacture of 1-aminoindanes |
| US3060091A (en) | 1961-02-13 | 1962-10-23 | Ciba Geigy Corp | Analgesic composition consisting of morphines and amino-indanes |
| US3178478A (en) | 1961-02-13 | 1965-04-13 | Ciba Geigy Corp | 2-amino-5-halo-indanes |
| US3253037A (en) | 1962-06-19 | 1966-05-24 | Ciba Geigy Corp | N-2-alkynyl-amino-benzocylo-alkanes |
| GB1187017A (en) | 1966-07-16 | 1970-04-08 | Aspro Nicholas Ltd | Substituted 1-Amino Indanes and Tetrahydronaphthalens |
| US3709996A (en) | 1963-08-02 | 1973-01-09 | Aspro Nicholas Ltd | Pharmaceutical compositions containing n-cyclopropyl-1-aminoindane compounds and adapted for administration to obtain inhibition of monoamine oxidase enzyme and process |
| NL6408165A (https=) | 1964-07-17 | 1966-01-18 | ||
| US3308157A (en) | 1964-08-07 | 1967-03-07 | Colgate Palmolive Co | N-(benzocyclobutene-1-loweralkyl)-carboxylic acid amides |
| US3637740A (en) | 1969-04-21 | 1972-01-25 | Pfizer | Aminobenzocycloalkane compounds |
| US3507962A (en) | 1969-05-09 | 1970-04-21 | Thompson Chem Co Hayward | Controlling leafminer insects with selected carbamate insecticides,including 3,5-dimethyl-4-dimethylamino-methyl phenyl-n-methylcarbamate |
| US3704323A (en) | 1969-12-23 | 1972-11-28 | Squibb & Sons Inc | Indane derivatives |
| NL7011683A (https=) | 1970-08-07 | 1972-02-09 | ||
| US3991207A (en) | 1971-03-18 | 1976-11-09 | Pfizer Inc. | Combination therapy for Parkinson's disease |
| US3751420A (en) | 1971-04-01 | 1973-08-07 | Squibb & Sons Inc | Monoolmonoene amines |
| BE786748A (fr) | 1971-07-26 | 1973-01-26 | Basf Ag | 1-aminomethyl-indanes-n-substitues |
| US4029731A (en) | 1974-11-06 | 1977-06-14 | Pfizer Inc. | Aminophenyltetralin compounds |
| US4134997A (en) | 1977-03-01 | 1979-01-16 | University Of Iowa Research Foundation | Effect of an aminotetralin derivative on coronary blood flow in infarcted hearts |
| US4096173A (en) | 1977-03-28 | 1978-06-20 | Eli Lilly And Company | Chlorinated 1-aminoindane N-methyl transferase inhibitors |
| US4128666A (en) | 1977-08-18 | 1978-12-05 | Smithkline Corporation | 4 AND 5-Halo substituted 2-indanamine compounds |
| US4132737A (en) | 1978-02-27 | 1979-01-02 | Eli Lilly And Company | Trifluoromethyl substituted 1-aminoindanes |
| US5286747A (en) | 1981-05-08 | 1994-02-15 | Per A. E. Carlsson | 1-alkyl-2-aminotetralin derivatives |
| ES530269A0 (es) | 1983-03-04 | 1985-12-01 | Otsuka Pharma Co Ltd | Derivados de indano y sus sales |
| US4529723A (en) | 1983-04-29 | 1985-07-16 | William H. Rorer, Inc. | Bicyclic benzenoid aminoalkylene ethers and thioethers, pharmaceutical compositions and use |
| JPS6169747A (ja) | 1984-08-31 | 1986-04-10 | Otsuka Pharmaceut Co Ltd | ２，３―ジヒドロ―１ｈ―インデン誘導体及びその製造法 |
| US5242919A (en) | 1984-08-31 | 1993-09-07 | Otsuka Pharmaceutical Co., Ltd. | 2,3-dihydro-1H-indene derivatives |
| US5654301A (en) | 1985-02-15 | 1997-08-05 | Research Corporation Technologies, Inc. | Amino acid derivative anticonvulsant |
| US5378729A (en) | 1985-02-15 | 1995-01-03 | Research Corporation Technologies, Inc. | Amino acid derivative anticonvulsant |
| IL74497A (en) | 1985-03-05 | 1990-02-09 | Proterra Ag | Pharmaceutical compositions containing phenyl carbamate derivatives and certain phenyl carbamate derivatives |
| US4632939A (en) | 1985-03-15 | 1986-12-30 | Eli Lilly And Company | Anticonvulsant agents |
| US4833273A (en) | 1986-02-03 | 1989-05-23 | Warner-Lambert Company | Process for the resolution of 1-aminoindanes |
| DE252290T1 (de) | 1986-06-10 | 1988-06-09 | Chiesi Farmaceutici S.P.A., Parma | Levodopa-methyl-ester enthaltende pharmazeutische zusammensetzungen, ihre herstellung und therapeutische verwendungen. |
| US5153225A (en) | 1986-12-10 | 1992-10-06 | Bayer Aktiengesellschaft | Substituted basic 2-aminotetralin in pharmaceuticals |
| NL195004C (nl) | 1987-03-04 | 2003-11-04 | Novartis Ag | Fenylcarbamaat bevattend farmaceutisch preparaat. |
| US5011995A (en) | 1987-07-28 | 1991-04-30 | Ciba-Geigy Corporation | Process for the preparation of optically active secondary amines |
| US4873241A (en) | 1988-10-31 | 1989-10-10 | Fisons Corporation | 2-amino-N-(2-phenylindan-2-yl)acetamides useful as anti-epileptics |
| US5225596A (en) | 1989-01-09 | 1993-07-06 | The Upjohn Company | Halo substituted aminotetralins |
| CA1335106C (en) | 1989-02-27 | 1995-04-04 | John Mehnert Schaus | Ring-substituted 2-amino-1,2,3,4-tetra-hydronaphthalenes |
| JP2725378B2 (ja) * | 1989-05-29 | 1998-03-11 | 武田薬品工業株式会社 | カルバミド酸エステル誘導体 |
| IE902294A1 (en) | 1989-07-06 | 1991-01-16 | Abbott Lab | Alkynyl amines that regulate cholinergic neurotransmission |
| US5118704A (en) | 1989-08-30 | 1992-06-02 | Whitby Research, Inc. | Substituted 2-aminotetralins useful as dopaminergics |
| US5071875A (en) | 1989-09-25 | 1991-12-10 | Northwestern University | Substituted 2-amidotetralins as melatonin agonists and antagonists |
| FR2654104B1 (fr) | 1989-11-07 | 1992-01-03 | Adir | Nouveaux derives du 1,2-benzisoxazole, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| JPH03176457A (ja) | 1989-12-04 | 1991-07-31 | Nippon Paint Co Ltd | 新規プロパルギル化合物、その製法ならびに該化合物を含む被覆材 |
| IL92952A (en) | 1990-01-03 | 1994-06-24 | Teva Pharma | R-enantiomers of n-propargyl-1-aminoindan compounds, their preparation and pharmaceutical compositions containing them |
| FR2662162B1 (fr) | 1990-05-18 | 1995-01-20 | Adir | Nouveaux derives de l'amino piperidine, de l'amino pyrrolidine et de l'amino perhydroazepine, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| TW197435B (https=) | 1990-11-22 | 1993-01-01 | Takeda Pharm Industry Co Ltd | |
| IL99759A (en) | 1991-10-16 | 1997-06-10 | Teva Pharma | Mono-fluorinated derivatives of n-propargyl-1-aminoindan, their preparation and pharmaceutical compositions containing them |
| KR100262254B1 (ko) | 1992-10-05 | 2000-07-15 | 나카히로 마오미 | 피리미딘 화합물 |
| US5350762A (en) | 1993-03-08 | 1994-09-27 | Hoechst-Roussel Pharmaceuticals Incorporated | Tetrahydrocyclopent[B]indole methanamines and related compounds |
| GB9315600D0 (en) | 1993-07-28 | 1993-09-08 | Smithkline Beecham Plc | Compounds |
| JP3342491B2 (ja) | 1993-08-06 | 2002-11-11 | ファルマシア・アンド・アップジョン・カンパニー | 選択的ドーパミンｄ３リガンドとしての２−アミノインダン類 |
| US5516943A (en) | 1993-09-14 | 1996-05-14 | Sepracor, Inc. | Process for preparing cyclic CIS-1-amino-2-alkanols |
| US5401758A (en) | 1993-10-07 | 1995-03-28 | Bristol-Myers Squibb Company | Pyridinyl cyanoguanidine compounds |
| IL111240A (en) | 1993-10-18 | 2001-10-31 | Teva Pharma | Salts of r(+) - enantiomers of n- propargyl-1-aminoindan and pharmaceutical compositions comprising them |
| US5914349A (en) | 1994-01-10 | 1999-06-22 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| DE69535315T2 (de) * | 1994-01-10 | 2007-06-28 | Teva Pharmaceutical Industries Ltd. | 1-aminoindanderivate und zusammensetzungen hiervon |
| FR2717175B1 (fr) | 1994-03-11 | 1996-06-14 | Adir | Nouveaux composés alkylaminoindanes, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent. |
| IT1271679B (it) | 1994-07-18 | 1997-06-04 | Mediolanum Farmaceutici Srl | Derivati del fenilcarbammato atti all'impiego come anticolinesterasici |
| US5646188A (en) | 1995-07-05 | 1997-07-08 | Teva Pharmaceutical Industries, Ltd. | Polyamine derivatives of 1-aminoindan |
| DE69738275T2 (de) * | 1996-12-18 | 2008-08-28 | Teva Pharmaceutical Industries Ltd. | Aminoindanderivate |
| US6251938B1 (en) | 1996-12-18 | 2001-06-26 | Teva Pharmaceutical Industries, Ltd., | Phenylethylamine derivatives |
| JP3002155B2 (ja) | 1997-06-25 | 2000-01-24 | 日本サーボ株式会社 | 景品懸吊装置 |
| US20040010038A1 (en) | 2002-02-27 | 2004-01-15 | Eran Blaugrund | Propargylamino indan derivatives and propargylamino tetralin derivatives as brain-selective MAO inhibitors |
-
1997
- 1997-12-18 DE DE69738275T patent/DE69738275T2/de not_active Expired - Lifetime
- 1997-12-18 AT AT97953541T patent/ATE292619T1/de not_active IP Right Cessation
- 1997-12-18 IL IL13052897A patent/IL130528A/en not_active IP Right Cessation
- 1997-12-18 DK DK97953541T patent/DK0966435T3/da active
- 1997-12-18 EP EP05002578A patent/EP1535902B1/en not_active Expired - Lifetime
- 1997-12-18 DE DE69732984T patent/DE69732984T2/de not_active Expired - Lifetime
- 1997-12-18 WO PCT/US1997/024155 patent/WO1998027055A1/en not_active Ceased
- 1997-12-18 HU HU0101130A patent/HU229507B1/hu unknown
- 1997-12-18 AU AU57268/98A patent/AU5726898A/en not_active Abandoned
- 1997-12-18 EP EP97953541A patent/EP0966435B1/en not_active Expired - Lifetime
- 1997-12-18 AT AT05002578T patent/ATE377585T1/de not_active IP Right Cessation
- 1997-12-18 ES ES97953541T patent/ES2241064T3/es not_active Expired - Lifetime
- 1997-12-18 PT PT97953541T patent/PT966435E/pt unknown
- 1997-12-18 JP JP52804898A patent/JP4222632B2/ja not_active Expired - Fee Related
- 1997-12-18 CA CA002275425A patent/CA2275425C/en not_active Expired - Lifetime
-
1999
- 1999-06-18 US US09/336,493 patent/US6303650B1/en not_active Expired - Lifetime
-
2001
- 2001-08-31 US US09/944,850 patent/US6462222B1/en not_active Expired - Lifetime
- 2001-08-31 US US09/944,912 patent/US6538025B2/en not_active Ceased
-
2005
- 2005-03-25 US US11/091,008 patent/USRE39616E1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK0966435T3 (da) | 2005-08-15 |
| WO1998027055A1 (en) | 1998-06-25 |
| EP0966435A1 (en) | 1999-12-29 |
| CA2275425A1 (en) | 1998-06-25 |
| HK1024462A1 (en) | 2000-10-13 |
| US6462222B1 (en) | 2002-10-08 |
| DE69738275D1 (de) | 2007-12-20 |
| US20020188020A1 (en) | 2002-12-12 |
| HUP0101130A2 (hu) | 2001-08-28 |
| AU5726898A (en) | 1998-07-15 |
| JP4222632B2 (ja) | 2009-02-12 |
| HK1076098A1 (en) | 2006-01-06 |
| EP0966435A4 (en) | 2003-04-16 |
| HUP0101130A3 (en) | 2003-02-28 |
| EP0966435B1 (en) | 2005-04-06 |
| DE69738275T2 (de) | 2008-08-28 |
| JP2001506269A (ja) | 2001-05-15 |
| ATE292619T1 (de) | 2005-04-15 |
| EP1535902B1 (en) | 2007-11-07 |
| EP1535902A1 (en) | 2005-06-01 |
| US6538025B2 (en) | 2003-03-25 |
| DE69732984D1 (de) | 2005-05-12 |
| ATE377585T1 (de) | 2007-11-15 |
| US6303650B1 (en) | 2001-10-16 |
| ES2241064T3 (es) | 2005-10-16 |
| PT966435E (pt) | 2005-06-30 |
| DE69732984T2 (de) | 2006-02-16 |
| HU229507B1 (en) | 2014-01-28 |
| IL130528A (en) | 2004-12-15 |
| USRE39616E1 (en) | 2007-05-08 |
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| EEER | Examination request | ||
| MKEX | Expiry |
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