US20050020632A1 - Optical isomers of an iloperidone metabolite - Google Patents
Optical isomers of an iloperidone metabolite Download PDFInfo
- Publication number
- US20050020632A1 US20050020632A1 US10/488,128 US48812804A US2005020632A1 US 20050020632 A1 US20050020632 A1 US 20050020632A1 US 48812804 A US48812804 A US 48812804A US 2005020632 A1 US2005020632 A1 US 2005020632A1
- Authority
- US
- United States
- Prior art keywords
- compound
- acid addition
- free base
- addition salt
- salt form
- 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
- XMXHEBAFVSFQEX-UHFFFAOYSA-N COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 description 3
- RFAFRVVHTGHKSW-UHFFFAOYSA-O [BH4-].[H]C12CCC[NH+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [BH4-].[H]C12CCC[NH+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 RFAFRVVHTGHKSW-UHFFFAOYSA-O 0.000 description 3
- VEXWGLPDOGEPNW-RRHAQCGESA-N COC1=CC([C@@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1.COC1=CC([C@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 Chemical compound COC1=CC([C@@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1.COC1=CC([C@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 VEXWGLPDOGEPNW-RRHAQCGESA-N 0.000 description 2
- 0 C[C@](c(cc1)cc(OC)c1O*N(CC1)CCC1c1n[o]c2c1ccc(F)c2)O Chemical compound C[C@](c(cc1)cc(OC)c1O*N(CC1)CCC1c1n[o]c2c1ccc(F)c2)O 0.000 description 2
- SBKZGLWZGZQVHA-UHFFFAOYSA-N COC1=CC(C(C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 Chemical compound COC1=CC(C(C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 SBKZGLWZGZQVHA-UHFFFAOYSA-N 0.000 description 1
- SBKZGLWZGZQVHA-MRXNPFEDSA-N COC1=CC([C@@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 Chemical compound COC1=CC([C@@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 SBKZGLWZGZQVHA-MRXNPFEDSA-N 0.000 description 1
- SBKZGLWZGZQVHA-INIZCTEOSA-N COC1=CC([C@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 Chemical compound COC1=CC([C@H](C)O)=CC=C1OCCCN1CCC(C2=NOC3=C2C=CC(F)=C3)CC1 SBKZGLWZGZQVHA-INIZCTEOSA-N 0.000 description 1
- RFAFRVVHTGHKSW-LMOVPXPDSA-O [BH4-].[H][C@@]12CCC[N@@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [BH4-].[H][C@@]12CCC[N@@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 RFAFRVVHTGHKSW-LMOVPXPDSA-O 0.000 description 1
- RFAFRVVHTGHKSW-UNTBIKODSA-O [BH4-].[H][C@]12CCC[N@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [BH4-].[H][C@]12CCC[N@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 RFAFRVVHTGHKSW-UNTBIKODSA-O 0.000 description 1
- QVUWCAKECDDLIR-QAOGLABXSA-P [H][C@@]12CCC[N@@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1.[H][C@]12CCC[N@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [H][C@@]12CCC[N@@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1.[H][C@]12CCC[N@H+]1B(C)OC2(C1=CC=CC=C1)C1=CC=CC=C1 QVUWCAKECDDLIR-QAOGLABXSA-P 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
Definitions
- the present invention relates to novel isomers of a metabolite of Iloperidone, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.
- the invention relates to optical isomers of the metabolite P-88-8991 of Iloperidone.
- Iloperidone is an atypical antipsychotic developed for the treatment of schizophrenia, having functional affinity for noradrenergic, dopaminergic and serotoninergic receptors. See for example Richelson E. and Souder T., Life Sciences, 68:29-39 (2000).
- P-88-8991 is a major circulating metabolite of Iloperidone in human plasma, having the formula A See for example Mutlib AE et al., Drug Metab. Dispos; 23(9):951-964 (1995). P-88-8991 has been shown to have plasma levels in human about 1.5 fold higher than the parent drug. It is roughly as active as Iloperidone.
- P-88-8991 consists of a mixture of two enantiomers which have never been disclosed in the literature. It has now surprisingly been found that humans produce only one enantiomer stereospecifically following administration of Iloperidone.
- the invention provides the enantiomers (R)-P-88-8991 and (S)-P-88-8991 of formulae I and II in free base or acid addition salt form.
- the invention provides a process for the production of the compounds of formulae I and II, comprising the reduction of Iloperidone of formula III with an optically active boran complex of formula IV
- the compound (S)-1-(4- ⁇ 3-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy ⁇ -3-methoxy-phenyl)-ethanol of formula I is obtained using the boran complex of (3aR, 7R)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole of formula IVa
- the compound (R)-1-(4- ⁇ 3-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]propoxy ⁇ -3-methoxy-phenyl)-ethanol of formula II is obtained using the boran complex of (3aS,7R)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole of formula IVb
- the reactions can be effected according to conventional methods, e.g. as described in the Examples.
- Acid addition salts may be produced from the free bases in known manner, and vice-versa.
- Suitable acid addition salts for use in accordance with the present invention include for example the hydrochloride.
- the boran complexes used as starting materials can be produced from the corresponding compounds of formula Va and Vb according to known procedures, e.g. as described in the Examples.
- agents of the invention exhibit valuable pharmacological properties when tested in vitro and in animals, and are therefore useful as pharmaceuticals.
- the agents of the invention display high affinity for adrenergic ⁇ 1 and ⁇ 2c receptors (pK I 8.9 and 7.8 respectively, for the compound of formula I, and 9.2 and 7.7 respectively, for the compound of formula II), high affinity for 5 HT 2A and 5 HT 6 receptors (pK I 8.9 and 8.1 respectively, for the compound of formula I, and 8.9 and 7.8 respectively, for the compound of formula II) and moderate affinity for the D 2 family (pK I 7.4 to 7.6 for the compound of formula I and 7.4 to 7.8 for the compound of formula II).
- Receptor affinity is determined with standard radioligand binding techniques, using human recombinant receptors and native rat brain receptors. Blockade of dopamine D 2 and noradrenergic ⁇ 2c receptors is tested in cell-lines using luciferase reporter gene assays based on 2 nd messenger responses.
- the agents of the invention exhibit antipsychotic activity, as assessed in standard tests such as the amphetamine-induced hypermotility and the phencyclidine-induced hyperlocomotion tests.
- the amphetamine-induced hypermotility test is performed according to the method described by Arnt J in Eur. J. Pharmacol. 283, 55-62 (1995).
- the agents of the invention significantly inhibit the amphetamine-induced locomotion of the animals at doses of about 0.01 to about 10 mg/kg s.c.
- the phencyclidine-induced hyperlocomotion test is performed according to a rat adaptation of the method described by Gleason SD and Shannon HE in Psychopharmacol. 129, 79-84 (1997).
- the agents of the invention significantly block the phencyclidine-induced hyperlocomotion of the rats at doses of about 0.01 to about 10 mg/kg s.c.
- the agents of the invention are therefore useful for the treatment of psychotic disorders such as schizophrenia and bipolar disorders.
- the appropriate dosage will of course vary depending upon, for example, the compound employed, the host, the mode of administration and the nature and severity of the condition being treated. However, in general, satisfactory results in animals are indicated to be obtained at a daily dosage of from about 0.1 to about 500, preferably from about 0.5 to about 100 mg/kg animal body weight. In larger mammals, for example humans, an indicated daily dosage is in the range from about 1 to about 500, preferably from about 1 to about 300 mg of an agent of the invention, conveniently administered, for example, in divided doses up to four times a day or in sustained release form.
- the agent of the invention may be administered by any conventional route, in particular enterally, preferably orally, for example in the form of tablets or capsules, or parenterally, for example in the form of injectable solutions or suspensions.
- agents of the invention may alternatively be administered e.g. topically in the form of a cream, gel or the like, or by inhalation, e.g. in dry powder form.
- compositions comprising an agent of the invention include, e.g. a solid dispersion, an aqueous solution, e.g. containing a solubilising agent, a microemulsion and a suspension of an agent of the invention.
- the composition may be buffered to a pH in the range of e.g. from 3.5 to 9.5, by a suitable buffer.
- the agents of the invention can be administered either alone or in combination with other pharmaceutical agents effective in the treatment of psychotic disorders such as schizophrenia or bipolar disorders.
- the present invention thus provides a combination comprising a therapeutically effective amount of an agent of the invention and a second drug substance, for simultaneous or sequential administration.
- the present invention also provides an agent of the invention, for use as a pharmaceutical, e.g. for the treatment of psychotic disorders.
- the present invention furthermore provides a pharmaceutical composition
- a pharmaceutical composition comprising an agent of the invention in association with at least one pharmaceutical carrier or diluent.
- Such compositions may be manufactured in conventional manner.
- Unit dosage forms contain, for example, from about 0.25 to about 150, preferably from 0.25 to about 25 mg of a compound according to the invention.
- the present invention provides the use of an agent of the invention, for the manufacture of a medicament for the treatment of psychotic disorders.
- the present invention provides a method for the treatment of psychotic disorders, in a subject in need of such treatment, which comprises administering to such subject a therapeutically effective amount of an agent of the invention.
- the boran complex used as starting material can be obtained as follows:
- This compound is produced in analogy to Example 1, using boran complex of (3aS, 7R)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/488,128 US20050020632A1 (en) | 2001-08-31 | 2002-08-30 | Optical isomers of an iloperidone metabolite |
| US12/403,755 US7977356B2 (en) | 2001-08-31 | 2009-03-13 | Optical isomers of an Iloperidone metabolite |
| US13/096,015 US8314129B2 (en) | 2001-08-31 | 2011-04-28 | Optical isomers of an iloperidone metabolite |
| US13/661,609 US20130296366A1 (en) | 2001-08-31 | 2012-10-26 | Optical isomers of an iloperidone metabolite |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31639001P | 2001-08-31 | 2001-08-31 | |
| US60316390 | 2001-08-31 | ||
| US10/488,128 US20050020632A1 (en) | 2001-08-31 | 2002-08-30 | Optical isomers of an iloperidone metabolite |
| PCT/EP2002/009700 WO2003020707A1 (en) | 2001-08-31 | 2002-08-30 | Optical isomers of an iloperidone metabolite |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/403,755 Continuation US7977356B2 (en) | 2001-08-31 | 2009-03-13 | Optical isomers of an Iloperidone metabolite |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20050020632A1 true US20050020632A1 (en) | 2005-01-27 |
Family
ID=23228843
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/488,128 Abandoned US20050020632A1 (en) | 2001-08-31 | 2002-08-30 | Optical isomers of an iloperidone metabolite |
| US12/403,755 Active US7977356B2 (en) | 2001-08-31 | 2009-03-13 | Optical isomers of an Iloperidone metabolite |
| US13/096,015 Active US8314129B2 (en) | 2001-08-31 | 2011-04-28 | Optical isomers of an iloperidone metabolite |
| US13/661,609 Abandoned US20130296366A1 (en) | 2001-08-31 | 2012-10-26 | Optical isomers of an iloperidone metabolite |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/403,755 Active US7977356B2 (en) | 2001-08-31 | 2009-03-13 | Optical isomers of an Iloperidone metabolite |
| US13/096,015 Active US8314129B2 (en) | 2001-08-31 | 2011-04-28 | Optical isomers of an iloperidone metabolite |
| US13/661,609 Abandoned US20130296366A1 (en) | 2001-08-31 | 2012-10-26 | Optical isomers of an iloperidone metabolite |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US20050020632A1 (pt) |
| EP (2) | EP1425272B1 (pt) |
| JP (6) | JP2005504783A (pt) |
| AT (1) | ATE518845T1 (pt) |
| CY (2) | CY1112039T1 (pt) |
| DK (2) | DK2305656T3 (pt) |
| ES (2) | ES2398434T3 (pt) |
| HK (2) | HK1066536A1 (pt) |
| PT (2) | PT2305656E (pt) |
| WO (1) | WO2003020707A1 (pt) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011077239A2 (en) | 2009-12-23 | 2011-06-30 | Lupin Limited | Slow release pharmaceutical compositions of iloperidone |
| US20110172272A1 (en) * | 2003-10-01 | 2011-07-14 | Joachim Nozulak | Benzisoxazoles |
| US8524561B2 (en) | 2008-11-05 | 2013-09-03 | Micron Technology, Inc. | Methods of forming a plurality of transistor gates, and methods of forming a plurality of transistor gates having at least two different work functions |
| US8692320B2 (en) | 2006-05-11 | 2014-04-08 | Micron Technology, Inc. | Recessed memory cell access devices and gate electrodes |
| US8710583B2 (en) | 2006-05-11 | 2014-04-29 | Micron Technology, Inc. | Dual work function recessed access device and methods of forming |
| WO2020172506A1 (en) * | 2019-02-21 | 2020-08-27 | Obi Pharma Inc. | Methods of making high enantioselective secondary alcohols |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60238780D1 (de) | 2001-10-30 | 2011-02-10 | Novartis Ag | Depot formulierungen von iloperidone und einem sternförmigen polymer |
| IL164108A0 (en) | 2002-03-27 | 2005-12-18 | Glaxo Group Ltd | Quinoline derivatives and their useas 5-ht6 ligands |
| GB0216416D0 (en) | 2002-07-15 | 2002-08-21 | Novartis Ag | Organic compounds |
| RS20060035A (en) | 2003-07-22 | 2008-08-07 | Arena Pharmaceuticals Inc., | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto |
| ES2825949T3 (es) | 2004-09-30 | 2021-05-17 | Vanda Pharmaceuticals Inc | Métodos para administrar iloperidona |
| US20100063093A1 (en) * | 2007-03-28 | 2010-03-11 | Curt Wolfgang | Methods for the administration of iloperidone |
| JP2009538331A (ja) * | 2006-05-22 | 2009-11-05 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | 抑うつ障害のための治療 |
| US20150259747A1 (en) | 2007-03-29 | 2015-09-17 | Vanda Pharmaceuticals Inc. | Method of predicting a predisposition to qt prolongation |
| EP2134873B1 (en) | 2007-03-29 | 2015-05-06 | Vanda Pharmaceuticals Inc. | Method of predicting a predisposition to qt prolongation |
| US8198305B2 (en) | 2007-04-13 | 2012-06-12 | Concert Pharmaceuticals Inc. | 1,2-benzisoxazol-3-yl compounds |
| WO2008144599A2 (en) | 2007-05-18 | 2008-11-27 | Vanda Pharmaceuticals Inc. | Genetic markers for efficacy of iloperidone in the treatment of psychotic symptoms |
| JP5653753B2 (ja) | 2007-09-10 | 2015-01-14 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | Ｓｎｐ遺伝子型に基づくｑｔ延長の予測 |
| EP2508177A1 (en) | 2007-12-12 | 2012-10-10 | Glaxo Group Limited | Combinations comprising 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline |
| MX2010006521A (es) | 2007-12-13 | 2010-08-10 | Vanda Pharmaceuticals Inc | Metodo y composicion para el tratamiento de una condicion mediada por el receptor de serotonina. |
| US8729100B2 (en) | 2007-12-13 | 2014-05-20 | Vanda Pharmaceuticals, Inc. | Method and composition for treating an alpha adrenoceptor-mediated condition |
| US20110061014A1 (en) | 2008-02-01 | 2011-03-10 | Energyhub | Interfacing to resource consumption management devices |
| US20110021538A1 (en) | 2008-04-02 | 2011-01-27 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| US9126946B2 (en) | 2008-10-28 | 2015-09-08 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto |
| EP2416778B1 (en) | 2009-04-06 | 2016-03-02 | Vanda Pharmaceuticals Inc. | Method of predicting a predisposition to qt prolongation based on abcc2 gene sequence or product thereof |
| JP5881597B2 (ja) | 2009-04-06 | 2016-03-09 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | Ｑｔ延長に対する素因を予測する方法 |
| JP5692872B2 (ja) | 2009-04-06 | 2015-04-01 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | Ｂａｉ遺伝子の配列又はその産物に基づいてｑｔ延長に対する素因を予測する方法 |
| JP5800798B2 (ja) | 2009-04-06 | 2015-10-28 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | Ｋｃｎｑ１遺伝子の多型に基づいた治療方法 |
| US9000221B2 (en) | 2010-09-07 | 2015-04-07 | Symed Labs Limited | Processes for the preparation of 4′-[3-[4-(6-Fluoro-1 ,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone and intermediates thereof |
| WO2012063269A2 (en) | 2010-11-12 | 2012-05-18 | Cadila Healthcare Limited | Process for preparing iloperidone |
| JP2015510893A (ja) * | 2012-03-14 | 2015-04-13 | ヴァンダ ファーマシューティカルズ インコーポレイテッド | 精神障害の治療における使用のためのイロペリドン代謝物 |
| BR112017017608A2 (pt) | 2015-02-17 | 2018-05-08 | Vanda Pharmaceuticals Inc | métodos para tratamento de esquizofrenia ou um sintoma de esquizofrenia, para prevenir uma recaída esquizofrênica e para manter o efeito de iloperidona para esquizofrenia. |
| JP2018516992A (ja) | 2015-06-12 | 2018-06-28 | アクソファント サイエンシーズ ゲーエムベーハーＡｘｏｖａｎｔ Ｓｃｉｅｎｃｅｓ Ｇｍｂｈ | レム睡眠行動障害の予防および処置のために有用なジアリールおよびアリールヘテロアリール尿素誘導体 |
| BR112018000728A2 (pt) | 2015-07-15 | 2018-09-04 | Axovant Sciences Gmbh | resumo método para a profilaxia e/ou tratamento de alucinações visuais em um sujeito com necessidade do mesmo |
| US11607408B2 (en) | 2019-10-15 | 2023-03-21 | Vanda Pharmaceuticals Inc. | Method of treatment of schizophrenia |
| WO2023201182A1 (en) | 2022-04-13 | 2023-10-19 | Vanda Pharmaceuticals Inc. | Treatment of parkinson's disease and parkinson's disease psychosis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4804663A (en) * | 1985-03-27 | 1989-02-14 | Janssen Pharmaceutica N.V. | 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles |
| US5158952A (en) * | 1988-11-07 | 1992-10-27 | Janssen Pharmaceutica N.V. | 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776963A (en) | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| DE69021645T2 (de) | 1989-05-19 | 1996-02-22 | Hoechst Roussel Pharma | N-(aryloxyalkyl)heteroarylpiperidine und -heteroarylpiperazine, Verfahren zu ihrer Herstellung und ihre Verwendung als Medikamente. |
| US5364866A (en) * | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| JPH05286868A (ja) | 1992-04-03 | 1993-11-02 | Kiyoshi Okawa | 制がん剤複合体およびそのスクリーニング法 |
| US5889006A (en) * | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| CA2296104A1 (en) * | 1997-07-03 | 1999-01-14 | Asahi Kasei Kogyo Kabushiki Kaisha | Novel tricyclic compounds having saturated rings and medicinal compositions containing the same |
| EP1551393A4 (en) | 2002-07-30 | 2010-06-16 | Peter Migaly | COMBINATION OF THERAPY FOR DEPRESSION, PREVENTION OF SUICIDE AND VARIOUS MEDICAL AND PSYCHIATRIC DISORDERS |
-
2002
- 2002-08-30 JP JP2003524978A patent/JP2005504783A/ja not_active Withdrawn
- 2002-08-30 PT PT100099159T patent/PT2305656E/pt unknown
- 2002-08-30 ES ES10009915T patent/ES2398434T3/es not_active Expired - Lifetime
- 2002-08-30 AT AT02767454T patent/ATE518845T1/de active
- 2002-08-30 EP EP02767454A patent/EP1425272B1/en not_active Expired - Lifetime
- 2002-08-30 ES ES02767454T patent/ES2370634T3/es not_active Expired - Lifetime
- 2002-08-30 DK DK10009915.9T patent/DK2305656T3/da active
- 2002-08-30 PT PT02767454T patent/PT1425272E/pt unknown
- 2002-08-30 WO PCT/EP2002/009700 patent/WO2003020707A1/en active Application Filing
- 2002-08-30 EP EP10009915A patent/EP2305656B1/en not_active Expired - Lifetime
- 2002-08-30 DK DK02767454.8T patent/DK1425272T3/da active
- 2002-08-30 US US10/488,128 patent/US20050020632A1/en not_active Abandoned
-
2004
- 2004-11-30 HK HK04109446.7A patent/HK1066536A1/xx not_active IP Right Cessation
-
2009
- 2009-03-13 US US12/403,755 patent/US7977356B2/en active Active
- 2009-12-11 JP JP2009281094A patent/JP2010100633A/ja not_active Withdrawn
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2011
- 2011-04-28 US US13/096,015 patent/US8314129B2/en active Active
- 2011-10-06 HK HK11110560.6A patent/HK1156309A1/xx not_active IP Right Cessation
- 2011-11-02 CY CY20111101053T patent/CY1112039T1/el unknown
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2012
- 2012-10-26 US US13/661,609 patent/US20130296366A1/en not_active Abandoned
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2013
- 2013-01-23 CY CY20131100058T patent/CY1113550T1/el unknown
- 2013-01-31 JP JP2013017050A patent/JP2013116905A/ja not_active Withdrawn
- 2013-07-08 JP JP2013142873A patent/JP2013227335A/ja active Pending
-
2015
- 2015-08-06 JP JP2015156358A patent/JP2015227368A/ja active Pending
- 2015-08-06 JP JP2015156359A patent/JP2015214577A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4804663A (en) * | 1985-03-27 | 1989-02-14 | Janssen Pharmaceutica N.V. | 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles |
| US5158952A (en) * | 1988-11-07 | 1992-10-27 | Janssen Pharmaceutica N.V. | 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110172272A1 (en) * | 2003-10-01 | 2011-07-14 | Joachim Nozulak | Benzisoxazoles |
| US8692320B2 (en) | 2006-05-11 | 2014-04-08 | Micron Technology, Inc. | Recessed memory cell access devices and gate electrodes |
| US8710583B2 (en) | 2006-05-11 | 2014-04-29 | Micron Technology, Inc. | Dual work function recessed access device and methods of forming |
| US9543433B2 (en) | 2006-05-11 | 2017-01-10 | Micron Technology, Inc. | Dual work function recessed access device and methods of forming |
| US8524561B2 (en) | 2008-11-05 | 2013-09-03 | Micron Technology, Inc. | Methods of forming a plurality of transistor gates, and methods of forming a plurality of transistor gates having at least two different work functions |
| WO2011077239A2 (en) | 2009-12-23 | 2011-06-30 | Lupin Limited | Slow release pharmaceutical compositions of iloperidone |
| WO2020172506A1 (en) * | 2019-02-21 | 2020-08-27 | Obi Pharma Inc. | Methods of making high enantioselective secondary alcohols |
| CN114941015A (zh) * | 2019-02-21 | 2022-08-26 | 深圳艾欣达伟医药科技有限公司 | 制造高镜像选择性二级醇的方法 |
| US11773118B2 (en) | 2019-02-21 | 2023-10-03 | Obi Pharma, Inc. | Methods of making high enantioselective secondary alcohols |
Also Published As
| Publication number | Publication date |
|---|---|
| PT2305656E (pt) | 2013-01-10 |
| EP1425272B1 (en) | 2011-08-03 |
| CY1113550T1 (el) | 2016-06-22 |
| ATE518845T1 (de) | 2011-08-15 |
| US20110201646A1 (en) | 2011-08-18 |
| ES2370634T3 (es) | 2011-12-21 |
| EP1425272A1 (en) | 2004-06-09 |
| CY1112039T1 (el) | 2015-11-04 |
| JP2013227335A (ja) | 2013-11-07 |
| DK1425272T3 (da) | 2011-11-21 |
| US7977356B2 (en) | 2011-07-12 |
| ES2398434T3 (es) | 2013-03-19 |
| JP2015214577A (ja) | 2015-12-03 |
| JP2005504783A (ja) | 2005-02-17 |
| ES2398434T8 (es) | 2017-10-09 |
| JP2010100633A (ja) | 2010-05-06 |
| HK1156309A1 (en) | 2012-09-07 |
| JP2015227368A (ja) | 2015-12-17 |
| US20090176739A1 (en) | 2009-07-09 |
| EP2305656B1 (en) | 2012-10-24 |
| EP2305656A1 (en) | 2011-04-06 |
| US8314129B2 (en) | 2012-11-20 |
| HK1066536A1 (en) | 2005-03-24 |
| JP2013116905A (ja) | 2013-06-13 |
| DK2305656T3 (da) | 2013-02-11 |
| PT1425272E (pt) | 2011-10-19 |
| WO2003020707A1 (en) | 2003-03-13 |
| US20130296366A1 (en) | 2013-11-07 |
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