Title:
METHODS FOR PRODUCING VILOXAZINE SALTS AND NOVEL POLYMORPHS THEREOF
Document Type and Number:
WIPO Patent Application WO/2011/130194
Kind Code:
A3
Abstract:
Provided here are methods of manufacture of viloxazine and its various salts, as well as viloxazine-related compounds, such as novel intermediate reaction products and polymorphs thereof. In particular, the methods provide a substantially pure API of viloxazine HC1 while avoiding undesirable impurities. The methods further provide for separating, identifying, and characterizing novel polymorphs of viloxazine. Further provided are methods for synthesis and identification and characterization of novel intermediates of viloxazine, as well as for some important metabolites and precursors of metabolites of viloxazine.
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Inventors:
LIANG LIKAN (US)
BHATT PADMANABH P (US)
DAIN DAVID (US)
TAQUET JEAN-PHILIPPE (FR)
PECHENOV ALEKSANDR (US)
TCHESNOKOV ALEXEI (US)
MARIAUX REYNOLD (CH)
BHATT PADMANABH P (US)
DAIN DAVID (US)
TAQUET JEAN-PHILIPPE (FR)
PECHENOV ALEKSANDR (US)
TCHESNOKOV ALEXEI (US)
MARIAUX REYNOLD (CH)
Application Number:
PCT/US2011/032013
Publication Date:
January 05, 2012
Filing Date:
April 12, 2011
Export Citation:
Assignee:
SUPERNUS PHARMACEUTICALS INC (US)
LIANG LIKAN (US)
BHATT PADMANABH P (US)
DAIN DAVID (US)
TAQUET JEAN-PHILIPPE (FR)
PECHENOV ALEKSANDR (US)
TCHESNOKOV ALEXEI (US)
MARIAUX REYNOLD (CH)
LIANG LIKAN (US)
BHATT PADMANABH P (US)
DAIN DAVID (US)
TAQUET JEAN-PHILIPPE (FR)
PECHENOV ALEKSANDR (US)
TCHESNOKOV ALEXEI (US)
MARIAUX REYNOLD (CH)
International Classes:
C07C217/54; A61K31/5375; A61P25/00; C07D265/30; C07D265/32
Domestic Patent References:
| WO2007030366A1 | 2007-03-15 |
Foreign References:
| US3712890A | 1973-01-23 | |||
| US3714161A | 1973-01-30 | |||
| EP0092945A2 | 1983-11-02 |
Other References:
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ANDREW G. MYERS ET AL: "A Solid-Supported, Enantioselective Synthesis Suitable for the Rapid Preparation of Large Numbers of Diverse Structural Analogues of (-)-Saframycin A", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 124, no. 44, 1 November 2002 (2002-11-01), pages 12969 - 12971, XP055008003, ISSN: 0002-7863, DOI: 10.1021/ja027729n
JINBO Y ET AL: "Synthesis and Antibacterial Activity of Thiazolopyrazine-incorporated Tetracyclic Quinolone Antibacterial Agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 37, no. 17, 1 January 1994 (1994-01-01), AMERICAN CHEMICAL SOCIETY, US, pages 2791 - 2796, XP002991758, ISSN: 0022-2623, DOI: 10.1021/JM00043A018
FIRESTONE R ET AL: "Selective Delivery of Cytotoxic Compounds to Cells by the LDL Pathway", JOURNAL OF MEDICINAL CHEMISTRY, vol. 27, no. 8, 1 January 1984 (1984-01-01), AMERICAN CHEMICAL SOCIETY, US, pages 1037 - 1043, XP002991759, ISSN: 0022-2623, DOI: 10.1021/JM00374A017
DATABASE WPI Week 200534, Derwent World Patents Index; AN 2005-326476, XP002660143, "New substituted phenoxy propanol amine derivatives, are tyrosinase inhibitors used in skin external preparations as skin-whitening agents"
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2 April 2010 (2010-04-02), XP002660039, retrieved from STN Database accession no. 1215605-65-4
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 13 September 2009 (2009-09-13), XP002660048, retrieved from STN Database accession no. 1183212-94-3
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 14 September 2008 (2008-09-14), XP002660049, retrieved from STN Database accession no. 1049188-99-9
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 8 September 2004 (2004-09-08), XP002660050, Database accession no. 741245-85-2
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 22 January 2003 (2003-01-22), XP002660051, retrieved from STN Database accession no. 479674-32-3
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 17 July 2002 (2002-07-17), XP002660052, retrieved from STN Database accession no. 439128-99-1
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; BAIRAMOV, M. R. ET AL: "Reaction of 2-(p-methoxyphenoxymethyl)oxirane with different amines and amino alcohols", XP002660053, retrieved from STN Database accession no. 1980:426024
DATABASE PubChem Compound [online] NCBI; 16 August 2005 (2005-08-16), "AC1MMD0Q - Compound Summary", XP002660054, Database accession no. CID 3236825
J. OUHABI ET AL: "Structure du chlorure d'[(éthoxy-2 phénoxy)méthyl]-2 morpholinium: chlorhydrate de viloxazine", ACTA CRYSTALLOGRAPHICA SECTION C CRYSTAL STRUCTURE COMMUNICATIONS, vol. 46, no. 11, 15 November 1990 (1990-11-15), pages 2160 - 2162, XP055008246, ISSN: 0108-2701, DOI: 10.1107/S0108270190001627
SERAJUDDIN ET AL: "Salt formation to improve drug solubility", ADVANCED DRUG DELIVERY REVIEWS, vol. 59, no. 7, 24 August 2007 (2007-08-24), ELSEVIER BV, AMSTERDAM, NL, pages 603 - 616, XP022211982, ISSN: 0169-409X, DOI: 10.1016/J.ADDR.2007.05.010
BYRN S ET AL: "PHARMACEUTICAL SOLIDS: A STRATEGIC APPROACH TO REGULATORY CONSIDERATIONS", PHARMACEUTICAL RESEARCH, vol. 12, no. 7, 1 July 1995 (1995-07-01), KLUWER ACADEMIC PUBLISHERS, NEW YORK, NY, US, pages 945 - 954, XP000996386, ISSN: 0724-8741, DOI: 10.1023/A:1016241927429
BLACKBURN T P ET AL: "Effects of viloxazine, its optical isomers and its major metabolites on biogenic amine uptake mechanisms in vitro and in vivo", EUROPEAN JOURNAL OF PHARMACOLOGY, ELSEVIER SCIENCE, NL, vol. 52, no. 3-4, 1 December 1978 (1978-12-01), pages 367 - 374, XP023840121, ISSN: 0014-2999, [retrieved on 19781201], DOI: 10.1016/0014-2999(78)90291-1
GÉRARD SOULA: "Tris(polyoxaalkyl)amines (Trident), anew class of solid-liquid phase-transfer catalysts", JOURNAL OF ORGANIC CHEMISTRY, vol. 50, no. 20, 4 October 1985 (1985-10-04), AMERICAN CHEMICAL SOCIETY, EASTON.; US, pages 3717 - 3721, XP002105964, ISSN: 0022-3263, DOI: 10.1021/JO00220A009
ANDREW G. MYERS ET AL: "A Solid-Supported, Enantioselective Synthesis Suitable for the Rapid Preparation of Large Numbers of Diverse Structural Analogues of (-)-Saframycin A", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 124, no. 44, 1 November 2002 (2002-11-01), pages 12969 - 12971, XP055008003, ISSN: 0002-7863, DOI: 10.1021/ja027729n
JINBO Y ET AL: "Synthesis and Antibacterial Activity of Thiazolopyrazine-incorporated Tetracyclic Quinolone Antibacterial Agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 37, no. 17, 1 January 1994 (1994-01-01), AMERICAN CHEMICAL SOCIETY, US, pages 2791 - 2796, XP002991758, ISSN: 0022-2623, DOI: 10.1021/JM00043A018
FIRESTONE R ET AL: "Selective Delivery of Cytotoxic Compounds to Cells by the LDL Pathway", JOURNAL OF MEDICINAL CHEMISTRY, vol. 27, no. 8, 1 January 1984 (1984-01-01), AMERICAN CHEMICAL SOCIETY, US, pages 1037 - 1043, XP002991759, ISSN: 0022-2623, DOI: 10.1021/JM00374A017
DATABASE WPI Week 200534, Derwent World Patents Index; AN 2005-326476, XP002660143, "New substituted phenoxy propanol amine derivatives, are tyrosinase inhibitors used in skin external preparations as skin-whitening agents"
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 2 April 2010 (2010-04-02), XP002660039, retrieved from STN Database accession no. 1215605-65-4
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 13 September 2009 (2009-09-13), XP002660048, retrieved from STN Database accession no. 1183212-94-3
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 14 September 2008 (2008-09-14), XP002660049, retrieved from STN Database accession no. 1049188-99-9
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 8 September 2004 (2004-09-08), XP002660050, Database accession no. 741245-85-2
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 22 January 2003 (2003-01-22), XP002660051, retrieved from STN Database accession no. 479674-32-3
DATABASE REGISTRY [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 17 July 2002 (2002-07-17), XP002660052, retrieved from STN Database accession no. 439128-99-1
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; BAIRAMOV, M. R. ET AL: "Reaction of 2-(p-methoxyphenoxymethyl)oxirane with different amines and amino alcohols", XP002660053, retrieved from STN Database accession no. 1980:426024
DATABASE PubChem Compound [online] NCBI; 16 August 2005 (2005-08-16), "AC1MMD0Q - Compound Summary", XP002660054, Database accession no. CID 3236825
J. OUHABI ET AL: "Structure du chlorure d'[(éthoxy-2 phénoxy)méthyl]-2 morpholinium: chlorhydrate de viloxazine", ACTA CRYSTALLOGRAPHICA SECTION C CRYSTAL STRUCTURE COMMUNICATIONS, vol. 46, no. 11, 15 November 1990 (1990-11-15), pages 2160 - 2162, XP055008246, ISSN: 0108-2701, DOI: 10.1107/S0108270190001627
SERAJUDDIN ET AL: "Salt formation to improve drug solubility", ADVANCED DRUG DELIVERY REVIEWS, vol. 59, no. 7, 24 August 2007 (2007-08-24), ELSEVIER BV, AMSTERDAM, NL, pages 603 - 616, XP022211982, ISSN: 0169-409X, DOI: 10.1016/J.ADDR.2007.05.010
BYRN S ET AL: "PHARMACEUTICAL SOLIDS: A STRATEGIC APPROACH TO REGULATORY CONSIDERATIONS", PHARMACEUTICAL RESEARCH, vol. 12, no. 7, 1 July 1995 (1995-07-01), KLUWER ACADEMIC PUBLISHERS, NEW YORK, NY, US, pages 945 - 954, XP000996386, ISSN: 0724-8741, DOI: 10.1023/A:1016241927429
BLACKBURN T P ET AL: "Effects of viloxazine, its optical isomers and its major metabolites on biogenic amine uptake mechanisms in vitro and in vivo", EUROPEAN JOURNAL OF PHARMACOLOGY, ELSEVIER SCIENCE, NL, vol. 52, no. 3-4, 1 December 1978 (1978-12-01), pages 367 - 374, XP023840121, ISSN: 0014-2999, [retrieved on 19781201], DOI: 10.1016/0014-2999(78)90291-1
GÉRARD SOULA: "Tris(polyoxaalkyl)amines (Trident), anew class of solid-liquid phase-transfer catalysts", JOURNAL OF ORGANIC CHEMISTRY, vol. 50, no. 20, 4 October 1985 (1985-10-04), AMERICAN CHEMICAL SOCIETY, EASTON.; US, pages 3717 - 3721, XP002105964, ISSN: 0022-3263, DOI: 10.1021/JO00220A009
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