Title:
VALPROIC ACID ANALOGUES AND PHARMACEUTICAL COMPOSITIONS THEREOF
Document Type and Number:
WIPO Patent Application WO2004054957
Kind Code:
A3
Abstract:
Analogues of valproic acid useful in treating neuroaffective disorders including convulsions, bipolar disorder, and migraine headache are disclosed. The analogues are halide substituted analogues, cyclic analogues, and conjugated diene analogues of valproic acid. Pharmaceutical compositions or prodrugs containing the analogues or pharmaceutically acceptable salts thereof are disclosed. Methods of making the compounds and treating mammals with neuroaffective disorders are also disclosed.
Inventors:
ABBOTT FRANK SLADE (CA)
KARAGIOZOV STOYAN KOSTADINOV (CA)
KARAGIOZOV STOYAN KOSTADINOV (CA)
Application Number:
PCT/CA2003/001960
Publication Date:
September 10, 2004
Filing Date:
December 16, 2003
Export Citation:
Assignee:
UNIV BRITISH COLUMBIA (CA)
ABBOTT FRANK SLADE (CA)
KARAGIOZOV STOYAN KOSTADINOV (CA)
ABBOTT FRANK SLADE (CA)
KARAGIOZOV STOYAN KOSTADINOV (CA)
International Classes:
A61K31/185; A61P25/00; C07C53/21; C07C53/23; C07C57/02; C07C57/03; C07C57/26; C07C57/52; C07C59/135; C07C59/21; C07C69/587; C07C69/608; C07C69/65; C07F9/535; (IPC1-7): C07C53/21; C07C53/23; C07C57/02; C07C57/52; C07C57/26; C07C59/21; C07C59/135; A61K31/185; A61P25/00
Domestic Patent References:
| WO1994006743A1 | 1994-03-31 |
Foreign References:
| US20020156320A1 | 2002-10-24 |
Other References:
PALATY, JAN ET AL: "Structure-Activity Relationships of Unsaturated Analogs of Valproic Acid", JOURNAL OF MEDICINAL CHEMISTRY , 38(17), 3398-406 CODEN: JMCMAR; ISSN: 0022-2623, 1995, XP002289407
LEE, RONALD D. ET AL: "Stereoselective synthesis of the diunsaturated metabolites of valproic acid", JOURNAL OF PHARMACEUTICAL SCIENCES , 78(8), 667-71 CODEN: JPMSAE; ISSN: 0022-3549, 1989, XP001189684
DREIDING, ANDRE S. ET AL: ".alpha.- and .gamma.-Additions in the Reformatskii reaction with methyl gamma- bromocrotonate", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 75, 3717-23 CODEN: JACSAT; ISSN: 0002-7863, 1953, XP002289408
TANG, WEI ET AL: "Fluorinated Analogs as Mechanistic Probes in Valproic Acid Hepatotoxicity: Hepatic Microvesicular Steatosis and Glutathione Status", CHEMICAL RESEARCH IN TOXICOLOGY , 8(5), 671-82 CODEN: CRTOEC; ISSN: 0893-228X, 1995, XP002289409
HAUCK, RALF SIEGBERT ET AL: "The enantiomers of the valproic acid analog 2-n-propyl-4-pentynoic acid (4-yn-VPA): asymmetric synthesis and highly stereoselective teratogenicity in mice", PHARMACEUTICAL RESEARCH , 9(7), 850-5 CODEN: PHREEB; ISSN: 0724-8741, 1992, XP008032113
TAKEUCHI, YOSHIO ET AL: "The first general and efficient method for the synthesis of tertiary alkyl fluorides", JOURNAL OF ORGANIC CHEMISTRY , 58(13), 3483-5 CODEN: JOCEAH; ISSN: 0022-3263, 1993, XP002289410
MYERS, ANDREW G. ET AL: "Synthesis of tertiary alkyl fluoride centers by asymmetric C-C(F) bond formation", TETRAHEDRON LETTERS , 38(40), 7037-7040 CODEN: TELEAY; ISSN: 0040-4039, 1997, XP004090413
ZHU, GUI-DONG ET AL: "Intramolecular Diels-Alder reaction of 8- trifluoromethyl -1,3,8-nonatrienes: an access to angular trifluoromethylated hydrindenes", BULLETIN DES SOCIETES CHIMIQUES BELGES , 103(5-6), 263-71 CODEN: BSCBAG; ISSN: 0037-9646, 1994, XP008032118
LEE, RONALD D. ET AL: "Stereoselective synthesis of the diunsaturated metabolites of valproic acid", JOURNAL OF PHARMACEUTICAL SCIENCES , 78(8), 667-71 CODEN: JPMSAE; ISSN: 0022-3549, 1989, XP001189684
DREIDING, ANDRE S. ET AL: ".alpha.- and .gamma.-Additions in the Reformatskii reaction with methyl gamma- bromocrotonate", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 75, 3717-23 CODEN: JACSAT; ISSN: 0002-7863, 1953, XP002289408
TANG, WEI ET AL: "Fluorinated Analogs as Mechanistic Probes in Valproic Acid Hepatotoxicity: Hepatic Microvesicular Steatosis and Glutathione Status", CHEMICAL RESEARCH IN TOXICOLOGY , 8(5), 671-82 CODEN: CRTOEC; ISSN: 0893-228X, 1995, XP002289409
HAUCK, RALF SIEGBERT ET AL: "The enantiomers of the valproic acid analog 2-n-propyl-4-pentynoic acid (4-yn-VPA): asymmetric synthesis and highly stereoselective teratogenicity in mice", PHARMACEUTICAL RESEARCH , 9(7), 850-5 CODEN: PHREEB; ISSN: 0724-8741, 1992, XP008032113
TAKEUCHI, YOSHIO ET AL: "The first general and efficient method for the synthesis of tertiary alkyl fluorides", JOURNAL OF ORGANIC CHEMISTRY , 58(13), 3483-5 CODEN: JOCEAH; ISSN: 0022-3263, 1993, XP002289410
MYERS, ANDREW G. ET AL: "Synthesis of tertiary alkyl fluoride centers by asymmetric C-C(F) bond formation", TETRAHEDRON LETTERS , 38(40), 7037-7040 CODEN: TELEAY; ISSN: 0040-4039, 1997, XP004090413
ZHU, GUI-DONG ET AL: "Intramolecular Diels-Alder reaction of 8- trifluoromethyl -1,3,8-nonatrienes: an access to angular trifluoromethylated hydrindenes", BULLETIN DES SOCIETES CHIMIQUES BELGES , 103(5-6), 263-71 CODEN: BSCBAG; ISSN: 0037-9646, 1994, XP008032118
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