Title:
IMPROVEMENTS IN PHARMACEUTICAL COMPOSITIONS
Document Type and Number:
WIPO Patent Application WO2003082813
Kind Code:
A3
Abstract:
A compound comprising a cyclopentanone, cyclopentenone, cyclohexanone or cyclohexenone group, wherein a first ring carbon atom carries an -SR substituent, R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, or aralkynyl group that, optionally, includes at least one heteroatom in its carbon skeleton, the remaining available ring carbon atoms are optionally substituted, and said compound either:- (a) is more soluble in water at a temperature of 20 - 40°C; (b) is less lipophilic; and/or, (c) has a greater therapeutic index; or; (d) is less soluble in water at a temperature of 20 - 40°C; (e) is more lipophilic; and/or, (f) has a greater therapeutic index; than an equivalent cyclohex-2-en-1-one or cyclopent-2-en-1-one derivative in which a hydrogen atom replaces said - SR group.
Inventors:
ROBERTS STANLEY MICHAEL (GB)
ROSS NICOLETTE CHRISTA (GB)
JADHAV VASUDEV (GB)
EVANS PAUL (GB)
SNAPE TIMOTHY JAMES (GB)
HAPPE ALAN MICHAEL (GB)
SANTORO GABRIELLA MARIA (IT)
ROSS NICOLETTE CHRISTA (GB)
JADHAV VASUDEV (GB)
EVANS PAUL (GB)
SNAPE TIMOTHY JAMES (GB)
HAPPE ALAN MICHAEL (GB)
SANTORO GABRIELLA MARIA (IT)
Application Number:
PCT/GB2003/001379
Publication Date:
January 22, 2004
Filing Date:
March 27, 2003
Export Citation:
Assignee:
CHARTERHOUSE THERAPEUTICS LTD (GB)
ROBERTS STANLEY MICHAEL (GB)
ROSS NICOLETTE CHRISTA (GB)
JADHAV VASUDEV (GB)
EVANS PAUL (GB)
SNAPE TIMOTHY JAMES (GB)
HAPPE ALAN MICHAEL (GB)
SANTORO GABRIELLA MARIA (IT)
ROBERTS STANLEY MICHAEL (GB)
ROSS NICOLETTE CHRISTA (GB)
JADHAV VASUDEV (GB)
EVANS PAUL (GB)
SNAPE TIMOTHY JAMES (GB)
HAPPE ALAN MICHAEL (GB)
SANTORO GABRIELLA MARIA (IT)
International Classes:
A23K1/16; A61K31/222; A61K31/27; A61K31/695; A61P1/02; A23K1/18; A61P1/04; A61P1/14; A61P1/16; A61P3/10; A61P9/00; A61P9/08; A61P9/10; A61P11/00; A61P17/02; A61P17/06; A61P17/16; A61P19/08; A61P25/00; A61P25/28; A61P29/00; A61P31/04; A61P31/12; A61P35/00; A61P37/02; A61P39/02; A61P39/06; A61P43/00; C07C323/22; C07C323/59; C07C323/60; C07F7/18; (IPC1-7): C07C323/22; C07C323/59; C07F7/18; A61K31/122; A61P25/28
Foreign References:
| EP0984001A1 | 2000-03-08 |
Other References:
T. TANAKA ET AL: "Synthesis of 7-thiaprostaglandin E1 congeners: potent inhibitors of platelet aggregation", CHEMICAL AND PHARMACEUTICAL BULLETIN, vol. 33, no. 6, 1985, PHARMACEUTICAL SOCIETY OF JAPAN, TOKYO, JP, pages 2359 - 2385, XP002095740, ISSN: 0009-2363
M.B. FLOYD, ET AL.: "Prostaglandins and congeners. 22. Synthesis of 11-substituted derivatives of 11-deoxyprostaglandins E1 and E2. Potential bronchodilators", JOURNAL OF MEDICINAL CHEMISTRY, vol. 23, 1980, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 903 - 913, XP000955991, ISSN: 0022-2623
P.M. BROPHY, ET AL.: "beta-Carbonyl substituted glutathione conjugates as inhibitors of O. volvulus GST2", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 9, May 2000 (2000-05-01), ELSEVIER SCIENCE, OXFORD, GB, pages 979 - 981, XP004199056, ISSN: 0960-894X
A. HAZATO, ET AL.: "Synthesis of thiaprostaglandin E1 derivatives", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 33, no. 5, May 1985 (1985-05-01), PHARMACEUTICAL SOCIETY OF JAPAN, TOKYO, JP, pages 1815 - 1825, XP002257910
T. MARUYAMA, ET AL.: "Design and synthesis of a highly selective EP4-receptor agonist. part 1: 3,7-dithiaPG derivatives with high selectivity", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 11, no. 15, 6 August 2001 (2001-08-06), ELSEVIER SCIENCE, OXFORD, GB, pages 2029 - 2031, XP002219417, ISSN: 0960-894X
T. MARUYAMA, ET AL.: "Design and synthesis of a highly selective EP4-receptor agonist. part 2: 5-thia and 9beta-haloPG derivatives with improved stability", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 15, 6 August 2001 (2001-08-06), ELSEVIER SCIENCE, OXFORD, GB, pages 2033 - 2035, XP002257911
Z.A. HOZIEN, ET AL.: "An efficient route for synthesis of 5,6-diphenylimidazo[2,1-b]thiazoles as antibacterial agents", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 37, no. 4, July 2000 (2000-07-01), HETEROCORPORATION, PROVO, US, pages 943 - 949, XP002257912
C.A. CHALLENGER, ET AL.: "Cyclopentenone formation via hydrogen activation in the reactions of chromium carbene complexes with alkynes", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 115, no. 4, 24 February 1993 (1993-02-24), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 1359 - 1376, XP002255883
S.H. BERTZ, ET AL.: "Conjugate addition of lithium isopropyl dithioisobutyrate to 4-acetoxycyclopent-2-enone. Assignment of stereochemistry in flexible 5-membered rings", JOURNAL OF THE CHEMICAL SOCIETY, CHEMICAL COMMUNICATIONS, no. 7, 1983, ROYAL SOCIETY OF CHEMISTRY, LETCHWORTH, GB, pages 388 - 390, XP002255885
N. IWASAWA, ET AL.: "Rearrangement of 1-(1-alkynyl)cyclopropanols to 2-cyclopentenones via their hexacarbonyldicobalt complexes. A new use of alkyne-Co(CO)6 complexes in organic synthesis", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 120, no. 16, 11 April 1998 (1998-04-11), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 3903 - 3914, XP002255886
P. BAKUZIS, ET AL.: "Oxidative functionalisation of the beta-carbon in alpha,beta-unsaturated systems. Preparation of 3-phenylthio enones, acrylates, and other vinyl derivatives", JOURNAL OF ORGANIC CHEMISTRY., vol. 46, no. 2, 16 January 1981 (1981-01-16), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 235 - 239, XP002255887
M.B. FLOYD, ET AL.: "Prostaglandins and congeners. 22. Synthesis of 11-substituted derivatives of 11-deoxyprostaglandins E1 and E2. Potential bronchodilators", JOURNAL OF MEDICINAL CHEMISTRY, vol. 23, 1980, AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 903 - 913, XP000955991, ISSN: 0022-2623
P.M. BROPHY, ET AL.: "beta-Carbonyl substituted glutathione conjugates as inhibitors of O. volvulus GST2", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 9, May 2000 (2000-05-01), ELSEVIER SCIENCE, OXFORD, GB, pages 979 - 981, XP004199056, ISSN: 0960-894X
A. HAZATO, ET AL.: "Synthesis of thiaprostaglandin E1 derivatives", CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 33, no. 5, May 1985 (1985-05-01), PHARMACEUTICAL SOCIETY OF JAPAN, TOKYO, JP, pages 1815 - 1825, XP002257910
T. MARUYAMA, ET AL.: "Design and synthesis of a highly selective EP4-receptor agonist. part 1: 3,7-dithiaPG derivatives with high selectivity", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 11, no. 15, 6 August 2001 (2001-08-06), ELSEVIER SCIENCE, OXFORD, GB, pages 2029 - 2031, XP002219417, ISSN: 0960-894X
T. MARUYAMA, ET AL.: "Design and synthesis of a highly selective EP4-receptor agonist. part 2: 5-thia and 9beta-haloPG derivatives with improved stability", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 15, 6 August 2001 (2001-08-06), ELSEVIER SCIENCE, OXFORD, GB, pages 2033 - 2035, XP002257911
Z.A. HOZIEN, ET AL.: "An efficient route for synthesis of 5,6-diphenylimidazo[2,1-b]thiazoles as antibacterial agents", JOURNAL OF HETEROCYCLIC CHEMISTRY., vol. 37, no. 4, July 2000 (2000-07-01), HETEROCORPORATION, PROVO, US, pages 943 - 949, XP002257912
C.A. CHALLENGER, ET AL.: "Cyclopentenone formation via hydrogen activation in the reactions of chromium carbene complexes with alkynes", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 115, no. 4, 24 February 1993 (1993-02-24), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 1359 - 1376, XP002255883
S.H. BERTZ, ET AL.: "Conjugate addition of lithium isopropyl dithioisobutyrate to 4-acetoxycyclopent-2-enone. Assignment of stereochemistry in flexible 5-membered rings", JOURNAL OF THE CHEMICAL SOCIETY, CHEMICAL COMMUNICATIONS, no. 7, 1983, ROYAL SOCIETY OF CHEMISTRY, LETCHWORTH, GB, pages 388 - 390, XP002255885
N. IWASAWA, ET AL.: "Rearrangement of 1-(1-alkynyl)cyclopropanols to 2-cyclopentenones via their hexacarbonyldicobalt complexes. A new use of alkyne-Co(CO)6 complexes in organic synthesis", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 120, no. 16, 11 April 1998 (1998-04-11), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 3903 - 3914, XP002255886
P. BAKUZIS, ET AL.: "Oxidative functionalisation of the beta-carbon in alpha,beta-unsaturated systems. Preparation of 3-phenylthio enones, acrylates, and other vinyl derivatives", JOURNAL OF ORGANIC CHEMISTRY., vol. 46, no. 2, 16 January 1981 (1981-01-16), AMERICAN CHEMICAL SOCIETY, WASHINGTON, DC, US, pages 235 - 239, XP002255887
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