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Title:
1' - SUBSTITUTED RIBOSE 5 ' - POLYPHOSPHATE ANALOGS AND THEIR USE AS MODULATORS OF P2Y RECEPTOR ACTIVITY
Document Type and Number:
WIPO Patent Application WO/2008/060632
Kind Code:
A3
Abstract:
The invention provides substituted 5'-bi- tri- or tetraphosphate ribose analog compounds that act at P2Y receptors, e.g., the P2Y2 receptor, including pharmaceutical compositions; and uses thereof to treat or prevent diseases associated with that receptor, e.g., disorders relating to mucus secretion, such as cystic fibrosis, chronic obstructive pulmonary disorder (COPD), asthma, constipation, chronic idiopathic constipation, dry mouth (xerostomia), gum disease, and gastrointestinal problems caused by radiation and chemotherapy for cancer.

Inventors:
BEN-ZEEV, Efrat (3 Hayetzira Street, Ramat Gan, Gan, IL)
JACQUES, Vincent (118 Roger Avenue, Apt. #2Somerville, MA, 02144, US)
MARANTZ, Yael (Pob 263, Kfar Shmuel, Shmuel, IL)
REDDY, A., Sekar (12 Gayland Street, Burlington, MA, 01803, US)
ZHANG, Zhaoda (4 Inwood Lane, Andover, MA, 01810, US)
BECKER, Oren (12 Motza Haktana Street, Mevaseret Zion, Zion, IL)
MCCAULAY, Dilara (100 Gore Street, Cambridge, MA, 02141, US)
ORBACH, Pini (15 Abbott Street, Needham, MA, 02492, US)
SHACHAM, Sharon (16 High Rock Terrace, Chestnut Hill, MA, 02467, US)
SAHA, Ashis, K. (6 Cardinal Court, Stow, MA, 01775, US)
XIE, Michael (28 Algonquin Drive, Natick, MA, 01760, US)
Application Number:
US2007/024150
Publication Date:
July 14, 2011
Filing Date:
November 16, 2007
Export Citation:
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Assignee:
EPIX DELAWARE, INC. (Four Maguire Road, Lexington, MA, 02421, US)
BEN-ZEEV, Efrat (3 Hayetzira Street, Ramat Gan, Gan, IL)
JACQUES, Vincent (118 Roger Avenue, Apt. #2Somerville, MA, 02144, US)
MARANTZ, Yael (Pob 263, Kfar Shmuel, Shmuel, IL)
REDDY, A., Sekar (12 Gayland Street, Burlington, MA, 01803, US)
ZHANG, Zhaoda (4 Inwood Lane, Andover, MA, 01810, US)
BECKER, Oren (12 Motza Haktana Street, Mevaseret Zion, Zion, IL)
MCCAULAY, Dilara (100 Gore Street, Cambridge, MA, 02141, US)
ORBACH, Pini (15 Abbott Street, Needham, MA, 02492, US)
SHACHAM, Sharon (16 High Rock Terrace, Chestnut Hill, MA, 02467, US)
SAHA, Ashis, K. (6 Cardinal Court, Stow, MA, 01775, US)
XIE, Michael (28 Algonquin Drive, Natick, MA, 01760, US)
International Classes:
C07H19/16; A61K31/70; A61P1/04; A61P11/00; C07H15/203; C07H19/20; C07H21/00
Domestic Patent References:
WO2003011885A12003-02-13
WO1998018430A21998-05-07
Foreign References:
US5620676A1997-04-15
US20050085439A12005-04-21
Other References:
JACOBSON K A ET AL: "Structure activity and molecular modeling analyses of ribose- and base-modified uridine 5'-triphosphate analogues at the human P2Y2 and P2Y4 receptors", BIOCHEMICAL PHARMACOLOGY, PERGAMON, OXFORD, GB, vol. 71, no. 4, 14 February 2006 (2006-02-14), pages 540 - 549, XP025043107, ISSN: 0006-2952, [retrieved on 20060214]
BRACHER ANDREAS ET AL: "Histidine 179 mutants of GTP cyclohydrolase I catalyze the formation of 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 24, 11 June 1999 (1999-06-11), pages 16727 - 16735, XP002637619, ISSN: 0021-9258
SHARKIN Y A ET AL: "Synthesis and substrate properties of modified nucleoside 5'-triphosphates mimicking dATP in the reactions of DNA synthesis catalyzed by DNA polymerases", RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY, MAIK NAUKA-INTERPERIODICA, RU, vol. 27, no. 5, 1 January 2001 (2001-01-01), pages 340 - 348, XP002343377, ISSN: 1068-1620, DOI: DOI:10.1023/A:1012348515833
IMOTO SHUHEI ET AL: "Synthesis, DNA polymerase incorporation, and enzymatic phosphate hydrolysis of formamidopyrimidine nucleoside triphosphates", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 128, no. 45, 25 October 2006 (2006-10-25), Web, pages 14606 - 14611, XP002637620, ISSN: 0002-7863
WOENCKHAUS C ET AL: "[Synthesis and biochemical properties of nicotinamide-phenyl-dinucleo tide].", CHEMISCHE BERICHTE MAY 1966 LNKD- PUBMED:4228732, vol. 99, no. 5, May 1966 (1966-05-01), pages 1712 - 1717, XP002637621, ISSN: 0009-2940
NOTTBOHM AMANDA C ET AL: "A colorimetric substrate for poly(ADP-ribose) polymerase-1, VPARP, and tankyrase-1", ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, WILEY VCH VERLAG, WEINHEIM, vol. 46, no. 12, 14 February 2007 (2007-02-14), Online, pages 2066 - 2069, XP002502780, ISSN: 1433-7851, DOI: DOI:10.1002/ANIE.200603988
Attorney, Agent or Firm:
DAVIS, Chad, E. et al. (Goodwin Procter LLP, Exchange PlaceBoston, MA, 02109, US)
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