Title:
HETEROCYCLIC INHIBITORS OF CBP/EP300 AND THEIR USE IN THE TREATMENT OF CANCER
Document Type and Number:
WIPO Patent Application WO/2017/205536
Kind Code:
A3
Abstract:
The present invention relates to compounds of formula (I) and formula (II): and to salts thereof, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II), or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.
Inventors:
CYR PATRICK (US)
BRONNER SARAH (US)
ROMERO F ANTHONY (US)
MAGNUSON STEVEN (US)
TSUI VICKIE HSIAO-WEI (US)
WAI JOHN (CN)
LAI KWONG WAH (CN)
WANG FEI (CN)
BRONNER SARAH (US)
ROMERO F ANTHONY (US)
MAGNUSON STEVEN (US)
TSUI VICKIE HSIAO-WEI (US)
WAI JOHN (CN)
LAI KWONG WAH (CN)
WANG FEI (CN)
Application Number:
PCT/US2017/034320
Publication Date:
January 04, 2018
Filing Date:
May 24, 2017
Export Citation:
Assignee:
GENENTECH INC (US)
CONSTELLATION PHARMACEUTICALS INC (US)
CONSTELLATION PHARMACEUTICALS INC (US)
International Classes:
C07D401/14; A61K31/475; A61K31/5513; A61K31/553; A61P35/00; C07D243/14; C07D267/14; C07D405/14; C07D409/14; C07D413/04; C07D413/10; C07D413/14; C07D417/14; C07D471/04; C07D487/04
Domestic Patent References:
| WO2016044694A1 | 2016-03-24 | |||
| WO2014133414A2 | 2014-09-04 | |||
| WO2013006485A1 | 2013-01-10 | |||
| WO2010138490A1 | 2010-12-02 | |||
| WO2010118208A1 | 2010-10-14 |
Foreign References:
| US6011029A | 2000-01-04 | |||
| US20120258953A1 | 2012-10-11 |
Other References:
PICAUD, S. ET AL.: "Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy", CANCER RESEARCH, vol. 75, no. 23, 9 November 2015 (2015-11-09), pages 5106 - 5119, XP055397832, ISSN: 0008-5472, DOI: 10.1158/0008-5472.CAN-15-0236
TAKEUCHI, C.S. ET AL.: "Discovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR)", JOURNAL OF MEDICINAL CHEMISTRY, vol. 56, no. 6, 8 February 2013 (2013-02-08), pages 2218 - 2234, XP055398003, ISSN: 0022-2623, DOI: 10.1021/jm3007933
CHAUBE, U. ET AL.: "3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 26, no. 3, 23 December 2015 (2015-12-23), pages 864 - 874, XP029391930, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2015.12.075
DING, C.Z. ET AL.: "Discovery and Structure-Activity Relationships of Imidazole-Containing Tetrahydrobenzodiazepine Inhibitors of Farnesyltransferase", JOURNAL OF MEDICINAL CHEMISTRY, vol. 42, no. 25, 1999, pages 5241 - 5253, XP003000948, ISSN: 0022-2623, DOI: 10.1021/JM990391W
POPP, T.A. ET AL.: "A new approach to monoprotected 1,4-benzodiazepines via a one-pot N-deprotection/reductive cyclization procedure", TETRAHEDRON, vol. 72, no. 13, 9 February 2016 (2016-02-09), pages 1668 - 1674, XP029444590, ISSN: 0040-4020, DOI: 10.1016/J.TET.2016.02.019
WILSON, J.E. ET AL.: "Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 26, no. 12, 15 June 2016 (2016-06-15), AMSTERDAM, NL, pages 2947 - 2951, XP055397920, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2016.04.018
POPP, T.A. ET AL.: "Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 59, no. 19, 27 September 2016 (2016-09-27), pages 8889 - 8912, XP055397844, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b00774
TAKEUCHI, C.S. ET AL.: "Discovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR)", JOURNAL OF MEDICINAL CHEMISTRY, vol. 56, no. 6, 8 February 2013 (2013-02-08), pages 2218 - 2234, XP055398003, ISSN: 0022-2623, DOI: 10.1021/jm3007933
CHAUBE, U. ET AL.: "3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 26, no. 3, 23 December 2015 (2015-12-23), pages 864 - 874, XP029391930, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2015.12.075
DING, C.Z. ET AL.: "Discovery and Structure-Activity Relationships of Imidazole-Containing Tetrahydrobenzodiazepine Inhibitors of Farnesyltransferase", JOURNAL OF MEDICINAL CHEMISTRY, vol. 42, no. 25, 1999, pages 5241 - 5253, XP003000948, ISSN: 0022-2623, DOI: 10.1021/JM990391W
POPP, T.A. ET AL.: "A new approach to monoprotected 1,4-benzodiazepines via a one-pot N-deprotection/reductive cyclization procedure", TETRAHEDRON, vol. 72, no. 13, 9 February 2016 (2016-02-09), pages 1668 - 1674, XP029444590, ISSN: 0040-4020, DOI: 10.1016/J.TET.2016.02.019
WILSON, J.E. ET AL.: "Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 26, no. 12, 15 June 2016 (2016-06-15), AMSTERDAM, NL, pages 2947 - 2951, XP055397920, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2016.04.018
POPP, T.A. ET AL.: "Development of Selective CBP/P300 Benzoxazepine Bromodomain Inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 59, no. 19, 27 September 2016 (2016-09-27), pages 8889 - 8912, XP055397844, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b00774
Attorney, Agent or Firm:
HARRIS, Robert J. et al. (US)
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