Title:
INHIBITORS OF THE USP1/UAF1 DEUBIQUITINASE COMPLEX AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2014/105952
Kind Code:
A3
Abstract:
Disclosed are inhibitors of the USP1/UAF1 deubiquitinase complex, for example. of formula (I), wherein R1, R2, and Q are as defined herein, which are useful in treating diseases such as cancer, and improving the efficacy of DNA damaging agents in cancer treatment. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of method of inhibiting a heterodimeric deubiquitinase complex in a cell, and a method of enhancing the chemotherapeutic treatment of cancer in a mammal undergoing treatment with an anti cancer agent. Further disclosed is a method of preparing compounds of the invention.
Inventors:
MALONEY DAVID J (US)
ROSENTHAL ANDREW S (US)
JADHAV AJIT (US)
DEXHEIMER THOMAS S (US)
SIMEONOV ANTON (US)
ZHUANG ZHIHAO (US)
LIANG QIN (US)
LUCI DIANE K (US)
ROSENTHAL ANDREW S (US)
JADHAV AJIT (US)
DEXHEIMER THOMAS S (US)
SIMEONOV ANTON (US)
ZHUANG ZHIHAO (US)
LIANG QIN (US)
LUCI DIANE K (US)
Application Number:
PCT/US2013/077804
Publication Date:
October 09, 2014
Filing Date:
December 26, 2013
Export Citation:
Assignee:
US HEALTH (US)
UNIV DELAWARE (US)
UNIV DELAWARE (US)
International Classes:
C07D409/12; A61K31/517; A61K31/519; A61K31/52; A61K31/53; C07D239/94; C07D473/00; C07D487/02; C07D491/048
Domestic Patent References:
| WO2008040753A1 | 2008-04-10 | |||
| WO2013004332A1 | 2013-01-10 | |||
| WO2005103022A1 | 2005-11-03 | |||
| WO2011026835A1 | 2011-03-10 | |||
| WO2003077656A1 | 2003-09-25 |
Foreign References:
| EP1254903A1 | 2002-11-06 | |||
| EP2360158A1 | 2011-08-24 |
Other References:
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SATO, JUNJI ET AL: "2-(Pyridin-2-yl)pyrimidin-4-amine compound and salt thereof, and their use for pharmaceutical composition for treatment of diseases related to RANKL/RANK signals", XP002720347, retrieved from STN Database accession no. 2013:516354
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; FUJIWARA, HIDEYASU ET AL: "Preparation of 4-aminopyrimidine derivatives as IKK2 inhibitors", XP002720348, retrieved from STN Database accession no. 2011:199450
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; KOKUBO, SHIGERU ET AL: "Preparation of heterocyclic compounds as CCR4 or TARC and/or MDC function regulators", XP002720349, retrieved from STN Database accession no. 2010:1193251
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; YONETOKU, YASUHIRO ET AL: "Preparation of 4-aminopyrimidine derivatives as insulin secretion accelerators", XP002720350, retrieved from STN Database accession no. 2003:261678
COOMBS THOMAS C ET AL: "Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 23, no. 12, 30 March 2013 (2013-03-30), pages 3654 - 3661, XP028543373, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2013.02.096
SUH, B.C. ET AL: "SYNTHESIS AND BIOLOGICAL EXAMINATION OF NEW PYRIMIDINE TYPE DERIVATIVES AS POTENTIAL PHOSPHODIESTERASE(PDE) INHIBITORS", CHEMINFORM, vol. 29, no. 47, 24 November 1998 (1998-11-24), XP002720351
MA Y ET AL: "COMBINATORIAL SYNTHESIS OF SUBSTITUTED BIARYLS AND HETEROCYCLIC ARYLAMINES", JOURNAL OF COMBINATORIAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 6, no. 3, 4 January 2004 (2004-01-04), pages 426 - 430, XP009064582, ISSN: 1520-4766, DOI: 10.1021/CC0340731
TAREK MOHAMED ET AL: "Design, synthesis and structure-activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and A-aggregation inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 19, no. 7, 16 February 2011 (2011-02-16), pages 2269 - 2281, XP028157411, ISSN: 0968-0896, [retrieved on 20110301], DOI: 10.1016/J.BMC.2011.02.030
JUNJI MIYATA ET AL: "Orally available pyridinylpyrimidine derivatives as novel RANKL-induced osteoclastogenesis inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 22, no. 17, 6 July 2012 (2012-07-06), pages 5681 - 5684, XP055064704, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2012.06.087
DING ET AL: "A Combinatorial Scaffold Approach toward Kinase-Directed Heterocycle Libraries", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, ACS PUBLICATIONS, US, vol. 124, no. 8, 2 February 2002 (2002-02-02), pages 1594 - 1596, XP002210160, ISSN: 0002-7863, DOI: 10.1021/JA0170302
JUNJUN CHEN ET AL: "Selective and Cell-Active Inhibitors of the USP1/UAF1 Deubiquitinase Complex Reverse Cisplatin Resistance in Non-small Cell Lung Cancer Cells", CHEMISTRY & BIOLOGY, vol. 18, 22 November 2011 (2011-11-22), pages 1390 - 1400, XP002720352
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; FUJIWARA, HIDEYASU ET AL: "Preparation of 4-aminopyrimidine derivatives as IKK2 inhibitors", XP002720348, retrieved from STN Database accession no. 2011:199450
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; KOKUBO, SHIGERU ET AL: "Preparation of heterocyclic compounds as CCR4 or TARC and/or MDC function regulators", XP002720349, retrieved from STN Database accession no. 2010:1193251
DATABASE CAPLUS [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; YONETOKU, YASUHIRO ET AL: "Preparation of 4-aminopyrimidine derivatives as insulin secretion accelerators", XP002720350, retrieved from STN Database accession no. 2003:261678
COOMBS THOMAS C ET AL: "Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: Development of chemical probe ML315", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 23, no. 12, 30 March 2013 (2013-03-30), pages 3654 - 3661, XP028543373, ISSN: 0960-894X, DOI: 10.1016/J.BMCL.2013.02.096
SUH, B.C. ET AL: "SYNTHESIS AND BIOLOGICAL EXAMINATION OF NEW PYRIMIDINE TYPE DERIVATIVES AS POTENTIAL PHOSPHODIESTERASE(PDE) INHIBITORS", CHEMINFORM, vol. 29, no. 47, 24 November 1998 (1998-11-24), XP002720351
MA Y ET AL: "COMBINATORIAL SYNTHESIS OF SUBSTITUTED BIARYLS AND HETEROCYCLIC ARYLAMINES", JOURNAL OF COMBINATORIAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 6, no. 3, 4 January 2004 (2004-01-04), pages 426 - 430, XP009064582, ISSN: 1520-4766, DOI: 10.1021/CC0340731
TAREK MOHAMED ET AL: "Design, synthesis and structure-activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and A-aggregation inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 19, no. 7, 16 February 2011 (2011-02-16), pages 2269 - 2281, XP028157411, ISSN: 0968-0896, [retrieved on 20110301], DOI: 10.1016/J.BMC.2011.02.030
JUNJI MIYATA ET AL: "Orally available pyridinylpyrimidine derivatives as novel RANKL-induced osteoclastogenesis inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 22, no. 17, 6 July 2012 (2012-07-06), pages 5681 - 5684, XP055064704, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2012.06.087
DING ET AL: "A Combinatorial Scaffold Approach toward Kinase-Directed Heterocycle Libraries", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, ACS PUBLICATIONS, US, vol. 124, no. 8, 2 February 2002 (2002-02-02), pages 1594 - 1596, XP002210160, ISSN: 0002-7863, DOI: 10.1021/JA0170302
JUNJUN CHEN ET AL: "Selective and Cell-Active Inhibitors of the USP1/UAF1 Deubiquitinase Complex Reverse Cisplatin Resistance in Non-small Cell Lung Cancer Cells", CHEMISTRY & BIOLOGY, vol. 18, 22 November 2011 (2011-11-22), pages 1390 - 1400, XP002720352
Attorney, Agent or Firm:
PILLAI, Xavier et al. (VOIT & MAYER LTD.,Two Prudential Plaza, Suite 4900,180 North Stetson Avenu, Chicago Illinois, US)
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