α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors

被引：45

作者：

Cui, Peng ^{[1
]}

McCalmont, William F. ^{[1
]}

Tomsig, Jose L. ^{[2
]}

Lynch, Kevin R. ^{[2
]}

Macdonald, Timothy L. ^{[1
]}

机构：

[1] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA

[2] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 05期

关键词：

autotaxin; ATX; phosphonates; LPA;

D O I：

10.1016/j.bmc.2007.11.078

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two beta-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated alpha- and beta-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of beta-hydroxy phosphonates was also studied. Published by Elsevier Ltd.

引用

页码：2212 / 2225

页数：14

共 40 条

[1]

DEHYDROGENATION OF A PHOSPHONATE SUBSTRATE ANALOG BY GLYCEROL 3-PHOSPHATE DEHYDROGENASE [J].

ADAMS, PR ;

HARRISON, R ;

INCH, TD .

BIOCHEMICAL JOURNAL, 1974, 141 (03) :729-732

[2]

Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis [J].

Baker, Daniel L. ;

Fujiwara, Yuko ;

Pigg, Kathryn R. ;

Tsukahara, Ryoko ;

Kobayashi, Susumu ;

Murofushi, Hiromu ;

Uchiyama, Ayako ;

Murakami-Murofushi, Kimiko ;

Koh, Eunjin ;

Bandle, Russell W. ;

Byun, Hoe-Sup ;

Bittman, Robert ;

Fan, Dominic ;

Murph, Mandi ;

Mills, Gordon B. ;

Tigyi, Gabor .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (32) :22786-22793

[3]

Nucleotide pyrophosphatases/phosphodiesterases on the move [J].

Bollen, M ;

Gijsbers, R ;

Ceulemans, H ;

Stalmans, W ;

Stefan, C .

CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2000, 35 (06) :393-432

[4]

AN EFFICIENT SYNTHESIS OF GAMMA-AMINO-BETA-KETOALKYLPHOSPHONATES FROM ALPHA-AMINO-ACIDS [J].

CHAKRAVARTY, PK ;

COMBS, P ;

ROTH, A ;

GREENLEE, WJ .

TETRAHEDRON LETTERS, 1987, 28 (06) :611-612

[5]

Lysophosphatidic acid receptors [J].

Contos, JJA ;

Ishii, I ;

Chun, J .

MOLECULAR PHARMACOLOGY, 2000, 58 (06) :1188-1196

[6]

Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors [J].

Cui, Peng ;

Tomsig, Jose L. ;

McCalmont, William F. ;

Lee, Sangderk ;

Becker, Christopher J. ;

Lynch, Kevin R. ;

Macdonald, Timothy L. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (06) :1634-1640

[7]

Lysophosphatidic acid protects and rescues intestinal epithelial cells from radiation- and chemotherapy-induced apoptosis [J].

Deng, WL ;

Balazs, L ;

Wang, DA ;

Van Middlesworth, L ;

Tigyi, G ;

Johnson, LR .

GASTROENTEROLOGY, 2002, 123 (01) :206-216

[8]

SYNTHESIS AND REDUCTION OF ALPHA-AMINO KETONES DERIVED FROM LEUCINE [J].

DUFOUR, MN ;

JOUIN, P ;

PONCET, J ;

PANTALONI, A ;

CASTRO, B .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1986, (11) :1895-1899

[9]

Synthesis and pharmacological evaluation of second-generation phosphatidic acid derivatives as lysophosphatidic acid receptor ligands [J].

Durgam, GG ;

Tsukahara, R ;

Makarova, N ;

Walker, MD ;

Fujiwara, Y ;

Pigg, KR ;

Baker, DL ;

Sardar, VM ;

Parrill, AL ;

Tigyi, G ;

Miller, DD .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (03) :633-640

[10]

Synthesis, structure-activity relationships, and biological evaluation of fatty alcohol phosphates as lysophosphatidic acid receptor ligands, activators of PPARγ, and inhibitors of autotaxin [J].

Durgam, GG ;

Virag, T ;

Walker, MD ;

Tsukahara, R ;

Yasuda, S ;

Liliom, K ;

van Meeteren, LA ;

Moolenaar, WH ;

Wilke, N ;

Siess, W ;

Tigyi, G ;

Miller, DD .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (15) :4919-4930

← 1 2 3 4 →