Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors

被引：29

作者：

Bauer, Udo ^{[1
]}

Giordanetto, Fabrizio ^{[1
]}

Bauer, Martin ^{[1
]}

O'Mahony, Gavin ^{[1
]}

Johansson, Kjell E. ^{[1
]}

Knecht, Wolfgang ^{[1
]}

Hartleib-Geschwindner, Judith ^{[1
]}

Carlsson, Eva Toppner ^{[1
]}

Enroth, Cristofer ^{[2
]}

机构：

[1] AstraZeneca, R&D Molndal, S-43183 Molndal, Sweden

[2] Katedralskolan, Dept Nat Sci, S-53288 Skara, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 05期

关键词：

PDE10A; Phosphodiesterase; Hit to lead; Enzyme inhibitor; Naphthyridine; DIHYDROOROTATE DEHYDROGENASE;

D O I：

10.1016/j.bmcl.2012.01.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1,6-naphthyridine-based compounds was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. Structure-based chemical modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1944 / 1948

页数：5

共 17 条

[1] Cross-linking of protein crystals as an aid in the generation of binary protein-ligand crystal complexes, exemplified by the human PDE10a-papaverine structure [J].

Andersen, Ole Andreas ;

Schoenfeld, Dorian Leo ;

Toogood-Johnson, Ian ;

Felicetti, Brunella ;

Albrecht, Claudia ;

Fryatt, Tara ;

Whittaker, Mark ;

Hallett, David ;

Barker, John .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2009, 65 :872-874

[2]

Black S. C., 2005, Patent Application, Patent No. [WO 2005120514 A1 20051222, 2005120514]

[3]

Burris HA, 1998, INVEST NEW DRUG, V16, P19

[4] PDE-10A inhibitors as insulin secretagogues [J].

Cantin, Louis-David ;

Magnuson, Steven ;

Gunn, David ;

Barucci, Nicole ;

Breuhaus, Marina ;

Bullock, William H. ;

Burke, Jennifer ;

Claus, Thomas H. ;

Daly, Michelle ;

DeCarr, Lynn ;

Gore-Willse, Ann ;

Hoover-Litty, Helana ;

Kumarasinghe, Ellalahewage S. ;

Li, Yaxin ;

Liang, Sidney X. ;

Livingston, James N. ;

Lowinger, Timothy ;

MacDougall, Margit ;

Ogutu, Herbert O. ;

Olague, Alan ;

Ott-Morgan, Ronda ;

Schoenleber, Robert W. ;

Tersteegen, Adrian ;

Wickens, Philip ;

Zhang, Zhonghua ;

Zhu, Jian ;

Zhu, Lei ;

Sweet, Laurel J. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (10) :2869-2873

[5]

Chappie T, 2009, CURR OPIN DRUG DISC, V12, P458

[6] Phosphodiesterase 10A Inhibitor Activity in Preclinical Models of the Positive, Cognitive, and Negative Symptoms of Schizophrenia [J].

Grauer, Steven M. ;

Pulito, Virginia L. ;

Navarra, Rachel L. ;

Kelly, Michele P. ;

Kelley, Cody ;

Graf, Radka ;

Langen, Barbara ;

Logue, Sheree ;

Brennan, Julie ;

Jiang, Lixin ;

Charych, Erik ;

Egerland, Ute ;

Liu, Feng ;

Marquis, Karen L. ;

Malamas, Michael ;

Hage, Thorsten ;

Comery, Thomas A. ;

Brandon, Nicholas J. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 331 (02) :574-590

[7] Discovery of Imidazo[1,5-a]pyrido[3,2-e]pyrazines as a New Class of Phosphodiesterase 10A Inhibitiors [J].

Hoefgen, Norbert ;

Stange, Hans ;

Schindler, Rudolf ;

Lankau, Hans-Joachim ;

Grunwald, Christian ;

Langen, Barbara ;

Egerland, Ute ;

Tremmel, Peter ;

Pangalos, Menelas N. ;

Marquis, Karen L. ;

Hage, Thorsten ;

Harrison, Boyd L. ;

Malamas, Michael S. ;

Brandon, Nicholas J. ;

Kronbach, Thomas .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (11) :4399-4411

[8] PROTOTROPIC TAUTOMERISM OF HETEROAROMATIC COMPOUNDS .1. GENERAL DISCUSSION AND METHODS OF STUDY [J].

KATRITZKY, AR ;

LAGOWSKI, JM .

ADVANCES IN HETEROCYCLIC CHEMISTRY, 1963, 1 :311-338

[9] Patented PDE10A inhibitors: novel compounds since 2007 [J].

Kehler, Jan ;

Kilburn, John Paul .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2009, 19 (12) :1715-1725

[10] Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid [J].

Knecht, W ;

Henseling, J ;

Löffler, M .

CHEMICO-BIOLOGICAL INTERACTIONS, 2000, 124 (01) :61-76

← 1 2 →